The Population Biology and Transmission Dynamics of Loa loa.

PubMed

Whittaker, Charles; Walker, Martin; Pion, Sébastien D S; Chesnais, Cédric B; Boussinesq, Michel; Basáñez, María-Gloria

2018-04-01

Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

In vitro activities of plant extracts on human Loa loa isolates and cytotoxicity for eukaryotic cells.

PubMed

Mengome, Line-Edwige; Akue, Jean Paul; Souza, Alain; Feuya Tchoua, Guy Raymond; Nsi Emvo, Edouard

2010-08-01

Loa loa, a filarial worm, can cause fatal encephalitis in humans. In an attempt to find alternatives to the standard treatments (ivermectin and diethylcarbamazine citrate), we tested 12 methanolic extracts of nine traditional plant remedies. The extracts (100-0.09 microg/ml) were incubated with 20 Loa loa microfilariae isolated from patients at 37 degrees C with 5% CO(2) in modified Eagle's medium supplemented with 10% fetal serum and antibiotics. Activity was evaluated 120 h later by counting live microfilariae under a microscope. Cytotoxicity for eukaryotic cells was estimated by measuring 3-[4,5-dimethylthiazol-2-yl]-2-5 diphenyl tetrazolium bromide transformation to formazan at 450 nM in a spectrophotometer. The plants tested were Lophira alata, Greenwayodendron suaveolens, Uapaca togoensis, Zanthoxylum heitzii, Peperomia pellucida, Piptadeniastrum africanum, Petersianthus macrocarpus, Vernonia conferta, and Vernonia hymenolepis. Chemical screening showed that most of the extracts contained reducing sugars, tannin or polyphenols, sterols or triterpenes, saponosides, and alkaloids. None contained carotinoids and few contained flavonoids. The 50% lethal concentration ranged from 0.22 to 70.28 microg/ml, while the 50% inhibitory concentration for eukaryotic cells (IC(50)) ranged from 8.52 to 119.52 microg/ml. Extracts of P. macrocarpus (selectivity index = 72.16), P. africanum (13.69), Z. heitzii (12.11), and L. alata (9.26) were highly selective for L. loa.

Positivity of Antigen Tests Used for Diagnosis of Lymphatic Filariasis in Individuals Without Wuchereria bancrofti Infection But with High Loa loa Microfilaremia.

PubMed

Pion, Sébastien D; Montavon, Céline; Chesnais, Cédric B; Kamgno, Joseph; Wanji, Samuel; Klion, Amy D; Nutman, Thomas B; Boussinesq, Michel

2016-12-07

Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detecting Wuchereria bancrofti circulating filarial antigens (CFAs), has been the backbone for mapping and monitoring lymphatic filariasis (LF) worldwide. Recently, there have been instances in which CFA positivity has been associated with Loa loa microfilaremia. Here, we examined the association, at both the community and individual levels, between L. loa and CFA using additional diagnostic tools (quantitative polymerase chain reaction [qPCR], Og4C3 enzyme-linked immunosorbent assay, and IgG4 antibodies to Wb123 assays) to demonstrate the relationship between L. loa microfilaremia and ICT positivity. In May 2013, peripheral blood was collected during the day from 1,812 individuals living in southern Cameroon. ICT tests were done on the spot, and positive individuals were resampled at night. Results of qPCR and Wb123 assays concurred proving the absence of W. bancrofti infection. Og4C3 assays indicate a quantitative relationship between the level of L. loa microfilaremia and that of CFA. This was confirmed by epidemiological analyses, which reveal a strong association between L. loa microfilaremia and ICT positivity, with 50% of ICT reacting to L. loa when its microfilarial density exceeds 30,000 microfilariae/mL. At the community level, the proportion of positive ICT would exceed 2% when the prevalence of L. loa microfilaremia in the total population is above 20%. This has significant implications in terms of mapping and control of LF caused by W. bancrofti in Loa-endemic areas. Cross-reactivity of ICT with L. loa has to be considered in the context of both individual and community diagnostics. © The American Society of Tropical Medicine and Hygiene.

A Generic Authentication LoA Derivation Model

NASA Astrophysics Data System (ADS)

Yao, Li; Zhang, Ning

One way of achieving a more fine-grained access control is to link an authentication level of assurance (LoA) derived from a requester’s authentication instance to the authorisation decision made to the requester. To realise this vision, there is a need for designing a LoA derivation model that supports the use and quantification of multiple LoA-effecting attributes, and analyse their composite effect on a given authentication instance. This paper reports the design of such a model, namely a generic LoA derivation model (GEA- LoADM). GEA-LoADM takes into account of multiple authentication attributes along with their relationships, abstracts the composite effect by the multiple attributes into a generic value, authentication LoA, and provides algorithms for the run-time derivation of LoA. The algorithms are tailored to reflect the relationships among the attributes involved in an authentication instance. The model has a number of valuable properties, including flexibility and extensibility; it can be applied to different application contexts and support easy addition of new attributes and removal of obsolete ones.

Evaluation of in vitro culture systems for the maintenance of microfilariae and infective larvae of Loa loa.

PubMed

Zofou, Denis; Fombad, Fanny Fri; Gandjui, Narcisse V T; Njouendou, Abdel Jelil; Kengne-Ouafo, Arnaud Jonas; Chounna Ndongmo, Patrick W; Datchoua-Poutcheu, Fabrice R; Enyong, Peter A; Bita, Dizzle Tayong; Taylor, Mark J; Turner, Joseph D; Wanji, Samuel

2018-05-02

Suitable and scalable in vitro culture conditions for parasite maintenance are needed to foster drug research for loiasis, one of the neglected tropical diseases which has attracted only limited attention over recent years, despite having important public health impacts. The present work aims to develop adequate in vitro culture systems for drug screening against both microfilariae (mf) and infective third-stage larvae (L3) of Loa loa. In vitro culture conditions were evaluated by varying three basic culture media: Roswell Park Memorial Institute (RPMI-1640), Dulbecco's modified Eagle's medium (DMEM) and Iscove's modified Dulbecco's medium (IMDM); four sera/proteins: newborn calf serum (NCS), foetal bovine serum (FBS), bovine serum albumin (BSA) and the lipid-enriched BSA (AlbuMax® II, ALB); and co-culture with the Monkey Kidney Epithelial Cell line (LLC-MK2) as a feeder layer. The various culture systems were tested on both mf and L3, using survival (% motile), motility (T 90 = mean duration (days) at which at least 90% of parasites were fully active) and moulting rates of L3 as the major criteria. The general linear model regression analysis was performed to assess the contribution of each variable on the viability of Loa loa L3 and microfilarie. All statistical tests were performed at 95% confidence interval. Of the three different media tested, DMEM and IMDM were the most suitable sustaining the maintenance of both L. loa L3 and mf. IMDM alone could sustain L3 for more than 5 days (T 90 = 6.5 ± 1.1 day). Serum supplements and LLC-MK2 co-cultures significantly improved the survival of parasites in DMEM and IMDM. In co-cultures with LLC-MK2 cells, L. loa mf were maintained in each of the three basic media (T 90 of 16.4-19.5 days) without any serum supplement. The most effective culture systems promoting significant moulting rate of L3 into L4 (at least 25%) with substantial maintenance time were: DMEM + BSA, DMEM + NCS, DMEM-AlbuMax®II, DMEM + FBS all in co

Is the Hawaiian Archipelago dominantly Loa-trend?

NASA Astrophysics Data System (ADS)

Weis, D.; Harrison, L.; Garcia, M. O.; Rhodes, M. M.

2015-12-01

Hawaiian volcanoes are distributed en echelon on the islands along two chains, the Loa and Kea trends, that are geographically and geochemically distinct1,2. These geochemical differences may be attributed to source zoning (concentric or bilateral) of the Hawaiian mantle plume (HMP) or to variations in pressure and temperature of melting. Most of these models assume a degree of independence of the two trends that is perhaps not realistic. To explore the isotopic characteristics of two "Kea"-trend volcanoes with transitional signatures, we analyzed 11 samples of Kohala shield-stage tholeiitic lavas and three from Haleakala for high-precision Pb-Nd-Sr-Hf isotopes. These samples are transitional in all isotopic systems between Loa and Kea compositions and cross-over the Pb-Pb boundary3. Minor cross-overs had been documented in Mauna Kea4, Kilauea5, and W Molokai6 basalts. A bilateral or concentric view of the HMP is thus too simplistic. Statistical analysis of the MC-ICP-MS or triple-spike shield tholeiite data (n>600) and the existence of three Pb-Pb trends originating from average Loa indicate that Loa is the dominant mantle source composition on the archipelago. Isotopically, four geochemical groups are identified: Kea (Mauna Kea, Kilauea), average Loa (Mauna Loa, Hualalai, Kauai, Waianae, W. Molokai, Loihi), enriched Loa (Koolau Makapuu, Lanai, Kahoolawe) and transitional Kea (E. Molokai, W. Maui, Haleakala, Kohala). The implications are: 1) HMP source components refresh and grade into and out of existence on a smaller timescale than previously thought; 2) the Kea trend is also heterogeneous; and 3) vertical heterogeneity of the plume is important on a regional scale as well as at the scale of individual volcanoes6. 1Jackson et al., 1972, GSA Bull. 83, 1-17. 2Weis et al., 2011, Nat. Geosci., 4, 831-838. 3Abouchami et al., 2005, Nature, 434, 851-856. 4Eisele et al., 2003, G-cubed, 4, 5, 32 pages. 5Marske et al., 2007, EPSL, 259, 34-50. 6Xu et al., 2014, GCA, 132

Mauna Loa Revealed: Structure, Composition, History, and Hazards

NASA Astrophysics Data System (ADS)

Rhodes, J. M.; Lockwood, John P.

Mauna Loa is a volcano of superlatives: it is the largest active volcano on Earth and among the most productive. This volume serves to place on record the current state of our knowledge concerning Mauna Loa at the beginning of the Decade Volcano Project. The scope is broad, encompassing the geologic and exploratory history of the volcano, an overview of its submarine geology, its structure, petrologic and geochemical characteristics, and what Mauna Loa has to tell us about the Hawaiian mantle plume; it covers also remote sensing methods and the use of gravity, seismic and deformational studies for eruption monitoring and forecasting, hazards associated with the volcano, and even the importance of a changing volcanic landscape with a wide spectrum of climate zones as an ecological laboratory. We have made a deliberate effort to present a comprehensive spectrum of current Mauna Loa research by building on a December 1993 symposium at the AGU Fall Meeting that considered (1) what is currently known about Mauna Loa, (2) critical problems that need to be addressed, and (3) the technical means to solve these problems, and by soliciting contributions that were not part of the symposium. We encouraged authors to consider how their papers relate to others in the volume through crossreferencing. The intent was that this monograph should be a book about Mauna Loa rather than a collection of disparate papers.

A Closer Look at Recent Deep Mauna Loa Seismicity

NASA Astrophysics Data System (ADS)

Okubo, P. G.; Wolfe, C. J.; Nakata, J. S.; Koyanagi, S. K.; Uribe, J. O.

2005-12-01

In 2002, Mauna Loa Volcano showed signs of reawakening, some 18 years since its last eruption in 1984. First, in April, a brief flurry of microearthquakes occurred at cataloged depths from 25 to 55 km beneath Mauna Loa's summit caldera. Then in May 2002, after the microearthquake swarm had ended, geodetic monitors across Mauna Loa's summit caldera registered a change, from line-length shortening to extension, interpreted as reinflation of a magma body approximately 4 km beneath the volcano's summit. Accordingly, the Hawaiian Volcano Observatory issued advisories related to Mauna Loa's stirring. In July 2004, HVO began to record deep long-period (LP) earthquakes beneath Mauna Loa. Historically, interpretations of such seismicity patterns have associated LP source volumes with magma chambers and magma pathways. Over a few weeks, this seismicity dramatically jumped to levels of several dozen per day. Between the months of July and December 2004, nearly 2000 Mauna Loa LPs were located between roughly 25 km and greater than 60 km depths by HVO seismic analysts. In late December, these earthquakes rather abruptly ceased, and their levels have remained low ever since. We seek a more detailed understanding of how these earthquakes may factor into Mauna Loa's eruptive framework. Given that their first arrivals are typically emergent, hypocentral estimates using only P-wave first-arrival times of LP earthquakes are often marginally constrained. With such hypocentral estimates, it is difficult to establish clear relationships among the earthquake locations themselves, or between the earthquakes and other processes like crustal extension or magma accumulation or withdrawl. Building on earlier applications to deep earthquakes in Hawaii and LP earthquakes beneath Kilauea, we are reexamining this unprecedented Mauna Loa deep seismicity with waveform correlation and precise earthquake relocation techniques. Work to date reveals that, although the waveform correlation coefficients

Filaricidal activities on Onchocerca ochengi and Loa loa, toxicity and phytochemical screening of extracts of Tragia benthami and Piper umbellatum.

PubMed

Cho-Ngwa, Fidelis; Monya, Elvis; Azantsa, Boris K; Manfo, Faustin Pascal T; Babiaka, Smith B; Mbah, James A; Samje, Moses

2016-08-30

Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf). Fourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively. At 500 μg/mL, all extracts showed 100 % activity on Onchocerca ochengi males and microfilariae, while 9 showed 100 % activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63 μg/mL and 35.65 μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9 μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts. These results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.

Mauna Loa eruptive history—The preliminary radiocarbon record

NASA Astrophysics Data System (ADS)

Lockwood, John P.

Radiocarbon dating of charcoal from beneath lava flows of Mauna Loa has provided the most detailed prehistoric eruptive chronology of any volcano on Earth. Three hundred and fifty-five 14C dates have been reviewed, stratigraphically contradictory dates have been rejected, and multiple dates on single flows averaged to give "reliable" ages on 170 separate lava flows (about 35% of the total number of prehistoric Mauna Loa flows mapped to date). The distribution of these ages has revealed fundamental variations in the time and place of Mauna Loa eruptive activity, particularly for Holocene time. As lava flow activity from Mauna Loa's summit waxes, activity on the rift zones wanes. A cyclic model is proposed which involves a period of concentrated summit shield-building activity associated with long-lived lava lakes and frequent overflows of pahoehoe lavas on the north and southeast flanks. At this time, compressive stresses across Mauna Loa's rift zones are relatively high, inhibiting eruptions in these areas. This period is then followed by a relaxation of stresses across Mauna Loa's rift zones and a long period of frequent rift zone eruptions as magma migrates downrift. This change of eruptive style is marked by summit caldera collapse (possibly associated with massive eruptions of picritic lavas low on the rift zones). Concurrent with this increased rift zone activity, the summit caldera is gradually filled by repeated summit eruptions, stress across the rift zones increases, magma rises more easily to the summit, rift activity wanes, and the cycle repeats itself. Two such cycles are suggested within the late Holocene, each lasting 1,500-2,000 years. Earlier evidence for such cycles is obscure. Mauna Loa appears to have been quiescent between 6-7 ka, for unknown reasons. A period of increased eruptive activity marked the period 8-11 ka, coincident with the Pleistocene-Holocene boundary. Other volcanoes on the Island of Hawaii for which (limited) radiocarbon dating

Loa loa vectors Chrysops spp.: perspectives on research, distribution, bionomics, and implications for elimination of lymphatic filariasis and onchocerciasis.

PubMed

Kelly-Hope, Louise; Paulo, Rossely; Thomas, Brent; Brito, Miguel; Unnasch, Thomas R; Molyneux, David

2017-04-05

Loiasis is a filarial disease caused Loa loa. The main vectors are Chrysops silacea and C. dimidiata which are confined to the tropical rainforests of Central and West Africa. Loiasis is a mild disease, but individuals with high microfilaria loads may suffer from severe adverse events if treated with ivermectin during mass drug administration campaigns for the elimination of lymphatic filariasis and onchocerciasis. This poses significant challenges for elimination programmes and alternative interventions are required in L. loa co-endemic areas. The control of Chrysops has not been considered as a viable cost-effective intervention; we reviewed the current knowledge of Chrysops vectors to assess the potential for control as well as identified areas for future research. We identified 89 primary published documents on the two main L. loa vectors C. silacea and C dimidiata. These were collated into a database summarising the publication, field and laboratory procedures, species distributions, ecology, habitats and methods of vector control. The majority of articles were from the 1950-1960s. Field studies conducted in Cameroon, Democratic Republic of Congo, Equatorial Guinea, Nigeria and Sudan highlighted that C. silacea is the most important and widespread vector. This species breeds in muddy streams or swampy areas of forests or plantations, descends from forest canopies to feed on humans during the day, is more readily adapted to human dwellings and attracted to wood fires. Main vector targeted measures proposed to impact on L. loa transmission included personal repellents, household screening, indoor residual spraying, community-based environmental management, adulticiding and larviciding. This is the first comprehensive review of the major L. loa vectors for several decades. It highlights key vector transmission characteristics that may be targeted for vector control providing insights into the potential for integrated vector management, with multiple diseases

Numerous Submarine Radial Vents Revealed on Mauna Loa Volcano

NASA Astrophysics Data System (ADS)

Wanless, D.; Garcia, M. O.; Rhodes, J. M.; Trusdell, F. A.; Schilling, S.; Weis, D.; Fornari, D.; Vollinger, M.

2003-12-01

Among Hawaiian shield volcanoes, Mauna Loa is distinct in having vents outside of its summit and rift zones. These radial vents are located on its northern and western flanks and account for approximately 10% of historic eruptions outside the summit region. Thirty-three subaerial and one submarine vent (active in 1877) were known prior to our work. During a recent Jason2 expedition to the volcano's western flank, nine new submarine radial vents were discovered. Eighty-five samples were collected from these and the 1877 radial vent. Bathymetry and side-scan imagery were acquired using an EM300 multibeam echo sounder. The high resolution data (vertical resolution of approximately 4 m and horizontal resolution of 25 m) allowed us to create the first detailed geologic map of Mauna Loa's western submarine flank. The map was compiled using video and still photography from the Jason2 ROV and geochemical analysis of the samples. The geochemistry includes microprobe glass and XRF whole rock major and trace element data. Eight of the submarine radial vents sampled erupted tholeiitic lavas that are geochemically similar to historical subaerial eruptions on Mauna Loa. However, in contrast to all previously collected Mauna Loa lavas, two of the young vents erupted alkalic basalts. These lavas may have been derived from Mauna Loa, as they have somewhat higher FeO and TiO2 values at a given MgO content than alkalic lavas from neighboring Hualalai volcano, whose vents are located only on rifts 16 km away. Alkalic lavas are indicative of the postshield stage of volcanism and may signal the impending demise of Mauna Loa volcano.

Further evidence of the cross-reactivity of the Binax NOW® Filariasis ICT cards to non-Wuchereria bancrofti filariae: experimental studies with Loa loa and Onchocerca ochengi.

PubMed

Wanji, Samuel; Amvongo-Adjia, Nathalie; Njouendou, Abdel Jelil; Kengne-Ouafo, Jonas Arnaud; Ndongmo, Winston Patrick Chounna; Fombad, Fanny Fri; Koudou, Benjamin; Enyong, Peter A; Bockarie, Moses

2016-05-05

The immunochromatographic test (ICT) for lymphatic filariasis is a serological test designed for unequivocal detection of circulating Wuchereria bancrofti antigen. It was validated and promoted by WHO as the primary diagnostic tool for mapping and impact monitoring for disease elimination following interventions. The initial tests for specificity and sensitivity were based on samples collected in areas free of loiasis and the results suggested a near 100% specificity for W. bancrofti. The possibility of cross-reactivity with non-Wuchereria bancrofti antigens was not investigated until recently, when false positive results were observed in three independent studies carried out in Central Africa. Associations were demonstrated between ICT positivity and Loa loa microfilaraemia, but it was not clearly established if these false positive results were due to L. loa or can be extended to other filarial nematodes. This study brought further evidences of the cross-reactivity of ICT card with L. loa and Onchocerca ochengi (related to O. volvulus parasite) using in vivo and in vitro systems. Two filarial/host experimental systems (L. loa-baboon and O. ochengi-cattle) and the in vitro maintenance of different stages (microfilariae, infective larvae and adult worm) of the two filariae were used in three experiments per filarial species. First, whole blood and sera samples were prepared from venous blood of patent baboons and cattle, and applied on ICT cards to detect circulating filarial antigens. Secondly, larval stages of L. loa and O. ochengi as well as O. ochengi adult males were maintained in vitro. Culture supernatants were collected and applied on ICT cards after 6, 12 and 24 h of in vitro maintenance. Finally, total worm extracts (TWE) were prepared using L. loa microfilariae (Mf) and O. ochengi microfilariae, infective larvae and adult male worms. TWE were also tested on ICT cards. For each experiment, control assays (whole blood and sera from uninfected babon

Lack of Association of Mutations in Optineurin With Disease in Patients With Adult-onset Primary Open-angle Glaucoma

PubMed Central

Wiggs, Janey L.; Auguste, Josette; Allingham, R. Rand; Flor, Jason D.; Pericak-Vance, Margaret A.; Rogers, Kathryn; LaRocque, Karen R.; Graham, Felicia L.; Broomer, Bob; Del Bono, Elizabeth; Haines, Jonathan L.; Hauser, Michael

2005-01-01

Objective: To determine whether mutations in the optineurin gene contribute to susceptibility to adult-onset primary open-angle glaucoma. Methods: The optineurin gene was screened in 86 probands with adult-onset primary open-angle glaucoma and in 80 age-matched control subjects. Exons 4 and 5, containing the recurrent mutations identified in patients with normal-tension glaucoma, were sequenced in all individuals studied, while the remaining exons were screened for DNA sequence variants with denaturing high-performance liquid chromatography. Results: The recurrent mutation, Met98Lys, previously found to be associated with an increased risk of disease was found in 8 (9%) of 86 probands. We also found the Met98Lys mutation in 10% of individuals from a control population of similar age, sex, and ethnicity. Consistent segregation of the mutation with the disease was not demonstrated in any of the 8 families. No other DNA changes altering the amino acid structure of the protein were found. Conclusion: The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma in this patient population. Clinical Relevance: Genetic abnormalities that render the optic nerve susceptible to degeneration are excellent candidates for genetic factors that could contribute to adult-onset primary open-angle glaucoma. Mutations in optineurin have been associated with normal-tension glaucoma, but are not associated with disease in patients with adult-onset primary open-angle glaucoma. This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma. PMID:12912697

Forecasting eruptions of Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Decker, Robert W.; Klein, Fred W.; Okamura, Arnold T.; Okubo, Paul G.

Past eruption patterns and various kinds of precursors are the two basic ingredients of eruption forecasts. The 39 historical eruptions of Mauna Loa from 1832 to 1984 have intervals as short as 104 days and as long as 9,165 days between the beginning of an eruption and the beginning of the next one. These recurrence times roughly fit a Poisson distribution pattern with a mean recurrence time of 1,459 days, yielding a probability of 22% (P=.22) for an eruption of Mauna Loa during any next year. The long recurrence times since 1950, however, suggest that the probability is not random, and that the current probability for an eruption during the next year may be as low as 6%. Seismicity beneath Mauna Loa increased for about two years prior to the 1975 and 1984 eruptions. Inflation of the summit area took place between eruptions with the highest rates occurring for a year or two before and after the 1975 and 1984 eruptions. Volcanic tremor beneath Mauna Loa began 51 minutes prior to the 1975 eruption and 115 minutes prior to the 1984 eruption. Eruption forecasts were published in 1975, 1976, and 1983. The 1975 and 1983 forecasts, though vaguely worded, were qualitatively correct regarding the timing of the next eruption. The 1976 forecast was more quantitative; it was wrong on timing but accurate on forecasting the location of the 1984 eruption. This paper urges that future forecasts be specific so they can be evaluated quantitatively.

Submarine radial vents on Mauna Loa Volcano, Hawai'i

USGS Publications Warehouse

Wanless, V. Dorsey; Garcia, M.O.; Trusdell, F.A.; Rhodes, J.M.; Norman, M.D.; Weis, Dominique; Fornari, D.J.; Kurz, M.D.; Guillou, Herve

2006-01-01

A 2002 multibeam sonar survey of Mauna Loa's western flank revealed ten submarine radial vents and three submarine lava flows. Only one submarine radial vent was known previously. The ages of these vents are constrained by eyewitness accounts, geologic relationships, Mn-Fe coatings, and geochemical stratigraphy; they range from 128 years B.P. to possibly 47 ka. Eight of the radial vents produced degassed lavas despite eruption in water depths sufficient to inhibit sulfur degassing. These vents formed truncated cones and short lava flows. Two vents produced undegassed lavas that created “irregular” cones and longer lava flows. Compositionally and isotopically, the submarine radial vent lavas are typical of Mauna Loa lavas, except two cones that erupted alkalic lavas. He-Sr isotopes for the radial vent lavas follow Mauna Loa's evolutionary trend. The compositional and isotopic heterogeneity of these lavas indicates most had distinct parental magmas. Bathymetry and acoustic backscatter results, along with photography and sampling during four JASON2 dives, are used to produce a detailed geologic map to evaluate Mauna Loa's submarine geologic history. The new map shows that the 1877 submarine eruption was much larger than previously thought, resulting in a 10% increase for recent volcanism. Furthermore, although alkalic lavas were found at two radial vents, there is no systematic increase in alkalinity among these or other Mauna Loa lavas as expected for a dying volcano. These results refute an interpretation that Mauna Loa's volcanism is waning. The submarine radial vents and flows cover 29 km2 of seafloor and comprise a total volume of ∼2×109 m3 of lava, reinforcing the idea that submarine lava eruptions are important in the growth of oceanic island volcanoes even after they emerged above sea level.

Dueling Volcanoes: How Activity Levels At Kilauea Influence Eruptions At Mauna Loa

NASA Astrophysics Data System (ADS)

Trusdell, F.

2011-12-01

The eruption of Kilauea at Pu`u `O`o is approaching its 29th anniversary. During this time, Mauna Loa has slowly inflated following its most recent eruption in 1984. This is Mauna Loa's longest inter-eruptive interval observed in HVO's 100 years of operation. When will the next eruption of Mauna Loa take place? Is the next eruption of Mauna Loa tied to the current activity at Kilauea? Historically, eruptive periods at Kilauea and Mauna Loa volcanoes appear to be inversely correlated. In the past, when Mauna Loa was exceptionally active, Kilauea Volcano was in repose, recovery, or in sustained lava lake activity. Swanson and co-workers (this meeting) have noted that explosive activity on Kilauea, albeit sporadic, was interspersed between episodes of effusive activity. Specifically, Swanson and co-workers note as explosive the time periods between 300 B.C.E.-1000 C.E and 1500-1800 C.E. They also point to evidence for low magma supply to Kilauea during these periods and few flank eruptions. During the former explosive period, Mauna Loa was exceedingly active, covering approximately 37% of its surface or 1882 km2, an area larger than Kilauea. This period is also marked by summit activity at Mauna Loa sustained for 300 years. In the 1500-1800 C.E. period, Mauna Loa was conspicuously active with 29 eruptions covering an area of 446 km2. In the late 19th and early 20th century, Kilauea was dominated by nearly continuous lava-lake activity. Meanwhile Mauna Loa was frequently active from 1843 C.E. to 1919 C.E., with 24 eruptions for an average repose time of 3.5 years. I propose that eruptive activity at one volcano may affect eruptions at the other, due to factors that impact magma supply, volcanic plumbing, and flank motion. This hypothesis is predicated on the notion that when the rift zones of Kilauea, and in turn its mobile south flank, are active, Mauna Loa's tendency to erupt is diminished. Kilauea's rift zones help drive the south flank seaward, in turn, as Mauna

Space radar image of Mauna Loa, Hawaii

NASA Technical Reports Server (NTRS)

1995-01-01

This image of the Mauna Loa volcano on the Big Island of Hawaii shows the capability of imaging radar to map lava flows and other volcanic structures. Mauna Loa has erupted more than 35 times since the island was first visited by westerners in the early 1800s. The large summit crater, called Mokuaweoweo Caldera, is clearly visible near the center of the image. Leading away from the caldera (towards top right and lower center) are the two main rift zones shown here in orange. Rift zones are areas of weakness within the upper part of the volcano that are often ripped open as new magma (molten rock) approaches the surface at the start of an eruption. The most recent eruption of Mauna Loa was in March and April 1984, when segments of the northeast rift zones were active. If the height of the volcano was measured from its base on the ocean floor instead of from sea level, Mauna Loa would be the tallest mountain on Earth. Its peak (center of the image) rises more than 8 kilometers (5 miles) above the ocean floor. The South Kona District, known for cultivation of macadamia nuts and coffee, can be seen in the lower left as white and blue areas along the coast. North is toward the upper left. The area shown is 41.5 by 75 kilometers (25.7 by 46.5 miles), centered at 19.5 degrees north latitude and 155.6 degrees west longitude. The image was acquired by the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/ X-SAR) aboard the space shuttle Endeavour on its 36th orbit on October 2, 1994. The radar illumination is from the left of the image. The colors in this image were obtained using the following radar channels: red represents the L-band (horizontally transmitted and received); green represents the L-band (horizontally transmitted, vertically received); blue represents the C-band (horizontally transmitted, vertically received). The resulting color combinations in this radar image are caused by differences in surface roughness of the lava flows. Smoother flows

Submarine radial vents on Mauna Loa Volcano, Hawaìi

NASA Astrophysics Data System (ADS)

Wanless, V. Dorsey; Garcia, M. O.; Trusdell, F. A.; Rhodes, J. M.; Norman, M. D.; Weis, Dominique; Fornari, D. J.; Kurz, M. D.; Guillou, Hervé

2006-05-01

A 2002 multibeam sonar survey of Mauna Loa's western flank revealed ten submarine radial vents and three submarine lava flows. Only one submarine radial vent was known previously. The ages of these vents are constrained by eyewitness accounts, geologic relationships, Mn-Fe coatings, and geochemical stratigraphy; they range from 128 years B.P. to possibly 47 ka. Eight of the radial vents produced degassed lavas despite eruption in water depths sufficient to inhibit sulfur degassing. These vents formed truncated cones and short lava flows. Two vents produced undegassed lavas that created "irregular" cones and longer lava flows. Compositionally and isotopically, the submarine radial vent lavas are typical of Mauna Loa lavas, except two cones that erupted alkalic lavas. He-Sr isotopes for the radial vent lavas follow Mauna Loa's evolutionary trend. The compositional and isotopic heterogeneity of these lavas indicates most had distinct parental magmas. Bathymetry and acoustic backscatter results, along with photography and sampling during four JASON2 dives, are used to produce a detailed geologic map to evaluate Mauna Loa's submarine geologic history. The new map shows that the 1877 submarine eruption was much larger than previously thought, resulting in a 10% increase for recent volcanism. Furthermore, although alkalic lavas were found at two radial vents, there is no systematic increase in alkalinity among these or other Mauna Loa lavas as expected for a dying volcano. These results refute an interpretation that Mauna Loa's volcanism is waning. The submarine radial vents and flows cover 29 km2 of seafloor and comprise a total volume of ˜2 × 109 m3 of lava, reinforcing the idea that submarine lava eruptions are important in the growth of oceanic island volcanoes even after they emerged above sea level.

Bi-directional volcano-earthquake interaction at Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Walter, T. R.; Amelung, F.

2004-12-01

At Mauna Loa volcano, Hawaii, large-magnitude earthquakes occur mostly at the west flank (Kona area), at the southeast flank (Hilea area), and at the east flank (Kaoiki area). Eruptions at Mauna Loa occur mostly at the summit region and along fissures at the southwest rift zone (SWRZ), or at the northeast rift zone (NERZ). Although historic earthquakes and eruptions at these zones appear to correlate in space and time, the mechanisms and implications of an eruption-earthquake interaction was not cleared. Our analysis of available factual data reveals the highly statistical significance of eruption-earthquake pairs, with a random probability of 5-to-15 percent. We clarify this correlation with the help of elastic stress-field models, where (i) we simulate earthquakes and calculate the resulting normal stress change at volcanic active zones of Mauna Loa, and (ii) we simulate intrusions in Mauna Loa and calculate the Coulomb stress change at the active fault zones. Our models suggest that Hilea earthquakes encourage dike intrusion in the SWRZ, Kona earthquakes encourage dike intrusion at the summit and in the SWRZ, and Kaoiki earthquakes encourage dike intrusion in the NERZ. Moreover, a dike in the SWRZ encourages earthquakes in the Hilea and Kona areas. A dike in the NERZ may encourage and discourage earthquakes in the Hilea and Kaoiki areas. The modeled stress change patterns coincide remarkably with the patterns of several historic eruption-earthquake pairs, clarifying the mechanisms of bi-directional volcano-earthquake interaction for Mauna Loa. The results imply that at Mauna Loa volcanic activity influences the timing and location of earthquakes, and that earthquakes influence the timing, location and the volume of eruptions. In combination with near real-time geodetic and seismic monitoring, these findings may improve volcano-tectonic risk assessment.

[Loa loa filariasis in Italy: review of the literature with a clinical report].

PubMed

Sgrelli, Alessio; De Socio, Giuseppe Vittorio Luigi; Papili, Rita; D'Annibale, Maria Letizia; Baldelli, Franco

2011-09-01

We present the case of an asymptomatic Loa loa disease in a 28-year-old Nigerian man living in Italy for 5 years. The man was admitted to our clinic for an occasional identification of hypereosinophilia (white blood cell count 5440/mmc, eosinophil 42%) and the presence of microfilaria at an hemoscopic evaluation. The diagnosis was made by testing the diurnal peripheral blood that showed a parasitaemia of 7000 microfilia/mL. The patient was treated with ivermectin 12 mg on the first day followed by albendazole 400 mg every 12 hours for 21 days with a reduction but no negativization of the parasitaemia and no collateral effect. Filariasis should be considered in all patients who come from or have stayed in endemic areas or who present alterations in the leukocyte formula, including hypereosinophilia, or some unexplainable allergic disorders. The lab diagnosis can be conducted through a hemoscopic test or directly with the identification of the adult worm, whereas the parasitaemia can be evaluated only through a hemoscopic test. The therapy can be non-conclusive or carried out with difficulty as finding diethylcarbamazine may be a hard task or potentially fatal anaphylactic reactions may occur.

Thermal areas on Kilauea and Mauna Loa Volcanoes, Hawaii

USGS Publications Warehouse

Casadevall, Thomas J.; Hazlett, Richard W.

1983-01-01

Active thermal areas are concentrated in three areas on Mauna Loa and three areas on Kilauea. High-temperature fumaroles (115-362°C) on Mauna Loa are restricted to the summit caldera, whereas high-temperature fumaroles on Kilauea are found in the upper East Rift Zone (Mauna Ulu summit fumaroles, 562°C), middle East Rift Zone (1977 eruptive fissure fumaroles), and in the summit caldera. Solfataric activity that has continued for several decades occurs along border faults of Kilauea caldera and at Sulphur Cone on the southwest rift zone of Mauna Loa. Solfataras that are only a few years old occur along recently active eruptive fissures in the summit caldera and along the rift zones of Kilauea. Steam vents and hot-air cracks also occur at the edges of cooling lava ponds, on the summits of lava shields, along faults and graben fractures, and in diffuse patches that may reflect shallow magmatic intrusions.

Composition and Structure of Mauna Loa's Submarine West Flank, Hawaii

NASA Astrophysics Data System (ADS)

Borchers, D.; Morgan, J. K.; Clague, D. A.; Moore, G. F.

2003-12-01

James Moore's pioneering work on submarine landslides in the Hawaiian Islands contributed significantly to early models for the structure and evolution of Mauna Loa's submarine western flank. The west flank experienced catastrophic failure in the past, generating massive blocks and debris fields offshore. Moore recognized that the midslope bench near the base of the submarine flank must have postdated the debris avalanche, but little data existed to determine if it formed in response to further landsliding or to deeper volcanic processes. As the processes that shaped Mauna Loa are thought to be analogous to those currently active at Kilauea, an improved understanding of Mauna Loa's history can provide valuable insight into the future of the younger Hawaiian volcanoes. Several recent marine surveys in the area, including submersible surveys conducted by MBARI and JAMSTEC, and a multi-channel seismic (MCS) survey carried out by the University of Hawaii, provide important new data about the composition and structure of Mauna Loa's submarine west flank. We carried out detailed geochemical, petrographic and structural analyses of rock samples and dive videos collected from the exposed northern wall of the midslope bench, documenting a repeated sequences of volcaniclastic sandstones and breccias. This stratigraphy contrasts with the predominantly subaerially erupted basalts composing the upper flank. Several thick ponded flows or sill-like diabase units are also interspersed in the section. The volcaniclastic units are highly cemented, and many contain hydrothermal alteration products, including chlorite, zeolites, and actinolite. The most altered rocks occur near the base of the bench and the degree of alteration decreases upward in the section. Samples collected from the outer scarp of the bench show evidence for intense shearing and cataclasis at all scales. The new MCS line crosses Mauna Loa's southern submarine flank and central bench. More than 500 m of finely

Cross-Reactivity of Filariais ICT Cards in Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for Shrinking of the Lymphatic Filariasis Map in the Central African Region.

PubMed

Wanji, Samuel; Amvongo-Adjia, Nathalie; Koudou, Benjamin; Njouendou, Abdel Jelil; Chounna Ndongmo, Patrick W; Kengne-Ouafo, Jonas A; Datchoua-Poutcheu, Fabrice R; Fovennso, Bridget Adzemye; Tayong, Dizzle Bita; Fombad, Fanny Fri; Fischer, Peter U; Enyong, Peter I; Bockarie, Moses

2015-11-01

Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon. A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1-39.0; p < 0.001). Similarly, a strong positive association (Spearman's rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area: a rate of 1% or more of positive ICT results

Cross-Reactivity of Filariais ICT Cards in Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for Shrinking of the Lymphatic Filariasis Map in the Central African Region

PubMed Central

Wanji, Samuel; Koudou, Benjamin; Chounna Ndongmo, Patrick W.; Kengne-Ouafo, Jonas A.; Datchoua-Poutcheu, Fabrice R.; Fovennso, Bridget Adzemye; Tayong, Dizzle Bita; Fombad, Fanny Fri; Fischer, Peter U.; Enyong, Peter I.; Bockarie, Moses

2015-01-01

Background Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon. Methodology/Principal Findings A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1–39.0; p < 0.001). Similarly, a strong positive association (Spearman’s rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area

47 CFR 54.632 - Letters of agency (LOA).

Code of Federal Regulations, 2013 CFR

2013-10-01

... SERVICE Universal Service Support for Health Care Providers Healthcare Connect Fund § 54.632 Letters of agency (LOA). (a) Authorizations. Under the Healthcare Connect Fund, the Consortium Leader must obtain...

47 CFR 54.632 - Letters of agency (LOA).

Code of Federal Regulations, 2014 CFR

2014-10-01

... SERVICE Universal Service Support for Health Care Providers Healthcare Connect Fund § 54.632 Letters of agency (LOA). (a) Authorizations. Under the Healthcare Connect Fund, the Consortium Leader must obtain...

Piggyback tectonics: Long-term growth of Kilauea on the south flank of Mauna Loa

USGS Publications Warehouse

Lipman, Peter W.; Sisson, Thomas W.; Coombs, Michelle L.; Calvert, Andrew T.; Kimura, Jun-Ichi

2006-01-01

Present-day Kilauea is the more dynamic edifice, but prior to inception of Kilauea and during its early growth, Mauna Loa is inferred to have undergone intense volcano spreading, involving the Kaoiki–Honuapo fault system (considered a geometric analog of the Hilina system on Kilauea). Cumulative deformation of Mauna Loa's south flank during growth of Kilauea since 200–300 ka is estimated to have involved > 10 km of seaward spreading, displacing the rift zones of Kīlauea while its deep plumbing system and summit magma reservoir remained nearly fixed in space. Kilauea's rift zones, rather than migrating southward with time solely due to dike emplacement preferentially on the mobile seaward side, alternatively are interpreted to have been transported passively southward, “piggyback” style, during shield-stage growth of Kilauea as a blister on the still-mobile south flank of Mauna Loa. Such an evolution of Kilauea accounts for the arcuate geometry of the present-day rift zones, proximity of the summit magma supply to the exposed flank of Mauna Loa, initial submarine growth of the ancestral edifice, and present-day location of Mauna Loa rocks at shallow depth beneath the south flank of Kilauea.

Map showing lava inundation zones for Mauna Loa, Hawai'i

USGS Publications Warehouse

Trusdell, F.A.; Graves, P.; Tincher, C.R.

2002-01-01

The Island of Hawai‘i is composed of five coalesced basaltic volcanoes. Lava flows constitute the greatest volcanic hazard from these volcanoes. This report is concerned with lava flow hazards on Mauna Loa, the largest of the island shield volcanoes. Hilo lies 58 km from the summit of Mauna Loa, the Kona coast 33 km, and the southernmost point of the island 61 km.Hawaiian volcanoes erupt two morphologically distinct types of lava, aa and pahoehoe. The surfaces of pahoehoe flows are rather smooth and undulating. Pahoehoe flows are commonly fed by lava tubes, which are well insulated, lava-filled conduits contained within the flows. The surfaces of aa flows are extremely rough and composed of lava fragments. Aa flows usually form lava channels rather than lava tubes.In Hawai‘i, lava flows are known to reach distances of 50 km or more. The flows usually advance slowly enough that people can escape from their paths. Anything overwhelmed by a flow will be damaged or destroyed by burial, crushing, or ignition. Mauna Loa makes up 51 percent of the surface area of the Island of Hawai‘i. Geologic mapping shows that lava flows have covered more than 40 percent of the surface every 1,000 years. Since written descriptions of its activity began in A.D. 1832, Mauna Loa has erupted 33 times. Some eruptions begin with only brief seismic unrest, whereas others start several months to a year following increased seismic activity. Once underway, the eruptions can produce lava flows that reach the sea in less than 24 hours, severing roads and utilities. For example, the 1950 flows from the southwest rift zone reached the ocean in approximately three hours. The two longest flows of Mauna Loa are pahoehoe flows from the 50-kilometer-long 1859 and the 48-kilometer-long 1880-81 eruptions.Mauna Loa will undoubtedly erupt again. When it does, the first critical question that must be answered is: Which areas are threatened with inundation? Once the threatened areas are established, we

Reproducibility and Agreement Between 2 Spectral Domain Optical Coherence Tomography Devices for Anterior Chamber Angle Measurements

PubMed Central

Marion, Kenneth M.; Maram, Jyotsna; Pan, Xiaojing; Dastiridou, Anna; Zhang, ZhouYuan; Ho, Alex; Francis, Brian A.; Sadda, Srinivas R.

2015-01-01

Purpose: To compare anterior chamber angle parameters based on the location of Schwalbe line (SL) from 2 spectral domain optical coherence tomography (SD-OCT) instruments and to measure their reproducibility. Methods: Forty-two eyes from 21 normal, healthy participants underwent imaging of the inferior irido-corneal angle with the Spectralis and Cirrus SD-OCT under tightly controlled low-light conditions. SL-angle opening distance (SL-AOD) and SL-trabecular iris space area (SL-TISA) were measured by masked, certified graders at the Doheny Imaging Reading Center using customized grading software. Interinstrument and intrainstrument, as well as interobserver and intraobserver reproducibility of SL-AOD and SL-TISA measurements were evaluated by intraclass correlation coefficients (ICCs) and Bland-Altman plots with limits of agreement (LoA). Results: The mean SL-AOD was 0.662±0.191 mm in Spectralis and 0.677±0.213 mm in Cirrus. The mean SL-TISA was 0.250±0.073 mm2 in Spectralis and 0.256±0.082 mm2 in Cirrus. The agreement for intrainstrument (ICCs>0.979), intragrader (ICCs>0.992), and intergrader (ICCs>0.929) was excellent. Excellent agreement between the 2 devices was also documented with a mean difference of −0.016 (LoA −0.125 to 0.092) mm for SL-AOD and −0.007 (LoA −0.056 to 0.043) mm2 in SL-TISA. Conclusions: Both SD-OCTs provided comparable measurements and permitted calculation of SL-based angle metrics. There was excellent interinstrument and intrainstrument and intraobserver and interobserver reproducibility for Spectralis and Cirrus SD-OCTs, suggesting true interchangeability between SD-OCT devices. This has the potential to lead to development of standardized grading assessments and quantification of angle parameters that would be valid across various SD-OCT devices. PMID:26200742

SBAS-InSAR analysis of a decade of surface deformation at Mauna Loa (Hawai'i): Preliminary results

NASA Astrophysics Data System (ADS)

La Marra, Daniele; Poland, Michael; Miklius, Asta; Acocella, Valerio

2015-04-01

The Big Island of Hawai`i consists five coalesced volcanoes: Hualālai, Mauna Loa, Kilauea, Mauna Kea, Kohala. Mauna Loa, the largest, has erupted 39 times since 1832, with the last eruption in 1984. The volcano summit hosts the Moku'aweoweo caldera from which two volcanic rift zones radiate: the Northeast Rift Zone (NERZ) and Southwest Rift Zone (SWRZ). These rifts are the reflection of past dike intrusions combined with instability of the SE flank of the volcano, possibly related to slip along a low angle decollement thrust fault 12-14 km beneath the volcano. Geodetic (InSAR, GPS) and seismic data have been used to characterize recent periods of unrest at Mauna Loa. InSAR studies spanning the period between 2002 and 2005 suggest a magma chamber 4.7-km depth below the summit, with a radius of 1.1 km, and a dike intrusion at 4 to 8-km depth and 8 km-long. These studies, however, are focused on relatively short-term processes (up to a few years), and a longer-term reconstruction of the volcano's evolution is lacking. In this work, we use SAR data, exploiting the SBAS technique, to study deformation of Mauna Loa from 2003 to 2014, and we try to relate this overall evolution to that the neighboring Kilauea. We use acquisitions from two satellites: ENVISAT (descending track 200 and ascending track 365), spanning from 2003 to the end of 2010, and COSMO-SkyMed (descending and ascending orbits), spanning from 2012 to the middle of 2014. These data are merged time series data from 24 continuously operating GPS stations, which allows us to calibrate the InSAR SBAS time series. Results show an overall good agreement between the InSAR and GPS time series. The displacement of each portion of the volcano between 2003-2014 has been thus constrained in detail. The summit area of Mauna Loa has under gone a long-term inflation from 2003 to 2014, with a peak of about 8 cm of vertical deformation between mid-2004 to mid-2005, especially on the summit. Part of this deformation may be

Mauna Loa Volcano: Historical eruptions, exploration, and observations (1779-1910)

NASA Astrophysics Data System (ADS)

Barnard, Walther M.

The period 1779-1910 spans the years from the first Western contact with the Island of Hawaii through the decade immediately preceding the establishment of the Hawaiian Volcano Observatory and the beginning of systematic scientific investigation of Hawaii's volcanoes. During this period Mauna Loa apparently erupted a minimum of 30 times. Many of those eruptions were visited and described by non-scientists, foremost among whom was the Reverend Titus Coon. Some highlights in the exploration of Mauna Loa include the first recorded attempt to ascend the summit, in 1779, by John Ledyard; the first recorded successful ascent, in 1794, by Archibald Menzies; the ascent in 1834 by David Douglas, whose "incredible" description provoked considerable controversy; the topographic mapping of the summit area by the U. S. Exploring Expedition under Charles Wilkes in 1840-41 and the first ascents by women in 1873. Among the many contributions made to the emerging science of volcanology were Coan's recognition of lava tubes as conduits of lava, and his recognition of the processes of formation of tumuli and lateral outbreaks of lava; Dana's precepts on a variety of topics relating to Hawaiian volcanism; W. D. Alexander's and Haskell's descriptions of pahoehoe and aa lava, and early accounts of flow morphology and structure; Dutton's recognition that the calderas of Kilauea and Mauna Loa resulted from collapse; Green's description of formation of pillow lavas; and Guppy's suggestion and justification for the establishment of an observatory that subsequently led to the founding of the Hawaiian Volcano Observatory. Many contributed insights to the continuing debate on the relationship between Mauna Loa and Kilauea.

The Ninole Basalt - Implications for the structural evolution of Mauna Loa volcano, Hawaii

USGS Publications Warehouse

Lipman, P.W.; Rhodes, J.M.; Dalrymple, G.B.

1990-01-01

Lava flows of the Ninole Basalt, the oldest rocks exposed on the south side of the island of Hawaii, provide age and compositional constraints on the evolution of Mauna Loa volcano and the southeastward age progression of Hawaiian volcanism. Although the tholeiitic Ninole Basalt differs from historic lavas of Mauna Loa volcano in most major-element contents (e.g., variably lower K, Na, Si; higher Al, Fe, Ti, Ca), REE and other relatively immobile minor elements are similar to historic and prehistoric Mauna Loa lavas, and the present major-element differences are mainly due to incipient weathering in the tropical environment. New K-Ar whole-rock ages, from relatively fresh roadcut samples, suggest that the age of the Ninole Basalt is approximately 0.1-0.2 Ma, although resolution is poor because of low contents of K and radiogenic Ar. Originally considered the remnants of a separate volcano, the Ninole Hills are here interpreted as faulted remnants of the old south flank of Mauna Loa. Deep canyons in the Ninole Hills, eroded after massive landslide failure of flanks of the southwest rift zone, have been preserved from burial by younger lava due to westward migration of the rift zone. Landslide-induced depressurization of the southwest rift zone may also have induced phreatomagmatic eruptions that could have deposited widespread Basaltic ash that overlies the Ninole Basalt. Subaerial presence of the Ninole Basalt documents that the southern part of Hawaii Island had grown to much of its present size above sea level by 0.1-0.2 Ma, and places significant limits on subsequent enlargement of the south flank of Mauna Loa. ?? 1990 Springer-Verlag.

40Ar/39Ar geochronology of submarine Mauna Loa volcano, Hawaii

NASA Astrophysics Data System (ADS)

Jicha, Brian R.; Rhodes, J. Michael; Singer, Brad S.; Garcia, Michael O.

2012-09-01

New geochronologic constraints refine the growth history of Mauna Loa volcano and enhance interpretations of the petrologic, geochemical, and isotopic evolution of Hawaiian magmatism. We report results of 40Ar/39Ar incremental heating experiments on low-K, tholeiitic lavas from the 1.6 km high Kahuku landslide scarp cutting Mauna Loa's submarine southwest rift zone, and from lavas in a deeper section of the rift. Obtaining precise40Ar/39Ar ages from young, tholeiitic lavas containing only 0.2-0.3 wt.% K2O is challenging due to their extremely low radiogenic 40Ar contents. Analyses of groundmass from 45 lavas yield 14 new age determinations (31% success rate) with plateau and isochron ages that agree with stratigraphic constraints. Lavas collected from a 1250 m thick section in the landslide scarp headwall were all erupted around 470 ± 10 ka, implying an extraordinary period of accumulation of ˜25 mm/yr, possibly correlating with the peak of the shield-building stage. This rate is three times higher than the estimated vertical lava accumulation rate for shield-building at Mauna Kea (8.6 ± 3.1 mm/yr) based on results from the Hawaii Scientific Drilling Project. Between ˜470 and 273 ka, the lava accumulation rate along the southwest rift zone decreased dramatically to ˜1 mm/yr. We propose that the marked reduction in lava accumulation rate does not mark the onset of post-shield volcanism as previously suggested, but rather indicates the upward migration of the magma system as Mauna Loa evolved from a submarine stage of growth to one that is predominantly subaerial, thereby cutting off supply to the distal rift zone. Prior to ˜250 ka, lavas with Loihi-like isotopic signatures were erupted along with lavas having typical Mauna Loa values, implying greater heterogeneity in the plume source earlier in Mauna Loa's growth. In addition to refining accumulation rates and the isotopic evolution of the lavas erupted along the southwest rift zone, our new40Ar/39Ar results

Isotopic evolution of Mauna Loa volcano

NASA Astrophysics Data System (ADS)

Kurz, Mark D.; Kammer, David P.

1991-04-01

In an effort to understand the temporal helium isotopic variations in Mauna Loa volcano, we have measured helium, strontium and lead isotopes in a suite of Mauna Loa lavas that span most of the subaerial eruptive history of the volcano. The lavas range in age from historical flows to Ninole basalt which are thought to be several hundred thousand years old. Most of the samples younger than 30 ka in age (Kau Basalt) are radiocarbon-dated flows, while the samples older than 30 ka are stratigraphically controlled (Kahuku and Ninole Basalt). The data reveal a striking change in the geochemistry of the lavas approximately 10 ka before present. The lavas older than 10 ka are characterized by high 3He/ 4He ( ˜ 16-20 times atmospheric), higher 206Pb/ 204Pb ( ˜ 18.2), and lower 87Sr/ 86Sr ( ˜ 0.70365) ratios than the younger Kau samples (having He, Pb and Sr ratios of approximately 8.5 × atmospheric, 18.1 and 0.70390, respectively). The historical lavas are distinct in having intermediate Sr and Pb isotopic compositions with 3He/ 4He ratios similar to the other young Kau basalt ( ˜ 8.5 × atmospheric). The isotopic variations are on a shorter time scale (100 to 10,000 years) than has previously been observed for Hawaiian volcanoes, and demonstrate the importance of geochronology and stratigraphy to geochemical studies. The data show consistency between all three isotope systems, which suggests that the variations are not related to magma chamber degassing processes, and that helium is not decoupled from the other isotopes. However, the complex temporal evolution suggests that three distinct mantle sources are required to explain the isotopic data. Most of the Mauna Loa isotopic variations could be explained by mixing between a plume type source, similar to Loihi, and an asthenospheric source with helium isotopic composition close to MORB and elevated Sr isotopic values. An asthenospheric source, or variation within the plume source, is considered more likely than

Lava flow hazards and risk assessment on Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Trusdell, Frank A.

"It is profoundly significant that the Hawaiians of Ka'u did not fear or cringe before, or hate, the power and destructive violence of Mauna Loa. They took unto them this huge mountain as their mother, and measured their personal dignity and powers in terms of its majesty and drama." (Pukui and Handy, 1952) The Island of Hawai'i is the fastest-growing region in the State of Hawai`i with over 100,000 residents. Because the population continues to grow at a rate of 3% per annum, more and more construction will occur on the flanks of active volcanoes. Since the last eruption of Mauna Loa in 1984, $2.3 billion have been invested in new construction on the volcano's flanks, posing an inevitable hazard to the people living there. Part of the mission of The U.S. Geological Survey's Hawaiian Volcano Observatory is to make the public aware of these hazards. Recent mapping has shown that lava flows on Mauna Loa have covered its surface area at a rate of 30-40% every 1000 years. Average effusion rates of up to 12 million cubic meters per day during eruptions, combined with slopes >10 degrees, increase the risk for the population of South Kona. Studies of Mauna Loa's long-term eruptive history will lead to more accurate volcanic hazards assessments and enable us to refine the boundaries between the hazards zones. Our work thus serves as a guide for land-use planners and developers to make more informed decisions for the future. Land-use planning is a powerful way to minimize risk in hazardous areas.

Tholeiitic basalt magmatism of Kilauea and Mauna Loa volcanoes of Hawaii

USGS Publications Warehouse

Murata, K.J.

1970-01-01

The primitive magmas of Kilauca and Mauna Loa are generated by partial melting of mantle peridotite at depths of -60 km or more. Results of high-pressure melting experiments indicate that the primitive melt must contain at least 20% MgO in order to have olivine as a liquidus mineral. The least fractionated lavas of both volcanoes have olivine (Fa13) on the liquidus at 1 atmosphere, suggesting that the only substance lost from the primitive melt, during a rather rapid ascent to the surface, is olivine. This relation allows the primitive composition to be computed by adding olivine to the composition of an erupted lava until total MgO is at least 20 percent. Although roughly similar, historic lavas of the two volcanoes show a consistent difference in composition. The primitive melt of Mauna Loa contains 20% more dissolved orthopyroxene, a high-temperature melting phase in the mantle, and is deficient in elements such as potassium, uranium, and niobium, which presumably occur in minor low-melting phases. Mauna Loa appears to be the older volcano, deriving its magma at higher temperature and greater depth from a more depleted source rock. ?? 1970 Springer-Verlag.

Swarms of similar long-period earthquakes in the mantle beneath Mauna Loa Volcano

USGS Publications Warehouse

Okubo, Paul G.; Wolfe, C.J.

2008-01-01

We present analyses of two swarms of long-period (LP) earthquakes at > 30 km depth that accompanied the geodetically observed 2002–2005 Mauna Loa intrusion. The first LP earthquake swarm in 2002 consisted of 31 events that were precursory and preceded the start of Mauna Loa inflation; the second LP swarm of two thousand events occurred from 2004–2005. The rate of LP earthquakes slowed significantly coincident with the occurrence of the December 26, 2004 Mw 9.3 Sumatra earthquake, suggesting that the seismic waves from this great earthquake may have had a dynamic triggering effect on the behavior of Mauna Loa's deep magma system. Using waveform cross correlation and double difference relocation, we find that a large number of earthquakes in each swarm are weakly similar and can be classified into two families. The relocated hypocenters for each family collapse to compact point source regions almost directly beneath the Mauna Loa intrusion. We suggest that the observed waveform characteristics are compatible with each family being associated with the resonance of a single fluid filled vertical crack of fixed geometry, with differences in waveforms between events being produced by slight variations in the trigger mechanism. If these LP earthquakes are part of the primary magma system that fed the 2002–2005 intrusion, as indicated by the spatial and temporal associations between mantle seismicity and surface deformation, then our results raise the possibility that this magma system may be quite focused at these depths as opposed to being a diffuse network. It is likely that only a few locations of Mauna Loa's deep magma system met the geometric and fluid dynamic conditions for generating LP earthquakes that were large enough to be recorded at the surface, and that much of the deep magma transfer associated with the 2002–2005 intrusion occurred aseismically.

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment.

PubMed

Wanji, Samuel; Eyong, Ebanga-Echi J; Tendongfor, Nicholas; Ngwa, Che J; Esuka, Elive N; Kengne-Ouafo, Arnaud J; Datchoua-Poutcheu, Fabrice R; Enyong, Peter; Agnew, Dalen; Eversole, Rob R; Hopkins, Adrian; Mackenzie, Charles D

2017-07-01

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM

The Ninole Basalt — Implications for the structural evolution of Mauna Loa volcano, Hawaii

NASA Astrophysics Data System (ADS)

Lipman, Peter W.; Rhodes, J. M.; Dalrymple, G. Brent

1990-12-01

Lava flows of the Ninole Basalt, the oldest rocks exposed on the south side of the island of Hawaii, provide age and compositional constraints on the evolution of Mauna Loa volcano and the southeastward age progression of Hawaiian volcanism. Although the tholeiitic Ninole Basalt differs from historic lavas of Mauna Loa volcano in most major-element contents (e.g., variably lower K, Na, Si; higher Al, Fe, Ti, Ca), REE and other relatively immobile minor elements are similar to historic and prehistoric Mauna Loa lavas, and the present major-element differences are mainly due to incipient weathering in the tropical environment. New K-Ar whole-rock ages, from relatively fresh roadcut samples, suggest that the age of the Ninole Basalt is approximately 0.1 0.2 Ma, although resolution is poor because of low contents of K and radiogenic Ar. Originally considered the remnants of a separate volcano, the Ninole Hills are here interpreted as faulted remnants of the old south flank of Mauna Loa. Deep canyons in the Ninole Hills, eroded after massive landslide failure of flanks of the southwest rift zone, have been preserved from burial by younger lava due to westward migration of the rift zone. Landslide-induced depressurization of the southwest rift zone may also have induced phreatomagmatic eruptions that could have deposited widespread Basaltic ash that overlies the Ninole Basalt. Subaerial presence of the Ninole Basalt documents that the southern part of Hawaii Island had grown to much of its present size above sea level by 0.1 0.2 Ma, and places significant limits on subsequent enlargement of the south flank of Mauna Loa.

Infrared measurements of atmospheric gases above Mauna Loa, Hawaii, in February 1987

NASA Technical Reports Server (NTRS)

Rinsland, C. P.; Goldman, A.; Murcray, F. J.; Murcray, F. H.; Blatherwick, R. D.

1988-01-01

The IR absorptions spectra of 13 minor and trace atmospheric gases, recorded by the NOAA's Geophysical Monitoring for Climate Change (GMCC) program station at Mauna Loa, Hawaii, for four days in February 1987, were analyzed to determine simultaneous total vertical column amounts for these gases. Comparisons with other data indicate that the NOAA GMCC surface volume mixing ratios are good measures of the mean volume mixing ratios of these gases in the troposphere and that Mauna Loa is a favorable site for IR monitoring of atmospheric gases. The ozone total columns deduced from the IR spectra agreed with the correlative Umkehr observations.

Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon

PubMed Central

Boussinesq, Michel; Gardon, Jacques; Gardon-Wendel, Nathalie; Chippaux, Jean-Philippe

2003-01-01

In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events were reported after ivermectin treatment. The first signs, occurring within the 12–24 hours following treatment, included fatigue, generalized arthralgia, and sometimes agitation, mutism, and incontinence. Disorders of consciousness, including coma, generally appeared between 24 and 72 hours, and showed a rapid variation with time. The most frequent objective neurological signs were extrapyramidal. The patients presented with haemorrhages of the conjunctiva and of the retina. Biological examinations showed a massive Loa microfilaruria, the passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an increase in the C-reactive protein, all of which have been correlated with the high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased dramatically within the first 24 hours, and then rose again rapidly. Electroencephalograms suggested the existence of a diffuse pathological process within the first weeks; the abnormalities disappearing after 3–6 months. Death may occur when patients are not properly managed, i.e. in the absence of good nursing. However, some patients who recovered showed sequelae such as aphasia, episodic amnesia, or extrapyramidal signs. The main risk factor for these encephalopathies is the intensity of the initial Loa microfilaraemia. The disorders of consciousness may occur when there are >50,000 Loa microfilariae per ml. The possible roles of co-factors, such as Loa strains, genetic predisposition of individuals, co-infestations with other parasites, or alcohol consumption, seem to be minor but they should be considered. The mechanisms of the post-ivermectin Loa-related encephalopathies should be investigated to improve the management of patients developing the condition. PMID:14975061

Phenology of Acacia koa on Mauna Loa, Hawaii

Treesearch

Ronald M. Lanner

1965-01-01

Flowering of koa was strongly seasonal on the Mauna Loa Strip. At 4,000 feet heavy flowering began in early December and lasted until early March. At 6,700 feet it extended from early March until mid-May. Heaviest flower losses occurred during anthesis, and were due to wind, rain, and possibly the dropping of unpollinated heads. Large insects were important as...

Coupling at Mauna Loa and Kīlauea by stress transfer in an asthenospheric melt layer

USGS Publications Warehouse

Gonnermann, Helge M.; Foster, James H.; Poland, Michael; Wolfe, Cecily J.; Brooks, Benjamin A.; Miklius, Asta

2012-01-01

The eruptive activity at the neighbouring Hawaiian volcanoes, Kīlauea and Mauna Loa, is thought to be linked despite both having separate lithospheric magmatic plumbing systems. Over the past century, activity at the two volcanoes has been anti-correlated, which could reflect a competition for the same magma supply. Yet, during the past decade Kīlauea and Mauna Loa have inflated simultaneously. Linked activity between adjacent volcanoes in general remains controversial. Here we present a numerical model for the dynamical interaction between Kīlauea and Mauna Loa, where both volcanoes are coupled by pore-pressure diffusion, occurring within a common, asthenospheric magma supply system. The model is constrained by measurements of gas emission rates indicative of eruptive activity, and it is calibrated to match geodetic measurements of surface deformation at both volcanoes, inferred to reflect changes in shallow magma storage. Although an increase in the asthenospheric magma supply can cause simultaneous inflation of Kīlauea and Mauna Loa, we find that eruptive activity at one volcano may inhibit eruptions of the adjacent volcano, if there is no concurrent increase in magma supply. We conclude that dynamic stress transfer by asthenospheric pore pressure is a viable mechanism for volcano coupling at Hawai‘i, and perhaps for adjacent volcanoes elsewhere.

Structure of the microfilarial reservoir of Loa loa in the human host and its implications for monitoring the progr,ammes of Community-Directed Treatment with Ivermectin carried out in Africa.

PubMed

Pion, D S S; Gardon, J; Kamgno, J; Gardon-Wendel, N; Chippaux, J P; Boussinesq, M

2004-11-01

This paper describes the structure of the microfilarial reservoir of Loa loa in an endemic population of central Cameroon. The possible effects of age and sex on the prevalence and intensity of microfilaraemia have been explored. Logistic analysis showed that the prevalence of microfilaraemia increased significantly with age, reaching 60 % in the oldest males. This result suggests that the figure commonly reported, according to which only one third of the infected individuals were microfilaraemic, should be reconsidered; in addition, as part of surveys of loiasis, crude microfilaraemia prevalence values should be replaced by adjusted ones. The intensity of infection did not show any age-specific change. As a result, even if the oldest members of the male population are clearly the most at risk of developing post-ivermectin serious adverse reactions, especially Loa-encephalopathy, the other members of the population are not risk-free. Therefore, in those areas where the African Programme for Onchocerciasis Control is undertaking regular mass distributions of ivermectin for onchocerciasis control, and where loiasis is co-endemic, no subpopulation should be excluded from surveillance and monitoring during community directed treatments with ivermectin.

The Mauna Loa Carbon Dioxide Record.

NASA Astrophysics Data System (ADS)

Tans, P. P.

2005-12-01

Continuous measurements of atmospheric carbon dioxide were started in 1958 by Dave Keeling as part of the International Geophysical Year. Precision and accuracy were both high from the very beginning, facilitating after only a few years the unambiguous discovery of the seasonal cycle of CO2, as well as the year-to-year rise in concentration. Essential to the definitive nature of the Mauna Loa CO2 and similar records are the careful and continuing attention to calibration procedures, the creation of a calibration scale for CO2-in- air based on the determination of its mole fraction through primary methods, and the deployment of some "redundant" independent methods duplicating the CO2 measurements at several sites. The example of Mauna Loa demonstrated the principles that were incorporated into the design of later measurement networks that are now coordinated in the Global Atmosphere Watch Programme of the World Meteorological Organization. The high quality of the CO2 measurements allowed the later discoveries of the trends in the seasonal cycle, the trend in the gradient from north to south, and the relationship of the growth rate of CO2 to climate variations. The high quality is also the basis for all inverse modeling, which uses numerical models of atmospheric transport to translate quite small differences in space and time of the mole fraction of CO2 to deduce patterns of sources and sinks that are consistent with the observations. Some examples will be shown of the information that would be irretrievably lost if the high standards of these measurements are not maintained.

The Mauna Loa carbon dioxide record: lessons for long-term Earth observations

USGS Publications Warehouse

Sundquist, Eric T.; Keeling, Ralph F.

2009-01-01

The Mauna Loa carbon dioxide record is an iconic symbol of the human capacity to alter the planet. Yet this record would not have been possible without the remarkable work of one man, Charles David Keeling. We describe three emergent themes that characterized his work: (1) his desire to study and understand the processes that control atmospheric CO2 and the global carbon cycle, (2) his campaign to identify and minimize systematic measurement error, and (3) his tenacious efforts to maintain continuous funding despite changing government priorities and institutions. In many ways, the story of the Mauna Loa record demonstrates that distinctions between research and “routine” measurements are not very useful in long-term monitoring of Earth properties and processes.

Volcano-earthquake interaction at Mauna Loa volcano, Hawaii

NASA Astrophysics Data System (ADS)

Walter, Thomas R.; Amelung, Falk

2006-05-01

The activity at Mauna Loa volcano, Hawaii, is characterized by eruptive fissures that propagate into the Southwest Rift Zone (SWRZ) or into the Northeast Rift Zone (NERZ) and by large earthquakes at the basal decollement fault. In this paper we examine the historic eruption and earthquake catalogues, and we test the hypothesis that the events are interconnected in time and space. Earthquakes in the Kaoiki area occur in sequence with eruptions from the NERZ, and earthquakes in the Kona and Hilea areas occur in sequence with eruptions from the SWRZ. Using three-dimensional numerical models, we demonstrate that elastic stress transfer can explain the observed volcano-earthquake interaction. We examine stress changes due to typical intrusions and earthquakes. We find that intrusions change the Coulomb failure stress along the decollement fault so that NERZ intrusions encourage Kaoiki earthquakes and SWRZ intrusions encourage Kona and Hilea earthquakes. On the other hand, earthquakes decompress the magma chamber and unclamp part of the Mauna Loa rift zone, i.e., Kaoiki earthquakes encourage NERZ intrusions, whereas Kona and Hilea earthquakes encourage SWRZ intrusions. We discuss how changes of the static stress field affect the occurrence of earthquakes as well as the occurrence, location, and volume of dikes and of associated eruptions and also the lava composition and fumarolic activity.

Isotopic evolution of Mauna Loa Volcano: A view from the submarine southwest rift zone

NASA Astrophysics Data System (ADS)

Kurz, Mark D.; Kenna, T. C.; Kammer, D. P.; Rhodes, J. Michael; Garcia, Michael O.

New isotopic and trace element measurements on lavas from the submarine southwest rift zone (SWR) of Mauna Loa continue the temporal trends of subaerial Mauna Loa flows, extending the known compositional range for this volcano, and suggesting that many of the SWR lavas are older than any exposed on land. He and Nd isotopic compositions are similar to those in the oldest subaerial Mauna Loa lavas (Kahuku and Ninole Basalts), while 87Sr/86Sr ratios are slightly lower (as low as .7036) and Pb isotopes are higher (206Pb'204Pb up to 18.30). The coherence of all the isotopes suggests that helium behaves as an incompatible element, and that helium isotopic variations in the Hawaiian lavas are produced by melting and mantle processes, rather than magma chamber or metasomatic processes unique to the gaseous elements. The variations of He, Sr, and Nd are most pronounced in lavas of approximately 10 ka age range [Kurz and Kammer, 1991], but the largest Pb isotopic variation occurs earlier. These variations are interpreted as resulting from the diminishing contribution from the upwelling mantle plume material as the shield building ends at Mauna Loa. The order of reduction in the plume isotopic signature is inferred to be Pb (at >100 ka), He (at ˜14 ka), Sr (at ˜9 ka), and Nd (at ˜8 ka); the different timing may relate to silicate/melt partition coefficients, with most incompatible elements removed first, and also to concentration variations within the plume. Zr/Nb, Sr/Nb, and fractionation-corrected Nb concentrations, correlate with the isotopes and are significantly higher in some of the submarine SWR lavas, suggesting temporal variability on time scales similar to the Pb isotopes (i.e. ˜ 100 ka). Historical lavas define trace element and isotopic trends that are distinct from the longer term (10 to 100 ka) variations, suggesting that different processes cause the short term variability. The temporal evolution of Mauna Loa, and particularly the new data from the

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial.

PubMed

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C

2016-03-01

Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥ 4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

PubMed Central

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C.

2016-01-01

Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas. PMID:26967331

Isotopic Study of the Mauna Loa Southwest Rift Mile High Section: Hawaiian Mantle Plume Components

NASA Astrophysics Data System (ADS)

Weis, D.; Rhodes, J. M.; Garcia, M. O.

2003-12-01

The new JASON2 ROV was employed to collect 51 samples from a 1.8 km thick submarine landslide scarp along the crest of the southwest rift zone of the Mauna Loa volcano to investigate the nature and history of Hawaiian mantle plume components. The rift zone section records about 400,000 years of eruptive activity, 50% of the volcano's total lifetime, which is comparable to the time-period sampled by the Hawaiian Scientific Drilling Project (HSPD2). Sr, Nd, Pb and Hf isotopes have been analyzed on 14 samples from the "Mile High" section. The range of variation observed falls typically within literature data for the Mauna Loa volcano with 87Sr/86Sr from 0.70368 to 0.70378 and 206Pb/204Pb from 18.16 to 18.26, and is somewhat more radiogenic than most Mauna Loa prehistoric (<31 ka) lavas. In the section, there is a distinct increase in Pb and Sr isotopes, which is also recorded by major and trace element data, at a depth of 1353 m. Isotope ratios continue to increase to the bottom of the section at 2290 m. High precision Pb-Pb isotopic systematics for Mauna Loa lavas do not show the binary mixing trends as also observed in the upper part of the HSDPI pilot hole and contrary to Mauna Kea lavas (Abouchami et al., Chemical Geology 2000). This might imply that the Mauna Loa plume source is more thoroughly mixed than the Mauna Kea source. Most of Mauna Loa isotopic compositions cluster at 18.15-18.20 for 206Pb/204Pb and ˜0.70370 for 87Sr/86Sr, which could be a ubiquitous refractory component in the Hawaiian mantle plume (Rhodes and Weis, Fall AGU 2001). Nevertheless, a more radiogenic plume component with higher 208Pb/204Pb and 208Pb*/206Pb* is clearly present in the lower part of the Mile High section and might be comparable to the Kilauea-like component observed in Mauna Kea lavas in HSDP2 (Blichert-Toft et al., G3 2003). Team members also include: D. Wanless and K. Kolysko, University of Hawaii; H. Guillou, CEA/CNRS, France; M. Kurz and D. Fornari, WHOI; M. Norman and V

Mauna Loa--history, hazards and risk of living with the world's largest volcano

USGS Publications Warehouse

Trusdell, Frank A.

2012-01-01

Mauna Loa on the Island Hawaiʻi is the world’s largest volcano. People residing on its flanks face many hazards that come with living on or near an active volcano, including lava flows, explosive eruptions, volcanic smog, damaging earthquakes, and local tsunami (giant seawaves). The County of Hawaiʻi (Island of Hawaiʻi) is the fastest growing County in the State of Hawaii. Its expanding population and increasing development mean that risk from volcano hazards will continue to grow. U.S. Geological Survey (USGS) scientists at the Hawaiian Volcano Observatory (HVO) closely monitor and study Mauna Loa Volcano to enable timely warning of hazardous activity and help protect lives and property.

Atmospheric Carbon Dioxide Record from Mauna Loa (1958-2008)

DOE Data Explorer

Keeling, R. F. [Scripps Institution of Oceanography, University of California, La Jolla, California; Piper, S. C. [Scripps Institution of Oceanography, University of California, La Jolla, California; Bollenbacher, A. F. [Scripps Institution of Oceanography, University of California, La Jolla, California; Walker, J. S. [Scripps Institution of Oceanography, University of California, La Jolla, California

2009-02-01

Air samples at Mauna Loa are collected continuously from air intakes at the top of four 7-m towers and one 27-m tower. Four air samples are collected each hour for the purpose of determining the CO2 concentration. Determinations of CO2 are made by using a Siemens Ultramat 3 nondispersive infrared gas analyzer with a water vapor freeze trap. This analyzer registers the concentration of CO2 in a stream of air flowing at ~0.5 L/min. Every 30 minutes, the flow is replaced by a stream of calibrating gas or "working reference gas". In December 1983, CO2-in-N2 calibration gases were replaced with the currently used CO2-in-air calibration gases. These calibration gases and other reference gases are compared periodically to determine the instrument sensitivity and to check for possible contamination in the air-handling system. These reference gases are themselves calibrated against specific standard gases whose CO2 concentrations are determined manometrically. Greater details about the sampling methods at Mauna Loa are given in Keeling et al. (1982) and Keeling et al. (2002).

Recent inflation and flank movement of Mauna Loa Volcano

NASA Astrophysics Data System (ADS)

Miklius, Asta; Lisowski, Michael; Delaney, Paul T.; Denlinger, Roger P.; Dvorak, John J.; Okamura, Arnold T.; Sakol, Maurice K.

Geodetic measurements on the summit of Mauna Loa reveal that since the last eruption in 1984, the shallow summit magma chamber has inflated approximately the same amount as between the 1975 and 1984 eruptions. However, it does not appear to have recovered the entire volume withdrawn during the 1984 eruption. Together with the lack of increased shallow earthquake activity, this observation suggests that, as of June 1995, the next eruption of Mauna Loa is not yet imminent. Global Positioning System measurements in 1993 and 1994 show southeastward movement of the southeast flank of over 4 cm/year, comparable to displacements measured on adjacent Kilauea Volcano's south flank over the same interval. The upper west flank appears to be stable, producing a strong asymmetry of motion about the summit. Gradients of motion on the southeast flank result in about one microstrain/year of compression and shear across the Kaoiki seismic zone, an area of persistent seismicity that has produced large historic earthquakes. The flank motions observed between 1993 and 1994 could be caused by the combined effects of slip along the basal Kaoiki decollement and inflation of a deep source.

Ambulant adults with spastic cerebral palsy: the validity of lower limb joint angle measurements from sagittal video recordings.

PubMed

Larsen, Kerstin L; Maanum, Grethe; Frøslie, Kathrine F; Jahnsen, Reidun

2012-02-01

In the development of a clinical program for ambulant adults with cerebral palsy (CP), we investigated the validity of joint angles measured from sagittal video recordings and explored if movements in the transversal plane identified with three-dimensional gait analysis (3DGA) affected the validity of sagittal video joint angle measurements. Ten observers, and 10 persons with spastic CP (19-63 years), Gross Motor Function Classification System I-II, participated in the study. Concurrent criterion validity between video joint angle measurements and 3DGA was assessed by Bland-Altman plots with mean differences and 95% limits of agreement (LoA). Pearson's correlation coefficients (r) and scatter plots were used supplementary. Transversal kinematics ≥2 SD from our reference band were defined as increased movement in the transversal plane. The overall mean differences in degrees between joint angles measured by 3DGA and video recordings (3°, 5° and -7° for the hip, knee and ankle respectively) and corresponding LoA (18°, 10° and 15° for the hip, knee and ankle, respectively) demonstrated substantial discrepancies between the two methods. The correlations ranged from low (r=0.39) to moderate (r=0.68). Discrepancy between the two measurements was seen both among persons with and without the presence of deviating transversal kinematics. Quantifying lower limb joint angles from sagittal video recordings in ambulant adults with spastic CP demonstrated low validity, and should be conducted with caution. This gives implications for selecting evaluation method of gait. Copyright © 2011 Elsevier B.V. All rights reserved.

Disruption of the Mauna Loa magma system by the 1868 Hawaiian earthquake - Geochemical evidence

NASA Astrophysics Data System (ADS)

Tilling, Robert I.; Rhodes, J. Michael; Sparks, Joel W.; Lockwood, John P.; Lipman, Peter W.

1987-01-01

To test whether a catastrophic earthquake could affect an active magma system, mean abundances (adjusted for 'olivine control') of titanium, potassium, phosphorus, strontium, zirconium, and niobium of historic lavas erupted from Mauna Loa Volcano, Hawaii, after 1868 were analyzed and were found to decrease sharply relative to lavas erupted before 1868. This abrupt change in lava chemistry, accompanied by a halved lava-production rate for Mauna Loa after 1877, is interpreted to reflect the disruptive effects of a magnitude 7.5 earthquake in 1868. This interpretation represents a documentable case of changes in magmatic chemical variations initiated or accelerated by a major tectonic event.

Disruption of the mauna loa magma system by the 1868 Hawaiian earthquake: Geochemical evidence

USGS Publications Warehouse

Tilling, R.I.; Michael, Rhodes J.; Sparks, J.W.; Lockwood, J.P.; Lipman, P.W.

1987-01-01

To test whether a catastrophic earthquake could affect an active magma system, mean abundances (adjusted for "olivine control") of titanium, potassium, phosphorus, strontium, zirconium, and niobium of historic lavas erupted from Mauna Loa Volcano, Hawaii, after 1868 were analyzed and were found to decrease sharply relative to lavas erupted before 1868. This abrupt change in lava chemistry, accompanied by a halved lava-production rate for Mauna Loa after 1877, is interpreted to reflect the disruptive effects of a magnitude 7.5 earthquake in 1868. This interpretation represents a documentable case of changes in magmatic chemical variations initiated or accelerated by a major tectonic event.

Melt migration and mantle chromatography, 2: a time-series Os isotope study of Mauna Loa volcano, Hawaii

NASA Astrophysics Data System (ADS)

Hauri, Erik H.; Kurz, Mark D.

1997-12-01

We have determined the major element, trace element, and Os isotopic compositions of a stratigraphic suite of tholeiitic basalts spanning >30,000 years of the eruptive history of Mauna Loa volcano. Good correlations are observed between Os isotopes and the isotopes of Sr, Nd, Pb and He. In addition, the isotopes correlate with fractionation-corrected major element abundances within this single volcano, and provide a record of increased melting of mafic material with time at Mauna Loa. Chromatographic element fractionation during melt transport is shown to be negligible based on the good correlations of the isotopes of the compatible element Os with the other incompatible element tracers. The temporal variation at Mauna Loa is best described by the translation of the volcano over a Hawaiian plume which is radially zoned in composition. The radial zonation is a predicted consequence of thermal entrainment during flow in a mantle plume conduit.

Rates of volcanic activity along the southwest rift zone of Mauna Loa volcano, Hawaii.

USGS Publications Warehouse

Lipman, P.W.

1981-01-01

Flow-by-flow mapping of the 65 km long subaerial part of the southwest rift zone and adjacent flanks of Mauna Loa Volcano, Hawaii, and about 50 new 14C dates on charcoal from beneath these flows permit estimates of rates of lava accumulation and volcanic growth over the past 10 000 years. The sequence of historic eruptions along the southwest rift zone, beginning in 1868, shows a general pattern of uprift migration and increasing eruptive volume, culminating in the great 1950 eruption. No event comparable to 1950, in terms of volume or vent length, is evident for at least the previous 1000 years. Rates of lava accumulation along the zone have been subequal to those of Kilauea Volcano during the historic period but they were much lower in late prehistoric time (unpubl. Kilauea data by R. T. Holcomb). Rates of surface covering and volcanic growth have been markedly asymmetric along Mauna Loa's southwest rift zone. Accumulation rates have been about half again as great on the northwest side of the rift zone in comparison with the southeast side. The difference apparently reflects a westward lateral shift of the rift zone of Mauna Loa away from Kilauea Volcano, which may have acted as a barrier to symmetrical growth of the rift zone. -Author

Lava inundation zone maps for Mauna Loa, Island of Hawaiʻi, Hawaii

USGS Publications Warehouse

Trusdell, Frank A.; Zoeller, Michael H.

2017-10-12

Lava flows from Mauna Loa volcano, on the Island of Hawaiʻi, constitute a significant hazard to people and property. This report addresses those lava flow hazards, mapping 18 potential lava inundation zones on the island.

MULTISCALE THERMAL-INFRARED MEASUREMENTS OF THE MAUNA LOA CALDERA, HAWAII

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

L. BALICK; A. GILLESPIE; ET AL

2001-03-01

Until recently, most thermal infrared measurements of natural scenes have been made at disparate scales, typically 10{sup {minus}3}-10{sup {minus}2} m (spectra) and 10{sup 2}-10{sup 3} m (satellite images), with occasional airborne images (10{sup 1} m) filling the gap. Temperature and emissivity fields are spatially heterogeneous over a similar range of scales, depending on scene composition. A common problem for the land surface, therefore, has been relating field spectral and temperature measurements to satellite data, yet in many cases this is necessary if satellite data are to be interpreted to yield meaningful information about the land surface. Recently, three new satellitesmore » with thermal imaging capability at the 10{sup 1}-10{sup 2} m scale have been launched: MTI, TERRA, and Landsat 7. MTI acquires multispectral images in the mid-infrared (3-5{micro}m) and longwave infrared (8-10{micro}m) with 20m resolution. ASTER and MODIS aboard TERRA acquire multispectral longwave images at 90m and 500-1000m, respectively, and MODIS also acquires multispectral mid-infrared images. Landsat 7 acquires broadband longwave images at 60m. As part of an experiment to validate the temperature and thermal emissivity values calculated from MTI and ASTER images, we have targeted the summit region of Mauna Loa for field characterization and near-simultaneous satellite imaging, both on daytime and nighttime overpasses, and compare the results to previously acquired 10{sup {minus}1} m airborne images, ground-level multispectral FLIR images, and the field spectra. Mauna Loa was chosen in large part because the 4x6km summit caldera, flooded with fresh basalt in 1984, appears to be spectrally homogeneous at scales between 10{sup {minus}1} and 10{sup 2} m, facilitating the comparison of sensed temperature. The validation results suggest that, with careful atmospheric compensation, it is possible to match ground measurements with measurements from space, and to use the Mauna Loa

An example of measurement and reporting of periodontal loss of attachment (LOA) in epidemiological studies: smoking and periodontal tissue destruction.

PubMed

Paidi, S; Pack, A R; Thomson, W M

1999-12-01

The measurement and reporting of periodontal disease in epidemiological studies can be complex, with the common indices having well-recognised shortcomings. The aim of this study was to illustrate the use of the periodontal loss of attachment (LOA) approach in investigating the association between cigarette smoking and loss of periodontal attachment in a convenience sample of adults, in order to determine whether or not smoking was a risk indicator for periodontal disease. All participants were given a detailed periodontal clinical examination in two randomly assigned contralateral diagonal quadrants, with LOA measurements made at six sites per tooth. Information was also collected on participants' socio-demographic characteristics, oral hygiene practices, smoking history, and attitudes towards smoking. The 240 participants examined comprised 81 current smokers (CS), 79 former smokers (FS) and 80 nonsmokers (NS). Substantial differences and a gradient in disease existed for LOA among the three groups. CS exhibited the greatest (and NS the least) prevalence, extent, and severity of LOA. CS had more plaque and calculus than either of the other two groups, but the groups did not differ with respect to bleeding on probing. Overall, smoking was associated with the disease outcome, and this persisted after potential confounders were controlled using multivariate analysis. Although the observed differences may have been due to the self-selected nature of the sample, the gradient evident across the three smoking exposure groups suggests that smoking cessation can slow the progression of the disease. The LOA approach appears to be a versatile and informative method for recording, analysing, and presenting data on periodontitis in epidemiological studies.

Perception of Lava Flow Hazards and Risk at Mauna Loa and Hualalai Volcanoes, Kona, Hawaii

NASA Astrophysics Data System (ADS)

Gregg, C. E.; Houghton, B. F.; Johnston, D. M.; Paton, D.; Swanson, D. A.

2001-12-01

The island of Hawaii is composed of five sub-aerially exposed volcanoes, three of which have been active since 1801 (Kilauea, Mauna Loa, Hualalai). Hawaii has the fastest population growth in the state and the local economy in the Kona districts (i.e., western portion of the island) is driven by tourism. Kona is directly vulnerable to future lava flows from Mauna Loa and Hualalai volcanoes, as well as indirectly from the effects of lava flows elsewhere that may sever the few roads that connect Kona to other vital areas on the island. A number of factors such as steep slopes, high volume eruptions, and high effusion rates, combine to mean that lava flows from Hualalai and Mauna Loa can be fast-moving and hence unusually hazardous. The proximity of lifelines and structures to potential eruptive sources exacerbates societies' risk to future lava flows. Approximately \\$2.3 billion has been invested on the flanks of Mauna Loa since its last eruption in 1984 (Trusdell 1995). An equivalent figure has not yet been determined for Hualalai, but an international airport, several large resort complexes, and Kailua-Kona, the second largest town on the island, are down-slope and within 15km of potential eruptive Hualalai vents. Public and perhaps official understanding of specific lava flow hazards and the perceptions of risk from renewed volcanism at each volcano are proportional to the time lapsed since the most recent eruption that impacted Kona, rather than a quantitative assessment of risk that takes into account recent growth patterns. Lava flows from Mauna Loa and Hualalai last directly impacted upon Kona during the notorious 1950 and circa 1801 eruptions, respectively. Various non-profit organizations; local, state and federal government entities; and academic institutions have disseminated natural hazard information in Kona but despite the intuitive appeal that increased hazard understanding and risk perception results in increased hazard adjustment adoption, this

Declining growth of Mauna Loa during the last 100,000 years: Rates of lava accumulation vs. gravitational subsidence

NASA Astrophysics Data System (ADS)

Lipman, Peter W.

Long-term growth rates of Hawaiian volcanoes are difficult to determine because of the short historical record, problems in dating tholeiitic basalt by K-Ar methods, and concealment of lower volcanic flanks by 5 km of seawater. Combined geologic mapping, petrologic and geochemical studies, geochronologic determinations, marine studies, and scientific drilling have shown that, despite frequent large historical eruptions (avg. 1 per 7 years since mid 19th century), the lower subaerial flanks of Mauna Loa have grown little during the last hundred thousand years. Coastal lava-accumulation rates have averaged less than 2 mm/year since 10 to 100 ka along the Mauna Loa shoreline, slightly less than recent isostatic subsidence rates of 2.4-2.6 mm/yr. Since 30 ka, lava accumulation has been greatest on upper flanks of the volcano at times of summit caldera overflows; rift eruptions have been largely confined to vents at elevations above +2,500 m, and activity has diminished lower along both rift zones. Additional indicators of limited volcanic construction at lower levels and declining eruptive activity include: (1) extensive near-surface preservation of Pahala Ash along the southeast coast, dated as older than about 30 ka; (2) preservation in the Ninole Hills of block-slumped ancestral Mauna Loa lavas erupted at 100-200 ka; (3) preservation low in the subaerial Kealakekua landslide fault scarp of lavas newly dated by K-Ar as 166±53 ka; (4) preservation of submerged coral reefs (150 m depth) dated at 14 ka and fossil shoreline features (as much as 350-400 m depth), with estimated ages of 130-150 ka, that have survived without burial by younger Mauna Loa lavas and related ocean-entry debris; (5) incomplete filling of old landslide breakaway scars; (6) limited deposition of post-landslide lava on lower submarine slopes (accumulation mostly <1,000 m depth); and (7) decreased deformation and gravitational instability of the volcanic edifice. In addition, the estimated recent

Sea surface temperature variation linked to elemental mercury concentrations measured on Mauna Loa

EPA Science Inventory

The Hg0 time series recorded at the Mauna Loa Observatory (MLO) in Hawaii between 2002 and 2009 has been analyzed using Empirical Mode Decomposition. This technique has been used in numerous contexts in order to identify periodical variations in time series data. The periodicitie...

Long, paired A'A/Pahoehoe flows of Mauna Loa: Volcanological significance and insights they provide into volcano plumbing systems

NASA Technical Reports Server (NTRS)

Rowland, Scott K.; Walker, George P. L.

1987-01-01

The long lava flows of Mauna Loa, Hawaii have been cited as Earth's closed analogs to the large Martian flows. It is therefore important to understand the flow mechanics and characteristics of the Mauna Loa flows and to make use of these in an attempt to gain insights into Martian eruptive processes. Two fundamentally different kinds of long lava flows can be distinguished on Hawaiian volcanoes as in Martian flows. The two kinds may have identical initial viscosities, chemical compositions, flow lengths, and flow volumes, but their flow mechanisms and thermal energy budgets are radically different. One travels a distance set by the discharge rate as envisaged by Walker and Wadge, and the other travels a distance set mainly by the eruption duration and ground slope. In the Mauna Loa lavas, yield strength becomes an important flow morphology control only in the distal part of a'a lavas. The occurrence of paired flows on Mauna Loa yields insights into the internal plumbing systems of the volcano, and it is significant that all of the volume of the a'a flow must be stored in a magma chamber before eruption, while none of the volume of the pahoehoe needs to be so stored. Differentiation between the two kinds of flows on images of Martian volcanoes is possible and hence an improved understanding of these huge structures is acquired.

Rapid Passage of a Small-Scale Mantle Heterogeneity Through the Melting Regions of Kilauea and Mauna Loa Volcanoes

NASA Astrophysics Data System (ADS)

Pietruszka, A. J.; Marske, J. P.; Weis, D.; Garcia, M. O.; Rhodes, J. M.

2006-12-01

There are few quantitative estimates for the size, shape, and distribution of small-scale compositional heterogeneities within the Hawaiian mantle plume. The chemistry of recent lavas from the two most active Hawaiian volcanoes, Kilauea and Mauna Loa, provide a snapshot of the heterogeneous structure of the plume beneath Hawaii. We present Pb and Sr isotope ratios of two suites of young prehistoric lavas from these volcanoes: (1) Kilauea lavas from AD 1000 to 1500, and (2) 14C-dated Mauna Loa flows from ~2,650- 140 years BP. Prior to this study, the Pb and Sr isotope ratios of lavas from these volcanoes were thought to be completely distinct (e.g., Abouchami et al., 2005). However, these prehistoric Kilauea and Mauna Loa lavas display a systematic isotopic fluctuation, and the Kilauea lavas (in particular) span the Pb and Sr isotopic divide that was previously thought to exist between these two volcanoes. For a brief period from AD 250 to 1500, the Pb and Sr isotope ratios of Kilauea and Mauna Loa lavas departed from values typical for each volcano's historical period, moved towards a common isotopic composition, and subsequently, returned to more typical values. This transient magmatic event was probably caused by the rapid passage of a small-scale compositional heterogeneity though the melting regions of these volcanoes. The heterogeneity is thought to be either a single body that extends between the summits of both Kilauea and Mauna Loa (~35 km long) or the ubiquitous plume matrix itself. The time scale of this event (centuries) is much shorter than previously noted for variations in the isotopic composition of Hawaiian lavas due to the upwelling of heterogeneities within the plume (thousands to tens of thousands of years; Blichert-Toft et al., 2003; Kurz et al., 2004). Calculations based on the duration of the isotopic excursion suggest a maximum thickness for the melting region (and thus, the heterogeneity) of only ~5-10 km.

The origin of Mauna Loa's Nīnole Hills: Evidence of rift zone reorganization

USGS Publications Warehouse

Zurek, Jeffrey; Williams-Jones, Glyn; Trusdell, Frank A.; Martin, Simon

2015-01-01

In order to identify the origin of Mauna Loa volcano's Nīnole Hills, Bouguer gravity was used to delineate density contrasts within the edifice. Our survey identified two residual anomalies beneath the Southwest Rift Zone (SWRZ) and the Nīnole Hills. The Nīnole Hills anomaly is elongated, striking northeast, and in inversions both anomalies merge at approximately −7 km above sea level. The positive anomaly, modeled as a rock volume of ~1200 km3 beneath the Nīnole Hills, is associated with old eruptive vents. Based on the geologic and geophysical data, we propose that the gravity anomaly under the Nīnole Hills records an early SWRZ orientation, now abandoned due to geologically rapid rift-zone reorganization. Catastrophic submarine landslides from Mauna Loa's western flank are the most likely cause for the concurrent abandonment of the Nīnole Hills section of the SWRZ. Rift zone reorganization induced by mass wasting is likely more common than currently recognized.

Volume predictability of historical eruptions at Kilauea and Mauna Loa volcanoes

NASA Astrophysics Data System (ADS)

King, Chi-Yu

1989-09-01

Cumulative volumes of eruptions at the Kilauea and Mauna Loa volcanoes in Hawaii appear to fit a volume-predictable model (i.e., the volume of an eruption episode is approximately proportional to the time since the previous episode) for many larger episodes during long periods of time (decades). This observation suggests that the magmatic pressure of each volcano tends to drop to a common level at the end of these episodes during each such period.

SBAS-InSAR analysis of surface deformation at Mauna Loa and Kilauea volcanoes in Hawaii

USGS Publications Warehouse

Casu, F.; Lanari, Riccardo; Sansosti, E.; Solaro, G.; Tizzani, Pietro; Poland, M.; Miklius, Asta

2009-01-01

We investigate the deformation of Mauna Loa and K??lauea volcanoes, Hawai'i, by exploiting the advanced differential Synthetic Aperture Radar Interferometry (InSAR) technique referred to as the Small BAseline Subset (SBAS) algorithm. In particular, we present time series of line-of-sight (LOS) displacements derived from SAR data acquired by the ASAR instrument, on board the ENVISAT satellite, from the ascending (track 93) and descending (track 429) orbits between 2003 and 2008. For each coherent pixel of the radar images we compute time-dependent surface displacements as well as the average LOS deformation rate. Our results quantify, in space and time, the complex deformation of Mauna Loa and K??lauea volcanoes. The derived InSAR measurements are compared to continuous GPS data to asses the quality of the SBAS-InSAR products. ??2009 IEEE.

Application of Earthquake Subspace Detectors at Kilauea and Mauna Loa Volcanoes, Hawai`i

NASA Astrophysics Data System (ADS)

Okubo, P.; Benz, H.; Yeck, W.

2016-12-01

Recent studies have demonstrated the capabilities of earthquake subspace detectors for detailed cataloging and tracking of seismicity in a number of regions and settings. We are exploring the application of subspace detectors at the United States Geological Survey's Hawaiian Volcano Observatory (HVO) to analyze seismicity at Kilauea and Mauna Loa volcanoes. Elevated levels of microseismicity and occasional swarms of earthquakes associated with active volcanism here present cataloging challenges due the sheer numbers of earthquakes and an intrinsically low signal-to-noise environment featuring oceanic microseism and volcanic tremor in the ambient seismic background. With high-quality continuous recording of seismic data at HVO, we apply subspace detectors (Harris and Dodge, 2011, Bull. Seismol. Soc. Am., doi: 10.1785/0120100103) during intervals of noteworthy seismicity. Waveform templates are drawn from Magnitude 2 and larger earthquakes within clusters of earthquakes cataloged in the HVO seismic database. At Kilauea, we focus on seismic swarms in the summit caldera region where, despite continuing eruptions from vents in the summit region and in the east rift zone, geodetic measurements reflect a relatively inflated volcanic state. We also focus on seismicity beneath and adjacent to Mauna Loa's summit caldera that appears to be associated with geodetic expressions of gradual volcanic inflation, and where precursory seismicity clustered prior to both Mauna Loa's most recent eruptions in 1975 and 1984. We recover several times more earthquakes with the subspace detectors - down to roughly 2 magnitude units below the templates, based on relative amplitudes - compared to the numbers of cataloged earthquakes. The increased numbers of detected earthquakes in these clusters, and the ability to associate and locate them, allow us to infer details of the spatial and temporal distributions and possible variations in stresses within these key regions of the volcanoes.

Temporal helium isotopic variations within Hawaiian volcanoes: Basalts from Mauna Loa and Haleakala

NASA Astrophysics Data System (ADS)

Kurz, Mark D.; Garcia, Michael O.; Frey, Fred A.; O'Brien, P. A.

1987-11-01

Helium isotope ratios in basalts spanning the subaerial eruptive history of Mauna Loa and Haleakala vary systematically with eruption age. In both volcanoes, olivine mineral separates from the oldest samples have the highest 3He /4He ratios. The Haleakala samples studied range in age from roughly one million years to historic time, while the Mauna Loa samples are radiocarbon dated flows younger than 30.000 years old. The Honomanu tholeiites are the oldest samples from Haleakala and have 3He /4He ratios that range from 13 to 16.8× atmospheric, while the younger Kula and Hana series alkali basalts all have 3He /4He close to 8×atmospheric. A similar range is observed on Mauna Loa; the oldest samples (roughly 30,000 years) have 3He /4He ratios of 15 to 20 × atmospheric, with a relatively smooth decrease to 8 × atmospheric with decreasing age. The consistent trend of decreasing 3He/ 4He ratio with time in both volcanoes, coherence between the helium and Sr and Nd isotopes (for Haleakala), and the similarity of 3He /4He in the late stage basalts to depleted mid-ocean ridge basalt (MORB) helium, argue against the decrease being the result of radiogenic ingrowth of 4He. The data strongly suggest an undegassed ( i.e., high 3He/(Th + U)) mantle source for the early shield building stages of Hawaiian volcanism. and are consistent with the hotspot/mantle plume model. The data are difficult to reconcile with models for Hawaiian volcanism that require recycled oceanic crust or derivation from a MORB-related upper mantle source. We interpret the decrease in 3He /4He with volcano evolution to result from an increasing involvement of depleted mantle and/or lithosphere during the late stages of Hawaiian volcanism.

[Construction and expression of recombinant Mycobacterium bovis BCG with the ompA-like membrane protein gene Loa22 of Leptospira interrogans serovar].

PubMed

Li, Dao-kun; Bao, Lang; Zhang, Ying; Sun, Zhan

2010-03-01

To study the immunity of Loa22 from Leptospira interrogans serovar Lai strain 56601 by expressing its protein in BCG. Amplified the mature peptide of Loa22 gene from the genome of of Leptospira interrogans serovar Lai strain 56601 and constructed recombinant plasmid rpMV36l-1oa22 with the E. coli-BCG integrating shuttle plasmid pMV361 and the Loa22 mature peptide gene. The rpMV36l-1oa22 plasmid was transformed into BCG by electroporation. The rBCG bearing rpMV36l-1oa22 was induced by high temperature of 45 degrees C and expressed protein was identified by SDS-PAGE and Western Blotting. Fifth 6-week-old BALB/c mice were randomly divided into five groups, which were inoculated intraperitoneally two times at 0-day and 21-day with BCG, rBCG-pMV361, rI3CG-1oa22, Loa22 and killed whole-leptospires respectively. All animals were dislocated from cervical vertebra on the 14Ih day after the last immunization. The proliferative reaction of splenic lymphocyte in tuitro were tested by XTT. The rpMV36l-1oa22 plasmid was constructed successfully and transformed into BCG. The rBCG expressed a 19 X io specifical protein identified by SDS-PAGE and Western Blotting. The splenic lymphocyte proliferate activity (SI) in rBCG-ioa22 group in intro was significantly higher than those in BCG group and rBCG-pMV361 group. We explored the expressing feasibility of Loa22 in Mycobacterium bovis BCG. may therefore make further researches on the induction of protective immunity against human and animal leptospirosis.

Volume predictability of historical eruptions at Kilauea and Mauna Loa volcanoes

USGS Publications Warehouse

King, C.-Y.

1989-01-01

Cumulative volumes of eruptions at the Kilauea and Mauna Loa volcanoes in Hawaii appear to fit a volume-predictable model (i.e., the volume of an eruption episode is approximately proportional to the time since the previous episode) for many larger episodes during long periods of time (decades). This observation suggests that the magmatic pressure of each volcano tends to drop to a common level at the end of these episodes during each such period. ?? 1989.

Relocation of Seismicity at Mauna Loa, Hawaii and Hengill, Iceland: Improved Delineation of Seismogenic Structures.

NASA Astrophysics Data System (ADS)

Baher, S. A.; Thurber, C.; Roberts, K.; Rowe, C.

2002-12-01

Waveform cross-correlation based refinement of P arrival times and subsequent relocation of earthquakes was determined for events that occurred near the summit of Mauna Loa, Hawaii prior to the March, 1984 eruption and at the Hengill volcano, Iceland during a two-month survey in 1991. Hengill and Mauna Loa volcanoes have a similar rift structure and are hot-spot related volcanoes. The relocated events at Mauna Loa illuminated a previously obscured structure beneath the northwestern flank. Simultaneous inversion for hypocenters and velocity model parameters using the refined arrival times resulted in well-constrained relative earthquake locations with very low arrival time misfits (average RMS 0.03 s). Pre-eruption seismicity from this time period occurred in two groups: a shallow group located near the Mauna Loa summit region, at depths of 1-3 km, and a deeper group located 4-6 km northwest of the summit, at depths of 5-10 km. After relocation, we found that most of the northwest flank earthquakes occurred along a 1 km planar feature striking about 60o E of North in a thin band about 500 m thick. This feature we interpret to be related to a rift zone that was stunted by the buttressing of the adjacent volcanoes Hualalai and Mauna Kea. Previous gravity and magnetic studies provide supporting evidence for the existence of a failed rift zone. Northwest flank focal mechanisms reveal a change in faulting from strike-slip in the southwest to a mix of strike-slip and normal faulting in the northeast. The near summit seismicity that was previously diffuse (4.5 km in width) is reduced to a 6 km long feature (0.5 km in width) extending from depth (6 km) toward the summit. The focal mechanisms analyzed from the summit events showed a mix of faulting without a consistent pattern. Previous studies at Hengill yielded locations of seismic activity that extend from 2-6 km in depth and no apparent correlation with surface features. The existence of non-double-couple focal

Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma.

PubMed

Zhao, Xin; Yang, Chaoshan; Tong, Yi; Zhang, Xiaohui; Xu, Liang; Li, Yang

2010-08-25

To describe the clinical and genetic findings in one Chinese family with juvenile-onset open angle glaucoma (JOAG). One family was examined clinically and a follow-up took place 5 years later. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed with three microsatellite markers around the MYOC gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA fragments and restriction fragment length polymorphism (RFLP) analysis. Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein. Clinical examination and pedigree analysis revealed a three- generation family with seven members diagnosed with JOAG, three with ocular hypertension, and five normal individuals. Through genotyping, the pedigree showed a linkage to the MYOC on chromosome 1q24-25. Mutation screening of MYOC in this family revealed an A-->T transition at position 1348 (p. N450Y) of the cDNA sequence. This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls. Secondary structure prediction of the p.N450Y by the GOR method revealed the replacement of a coil with a beta sheet at the amino acid 447. Early onset JOAG, with incomplete penetrance, is consistent with a novel mutation in MYOC. The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.

Mauna Loa lava accumulation rates at the Hilo drill site: Formation of lava deltas during a period of declining overall volcanic growth

USGS Publications Warehouse

Lipman, P.W.; Moore, J.G.

1996-01-01

Accumulation rates for lava flows erupted from Mauna Loa, as sampled in the uppermost 280 m of the Hilo drill hole, vary widely for short time intervals (several thousand years), but overall are broadly similar to those documented elsewhere on this volcano since 100 ka. Thickness variations and accumulation rates for Mauna Loa lavas at the Hilo drill site have been strongly affected by local paleotopography, including funneling and ponding between Mauna Kea and Kilauea. In addition, gentle submerged slopes of Mauna Kea in Hilo Bay have permitted large shoreline displacements by Mauna Loa flows. Ages of eruptive intervals have been determined from published isotopic data and from eustatic sea level curves modified to include the isostatic subsidence of the island of Hawaii at 2.2-2.6 mm/yr. Prior to 10 ka, rates of Mauna Loa lava accumulation at the drill site varied from 0.6 to 4.3 mm/yr for dateable intervals, with an overall rate of 1.8 mm/yr. Major eruptive pulses at about 1.3 and 10 ka, each probably representing a single long-lived eruption based on lack of weathering between flow units, increase the overall accumulation rate to 2.4 mm/yr. The higher rate since 10 ka reflects construction of thick near-shoreline lava deltas as postglacial sea levels rose rapidly. Large lava deltas form only along coastal segments where initially subaerial slopes have been submerged by the combined effects of eustatic sea level rise, isostatic subsidence, or spreading of volcano flanks. Overall accumulation of 239 m of lava at the drill site since 100-120 ka closely balances submergence of the Hilo area, suggesting that processes of coastal lava deposition have been modulated by rise in sea level. The Hilo accumulation rate is slightly higher than average rates of 1-2 mm/yr determined elsewhere along the Mauna Loa coast, based on rates of shoreline coverage and dated sea cliff and fault scarp exposures. Low rates of coastal lava accumulation since 100 ka, near or below the rate

Trace element abundances of high-MgO glasses from Kilauea, Mauna Loa and Haleakala volcanoes, Hawaii

USGS Publications Warehouse

Wagner, T.P.; Clague, D.A.; Hauri, E.H.; Grove, T.L.

1998-01-01

We performed an ion-microprobe study of eleven high-MgO (6.7-14.8 wt%) tholeiite glasses from the Hawaiian volcanoes Kilauea, Mauna Loa and Haleakala. We determined the rare earth (RE), high field strength, and other selected trace element abundances of these glasses, and used the data to establish their relationship to typical Hawaiian shield tholeiite and to infer characteristics of their source. The glasses have trace element abundance characteristics generally similar to those of typical shield tholeiites, e.g. L(light)REE/H(heavy)REE(C1) > 1. The Kilauea and Mauna Loa glasses, however, display trace and major element characteristics that cross geochemical discriminants observed between Kilauea and Mauna Loa shield lavas. The glasses contain a blend of these discriminating chemical characteristics, and are not exactly like the typical shield lavas from either volcano. The production of these hybrid magmas likely requires a complexly zoned source, rather than two unique sources. When corrected for olivine fractionation, the glass data show correlations between CaO concentration and incompatible trace element abundances, indicating that CaO may behave incompatibly during melting of the tholeiite source. Furthermore, the tholeiite source must contain residual garnet and clinopyroxene to account for the variation in trace element abundances of the Kilauea glasses. Inversion modeling indicates that the Kilauea source is flat relative to C1 chondrites, and has a higher bulk distribution coefficient for the HREE than the LREE.

Imaging the crustal magma sources beneath Mauna Loa and Kilauea volcanoes, Hawaii

USGS Publications Warehouse

Okubo, Paul G.; Benz, Harley M.; Chouet, Bernard A.

1997-01-01

Three-dimensional seismic P-wave traveltime tomography is used to image the magma sources beneath Mauna Loa and Kilauea volcanoes, Hawaii. High-velocity bodies (>6.4 km/s) in the upper 9 km of the crust beneath the summits and rift zones of the volcanoes correlate with zones of high magnetic intensities and are interpreted as solidified gabbro-ultramafic cumulates from which the surface volcanism is derived. The proximity of these high-velocity features to the rift zones is consistent with a ridge-spreading model of the volcanic flank. Southeast of the Hilina fault zone, along the south flank of Kilauea, low-velocity material (<6.0 km/s) is observed extending to depths of 9–11 km, indicating that the Hilina fault may extend possibly as deep as the basal decollement. Along the southeast flank of Mauna Loa, a similar low-velocity zone associated with the Kaoiki fault zone is observed extending to depths of 6–8 km. These two upper crustal low-velocity zones suggest common stages in the evolution of the Hawaiian shield volcanoes in which these fault systems are formed as a result of upper crustal deformation in response to magma injection within the volcanic edifice.

IR temperatures of Mauna Loa caldera obtained with multispectral thermal imager

NASA Astrophysics Data System (ADS)

Pendergast, Malcolm M.; O'Steen, Byron L.; Kurzeja, Robert J.

2002-01-01

A survey of surface temperatures of the Mauna Loa caldera during 7/14/00 and 7/15/00 was made by SRTC in conjunction with a MTI satellite image collection. The general variation of surface temperature appears quite predictable responding to solar heating. The analysis of detailed times series of temperature indicates systematic variations in temperature of 5 C corresponding to time scales of 3-5 minutes and space scales of 10-20 m. The average temperature patterns are consistent with those predicted by the Regional Atmospheric Modeling System (RAMS).

The 1984 Mauna Loa eruption and planetary geolgoy

NASA Technical Reports Server (NTRS)

Moore, Henry J.

1987-01-01

In planetary geology, lava flows on the Moon and Mars are commonly treated as relatively simple systems. Some of the complexities of actual lava flows are illustrated using the main flow system of the 1984 Mauna Loa eruption. The outline, brief narrative, and results given are based on a number of sources. The implications of the results to planetary geology are clear. Volume flow rates during an eruption depend, in part, on the volatile content of the lava. These differ from the volume flow rates calculated from post eruption flow dimensions and the duration of the eruption and from those using models that assume a constant density. Mass flow rates might be more appropriate because the masses of volatiles in lavas are usually small, but variable and sometimes unknown densities impose severe restrictions on mass estimates.

Infrared Measurements of Atmospheric Gases Above Mauna Loa, Hawaii, in February 1987

NASA Technical Reports Server (NTRS)

Rinsland, C. P.; Goldman, A.; Murcray, F. J.; Murcray, F. H.; Blatherwick, R. D.; Murcray, D. G.

1988-01-01

Infrared solar absorption spectra recorded at 0.02/ cm resolution from the National Oceanic and Atmospheric Administration (NOAA) Geophysical Monitoring for Climate Change (GMCC) program station at Mauna Loa, Hawaii (latitude 19.5 deg N, longitude 155.6 deg W, elevation 3.40 km), in February 1997 have been analyzed to determine simultaneous total vertical column amounts for 13 atmospheric gases. Average tropospheric concentrations of CO2, N2O, CH4, and CHCIF2 and the daytime diurnal variations or the total columns of NO and NO2 have also been inferred. The retrieved total columns (in molecules /sq cm) of the nondiurnally varying gases are 1.6 +/- 0.2 x 10(exp 15) for HCl, 5.9 +/- 1.2 x 10(exp 15) for HNO3, 2.0 +/- 0.2 x 10(exp 21) for H2O16, 4.4 +/- 0.7 x 10(exp 18) for H2O18, 2.7 +/- 0.1 x 10(exp 17) for HDO, 2.3 +/- 0.2 x 10(exp 19) for CH4, 5.0 +/- 0.5 x 10(exp 21) for CO2, 6.7 +/- 0.8 x 10(exp 18) for O3, 4.3 +/- 0.4 x 10(exp 18) for N2O, 1.0 +/- 0.2 x 10(exp 16) for C2H6, and 9.7 +/- 2.5 x 10(exp 14) for CHClF2. We compare the total column measurements of HCl and HNO3 with previously reported ground-based, aircraft, and satellite measurements. The results for HCl are or particular interest because of the expected temporal increase in the concentration of this gas in the stratosphere. However, systematic differences among stratospheric HCl total column measurements from 1978 to 1980 and the absence of observations of free tropospheric HCl above Mauna Loa make it impossible to obtain a reliable estimate of the trend in the total burden of HCl. The measured HNO3 total column is consistent with aircraft measurements from approx. 12 km altitude. The O3 total column deduced from the IR spectra agrees with correlative Mauna Loa Umkehr measurements within the estimated error limits. The column-averaged D/H ratio of water vapor is (68 +/- 9) x- 10(exp -6), which is 0.44 +/- 0.06 times the reference value of 155.76 x 10(exp -6) for standard mean ocean water (SMOW). This

"The upper limits of vegetation on Mauna Loa, Hawaii": a 50th-anniversary reassessment.

PubMed

Juvik, James O; Rodomsky, Brett T; Price, Jonathan P; Hansen, Eric W; Kueffer, Christoph

2011-02-01

In January 1958, a survey of alpine flora was conducted along a recently constructed access road across the upper volcanic slopes of Mauna Loa, Hawaii (2525-3397 m). Only five native Hawaiian species were encountered on sparsely vegetated historic and prehistoric lava flows adjacent to the roadway. A resurvey of roadside flora in 2008 yielded a more than fourfold increase to 22 species, including nine native species not previously recorded. Eight new alien species have now invaded this alpine environment, although exclusively limited to a few individuals in ruderal habitat along the roadway. Alternative explanations for species invasion and altitudinal change over the past 50 years are evaluated: (1) changes related to continuing primary succession on ameliorating (weathering) young lava substrates; (2) local climate change; and (3) road improvements and increased vehicular access which promote enhanced car-borne dispersal of alien species derived from the expanding pool of potential colonizers naturalized on the island in recent decades. Unlike alpine environments in temperate latitudes, the energy component (warming) in climate change on Mauna Loa does not appear to be the unequivocal driver of plant invasion and range extension. Warming may be offset by other climate change factors including rainfall and evapotranspiration.

Three-dimensional seismic velocity structure of Mauna Loa and Kilauea volcanoes in Hawaii from local seismic tomography

USGS Publications Warehouse

Lin, Guoqing; Shearer, Peter M.; Matoza, Robin S.; Okubo, Paul G.; Amelung, Falk

2016-01-01

We present a new three-dimensional seismic velocity model of the crustal and upper mantle structure for Mauna Loa and Kilauea volcanoes in Hawaii. Our model is derived from the first-arrival times of the compressional and shear waves from about 53,000 events on and near the Island of Hawaii between 1992 and 2009 recorded by the Hawaiian Volcano Observatory stations. The Vp model generally agrees with previous studies, showing high-velocity anomalies near the calderas and rift zones and low-velocity anomalies in the fault systems. The most significant difference from previous models is in Vp/Vs structure. The high-Vp and high-Vp/Vs anomalies below Mauna Loa caldera are interpreted as mafic magmatic cumulates. The observed low-Vp and high-Vp/Vs bodies in the Kaoiki seismic zone between 5 and 15 km depth are attributed to the underlying volcaniclastic sediments. The high-Vp and moderate- to low-Vp/Vs anomalies beneath Kilauea caldera can be explained by a combination of different mafic compositions, likely to be olivine-rich gabbro and dunite. The systematically low-Vp and low-Vp/Vs bodies in the southeast flank of Kilauea may be caused by the presence of volatiles. Another difference between this study and previous ones is the improved Vp model resolution in deeper layers, owing to the inclusion of events with large epicentral distances. The new velocity model is used to relocate the seismicity of Mauna Loa and Kilauea for improved absolute locations and ultimately to develop a high-precision earthquake catalog using waveform cross-correlation data.

A Geochemical Study of Magmatic Processes and Evolution along the Submarine Southwest Rift zone of Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Rhodes, J. M.; Garcia, M. O.; Weis, D.; Trusdell, F. A.; Vollinger, M. J.

2003-12-01

Mauna Loa's southwest rift zone (SWR) extends for 102 km from its summit caldera, at an elevation of 4,170 m above sea level, to submarine depths of over 4,500 m. About 65% of the rift zone is subaerial and 35% submarine. Recent sampling with the Jason II submersible of the `mile-high' (1800 m) Ka Lae submarine landslide scarp and the deepest section of the rift zone, in conjunction with previous submersible and dredge-haul collecting, provides petrological and geochemical understanding of rift zone processes, as well as a record of Mauna Loa's eruptive history extending back about 400 ka. The major and trace element trends of the submarine lavas are remarkably similar to those of historical and young prehistoric lavas (<31 ka) erupted along the subaerial SWR. We take this to imply that magma-forming processes have remained relatively constant over much of the volcano's recorded eruptive history. However, the distribution of samples along these trends has varied, and is correlated with elevation. There are very few picrites (>12% MgO) among the subaerial lavas, and compositions tend to cluster around 6.8-8.0% MgO. In contrast, picritic lavas are extremely abundant in the submarine samples, increasing in frequency with depth, especially below 1200 m. These observations support earlier interpretations that the submarine lavas are derived directly from deeper levels in the magma column, and that magmas from a shallow, steady-state, magma reservoir are of uncommon at these depths. Isotopic ratios of Pb and Sr in the submarine lavas, in conjunction with Nb/Y and Zr/Nb ratios, extend from values that are identical with subaerial historical Mauna Loa lavas to lavas with markedly lower 87Sr/86Sr and higher 206Pb/204Pb isotopic ratios. As yet, we see no correlation with depth or age, but the implications are that, in the past, the plume source of Mauna Loa magmas was more variable than in the last 31 ka, and contained a greater proportion of the Kea component. *Team members

Ups and downs on spreading flanks of ocean-island volcanoes: evidence from Mauna Loa and Kīlauea

USGS Publications Warehouse

Lipman, Peter W.; Eakins, Barry W.; Yokose, Hisayoshi

2003-01-01

Submarine-flank deposits of Hawaiian volcanoes are widely recognized to have formed largely by gravitationally driven volcano spreading and associated landsliding. Observations from submersibles show that prominent benches at middepths on flanks of Mauna Loa and Kilauea consist of volcaniclastic debris derived by landsliding from nearby shallow submarine and subaerial flanks of the same edifice. Massive slide breccias from the mature subaerial tholeiitic shield of Mauna Loa underlie the frontal scarp of its South Kona bench. In contrast, coarse volcaniclastic sediments derived largely from submarine-erupted preshield alkalic and transitional basalts of ancestral Kilauea underlie its Hilina bench. Both midslope benches record the same general processes of slope failure, followed by modest compression during continued volcano spreading, even though they record development during different stages of edifice growth. The dive results suggest that volcaniclastic rocks at the north end of the Kona bench, interpreted by others as distal sediments from older volcanoes that were offscraped, uplifted, and accreted to the island by far-traveled thrusts, alternatively are a largely coherent stratigraphic assemblage deposited in a basin behind the South Kona bench.

Aerosol Backscatter Profiles at 10.59 and 9.25 Micrometers near Mauna Loa, Hawaii, 1988

NASA Astrophysics Data System (ADS)

Post, Madison J.

1989-12-01

The NOAA Doppler lidar trailer was transported from Boulder, Colorado, to the 3.231km level of Hawaii's Mauna Loa volcano (lat. 19.55°N, long. 155.56°W) in No-vember 1988 to participate in the NASA-sponsored Mauna Loa Backscatter Intercomparison Experiment (MABIE) for 1988. Our purpose was multifold. Among the aerosol studies our goals were to gather a statistically meaningful set of vertical backscatter pro-files at two wavelengths in the clean Pacific environment, to compare data from several microphysical sensors located at the GMCC observatory 3 km away, to assess the representativeness of the ground-based GMCC samplers with respect to the air mass over-head, and to understand the depth of the upslope and downslope flows that have historically affected the GMCC samplers. We were highly successful on all counts, having gathered 243 vertical profiles at 10.59 gm, 49 profiles at 9.25 vim, 278 GMCC intercom-parisons, and 404 wind profiles and cross sections. Our data-gathering period extended over 24 days through December 11. We calibrated the system on seven different days, usually at both wavelengths, to insure accuracy in our results. We also acquired data close in time to nearby SAGE 11. sampling, and twice took data simultaneously with GMCC's ruby lidar.

Automatic Near-Real-Time Detection of CMEs in Mauna Loa K-Cor Coronagraph Images

NASA Astrophysics Data System (ADS)

Thompson, W. T.; St. Cyr, O. C.; Burkepile, J. T.; Posner, A.

2017-10-01

A simple algorithm has been developed to detect the onset of coronal mass ejections (CMEs), together with speed estimates, in near-real time using linearly polarized white-light solar coronal images from the Mauna Loa Solar Observatory K-Cor telescope. Ground observations in the low corona can warn of CMEs well before they appear in space coronagraphs. The algorithm used is a variation on the Solar Eruptive Event Detection System developed at George Mason University. It was tested against K-Cor data taken between 29 April 2014 and 20 February 2017, on days identified as containing CMEs. This resulted in testing of 139 days' worth of data containing 171 CMEs. The detection rate varied from close to 80% when solar activity was high down to as low as 20-30% when activity was low. The difference in effectiveness with solar cycle is attributed to the relative prevalence of strong CMEs between active and quiet periods. There were also 12 false detections, leading to an average false detection rate of 8.6%. The K-Cor data were also compared with major solar energetic particle (SEP) storms during this time period. There were three SEP events detected either at Earth or at one of the two STEREO spacecraft when K-Cor was observing during the relevant time period. The algorithm successfully generated alerts for two of these events, with lead times of 1-3 h before the SEP onset at 1 AU. The third event was not detected by the automatic algorithm because of the unusually broad width in position angle.

Rapid passage of a small-scale mantle heterogeneity through the melting regions of Kilauea and Mauna Loa Volcanoes

NASA Astrophysics Data System (ADS)

Marske, Jared P.; Pietruszka, Aaron J.; Weis, Dominique; Garcia, Michael O.; Rhodes, J. Michael

2007-07-01

Recent Kilauea and Mauna Loa lavas provide a snapshot of the size, shape, and distribution of compositional heterogeneities within the Hawaiian mantle plume. Here we present a study of the Pb, Sr, and Nd isotope ratios of two suites of young prehistoric lavas from these volcanoes: (1) Kilauea summit lavas erupted from AD 900 to 1400, and (2) 14C-dated Mauna Loa flows erupted from ˜ 2580-140 yr before present (relative to AD 1950). These lavas display systematic isotopic fluctuations, and the Kilauea lavas span the Pb isotopic divide that was previously thought to exist between these two volcanoes. For a brief period from AD 250 to 1400, the 206Pb/ 204Pb and 87Sr/ 86Sr isotope ratios and ɛNd values of Kilauea and Mauna Loa lavas departed from values typical for each volcano (based on historical and other young prehistoric lavas), moved towards an intermediate composition, and subsequently returned to typical values. This is the only known period in the eruptive history of these volcanoes when such a simultaneous convergence of Pb, Sr, and Nd isotope ratios has occurred. The common isotopic composition of lavas erupted from both Kilauea and Mauna Loa during this transient magmatic event was probably caused by the rapid passage of a small-scale compositional heterogeneity through the melting regions of both volcanoes. This heterogeneity is thought to have been either a single body (˜ 35 km long based on the distance between the summits of these volcanoes) or the plume matrix itself (which would be expected to be present beneath both volcanoes). The time scale of this event (centuries) is much shorter than previously noted for variations in the isotopic composition of Hawaiian lavas due to the upwelling of heterogeneities within the plume (thousands to tens of thousands of years). Calculations based on the timing of the isotopic convergence suggest a maximum thickness for the melting region (and thus, the heterogeneity) of ˜ 5-10 km. The small size of the

Geologic map of the northeast flank of Mauna Loa volcano, Island of Hawai'i, Hawaii

USGS Publications Warehouse

Trusdell, Frank A.; Lockwood, John P.

2017-05-01

SummaryMauna Loa, the largest volcano on Earth, has erupted 33 times since written descriptions became available in 1832. Some eruptions were preceded by only brief seismic unrest, while others followed several months to a year of increased seismicity.The majority of the eruptions of Mauna Loa began in the summit area (>12,000-ft elevation; Lockwood and Lipman, 1987); yet the Northeast Rift Zone (NERZ) was the source of eight flank eruptions since 1843 (table 1). This zone extends from the 13,680-ft-high summit towards Hilo (population ~60,000), the second largest city in the State of Hawaii. Although most of the source vents are farther than 30 km away, the 1880 flow from one of the vents extends into Hilo, nearly reaching Hilo Bay. The city is built entirely on flows erupted from the NERZ, most older than that erupted in 1843.Once underway, Mauna Loa's eruptions can produce lava flows that reach the sea in less than 24 hours, severing roads and utilities in their path. For example, lava flows erupted from the Southwest Rift Zone (SWRZ) in 1950 advanced at an average rate of 9.3 km per hour, and all three lobes reached the ocean within approximately 24 hours (Finch and Macdonald, 1953). The flows near the eruptive vents must have traveled even faster.In terms of eruption frequency, pre-eruption warning, and rapid flow emplacement, Mauna Loa poses an enormous volcanic-hazard threat to the Island of Hawai‘i. By documenting past activity and by alerting the public and local government officials of our findings, we can anticipate the volcanic hazards and substantially mitigate the risks associated with an eruption of this massive edifice.From the geologic record, we can deduce several generalized facts about the geologic history of the NERZ. The middle to the uppermost section of the rift zone were more active in the past 4,000 years than the lower part, perhaps due to buttressing of the lower east rift zone by Mauna Kea and Kīlauea volcanoes. The historical flows

40Ar/39Ar geochronology of submarine Mauna Loa volcano, Hawaii

NASA Astrophysics Data System (ADS)

Jicha, B.; Rhodes, J. M.; Singer, B. S.; Vollinger, M. J.; Garcia, M. O.

2009-12-01

A major impediment to our understanding of the nature and structure of the Hawaiian plume, and evaluating the competing plume models has been a lack of thick stratigraphic sections from which to obtain long temporal records of magmatic history. The Hawaii Scientific Drilling Project (HSDP) made a significant advance towards solving this problem by documenting the long-term magmatic evolution of Mauna Kea volcano on the Kea side of the plume. To evaluate comparable long-term magmatic history on the Loa side of the plume we collected a stratigraphically controlled sample suite using Jason and Pisces dives from three vertical transects of the 1.6 km high Kae Lae landslide scarp cut into Mauna Loa’s submarine southwest rift zone (SWR). We have undertaken an 40Ar/39Ar investigation of Mauna Loa’s growth history to integrate new geochronologic constraints with geochemical, and isotopic data, illuminating temporal trends within the Hawaiian plume. Obtaining precise 40Ar/39Ar ages from tholeiitic lavas younger than 500 ka containing only 0.2-0.6 wt.% K2O is challenging due to the extremely low radiogenic 40Ar contents. Furnace incremental heating experiments of groundmass separated from 15 submarine lavas have yielded four new age determinations (a 27% success rate). These four lavas give concordant age spectra with plateau and isochron ages that agree with stratigraphy. We also analyzed two previously-dated subaerial Mauna Kea tholeiites from the HSDP-2 drill core, to assess inter-laboratory reproducibility and calibrate our results to those obtained for the core. Two experiments on sample SR413-4.0 and one experiment from SR781-21.2 gave weighted mean plateau ages of 364 ± 95 ka and 473 ± 109, respectively, which are indistinguishable from the published 40Ar/39Ar ages of 390 ± 70 ka and 482 ± 67. Although Sharp and Renne (2005) preferred isochron ages for the submarine Mauna Kea tholeiites recovered from HSDP, we find that submarine Mauna Loa lavas contain

Differential arsenic binding in the sediments of two sites in Chile's lower Loa River basin.

PubMed

Bugueño, Manuel P; Acevedo, Sara E; Bonilla, Carlos A; Pizarro, Gonzalo E; Pasten, Pablo A

2014-01-01

Fluvial sediments from two lower Loa River basin sites in northern Chile were compared in order to probe the effects of vegetation and organic matter (OM) on As accumulation in fluvial environments. The two sites were the Sloman dam, which lacks macrophytes and has a low OM content (2.4%) in sediments, and the Quillagua Oasis, which is 23 km downstream from the Sloman site and has a higher OM (6.2%) in sediments and abundant aquatic plant life. The Quillagua site had preferential As enrichment with a co-occurrence pattern that differed from that of the Sloman site, which had a lower As concentration (1528 vs. 262 mg/kg d.w., respectively). At the Quillagua site, As concentration was strongly correlated with Mn and OM (r = 0.91 and 0.85, respectively); while at the Sloman site, As concentration in sediments was significantly correlated with Ca and Sr (r = 0.63 and 0.54, respectively). Sequential extraction analyses showed that the Sloman site had higher percentage of easily exchangeable As within the surface sediment (12%, 45 mg/kg d.w.) compared with the Quillagua site (3%, 40 mg/kg d.w.). These contrasting results suggest that both vegetation and OM control the immobilization and accumulation of As in the arid Loa River basin. © 2013 Elsevier B.V. All rights reserved.

Implications of historical eruptive-vent migration on the northeast rift zone of Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Lockwood, John P.

1990-07-01

Five times within the past 138 yr (1852, 1855-1856, 1880-1881, 1942, and 1984), lava flows from vents on the northeast rift zone of Mauna Loa Volcano have reached within a few kilometres of Hilo (the largest city on the Island of Hawaii). Most lavas erupted on this rift zone in historical time have traveled northeastward (toward Hilo), because their eruptive vents have been concentrated north of the rift zone's broad topographic axis. However, with few exceptions each successive historical eruption on the northeast rift zone has occurred farther southeast than the preceding one. Had the 1984 eruptive vents (the most southeasterly yet) opened less than 200 m farther southeast, the bulk of the 1984 lavas would have flowed away from Hilo. If this historical vent-migration pattern continues, the next eruption on the northeast rift zone could send lavas to the southeast, toward less populated areas. The historical Mauna Loa vent-migration patterns mimic the southeastern "younging" of the Hawaiian-Emperor volcanic chain and may be cryptically related to northwestward movement of the Pacific plate. Systematic temporal-spatial vent-migration patterns may characterize eruptive activity at other volcanoes with flank activity and should be considered as an aid to long-term prediction of eruption sites.

Episodic trace element and isotopic variations in historical Mauna Loa Lavas: Implications for magma and plume dynamics

NASA Astrophysics Data System (ADS)

Rhodes, J. M.; Hart, S. R.

Over the past 152 years, Mauna Loa volcano has erupted lavas with almost constant major element, and compatible and moderately incompatible trace element abundances at a given MgO content. This uniformity is attributed to continuing replenishment of a shallow magma reservoir. In contrast, incompatible element abundances and ratios, together with Sr, Nd and Pb isotopic ratios, vary systematically with time. The greatest rate of change occurred at a time (1843-1887) when Mauna Loa was vigorously active with high eruption rates, presumably a consequence of a high magma supply rate. Detailed analysis confirms what is evident from the isotopic data: that this open-system magmatism requires two or more parental magmas. One has the compositional attributes of lavas erupted in 1843, the other the characteristics of lavas erupted at the summit early in 1880. All other historical lavas can be considered as mixtures of these two end-members, modified by contemporaneous eruption and olivine crystallization. Both parental magmas have Sr, Pb and Nd isotopic ratios typical of magmas in the Hawaiian tholeiitic array, and intermediate between those of Kilauea and Koolau lavas, the end-members of the array. The 1843 parental magma has incompatible element ratios that are similar to, and overlap with the Koolau and Kilauea data. The inferred 1880 parental magma, however, is more depleted than the 1843 parental magma (and most other Hawaiian lavas), and is also isotopically closer to the Kilauea end-member of the tholeiitic array. The origin of these parental magmas is discussed in terms of melting within a radially heterogeneous plume in which the heterogeneity may develop at the source or through subsequent mantle entrainment. Two models are explored, both depend on the location of Mauna Loa at, or close to the plume margin. In the simplest case the parental magmas are produced by progressive melting of the heterogeneous outer plume. The second model is more dynamic, involving melt

Highlights from the 2002 JASON2 marine expedition to Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Weis, D.; Submarine Mauna Loa Science Team

2003-04-01

The new JASON2 ROV was used for 12 dives to explore and sample the submarine flanks of Mauna Loa, the world’s largest active volcano. JASON2 collected 215 visually (using video and still camera) and spatially well-documented rock and sediment samples totaling 1130 kg from the volcano’s southwest rift zone and western flank. The goals of the expedition were to investigate the nature and history of the Hawaiian mantle plume as revealed in a 1.6 km thick, submarine landslide scarp, to examine volcanic processes along the 37 km long, submarine portion of the southwest rift zone, which has 4.5 km of relief, and to sample the newly discovered submarine radial vents. In addition, detailed bathymetric data was collected for an area of 2000 km2 using an EM300 system, which has a pixel resolution of 30 m allowing for identification of small (horizontal) scale volcanic and tectonic features. These surveys provide the first detailed examination of the volcano’s submarine rift zone and western flank. They revealed 11 new radial vents, many of which appear to be young based on examination by JASON2. Radial vents are uncommon on Hawaiian volcanoes and represent only 2 of the 39 historical Mauna Loa eruptions. Picritic basalts are remarkably abundant in the rift zone section, which may record 400,000 years of eruptive activity representing about one half of the volcano’s total lifetime. This time period is comparable to that sampled by phase 2 of the Hawaiian Scientific Drilling Project. The initial bathymetric and geologic results from this cruise will be presented.

Composition and spectral characteristics of ambient aerosol at Mauna Loa Observatory

NASA Technical Reports Server (NTRS)

Johnson, Stanley A.; Kumar, Romesh

1991-01-01

The spectral and the chemical characteristics of ambient aerosol at Mauna Loa Observatory (Hawaii) were determined in aerosol particles continuously sampled during an 8-day period in August 1986. During this period, the chemical species in the ambient aerosol varied considerably. During the major fraction of the sampling period, the aerosol was acidic due to predominance of (NH4)3H(SO4)2, NH4HSO4, or H2SO4. Aerosol samples showed much higher absorbance at 9.1 microns than at 10.6 microns. Moreover, changes in chemical composition from the neutral (NH4)2SO4 aerosol to more acidic sulphate forms were accompanied by substantial changes in the samples' absorbance at 9.1 microns (with lesser changes in the 10.6-micron absorptions).

New insights into the magma chamber activity under Mauna Loa inferred from SBAS-InSAR and geodetic inversion modelling

NASA Astrophysics Data System (ADS)

Varugu, B. K.; Amelung, F.

2017-12-01

Mauna Loa volcano, located on the Big Island, Hawaii, is the largest volcano on the earth and historically been one of the most active volcanoes on the earth. Since its last eruption in 1984, there was a decrease in the magmatic activity, yet episodic inflations with increased seismicity sparks interests in the scientific community and there is strong need to monitor the volcano with growing infrastructure close to the flanks of the volcano. Geodetic modelling of the previous inflations illustrate that the magma activity is due to inflation of hydraulically connected dike and magma chamber located from 4-8km beneath the summit (Amelung et al. 2007). Most of the seismicity observed on Mauna Loa is due to the movement along a decollement fault situated at the base of the volcano. Magma inflation under Mauna Loa has started again during the last quarter of 2013 and is continuing still with an increased seismicity. In this study, we used 140 images form COSMO SkyMED between 2013-2017 to derive and model the ground deformation. We carried out time series InSAR analysis using Small Baseline (SB) approach. While the deformation pattern seems similar in many ways to the previous inflation periods, geodetic modelling for inversion of source parameters indicate a significant propagation of the dike ( 1 km) into the South West Rift Zone(SWRZ) and a decreased depth of the dike top from summit, compared to the previous inflations. Such propagation needs to be studied further in view of the steep slope of SWRZ. In understanding the dynamics of this propagating dike, we also observed an increased seismic activity since 2014 in the vicinity of the modelled dike. Here in this study we attempt to characterize the stresses induced by the propagating dike and seaward slipping movement along the basal decollement, to explain the increased seismicity using a finite element model.

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.

Perspectives on basaltic magma crystallization and differentiation: Lava-lake blocks erupted at Mauna Loa volcano summit, Hawaii

USGS Publications Warehouse

McCarter, Renee L.; Fodor, R.V.; Trusdell, Frank A.

2006-01-01

Explosive eruptions at Mauna Loa summit ejected coarse-grained blocks (free of lava coatings) from Moku'aweoweo caldera. Most are gabbronorites and gabbros that have 0–26 vol.% olivine and 1–29 vol.% oikocrystic orthopyroxene. Some blocks are ferrogabbros and diorites with micrographic matrices, and diorite veins (≤2 cm) cross-cut some gabbronorites and gabbros. One block is an open-textured dunite.The MgO of the gabbronorites and gabbros ranges ∼ 7–21 wt.%. Those with MgO >10 wt.% have some incompatible-element abundances (Zr, Y, REE; positive Eu anomalies) lower than those in Mauna Loa lavas of comparable MgO; gabbros (MgO <10 wt.%) generally overlap lava compositions. Olivines range Fo83–58, clinopyroxenes have Mg#s ∼83–62, and orthopyroxene Mg#s are 84–63 — all evolved beyond the mineral-Mg#s of Mauna Loa lavas. Plagioclase is An75–50. Ferrogabbro and diorite blocks have ∼ 3–5 wt.% MgO (TiO2 3.2–5.4%; K2O 0.8–1.3%; La 16–27 ppm), and a diorite vein is the most evolved (SiO2 59%, K2O 1.5%, La 38 ppm). They have clinopyroxene Mg#s 67–46, and plagioclase An57–40. The open-textured dunite has olivine ∼ Fo83.5. Seven isotope ratios are 87Sr/86Sr 0.70394–0.70374 and 143Nd/144Nd 0.51293–0.51286, and identify the suite as belonging to the Mauna Loa system.Gabbronorites and gabbros originated in solidification zones of Moku'aweoweo lava lakes where they acquired orthocumulate textures and incompatible-element depletions. These features suggest deeper and slower cooling lakes than the lava lake paradigm, Kilauea Iki, which is basalt and picrite. Clinopyroxene geobarometry suggests crystallization at <1 kbar P. Highly evolved mineral Mg#s, <75, are largely explained by cumulus phases exposed to evolving intercumulus liquids causing compositional ‘shifts.’ Ferrogabbro and diorite represent segregation veins from differentiated intercumulus liquids filter pressed into rigid zones of cooling lakes. Clinopyroxene

Automatic near-real-time detection of CMEs in Mauna Loa K-Cor coronagraph images

NASA Astrophysics Data System (ADS)

Thompson, William T.; St. Cyr, Orville Chris; Burkepile, Joan; Posner, Arik

2017-08-01

A simple algorithm has been developed to detect the onset of coronal mass ejections (CMEs), together with an estimate of their speed, in near-real-time using images of the linearly polarized white-light solar corona taken by the K-Cor telescope at the Mauna Loa Solar Observatory (MLSO). The algorithm used is a variation on the Solar Eruptive Event Detection System (SEEDS) developed at George Mason University. The algorithm was tested against K-Cor data taken between 29 April 2014 and 20 February 2017, on days which the MLSO website marked as containing CMEs. This resulted in testing of 139 days worth of data containing 171 CMEs. The detection rate varied from close to 80% in 2014-2015 when solar activity was high, down to as low as 20-30% in 2017 when activity was low. The difference in effectiveness with solar cycle is attributed to the difference in relative prevalance of strong CMEs between active and quiet periods. There were also twelve false detections during this time period, leading to an average false detection rate of 8.6% on any given day. However, half of the false detections were clustered into two short periods of a few days each when special conditions prevailed to increase the false detection rate. The K-Cor data were also compared with major Solar Energetic Particle (SEP) storms during this time period. There were three SEP events detected either at Earth or at one of the two STEREO spacecraft where K-Cor was observing during the relevant time period. The K-Cor CME detection algorithm successfully generated alerts for two of these events, with lead times of 1-3 hours before the SEP onset at 1 AU. The third event was not detected by the automatic algorithm because of the unusually broad width of the CME in position angle.

Increase in background stratospheric aerosol observed with lidar at Mauna Loa Observatory and Boulder, Colorado - article no. L15808

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

Hofmann, D.; Barnes, J.; O'Neill, M.

2009-08-15

The stratospheric aerosol layer has been monitored with lidars at Mauna Loa Observatory in Hawaii and Boulder in Colorado since 1975 and 2000, respectively. Following the Pinatubo volcanic eruption in June 1991, the global stratosphere has not been perturbed by a major volcanic eruption providing an unprecedented opportunity to study the background aerosol. Since about 2000, an increase of 4-7% per year in the aerosol backscatter in the altitude range 20-30 km has been detected at both Mauna Loa and Boulder. This increase is superimposed on a seasonal cycle with a winter maximum that is modulated by the quasi-biennial oscillationmore » (QBO) in tropical winds. Of the three major causes for a stratospheric aerosol increase: volcanic emissions to the stratosphere, increased tropical upwelling, and an increase in anthropogenic sulfur gas emissions in the troposphere, it appears that a large increase in coal burning since 2002, mainly in China, is the likely source of sulfur dioxide that ultimately ends up as the sulfate aerosol responsible for the increased backscatter from the stratospheric aerosol layer. The results are consistent with 0.6-0.8% of tropospheric sulfur entering the stratosphere.« less

Comparison of TIMS and MC-ICP-MS Analyses of Pb Isotopic Compositions on Prehistoric Mauna Loa Basalts: Implications for Plume Source Components

NASA Astrophysics Data System (ADS)

De Jong, J.; Weis, D.; Maerschalk, C.; Rhodes, J. M.

2001-12-01

Recent isotopic studies on Hawaiian lavas have shown the necessity of constraining fractionation for Pb isotopes. This isotopic system presents systematic variations reflecting the presence of different plume components in the source of Hawaiian basalts. We have analyzed a series of 23 tholeiitic Mauna Loa basalts ranging in age from 36,780 to 140 y for their Pb isotopic compositions by TIMS (Micromass Sector 54) and MC-ICP-MS (Nu Plasma) to directly compare results from the same, carefully leached, samples. These analyses indicate an internal precision better than 120 ppm for the MC-ICP-MS Pb ratios, while for the TIMS ratios, it is in the per mil range. This results in a more coherent dataset for the MC-ICP-MS analyses, with the range of 207Pb/204Pb variations decreasing by a factor of 3 and of 208Pb/204Pb ratios by a factor of 1.5. The co-variations between the Pb isotopic data and other geochemical parameters for the Hawaiian lavas are now much stronger and better defined. There are clearly two groups amongst the prehistoric Mauna Loa basalts: one group with higher 87Sr/86Sr (>0.7038) and low 206Pb/204Pb (<18.15) that covers the entire range of Nb/Y (0.31 to 0.51) observed in this volcano, and the other group with low 87Sr/86Sr (<0.7038) and higher 206Pb/204Pb with Nb/Y<0.4. The second group is only present in basalts younger than 3,000 y or older than 24,000 y. The high 87Sr/86Sr group was not sampled in the HSDP I drill core, which covers an age range of 100,000 y. This either reflects a sampling bias, as the upper flow units (<10,000 y) were not sampled for geochemistry, or variations in magma supply. Altogether, Mauna Loa lava flows that are younger than 20,000 y show much more isotopic variation than older flows and there is a nearly continuous transition away from the Kilauea component. This may indicate that the transition between the Mauna Loa and Mauna Kea trends is not as sharp as previously documented. This study shows the importance of reducing the

The length of channelized lava flows: Insight from the 1859 eruption of Mauna Loa Volcano, Hawai‘i

NASA Astrophysics Data System (ADS)

Riker, Jenny M.; Cashman, Katharine V.; Kauahikaua, James P.; Montierth, Charlene M.

2009-06-01

The 1859 eruption of Mauna Loa Volcano, Hawai'i, produced paired 'a'ā and pāhoehoe flows of exceptional length (51 km). The 'a'ā flow field is distinguished by a long (> 36 km) and well-defined pāhoehoe-lined channel, indicating that channelized lava remained fluid to great distances from the vent. The 1859 eruption was further unusual in initiating at a radial vent on the volcano's northwest flank, instead of along the well-defined rift zone that has been the source of most historic activity. As such, it presents an opportunity both to examine controls on the emplacement of long lava channels and to assess hazards posed by future flank eruptions of Mauna Loa. Here we combine evidence from historical chronicles with analysis of bulk compositions, glass geothermometry, and microlite textures of samples collected along the 1859 lava flows to constrain eruption and flow emplacement conditions. The bulk compositions of samples from the 'a'ā and pāhoehoe flow fields are bimodally distributed and indicate tapping of two discrete magma bodies during eruption. Samples from the pāhoehoe flow field have bulk compositions similar to those of historically-erupted lavas (< 8 wt.% MgO); lava that fed the 'a'ā channel is more primitive (> 8 wt.% MgO), nearly aphyric, and was erupted at high temperatures (1194-1216 °C). We suggest that the physical properties of proximal channel-fed lava (i.e., high-temperature, low crystallinity, and low bulk viscosity) promoted both rapid flow advance and development of long pāhoehoe-lined channels. Critical for the latter was the large temperature decrease (~ 50 °C) required to reach the point at which plagioclase and pyroxene started to crystallize; the importance of phase constraints are emphasized by our difficulty in replicating patterns of cooling and crystallization recorded by high-temperature field samples using common models of flow emplacement. Placement of the 1859 eruption within the context of historic activity at Mauna

The effect of El Chichon on the intensity and polarization of skylight at Mauna Loa

NASA Technical Reports Server (NTRS)

King, M. D.; Fraser, R. S.

1983-01-01

An empirical model of the stratospheric aerosol over Mauna Loa Observatory (MLO) has been developed, in order to study the effect of aerosol particles from the eruption of the El Chichon volcano on the intensity and degree of skylight polarization. The modeling computations were based on measurements of monthly mean optical thickness for July 1982, together with lidar measurements of the vertical distribution of aerosols. On the basis of the theoretical computations, it is shown that the number and location of polarization neutral points, and the location and magnitude of the peak polarization were both functions of the relatively narrow distribution of aerosol particle size near 0.4 microns.

Effects of surface reflectance on skylight polarization measurements at the Mauna Loa Observatory.

PubMed

Dahlberg, Andrew R; Pust, Nathan J; Shaw, Joseph A

2011-08-15

An all-sky imaging polarimeter was deployed in summer 2008 to the Mauna Loa Observatory in Hawaii to study clear-sky atmospheric skylight polarization. The imager operates in five wavebands in the visible and near infrared spectrum and has a fisheye lens for all-sky viewing. This paper describes the deployment and presents comparisons of the degree of skylight polarization observed to similar data observed by Coulson with a principal-plane scanning polarimeter in the late 1970s. In general, the results compared favorably to those of Coulson. In addition, we present quantitative results correlating a variation of the maximum degree of polarization over a range of 70-85% to fluctuation in underlying surface reflectance and upwelling radiance data from the GOES satellite. © 2011 Optical Society of America

Isotopic evolution of Mauna Loa and the chemical structure of the Hawaiian plume

NASA Astrophysics Data System (ADS)

Depaolo, Donald J.; Bryce, Julia G.; Dodson, Allen; Shuster, David L.; Kennedy, B. Mack

2001-07-01

New He isotopic data from the HSDP pilot hole core, lava accumulation rate models, and data from the literature are used to develop a 200,000 year isotopic record for the lava erupted from the Mauna Loa volcano. This record, coupled with an analogous record from Mauna Kea from the Hawaii Scientific Drilling Project (HSDP) pilot hole project and other literature data from the GEOROC database, are used to construct a "map" of lava isotopic compositions for the island of Hawaii. The isotopic map is converted to a map of the He and Nd isotopic compositions of melts from the mantle plume, which can be compared with a published melt supply map derived from geodynamic modeling. The resulting map of the plume indicates that values of helium 3He/4He > 20 Ra are confined to the core of the plume (radius ≈ 20-25 km) and correspond to potential temperatures >1565°C, suggesting the He isotopic signal is derived from deep in the mantle. The 3He/4He map has closed contours down to 10 Ra; the contours are teardrop-shaped and elongated in the general direction of plate motion. The closed contours indicate that most of the plume He signal is lost during the early stages of melting, which is consistent with helium behaving as a strongly incompatible element (KHe ≤ 0.001). The ɛNd contours (and by inference the contours for Sr, Pb, Hf, and Os) do not all close on the scale of the island of Hawaii but instead partially follow material flow lines within the plume beneath the lithosphere. The plume signal for Nd extends circa 100 km in the direction of plate motion, which is consistent with the moderately incompatible behavior of Nd (KNd ≈ 0.02). Downstream from the plume core epicenter, plume Nd occurs with asthenospheric He; this could be mistaken for an additional plume component, whereas it may be only a manifestation of differing incompatibility. Data from Mauna Loa suggest the presence of a low-3He/4He plume component that has low ɛNd and high 87Sr/86Sr. The plume map

Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog.

PubMed

Oliver, James A C; Forman, Oliver P; Pettitt, Louise; Mellersh, Cathryn S

2015-01-01

Mutations in ADAMTS10 (CFA20) have previously been associated with primary open angle glaucoma (POAG) in the Beagle and Norwegian Elkhound. The closely related gene, ADAMTS17, has also been associated with several different ocular phenotypes in multiple breeds of dog, including primary lens luxation and POAG. We investigated ADAMTS17 as a candidate gene for POAG in the Basset Hound and Basset Fauve de Bretagne dog breeds. We performed ADAMTS17 exon resequencing in three Basset Hounds and three Basset Fauve de Bretagne dogs with POAG. Identified variants were genotyped in additional sample cohorts of both breeds and dogs of other breeds to confirm their association with disease. All affected Basset Hounds were homozygous for a 19 bp deletion in exon 2 that alters the reading frame and is predicted to lead to a truncated protein. Fifty clinically unaffected Basset Hounds were genotyped for this mutation and all were either heterozygous or homozygous for the wild type allele. Genotyping of 223 Basset Hounds recruited for a different study revealed a mutation frequency of 0.081 and predicted frequency of affected dogs in the population to be 0.007. Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 1.26 x 10-10. All affected Basset Fauve de Bretagne dogs were homozygous for a missense mutation in exon 11 causing a glycine to serine amino acid substitution (G519S) in the disintegrin-like domain of ADAMTS17 which is predicted to alter protein function. Unaffected Basset Fauve de Bretagne dogs were either heterozygous for the mutation (5/24) or homozygous for the wild type allele (19/24). Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 2.80 x 10-7. Genotyping of 85 dogs of unrelated breeds and 90 dogs of related breeds for this variant was negative. This report documents strong associations between two independent ADAMTS17 mutations and POAG in two different

Assessing individual and organizational response to volcanic crisis and unrest at Kīlauea and Mauna Loa volcanoes, Hawai'i

NASA Astrophysics Data System (ADS)

Reeves, Ashleigh; Gregg, Chris; Lindell, Michael; Prater, Carla; Joyner, Timothy; Eggert, Sarah

2017-04-01

This study describes response to and preparedness for eruption and unrest at Kīlauea and Mauna Loa volcanoes, respectively. The on-going 1983-present eruption of Kīlauea's East Rift Zone (ERZ) has generated a series of lava flow crises, the latest occurring in 2014 and 2015 when lava from a new vent flowed northeast and into the perimeter of developed areas in the lower Puna District, some 20km distant. It took ca. 2 months for the June 27 lava flow to advance a distance to which scientists reported it might be a concern to people downslope, but this prompted widespread formal and informal responses and culminated in improvements to infrastructure, voluntary evacuations of residents and businesses and closure of schools. Unlike Kīlauea, which has had frequent crises since the mid-20th century, the last eruption of nearby Mauna Loa occurred in 1984 and the last eruption and crisis on its Southwest Rift Zone (SWZ) was in 1950, so residents there are less familiar with eruptions than in Puna. In September 2015, the US Geological Survey, Hawaiian Volcano Observatory upgraded Mauna Loa's Alert Level from Normal to Advisory due to increases in unrest above known background levels. A crisis on Mauna Loa's SWZ would likely be much different than the recent 2014-15 crisis at Kīlauea as steep topography downslope of the SWZ and typical high discharge rates mean lava flows move fast, posing increased risk to areas downslope. Typically, volcanic eruptions have significant economic consequences out of proportion with their magnitudes. Furthermore, uncertainties regarding the physical and organizational communication of risk information amplify these economic losses. One significant impediment to risk communication is limited knowledge about the most effective ways to verbally, numerically and graphically communicate scientific uncertainty. This was a challenge in the recent lava flow crisis on Kīlauea. The public's demand for near-real time information updates, including

The loss-of-allele assay for ES cell screening and mouse genotyping.

PubMed

Frendewey, David; Chernomorsky, Rostislav; Esau, Lakeisha; Om, Jinsop; Xue, Yingzi; Murphy, Andrew J; Yancopoulos, George D; Valenzuela, David M

2010-01-01

Targeting vectors used to create directed mutations in mouse embryonic stem (ES) cells consist, in their simplest form, of a gene for drug selection flanked by mouse genomic sequences, the so-called homology arms that promote site-directed homologous recombination between the vector and the target gene. The VelociGene method for the creation of targeted mutations in ES cells employs targeting vectors, called BACVecs, that are based on bacterial artificial chromosomes. Compared with conventional short targeting vectors, BacVecs provide two major advantages: (1) their much larger homology arms promote high targeting efficiencies without the need for isogenicity or negative selection strategies; and (2) they enable deletions and insertions of up to 100kb in a single targeting event, making possible gene-ablating definitive null alleles and other large-scale genomic modifications. Because of their large arm sizes, however, BACVecs do not permit screening by conventional assays, such as long-range PCR or Southern blotting, that link the inserted targeting vector to the targeted locus. To exploit the advantages of BACVecs for gene targeting, we inverted the conventional screening logic in developing the loss-of-allele (LOA) assay, which quantifies the number of copies of the native locus to which the mutation was directed. In a correctly targeted ES cell clone, the LOA assay detects one of the two native alleles (for genes not on the X or Y chromosome), the other allele being disrupted by the targeted modification. We apply the same principle in reverse as a gain-of-allele assay to quantify the copy number of the inserted targeting vector. The LOA assay reveals a correctly targeted clone as having lost one copy of the native target gene and gained one copy of the drug resistance gene or other inserted marker. The combination of these quantitative assays makes LOA genotyping unequivocal and amenable to automated scoring. We use the quantitative polymerase chain reaction

Surface deformation analysis of the Mauna Loa and Kilauea volcanoes, Hawaii , revealed by InSAR measurements

NASA Astrophysics Data System (ADS)

Casu, F.; Poland, M.; Solaro, G.; Tizzani, P.; Miklius, A.; Sansosti, E.; Lanari, R.

2009-04-01

The Big Island of Hawaii is home to three volcanoes that have historically erupted. Hualālai, on the east side of the island, Mauna Loa, the largest volcano on the planet which has erupted 39 times since 1832 (most recently in 1984) and Kilauea, which has been in a state of continuous eruption since 1983 from vents on the volcano's east rift zone. Deformation at Kilauea is characterized by summit and rift zone displacements related to magmatic activity and seaward motion of the south flank caused by slip along a basal decollement. In this work we investigate the deformation affecting the Mauna Loa and Kilauea volcanoes, Hawaii , by exploiting the advanced Interferometric Synthetic Aperture Radar (InSAR) technique referred to as Small BAseline Subset (SBAS) algorithm. In particular, we present time series of line-of-sight (LOS) displacements derived from the SAR data acquired by the ASAR instrument, on board the ENVISAT satellite, from the ascending (track 93, frame 387) and descending (track 429, frame 3213) orbits over a time period between 2003 and 2008. For each coherent pixel of the radar images we compute time-dependent surface displacements as well as the average LOS deformation velocity. We also benefit from the use of the multi-orbit (ascending and descending) data which permit us to discriminate the vertical and east-west components of the revealed displacements. The retrieved InSAR measurements are also favourably compared to the continuous GPS data available in the area in order to asses the quality of the SBAS-InSAR products. The presented results show the complex and articulated deformation behavior of the investigated volcanoes; moreover, the possibility to invert the retrieved DInSAR products, in order to model both deep geological structures and magmatic sources, represents a relevant issue for the comprehension of the volcanoes dynamics.

Dync1h1 Mutation Causes Proprioceptive Sensory Neuron Loss and Impaired Retrograde Axonal Transport of Dorsal Root Ganglion Neurons.

PubMed

Zhao, Jing; Wang, Yi; Xu, Huan; Fu, Yuan; Qian, Ting; Bo, Deng; Lu, Yan-Xin; Xiong, Yi; Wan, Jun; Zhang, Xiang; Dong, Qiang; Chen, Xiang-Jun

2016-07-01

Sprawling (Swl) is a radiation-induced mutation which has been identified to have a nine base pair deletion in dynein heavy chain 1 (DYNC1H1: encoded by a single gene Dync1h1). This study is to investigate the phenotype and the underlying mechanism of the Dync1h1 mutant. To display the phenotype of Swl mutant mice, we examined the embryos of homozygous (Swl/Swl) and heterozygous (Swl/+) mice and their postnatal dorsal root ganglion (DRG) of surviving Swl/+ mice. The Swl/+ mice could survive for a normal life span, while Swl/Swl could only survive till embryonic (E) 8.5 days. Excessive apoptosis of Swl/+ DRG neurons was revealed during E11.5-E15.5 days, and the peak rate was at E13.5 days. In vitro study of mutated DRG neurons showed impaired retrograde transport of dynein-driven nerve growth factor (NGF). Mitochondria, another dynein-driven cargo, demonstrated much slower retrograde transport velocity in Swl/+ neurons than in wild-type (WT) neurons. Nevertheless, the Swl, Loa, and Cra mutations did not affect homodimerization of DYNC1H1. The Swl/Swl mutation of Dync1h1 gene led to embryonic mal-development and lethality, whereas the Swl/+ DRG neurons demonstrated deficient retrograde transport in dynein-driven cargos and excessive apoptosis during mid- to late-developmental stages. The underlying mechanism of the mutation may not be due to impaired homodimerization of DYNC1H1. © 2016 John Wiley & Sons Ltd.

Influence of accommodative lag upon the far-gradient measurement of accommodative convergence to accommodation ratio in strabismic patients.

PubMed

Miyata, Manabu; Hasebe, Satoshi; Ohtsuki, Hiroshi

2006-01-01

To determine the influence of the lag of accommodation (LOA) on the accommodative convergence to accommodation (AC/A) ratio measured by the far-gradient method in strabismic patients. The AC/A ratio was measured with a distance target viewed with and without -3.00 diopter (D) addition lenses in 63 patients with different types of strabismus (age range, 7-34 years; range of strabismic angle, -60 to +40 prism diopters; refractive error range, -7.33 to +6.63 D). The LOA for the same lens was measured with an open-view-type autorefractometer. The stimulus AC/A ratio and the AC/A ratio adjusted by the individually measured LOA (adjusted AC/A ratio) were compared. The mean +/- SD of the LOA to the -3.00 D lenses was 1.06 +/- 0.43 D. The mean adjusted AC/A ratio was 41% greater than the stimulus AC/A ratio. The LOA differed widely among patients (0.13 to 2.14 D), and a large LOA tended to appear in myopic or young patients. The AC/A ratio obtained using the conventional far-gradient method is significantly biased by the LOA, and thus does not always represent the actual relationship between accommodation and vergence control systems. Copyright Japanese Ophthalmological Society 2006.

Melt Inclusions Record Extreme Compositional Variability in Primitive Magmas at Mauna Loa Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Kamenetsky, V. S.; Norman, M. D.; Garcia, M. O.

2002-12-01

Melt inclusions carry potentially unique information about magmatic processes and the compositional evolution of erupted lavas. Major element compositions of olivine-hosted melt inclusions in submarine tholeiitic picrites from the southwest rift zone of Mauna Loa volcano have been studied to examine the compositional variability of primitive magmas feeding the world's largest volcano. Approximately 600 naturally quenched inclusions were examined from 8 samples with 3-25 vol% olivine phenocrysts and 9-22 wt% MgO. Olivine compositions ranged from Fo91-Fo82. The inclusions show a continuous variation in FeO contents from near-magmatic values (9 to 11 wt%) in the most evolved olivines to extremely low values (3.5 to 7.0 wt%) in the most primitive olivines. This appears to reflect a complex magmatic history for these crystals involving extensive re-equlibration of melts trapped by early formed phenocrysts with their host olivine. Extreme compositional variability also characterizes incompatible elements that would not be affected by equilibration with the host olivine. Inclusions trapped in relatively primitive olivines (Fo88-91) show a large range of K2O contents (0.1 to 2.1 wt%), whereas inclusions in more evolved olivines converge on whole rock compositions with 0.3 to 0.4 wt% K2O. Similarly, TiO2/K2O, Na2O/K2O, and K2O/P2O5 ratios of inclusions in primitive olivines span a much larger range than do inclusions hosted by more evolved olivines, with TiO2/K2O ratios extending from enriched to depleted compositions (1.2 to 24.7) in primitive olivines, and converging on whole rock compositions (TiO2/K2O = 6-9) in more evolved host olivine. This points toward extreme compositional variability in melts feeding Mauna Loa, and effective mixing of these melt parcels in the shallower summit reservoir to produce the restricted range of whole rock compositions sampled by erupted lavas. Whole rock compositions, therefore provide an integrated view of melting and high-level mixing

Lack of Correlated Isotopic and Compositional Variations in Mauna Loa Lavas: A Serious Problem for Pyroxenite/Eclogite Plume Source Models

NASA Astrophysics Data System (ADS)

Rhodes, J. M.; Weis, D.; Norman, M. D.; Garcia, M. O.

2007-12-01

The long held notion that basaltic magmas are produced by decompressional melting of peridotite is under challenge. Recent models for the Hawaiian and other plumes argue that they consist of a heterogeneous mix of peridotite and discrete eclogite blobs, the latter derived from recycled subducted crust. Eclogite melting produces relatively siliceous magmas (dacite to andesite) which either mix with picritic melts from the peridotite, or, more plausibly, react with the peridotite to produce pyroxenite. Melting of varying proportions of the peridotite/pyroxenite mix is thought to produce the correlated compositional and isotopic characteristics of Hawaiian volcanoes. Magmas from Mauna Loa and Koolau volcanoes are thought to contain more of the recycled component; those from Loihi and Kilauea volcanoes contain less. A simple test of these mixed source models examines whether isotopic changes within the long magmatic history of a single volcano are accompanied by corresponding changes in major and trace element characteristics. Mauna Loa, where we have sampled around 400 - 500 ka of the volcano's eruptive history, provides an excellent opportunity for such a test. During this time, Mauna Loa will have traversed almost half the Hawaiian plume. According to the models, it should have erupted magmas produced from a range of pyroxenite/peridotite mixes with corresponding differences in both isotopic ratios and major and trace elements. Our data show that there is only minor isotopic (Sr, Pb, Nd, Hf) diversity in young lavas (<100 ka), but older lavas are highly diverse, ranging from modern values to those that are close to, and overlap with, those of Loihi volcano. If this isotopic diversity is a consequence of different proportions of pyroxenite and peridotite in the plume source, as the new models predict, we should expect to see correlated changes in bulk composition, particularly. in normalized SiO2, CaO/Al2O3, FeO/MgO and Ni - MgO relationships, as well as changes in

Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis)

PubMed Central

Fingert, John H.; Robin, Alan L.; Scheetz, Todd E.; Kwon, Young H.; Liebmann, Jeffrey M.; Ritch, Robert; Alward, Wallace L.M.

2016-01-01

Purpose To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. Methods In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas—juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)—using a quantitative polymerase chain reaction assay. Results No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. Conclusions TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma. PMID:27881886

Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis).

PubMed

Fingert, John H; Robin, Alan L; Scheetz, Todd E; Kwon, Young H; Liebmann, Jeffrey M; Ritch, Robert; Alward, Wallace L M

2016-08-01

To investigate the role of TANK-binding kinase 1 ( TBK1 ) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction assay. No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma.

Radiocarbon dates for lava flows from northeast rift zone of Mauna Loa Volcano, Hilo 7 1/2 minute quadrangle, Island of Hawaii

USGS Publications Warehouse

Buchanan-Banks, J. M.; Lockwood, J.P.; Rubin, M.

1989-01-01

Twenty-eight 14C analyses are reported for carbonized roots and other plant material collected from beneath 15 prehistoric lava flows erupted from the northeast rift zone (NERZ) of Mauna Loa Volcano (ML). The new 14C dates establish ages for 13 previously undated lava flows, and correct or add to information previously reported. Limiting ages on other flows that lie either above or below the dated flows are also established. These dates help to unravel the eruptive history of ML's NERZ. -from Authors

TCP transcription factor, BRANCH ANGLE DEFECTIVE 1 (BAD1), is required for normal tassel branch angle formation in maize.

PubMed

Bai, Fang; Reinheimer, Renata; Durantini, Diego; Kellogg, Elizabeth A; Schmidt, Robert J

2012-07-24

In grass inflorescences, a structure called the "pulvinus" is found between the inflorescence main stem and lateral branches. The size of the pulvinus affects the angle of the lateral branches that emerge from the main axis and therefore has a large impact on inflorescence architecture. Through EMS mutagenesis we have identified three complementation groups of recessive mutants in maize having defects in pulvinus formation. All mutants showed extremely acute tassel branch angles accompanied by a significant reduction in the size of the pulvinus compared with normal plants. Two of the complementation groups correspond to mutations in the previously identified genes, RAMOSA2 (RA2) and LIGULELESS1 (LG1). Mutants corresponding to a third group were cloned using mapped-based approaches and found to encode a new member of the plant-specific TCP (TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR) family of DNA-binding proteins, BRANCH ANGLE DEFECTIVE 1 (BAD1). BAD1 is expressed in the developing pulvinus as well as in other developing tissues, including the tassels and juvenile leaves. Both molecular and genetics studies show that RA2 is upstream of BAD1, whereas LG1 may function in a separate pathway. Our findings demonstrate that BAD1 is a TCP class II gene that functions to promote cell proliferation in a lateral organ, the pulvinus, and influences inflorescence architecture by impacting the angle of lateral branch emergence.

Total ozone column retrieval from UV-MFRSR irradiance measurements: evaluation at Mauna Loa station

NASA Astrophysics Data System (ADS)

Zempila, Melina Maria; Fragkos, Konstantinos; Davis, John; Sun, Zhibin; Chen, Maosi; Gao, Wei

2017-09-01

The USDA UV-B Monitoring and Research Program (UVMRP) comprises of 36 climatological sites along with 4 long-duration research sites, in 27 states, one Canadian province, and the south island of New Zealand. Each station is equipped with an Ultraviolet multi-filter rotating shadowband radiometer (UV-MFRSR) which can provide response-weighted irradiances at 7 wavelengths (300, 305.5, 311.4, 317.6, 325.4, and 368 nm) with a nominal full width at half maximun of 2 nm. These UV irradiance data from the long term monitoring station at Mauna Loa, Hawaii, are used as input to a retrieval algorithm in order to derive high time frequency total ozone columns. The sensitivity of the algorithm to the different wavelength inputs is tested and the uncertainty of the retrievals is assessed based on error propagation methods. For the validation of the method, collocated hourly ozone data from the Dobson Network of the Global Monitoring Division (GMD) of the Earth System Radiation Laboratory (ESRL) under the jurisdiction of the US National Oceanic & Atmospheric Administration (NOAA) for the period 2010-2015 were used.

Variability of the 2014-present inflation source at Mauna Loa volcano revealed using time-dependent modeling

NASA Astrophysics Data System (ADS)

Johanson, I. A.; Miklius, A.; Okubo, P.; Montgomery-Brown, E. K.

2017-12-01

Mauna Loa volcano is the largest active volcano on earth and in the 20thcentury produced roughly one eruption every seven years. The 33-year quiescence since its last eruption 1984 has been punctuated by three inflation episodes where magma likely entered the shallow plumbing system, but was not erupted. The most recent began in 2014 and is ongoing. Unlike prior inflation episodes, the current one is accompanied by a significant increase in shallow seismicity, a pattern that is similar to earlier pre-eruptive periods. We apply the Kalman filter based Network Inversion Filter (NIF) to the 2014-present inflation episode using data from a 27 station continuous GPS network on Mauna Loa. The model geometry consists of a point volume source and tabular, dike-like body, which have previously been shown to provide a good fit to deformation data from a 2004-2009 inflation episode. The tabular body is discretized into 1km x 1km segments. For each day, the NIF solves for the rates of opening on the tabular body segments (subject to smoothing and positivity constraints), volume change rate in the point source, and slip rate on a deep décollement fault surface, which is constrained to a constant (no transient slip allowed). The Kalman filter in the NIF provides for smoothing both forwards and backwards in time. The model shows that the 2014-present inflation episode occurred as several sub-events, rather than steady inflation. It shows some spatial variability in the location of the inflation sub-events. In the model, opening in the tabular body is initially concentrated below the volcano's summit, in an area roughly outlined by shallow seismicity. In October, 2015 opening in the tabular body shifts to be centered beneath the southwest portion of the summit and seismicity becomes concentrated in this area. By late 2016, the opening rate on the tabular body decreases and is once again under the central part of summit. This modeling approach has allowed us to track these

Community preparedness for lava flows from Mauna Loa and Hualālai volcanoes, Kona, Hawai'i

USGS Publications Warehouse

Gregg, Chris E.; Houghton, Bruce F.; Paton, Douglas; Swanson, Donald A.; Johnston, David M.

2004-01-01

Lava flows from Mauna Loa and Huala??lai volcanoes are a major volcanic hazard that could impact the western portion of the island of Hawai'i (e.g., Kona). The most recent eruptions of these two volcanoes to affect Kona occurred in A.D. 1950 and ca. 1800, respectively. In contrast, in eastern Hawai'i, eruptions of neighboring Ki??lauea volcano have occurred frequently since 1955, and therefore have been the focus for hazard mitigation. Official preparedness and response measures are therefore modeled on typical eruptions of Ki??lauea. The combinations of short-lived precursory activity (e.g., volcanic tremor) at Mauna Loa, the potential for fast-moving lava flows, and the proximity of Kona communities to potential vents represent significant emergency management concerns in Kona. Less is known about past eruptions of Huala??lai, but similar concerns exist. Future lava flows present an increased threat to personal safety because of the short times that may be available for responding. Mitigation must address not only the specific characteristics of volcanic hazards in Kona, but also the manner in which the hazards relate to the communities likely to be affected. This paper describes the first steps in developing effective mitigation plans: measuring the current state of people's knowledge of eruption parameters and the implications for their safety. We present results of a questionnaire survey administered to 462 high school students and adults in Kona. The rationale for this study was the long lapsed time since the last Kona eruption, and the high population growth and expansion of infrastructure over this time interval. Anticipated future growth in social and economic infrastructure in this area provides additional justification for this work. The residents of Kona have received little or no specific information about how to react to future volcanic eruptions or warnings, and short-term preparedness levels are low. Respondents appear uncertain about how to respond

Low phosphate alters lateral root setpoint angle and gravitropism.

PubMed

Bai, Hanwen; Murali, Bhavna; Barber, Kevin; Wolverton, Chris

2013-01-01

Lateral roots, responsible for water and nutrient uptake, maintain nonvertical angles throughout development. Soil phosphate is one limiting nutrient for plant growth that is known to induce changes to root system architecture, such as increased lateral root formation. This study seeks to determine whether phosphate concentration affects lateral root orientation in addition to its previously described influences on root architecture. Images of intact Arabidopsis root systems were recorded for 24 h, and lateral root tip angles were measured for wild-type and mutant pgm-1 and pin3-1 roots on a full or low phosphate medium. Setpoint angles of unstimulated root systems were determined, as were gravitropic responses of lateral roots over time. The root system setpoint angles of wild-type and mutant pin3-1 roots showed a shift toward a more vertical orientation on low orthophosphate (Pi) medium. The gravitropic responses of both pgm-1 and pin3-1 roots on low Pi medium was elevated relative to control Pi medium. Mutations in two phosphate transporters with high levels of expression in the root showed a gravitropic response similar to wild-type roots grown on low Pi, supporting a role for Pi status in regulating lateral root gravitropism. Lateral root orientation and gravitropism are affected by Pi status and may provide an important additional parameter for describing root responses to low Pi. The data also support the conclusion that gravitropic setpoint angle reacts to nutrient status and is under dynamic regulation.

Crystallographic and mutational analyses of cystathionine β-synthase in the H2 S-synthetic gene cluster in Lactobacillus plantarum.

PubMed

Matoba, Yasuyuki; Yoshida, Tomoki; Izuhara-Kihara, Hisae; Noda, Masafumi; Sugiyama, Masanori

2017-04-01

Cystathionine β-synthase (CBS) catalyzes the formation of l-cystathionine from l-serine and l-homocysteine. The resulting l-cystathionine is decomposed into l-cysteine, ammonia, and α-ketobutylic acid by cystathionine γ-lyase (CGL). This reverse transsulfuration pathway, which is catalyzed by both enzymes, mainly occurs in eukaryotic cells. The eukaryotic CBS and CGL have recently been recognized as major physiological enzymes for the generation of hydrogen sulfide (H 2 S). In some bacteria, including the plant-derived lactic acid bacterium Lactobacillus plantarum, the CBS- and CGL-encoding genes form a cluster in their genomes. Inactivation of these enzymes has been reported to suppress H 2 S production in bacteria; interestingly, it has been shown that H 2 S suppression increases their susceptibility to various antibiotics. In the present study, we characterized the enzymatic properties of the L. plantarum CBS, whose amino acid sequence displays a similarity with those of O-acetyl-l-serine sulfhydrylase (OASS) that catalyzes the generation of l-cysteine from O-acetyl-l-serine (l-OAS) and H 2 S. The L. plantarum CBS shows l-OAS- and l-cysteine-dependent CBS activities together with OASS activity. Especially, it catalyzes the formation of H 2 S in the presence of l-cysteine and l-homocysteine, together with the formation of l-cystathionine. The high affinity toward l-cysteine as a first substrate and tendency to use l-homocysteine as a second substrate might be associated with its enzymatic ability to generate H 2 S. Crystallographic and mutational analyses of CBS indicate that the Ala70 and Glu223 residues at the substrate binding pocket are important for the H 2 S-generating activity. © 2017 The Protein Society.

Mitigation of Atmospheric Errors in Differential InSAR Data Using a High-Resolution Weather Model, Mauna Loa and Kilauea volcanoes, Hawaii

NASA Astrophysics Data System (ADS)

Brooks, B. A.; Foster, J.; Cherubini, T.; Businger, S.; Miklius, A.; Mouginis-Mark, P.

2004-12-01

We investigate the utility of a mesoscale weather model for mitigating atmospheric errors in InSAR-derived displacement fields associated with volcanotectonic phenomena at Mauna Loa and Kilauea volcanoes on the Island of Hawaii. The MM5 (NCAR-Penn State Mesoscale Model Version 5) forecast is run twice daily for the island of Hawaii by the Mauna Kea Weather Center in support of Mauna Kea's astronomical observatories. MM5 has a 60-hour forecast window and the forecast fields are output in 3-hour increments. A high-resolution analysis that incorporates weather observations from National Weather Service and satellite-derived winds from the University of Wisconsin, provides the initial conditions for MM5. In turn, MM5 produces predictions of thermodynamic properties of the atmosphere, including temperature, pressure, and moisture fields at a 3 km horizontal resolution. The vertical resolution is density weighted with the greatest vertical resolution (10s of meters) near the surface. For any radar image acquisition there is a high-resolution 3D simulation of atmospheric water vapor valid within 1.5 hours of the acquisition time and predicted forward no more than 12 hours from the initial observations. Using MM5 forecast water vapor, we create line-of-sight delay maps that can be either directly removed from InSAR differential pairs or used to create synthetic radar interferograms that can be compared with the observed interferogram. We analyze Envisat ASAR radar data collected during 2003-2004 and find, qualitatively, that contours of excess path delay in MM5 model runs often closely mimic both topographic contours and fringes observed in differential interferograms which have had topographic phase removed. Over periods of days, the delays can vary in magnitude and spatial scale by 10s of mms and 10s of kms, respectively. Individual models can predict peak delays associated with moist layer inversions of order ~20 mm around the summits of Mauna Loa and Kilauea, both

Statistical analysis of the mesospheric inversion layers over two symmetrical tropical sites: Réunion (20.8° S, 55.5° E) and Mauna Loa (19.5° N, 155.6° W)

NASA Astrophysics Data System (ADS)

Bègue, Nelson; Mbatha, Nkanyiso; Bencherif, Hassan; Tato Loua, René; Sivakumar, Venkataraman; Leblanc, Thierry

2017-11-01

In this investigation a statistical analysis of the characteristics of mesospheric inversion layers (MILs) over tropical regions is presented. This study involves the analysis of 16 years of lidar observations recorded at Réunion (20.8° S, 55.5° E) and 21 years of lidar observations recorded at Mauna Loa (19.5° N, 155.6° W) together with SABER observations at these two locations. MILs appear in 10 and 9.3 % of the observed temperature profiles recorded by Rayleigh lidar at Réunion and Mauna Loa, respectively. The parameters defining MILs show a semi-annual cycle over the two selected sites with maxima occurring near the equinoxes and minima occurring during the solstices. Over both sites, the maximum mean amplitude is observed in April and October, and this corresponds to a value greater than 35 K. According to lidar observations, the maximum and minimum mean of the base height ranged from 79 to 80.5 km and from 76 to 77.5 km, respectively. The MILs at Réunion appear on average ˜ 1 km thinner and ˜ 1 km lower, with an amplitude of ˜ 2 K higher than Mauna Loa. Generally, the statistical results for these two tropical locations as presented in this investigation are in fairly good agreement with previous studies. When compared to lidar measurements, on average SABER observations show MILs with greater amplitude, thickness and base altitudes of 4 K, 0.75 and 1.1 km, respectively. Taking into account the temperature error by SABER in the mesosphere, it can therefore be concluded that the measurements obtained from lidar and SABER observations are in significant agreement. The frequency spectrum analysis based on the lidar profiles and the 60-day averaged profile from SABER confirms the presence of the semi-annual oscillation where the magnitude maximum is found to coincide with the height range of the temperature inversion zone. This connection between increases in the semi-annual component close to the inversion zone is in agreement with most previously

Water Vapor Variations over Mauna Loa and Table Mountain since 2010

NASA Astrophysics Data System (ADS)

Nedoluha, G. E.; Gomez, R. M.; Allen, D. R.; Boone, C.; Lambert, A.; Stiller, G. P.; Hurst, D. F.

2012-12-01

The Vapor Millimeter-wave Spectrometer (WVMS) instrument deployed at Network for the Detection of Atmospheric Composition Change (NDACC) sites at Table Mountain, California (34.4N, 242.3E) and at Mauna Loa, Hawaii (19.5N, 204.4E) have, since 2010, been able to make measurements down to ~26km. With this extended retrieval capability these instruments can now make measurements from ~26-80km. There is an increase from 2010 to 2012 which appears to be caused primarily by dynamical variations, although an increase in water vapor entering the stratosphere probably also plays a role at the lower altitudes. Water vapor mixing ratios at both of these NDACC sites are now higher than they have been for about a decade from the lower stratosphere through the mid-mesosphere. In addition to the WVMS measurements, we will present coincident satellite measurements from the Aura Microwave Limb Sounder (MLS), the Atmospheric Chemistry Experiment (ACE), and the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). We will also compare the lowest altitude WVMS measurements with frostpoint hygrometer measurements from Boulder, Colorado (40N, 255E), and Hilo, Hawaii (19.7N, 205E). In order to understand the interannual dynamically-driven changes in water vapor, we will investigate interannual variations in mixing using equivalent length and tracer equivalent latitude from 2010-2012. Since dynamical variations affect H2O in the stratosphere primarily by changing the amount of CH4 oxidation that has occurred in a particular region, we will also examine CH4 variations from the GMI model.

Seismic hazards at Kilauea and Mauna Loa volcanoes, Hawaii

NASA Astrophysics Data System (ADS)

Klein, Fred W.

1994-04-01

A significant seismic hazard exists in south Hawaii from large tectonic earthquakes that can reach magnitude 8 and intensity XII. This paper quantifies the hazard by estimating the horizontal peak ground acceleration (PGA) in south Hawaii which occurs with a 90% probability of not being exceeded during exposure times from 10 to 250 years. The largest earthquakes occur beneath active, unbuttressed and mobile flanks of volcanos in their shield building stage. The flanks are compressed and pushed laterally by rift zone intrusions. The largest earthquakes are thus not directly caused by volcanic activity. Historic earthquakes (since 1823) and the best Hawaiian Volcano Observatory catalog (since 1970) under the south side of the island define linear frequency-magnitude distributions that imply average recurrence intervals for M greater than 5.5 earthquakes of 3.4-5 years, for M greater than 7 events of 29-44 years, and for M greater than 8 earthquakes of 120-190 years. These estimated recurrences are compatable with the 107 year interval between the two major April 2, 1868 (M(approximately)7.9) and November 29, 1975 (M=7.2) earthquakes. Frequency-magnitude distributions define the activity levels of 19 different seismic source zones for probabilistic ground motion estimations. The available measurements of PGA (33 from 7 moderate earthquakes) are insufficient to define a new attenuation curve. We use the Boore et al. (1993) curve shifted upward by a factor of 1.2 to fit Hawaiian data. Amplification of sites on volcanic ash or unconsolidated soil are about two times those of hard lava sites. On a map for a 50 year exposure time with a 90% probability of not being exceeded, the peak ground accelerations are 1.0 g Kilauea's and Mauna Loa's mobile south flanks and 0.9 g in the Kaoiki seismic zone. This hazard from strong ground shaking is comparable to that near the San Andreas Fault in California or the subduction zone in the Gulf of Alaska.

Results from the 1995 Stratospheric Ozone Profile Intercomparison at Mauna Loa (MLO3)

NASA Technical Reports Server (NTRS)

McPeters, R. D.; Hofmann, D. J.; Clark, M.; Flynn, L.; Froidevaux, L.; Gross, M.; Johnson, B.; Koenig, G.; Liu, X.; McDermid, S.;

Inflation Features of the Distal Pahoehoe Portion of the 1859 Mauna Loa Flow, Hawaii; Implications for Evaluating Planetary Lava Flows

NASA Technical Reports Server (NTRS)

Zimbelman, J. R.; Garry, W. B.; Bleacher, Jacob E.; Crumpler, L S.

2011-01-01

The 1859 eruption of Mauna Loa, Hawaii, resulted in the longest subaerial lava flow on the Big Island. Detailed descriptions were made of the eruption both from ships and following hikes by groups of observers; the first three weeks of the eruption produced an `a`a flow that reached the ocean, and the following 10 months produced a pahoehoe flow that also eventually reached the ocean. The distal portion of the 1859 pahoehoe flow component includes many distinctive features indicative of flow inflation. Field work was conducted on the distal 1859 pahoehoe flow during 2/09 and 3/10, which allowed us to document several inflation features, in or-der evaluate how well inflated landforms might be detected in remote sensing data of lava flows on other planets.

Familial schwannomatosis with a germline mutation of SMARCB1 in Japan.

PubMed

Asai, Katsunori; Tani, Shoichi; Mineharu, Yohei; Tsurusaki, Yoshinori; Imai, Yukihiro; Agawa, Yuji; Iwaki, Koichi; Matsumoto, Naomichi; Sakai, Nobuyuki

2015-07-01

Schwannomatosis is the third major form of neurofibromatosis (NF) and is distinct from NF1 and NF2. The disease is not well recognized in Asian countries and the role of germline SMARCB1 mutations requires investigation. A 35-year-old Japanese man complaining of headache underwent an MRI examination, which showed a cystic tumor at the left cerebellopontine angle. The tumor was surgically removed and diagnosed as vagus nerve schwannoma. He had a past medical history of multiple schwannomas of the neck, groin and intercostal nerves, which were also treated surgically. He had a family history of multiple schwannomas for his father and sister. Systemic examinations of these family members ruled out a diagnosis of NF1 or NF2, and thus schwannomatosis was suspected. Genetic analysis revealed a germline mutation (c. *82C > T) of SMARCB1, and a somatic mutation of NF2 without loss of heterozygosity at the chromosome 22 locus. This is the first report of familial schwannomatosis associated with a germline mutation of SMARCB1 in an Asian country.

Equilibrium contact angle or the most-stable contact angle?

PubMed

Montes Ruiz-Cabello, F J; Rodríguez-Valverde, M A; Cabrerizo-Vílchez, M A

2014-04-01

It is well-established that the equilibrium contact angle in a thermodynamic framework is an "unattainable" contact angle. Instead, the most-stable contact angle obtained from mechanical stimuli of the system is indeed experimentally accessible. Monitoring the susceptibility of a sessile drop to a mechanical stimulus enables to identify the most stable drop configuration within the practical range of contact angle hysteresis. Two different stimuli may be used with sessile drops: mechanical vibration and tilting. The most stable drop against vibration should reveal the changeless contact angle but against the gravity force, it should reveal the highest resistance to slide down. After the corresponding mechanical stimulus, once the excited drop configuration is examined, the focus will be on the contact angle of the initial drop configuration. This methodology needs to map significantly the static drop configurations with different stable contact angles. The most-stable contact angle, together with the advancing and receding contact angles, completes the description of physically realizable configurations of a solid-liquid system. Since the most-stable contact angle is energetically significant, it may be used in the Wenzel, Cassie or Cassie-Baxter equations accordingly or for the surface energy evaluation. © 2013 Elsevier B.V. All rights reserved.

Longitudinal changes of angle configuration in primary angle-closure suspects: the Zhongshan Angle-Closure Prevention Trial.

PubMed

Jiang, Yuzhen; Chang, Dolly S; Zhu, Haogang; Khawaja, Anthony P; Aung, Tin; Huang, Shengsong; Chen, Qianyun; Munoz, Beatriz; Grossi, Carlota M; He, Mingguang; Friedman, David S; Foster, Paul J

2014-09-01

To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes. Longitudinal cohort study. Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled clinical trial. Each participant was treated by LPI in 1 randomly selected eye, with the fellow eye serving as a control. Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coherence tomography (AS-OCT) before and at 2 weeks, 6 months, and 18 months after LPI. Angle width in degrees was calculated from Shaffer grades assessed under static gonioscopy. Angle configuration was also evaluated using angle opening distance (AOD250, AOD500, AOD750), trabecular-iris space area (TISA500, TISA750), and angle recess area (ARA) measured in AS-OCT images. No significant difference was found in baseline measures of angle configuration between treated and untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5° at baseline to a mean of 25.7° in treated eyes, which was also confirmed by significant increases in all AS-OCT angle width measures (P<0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed over time in treated eyes (P<0.001 for all variables), although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy (P = 0.18), AOD250 (P = 0.167) and ARA (P = 0.83). In untreated eyes, angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes (P values for all variables ≤0.003). The annual rate of change in angle width was equivalent to 1.2°/year (95% confidence interval [CI], 0.8-1.6) in treated eyes and 1.6°/year (95% CI, 1.3-2.0) in untreated eyes (P<0.001). Angle width of treated eyes

Longitudinal Changes of Angle Configuration in Primary Angle-Closure Suspects

PubMed Central

Jiang, Yuzhen; Chang, Dolly S.; Zhu, Haogang; Khawaja, Anthony P.; Aung, Tin; Huang, Shengsong; Chen, Qianyun; Munoz, Beatriz; Grossi, Carlota M.

2015-01-01

Objective To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes. Design Longitudinal cohort study. Participants Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled clinical trial. Methods Each participant was treated by LPI in 1 randomly selected eye, with the fellow eye serving as a control. Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coherence tomography (AS-OCT) before and at 2 weeks, 6 months, and 18 months after LPI. Main Outcome Measures Angle width in degrees was calculated from Shaffer grades assessed under static gonioscopy. Angle configuration was also evaluated using angle opening distance (AOD250, AOD500, AOD750), trabecular-iris space area (TISA500, TISA750), and angle recess area (ARA) measured in AS-OCT images. Results No significant difference was found in baseline measures of angle configuration between treated and untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5° at baseline to a mean of 25.7° in treated eyes, which was also confirmed by significant increases in all AS-OCT angle width measures (P<0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed over time in treated eyes (P<0.001 for all variables), although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy (P = 0.18), AOD250 (P = 0.167) and ARA (P = 0.83). In untreated eyes, angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes (P values for all variables ≤0.003). The annual rate of change in angle width was equivalent to 1.2°/year (95% confidence interval [CI], 0.8–1.6) in treated eyes and 1.6°/year (95% CI, 1

COR1 Engineering Test Unit Measurements at the Mauna Loa Solar Observatory, September 2003

NASA Technical Reports Server (NTRS)

Thompson, William; Reginald, Nelson; Streander, Kim

2003-01-01

The COR1 Engineering Test Unit (ETU), which had been previously tested at the NCAR/HAO and NRL test facilities, was modified into an instrument capable of observing the Sun. It was then taken to the Mauna Loa Solar Observatory to observe the corona. The changes made to observe the Sun were as follows: 1. The plate scale was changed to accommodate the smaller Apogee camera. This change had already been made for the NRL tests. 2. The previous Oriel polarizer was replaced with a commercial Polarcor polarizer from Newport to be more flight-like. However, because of cost and availability considerations, this polarizer was smaller than those which will be used for flight. 3. A structure was placed around the back section of the instrument, to protect it from stray light. 4. A pointing spar borrowed from HAO was used to track the Sun. A few days into the test, it became evident that some artifacts were appearing in the data, and these artifacts were changing as the polarizer was rotated. It was decided to test two other polarizers, the Oriel polarizer which had been used in the previous tests at HAO and NRL, and a Nikon polarizer which was borrowed from a camera belonging to one of the observatory staff members. These three polarizers had much different qualities are shown.

Ashra (All-sky Survey High Resolution Air-shower detector)Current Status on Mauna Loa, Hawai`i

NASA Astrophysics Data System (ADS)

Hamilton, John; Fox, R. A.; Sasaki, M.; Asaoka, Y.; Ashra Collaboration

2008-09-01

Now in its third year of on-site activities, Ashra is commencing full testing of its array of Cherenkov and Nitrogen Fluorescence detectors. The All-sky Survey High Resolution Air-shower detector is located on the northern upper slopes of Mauna Loa at the 11,000 ft elevation level. Utilizing a clear view of 80% of the sky and an unobstructed view of Mauna Kea, anglular resolution of 1.2 arcmin, sensitive to the blue to UV light with the use of image intensifier and CMOS technology, Ashra is in a unique position for studying the sources of High Energy Cosmic Ray sources (GRB, etc) as well as potential observations of earth-grazing neutrino interactions. 2004 saw the successful deployment of a prototype detector on Haleakala, with confirmed detection of several GRBs. Since the summer of 2005, steady progress was made in constructing and installation of detectors and their weather-proofed housings. UH-Hilo undergraduate students provided summer interns for this international collaboration between ICRR Univ. Tokyo, Univ. Hawai`i-Hilo, Univ Hawai`i-Manoa, Ibaraki Univ., Toho Univ. Chiba Univ., Kanagawa Univ., Nagoya Univ. & Tokyo Institute of Technology.

Water vapor isotopes measurements at Mauna Loa, Hawaii: Comparison of laser spectroscopy and remote sensing with traditional methods, and the need for ongoing monitoring

NASA Astrophysics Data System (ADS)

Noone, D.; Galewsky, J.; Sharp, Z.; Worden, J.

2008-12-01

The isotopic composition of water vapor (2H/1H and 18O/16 ratios) provides unique information on the transport pathways that link the water sources to regional sinks, and thus proves useful in understanding the large scale humidity budgets. Recent advances in measurement technology allow the monitoring of water vapor isotope composition in ways which has can revolutionize investigations of atmospheric hydrology. Traditional measurement of isotopic composition requires trapping of samples with either large volume vacuum flasks or by trapping liquid samples with cryogens for later analyses using mass spectrometry, and are laborious and seldom span more than just short dedicated observational periods. On the other hand, laser absorption spectroscopy can provide almost continuous and autonomous in situ measurements of isotope abundances with precision almost that of traditional mass spectrometry, and observations from spacecraft can make almost daily maps of the global isotope distributions. In October of 2008 three laser based spectrometers were deployed at the Mauna Loa Laboratory in Hawaii to make continuous measurement of the 2H and 18O abundance of free tropospheric water vapor. These results are compared with traditional measurements and with measurements from two satellite platforms. While providing field validation of the new methodologies, the data show variability which captures the transport processes in the region. The data are used to characterize the role of large scale mixing of dry air, the influence of the boundary layer and the importance of moist convection in controlling the low humidity of subtropical air near Hawaii. Although the record is short, it demonstrates the usefulness of using robust isotope measurements to understand the budgets of the most important greenhouse gas. This work motivates establishing a continuous record of isotopes measurement at baseline sites, like Mauna Loa, such that the changes in water cycle can be understood and

Water vapor isotopes measurements at Mauna Loa, Hawaii: Comparison of laser spectroscopy and remote sensing with traditional methods, and the need for ongoing monitoring

NASA Astrophysics Data System (ADS)

Galewsky, J.; Noone, D.; Sharp, Z.; Worden, J.

2009-04-01

The isotopic composition of water vapor (2H/1H and 18O/16 ratios) provides unique information on the transport pathways that link water sources to regional sinks, and thus proves useful in understanding large scale atmospheric humidity budgets. Recent advances in measurement technology allow the monitoring of water vapor isotope composition in ways which has can revolutionize investigations of atmospheric hydrology. Traditional measurement of isotopic composition requires trapping of samples with either large volume vacuum flasks or by trapping liquid samples with cryogens for later analyses using mass spectrometry, and are laborious and seldom span more than just short dedicated observational periods. On the other hand, laser absorption spectroscopy can provide almost continuous and autonomous in situ measurements of isotope abundances with precision almost that of traditional mass spectrometry, and observations from spacecraft can make almost daily maps of the global isotope distributions. In October of 2008 three laser based spectrometers were deployed at the Mauna Loa Laboratory in Hawaii to make continuous measurement of the 2H and 18O abundance of free tropospheric water vapor. These results are compared with traditional measurements and with measurements from two satellite platforms. While providing field validation of the new methodologies, the data show variability which captures the transport processes in the region. The data are used to characterize the role of large scale mixing of dry air, the influence of the boundary layer and the importance of moist convection in controlling the low humidity of subtropical air near Hawaii. Although the record is short, it demonstrates the usefulness of using robust isotope measurements to understand the budgets of the most important greenhouse gas. This work motivates establishing a continuous record of isotopes measurement at baseline sites, like Mauna Loa, such that the changes in water cycle can be understood and

Infrared Spectroscopic Measurements of the Ethane (C2H6) Total Column Abundance Above Mauna Loa, Hawaii: Seasonal Variations

NASA Technical Reports Server (NTRS)

Rinsland, C. P.; Goldman, A.; Murcray, F. J.; David, S. J.; Blatherwick, R. D.; Murcray, D. G.

1994-01-01

About 200 i.r. solar spectra recorded at 0.01/ cm resolution on 71 days between November 1991 and July 1993 at the Network for the Detection of Stratospheric Change (NDSC) station at Mauna Loa, Hawaii (latitude 19.53 deg N, longitude 155.58 deg W, elevation 3.459 km) have been analyzed with a nonlinear least-squares spectral fitting technique to study temporal variations in the total column of atmospheric ethane (C2H6) above the site. The results were derived from the analysis of the unresolved nu(sub 7) band (sup P)Q(sub 3) subbranch at 2976.8/cm. A distinct seasonal cycle is observed with a factor of 2 variation, a maximum total column of 1.1 6 x 10(exp 16) mol /sq cm at the end of winter, and a minimum total column of 0.53 x 10(exp 16) mol/sq cm at the end of summer. Our measurements are compared with previous observations and model predictions.

Infrared spectroscopic measurements of the ethane (C2H6) total column abundance above Mauna Loa, Hawaii -- seasonal variations

NASA Technical Reports Server (NTRS)

Rinsland, C. P.; Goldman, A.; Murcray, F. J.; David, S. J.; Blatherwick, R. D.; Murcray, D. G.

1994-01-01

About 200 i.r. solar spectra recorded at 0.01/cm resolution on 71 days between November 1991 and July 1993 at the Network for the Detection of Stratospheric Change (NDSC) station at Mauna Loa, Hawaii (latitude 19.53 deg N, longitude 155.58 deg W, elevation 3.459 km) have been analyzed with a nonlinear least-squares spectral fitting technique to study temporal variations in the total column of atmospheric ethane (C2H6) above the site. The results were derived from the analysis of the unresolved nu(sub 7) band (P)Q(sub 3) subbranch at 2976.8/cm. A distinct seasonal cycle is observed with a factor of 2 variation, a maximum total column of 1.16 x 10(exp 16) mol/sq cm at the end of winter, and a minimum total column of 0.53 x 10(exp 16) mol/sq cm at the end of summer. Our measurements are compared with previous observations and model predictions.

Population estimates of the Endangered Hawaiʻi ʻĀkepa (Loxops coccineus) in different habitats on windward Mauna Loa

USGS Publications Warehouse

Judge, Seth W.; Camp, Richard J.; Hart, Patrick J.; Kichman, Scott T.

2018-01-01

Endangered Hawai‘i ʻĀkepas (Loxops coccineus) are endemic to Hawai‘i island, where they occur in five spatially distinct populations. Data concerning the status and population trends of these unique Hawaiian honeycreepers are crucial for assessing the effectiveness of recovery and management actions. In 2016, we used point‐transect distance sampling to estimate the abundance of Hawai‘i ʻĀkepas in portions of Hawai‘i Volcanoes National Park (HAVO) and the Kaʻū Forest Reserve (KFR) on Mauna Loa volcano. We then compiled the survey data from four other populations to provide a global population estimate. In our HAVO and KFR study area, we mapped habitat classes to determine the population densities in each habitat. Densities were highest (1.03 birds/ha) in open‐canopy montane ʻōhiʻa (Metrosideros polymorpha) woodland. In contrast, densities of the largest ʻĀkepa population on Mauna Kea volcano were highest in closed‐canopy ʻōhiʻa and koa (Acacia koa) forest where the species is dependent on nest cavities in tall (> 15 m), large (> 50‐cm diameter at breast height) trees. We surveyed potential nesting habitat in HAVO and KFR and found only one cavity in the short‐stature montane ʻōhiʻa woodland and five cavities in the tall‐stature forest. Differences in densities between the Mauna Kea and Mauna Loa populations suggest that Hawai‘i ʻĀkepas may exhibit different foraging and nesting behaviors in the two habitats. The estimated overall population density in the HAVO and KFR study area was 0.52 birds/ha, which equates to 3663 (95% CI 1725–6961) birds in their 11,377‐ha population range. We calculated a global population of 16,428 (95% CI 10,065–25,198) birds, which is similar to an estimate of 13,892 (95% CI 10,315–17,469) birds made in 1986. Our results suggest that populations are stable to increasing in the two largest populations, but the three other populations are smaller (range = 77–1443 birds) and trends

Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

PubMed

Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

2016-05-01

Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type. Copyright © 2016 Elsevier Inc. All rights reserved.

Apparent contact angle and contact angle hysteresis on liquid infused surfaces.

PubMed

Semprebon, Ciro; McHale, Glen; Kusumaatmaja, Halim

2016-12-21

We theoretically investigate the apparent contact angle and contact angle hysteresis of a droplet placed on a liquid infused surface. We show that the apparent contact angle is not uniquely defined by material parameters, but also has a dependence on the relative size between the droplet and its surrounding wetting ridge formed by the infusing liquid. We derive a closed form expression for the contact angle in the limit of vanishing wetting ridge, and compute the correction for small but finite ridge, which corresponds to an effective line tension term. We also predict contact angle hysteresis on liquid infused surfaces generated by the pinning of the contact lines by the surface corrugations. Our analytical expressions for both the apparent contact angle and contact angle hysteresis can be interpreted as 'weighted sums' between the contact angles of the infusing liquid relative to the droplet and surrounding gas phases, where the weighting coefficients are given by ratios of the fluid surface tensions.

Automated analysis of angle closure from anterior chamber angle images.

PubMed

Baskaran, Mani; Cheng, Jun; Perera, Shamira A; Tun, Tin A; Liu, Jiang; Aung, Tin

2014-10-21

To evaluate a novel software capable of automatically grading angle closure on EyeCam angle images in comparison with manual grading of images, with gonioscopy as the reference standard. In this hospital-based, prospective study, subjects underwent gonioscopy by a single observer, and EyeCam imaging by a different operator. The anterior chamber angle in a quadrant was classified as closed if the posterior trabecular meshwork could not be seen. An eye was classified as having angle closure if there were two or more quadrants of closure. Automated grading of the angle images was performed using customized software. Agreement between the methods was ascertained by κ statistic and comparison of area under receiver operating characteristic curves (AUC). One hundred forty subjects (140 eyes) were included, most of whom were Chinese (102/140, 72.9%) and women (72/140, 51.5%). Angle closure was detected in 61 eyes (43.6%) with gonioscopy in comparison with 59 eyes (42.1%, P = 0.73) using manual grading, and 67 eyes (47.9%, P = 0.24) with automated grading of EyeCam images. The agreement for angle closure diagnosis between gonioscopy and both manual (κ = 0.88; 95% confidence interval [CI), 0.81-0.96) and automated grading of EyeCam images was good (κ = 0.74; 95% CI, 0.63-0.85). The AUC for detecting eyes with gonioscopic angle closure was comparable for manual and automated grading (AUC 0.974 vs. 0.954, P = 0.31) of EyeCam images. Customized software for automated grading of EyeCam angle images was found to have good agreement with gonioscopy. Human observation of the EyeCam images may still be needed to avoid gross misclassification, especially in eyes with extensive angle closure. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Simultaneous lidar and EOS MLS measurements, and modeling, of a rare polar ozone filament event over Mauna Loa Observatory, Hawaii

NASA Astrophysics Data System (ADS)

Leblanc, Thierry; Tripathi, Om Prakash; McDermid, I. Stuart; Froidevaux, Lucien; Livesey, N. J.; Read, W. G.; Waters, J. W.

2006-08-01

In mid-March 2005, a rare lower stratospheric polar vortex filamentation event was observed simultaneously by the JPL lidar at Mauna Loa Observatory, Hawaii, and by the EOS MLS instrument onboard the Aura satellite. The event coincided with the beginning of the spring 2005 final warming. On 16 March, the filament was observed by lidar around 0600 UT between 415 K and 455 K, and by MLS six hours earlier. It was seen on both the lidar and MLS profiles as a layer of enhanced ozone, peaking at 1.7 ppmv in a region where the climatological values are usually around or below 1 ppmv. Ozone profiles measured by lidar and MLS were compared to profiles from the Chemical Transport Model MIMOSA-CHIM. The agreement between lidar, MLS, and the model is excellent considering the difference in the sampling techniques. MLS was also able to identify the filament at another location north of Hawaii.

Mutational landscape of yeast mutator strains.

PubMed

Serero, Alexandre; Jubin, Claire; Loeillet, Sophie; Legoix-Né, Patricia; Nicolas, Alain G

2014-02-04

The acquisition of mutations is relevant to every aspect of genetics, including cancer and evolution of species on Darwinian selection. Genome variations arise from rare stochastic imperfections of cellular metabolism and deficiencies in maintenance genes. Here, we established the genome-wide spectrum of mutations that accumulate in a WT and in nine Saccharomyces cerevisiae mutator strains deficient for distinct genome maintenance processes: pol32Δ and rad27Δ (replication), msh2Δ (mismatch repair), tsa1Δ (oxidative stress), mre11Δ (recombination), mec1Δ tel1Δ (DNA damage/S-phase checkpoints), pif1Δ (maintenance of mitochondrial genome and telomere length), cac1Δ cac3Δ (nucleosome deposition), and clb5Δ (cell cycle progression). This study reveals the diversity, complexity, and ultimate unique nature of each mutational spectrum, composed of punctual mutations, chromosomal structural variations, and/or aneuploidies. The mutations produced in clb5Δ/CCNB1, mec1Δ/ATR, tel1Δ/ATM, and rad27Δ/FEN1 strains extensively reshape the genome, following a trajectory dependent on previous events. It comprises the transmission of unstable genomes that lead to colony mosaicisms. This comprehensive analytical approach of mutator defects provides a model to understand how genome variations might accumulate during clonal evolution of somatic cell populations, including tumor cells.

Optimal reconstruction angles

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

Cook, G.O. Jr.; Knight, L.

1979-07-01

The question of optimal projection angles has recently become of interest in the field of reconstruction from projections. Here, studies are concentrated on the n x n pixel space, where literative algorithms such as ART and direct matrix techniques due to Katz are considered. The best angles are determined in a Gauss--Markov statistical sense as well as with respect to a function-theoretical error bound. The possibility of making photon intensity a function of angle is also examined. Finally, the best angles to use in an ART-like algorithm are studied. A certain set of unequally spaced angles was found to bemore » preferred in several contexts. 15 figures, 6 tables.« less

{l_angle}110{r_angle} dendrite growth in aluminum feathery grains

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

Henry, S.; Rappaz, M.; Jarry, P.

1998-11-01

Automatic indexing of electron backscattered diffraction patterns, scanning electron microscopy, and optical microscopy observations have been carried out on aluminum-magnesium-silicon, aluminum-copper, and aluminum-silicon alloys directionally solidified or semicontinuously cast using the direct chill casting process. From these combined observations, it is shown that the feathery grains are made of {l_angle}110{r_angle} primary dendrite trunks (e.g., [011{bar 1}]) split in their centers by a coherent (111) twin plane. The average spacing of the dendrite trunks in the twin plane (about 10 to 20 {micro}m) is typically one order of magnitude smaller than that separating successive rows of trunks (or twin planes). Themore » [011{bar 1}] orientation of these trunks is close to the thermal gradient direction (typically within 15 deg)--a feature probably resulting from a growth competition mechanism similar to that occurring during normal <100> columnar dendrite growth. On both sides of these trunks, secondary dendrite arms also grow along {l_angle}110{r_angle} directions. Their impingement creates wavy noncoherent twin boundaries between the coherent twin planes. In the twin plane, evidence is shown that {l_angle}110{r_angle} branching mechanisms lead to the propagation of the twinned regions, to the regular arrangement of the primary dendrite trunks along a [{bar 2}11] direction, and to coherent planar twin boundaries. From these observations, it is concluded that the feathery grains are probably the result of a change from a normal <100> to a {l_angle}110{r_angle} surface tension/attachment kinetics anisotropy growth mode. Finally, the proposed mechanisms of leathery grain growth are further supported by the observation of {l_angle}110{r_angle} dendrite growth morphologies in thin aluminum-zinc coatings.« less

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme

DOE PAGES

Lee, Hui-Ting; Kilburn, D.; Behrouzi, R.; ...

2014-12-05

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg2+ concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg2+more » concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.« less

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme

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

Lee, Hui-Ting; Kilburn, D.; Behrouzi, R.

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg2+ concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg2+more » concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.« less

The Critical Angle Can Override the Brewster Angle

ERIC Educational Resources Information Center

Froehle, Peter H.

2009-01-01

As a culminating activity in their study of optics, my students investigate polarized light and the Brewster angle. In this exercise they encounter a situation in which it is impossible to measure the Brewster angle for light reflecting from a particular surface. This paper describes the activity and explains the students' observations.

Undetected angle closure in patients with a diagnosis of open-angle glaucoma.

PubMed

Varma, Devesh K; Simpson, Sarah M; Rai, Amandeep S; Ahmed, Iqbal Ike K

2017-08-01

The aim of this study was to identify the proportion of patients referred to a tertiary glaucoma centre with a diagnosis of open-angle glaucoma (OAG) who were found to have angle closure glaucoma. Retrospective chart review. Consecutive new patients referred for glaucoma management to a tertiary centre between July 2010 and December 2011 were reviewed. Patients whose referrals for glaucoma assessment specified angle status as "open" were included. The data collected included glaucoma specialist's angle assessment, diagnosis, and glaucoma severity. The status of those with 180 degrees or more Shaffer angle grading of 0 was classified as "closed." From 1234 glaucoma referrals, 179 cases were specified to have a diagnosis of OAG or when angles were known to be open. Of these, 16 (8.9%) were found on examination by the glaucoma specialist to have angle closure. Pseudoexfoliation was present in 4 of 16 patients (25%) in the missed angle-closure glaucoma (ACG) group and 22 of 108 patients (13.5%) in the remaining OAG group. There was no difference found in demographic or ocular biometric parameters between those with confirmed OAG versus those with missed ACG. Almost 1 in 11 patients referred by ophthalmologists to a tertiary glaucoma centre with a diagnosis of OAG were in fact found to have angle closure. Given the different treatment approaches for ACG versus OAG, this study suggests a need to strengthen angle evaluations. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Evaluation of blotchy pigments in the anterior chamber angle as a sign of angle closure

PubMed Central

Rao, Harsha L; Mungale, Sachin C; Kumbar, Tukaram; Parikh, Rajul S; Garudadri, Chandra S

2012-01-01

Background: Blotchy pigments in the anterior chamber (AC) angle are considered diagnostic of primary angle closure (PAC). But there are no reports either on the prevalence of blotchy pigments in AC angles or the validity of this sign. Aims: To determine the prevalence of blotchy pigments in AC angles and to evaluate their relationship with glaucomatous optic neuropathy (GON) in eyes with occludable angles. Setting and Design: Cross-sectional, comparative study. Materials and Methods: Gonioscopy was performed in 1001 eyes of 526 subjects (245 eyes of 148 consecutive, occludable angle subjects and 756 eyes of 378 non-consecutive, open angle subjects), above 35 years of age. Quadrant-wise location of blotchy pigments was documented. Statistical Analysis: Odds of blotchy pigments in occludable angles against that in open angles were evaluated. Relationship of GON with blotchy pigments in occludable angle eyes was evaluated using a multivariate model. Results: Prevalence of blotchy pigments in occludable angles was 28.6% (95% CI, 22.9-34.3) and in open angles was 4.7% (95% CI, 3.2-6.3). Blotchy pigments were more frequently seen in inferior (16%) and superior quadrants (15%) of occludable angles, and inferior quadrant of open angles (4%). Odds of superior quadrant blotchy pigments in occludable angles were 33 times that in open angles. GON was seen in 107 occludable angle eyes. Blotchy pigments were not significantly associated with GON (odds ratio = 0.5; P = 0.1). Conclusions: Blotchy pigments were seen in 28.6% of occludable angle eyes and 4.7% of open angles eyes. Presence of blotchy pigments in the superior quadrant is more common in occludable angles. Presence of GON in occludable angle eyes was not associated with blotchy pigments. PMID:23202393

Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer.

PubMed

Castellanos, Emily; Feld, Emily; Horn, Leora

2017-04-01

EGFR-mutated NSCLC is a genetically heterogeneous disease that includes more than 200 distinct mutations. The implications of mutational subtype for both prognostic and predictive value are being increasingly understood. Although the most common EGFR mutations-exon 19 deletions or L858R mutations-predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), it is now being recognized that outcomes may be improved in patients with exon 19 deletions. Additionally, 10% of patients will have an uncommon EGFR mutation, and response to EGFR TKI therapy is highly variable depending on the mutation. Given the growing recognition of the genetic and clinical variation seen in this disease, the development of comprehensive bioinformatics-driven tools to both analyze response in uncommon mutation subtypes and inform clinical decision making will be increasingly important. Clinical trials of novel EGFR TKIs should prospectively account for the presence of uncommon mutation subtypes in study design. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

IDH1 R132H mutation generates a distinct phospholipid metabolite profile in glioma.

PubMed

Esmaeili, Morteza; Hamans, Bob C; Navis, Anna C; van Horssen, Remco; Bathen, Tone F; Gribbestad, Ingrid S; Leenders, William P; Heerschap, Arend

2014-09-01

Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed (31)P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation. (31)P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by (31)P high-resolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro (31)P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma. ©2014 American Association for Cancer Research.

The perception of volcanic risk in Kona communities from Mauna Loa and Hualālai volcanoes, Hawai‵i

NASA Astrophysics Data System (ADS)

Gregg, C. E.; Houghton, B. F.; Johnston, D. M.; Paton, D.; Swanson, D. A.

2004-02-01

Volcanic hazards in Kona (i.e. the western side of the island of Hawai‵i) stem primarily from Mauna Loa and Hualālai volcanoes. The former has erupted 39 times since 1832. Lava flows were emplaced in Kona during seven of these eruptions and last impacted Kona in 1950. Hualālai last erupted in ca. 1800. Society's proximity to potential eruptive sources and the potential for relatively fast-moving lava flows, coupled with relatively long time intervals since the last eruptions in Kona, are the underlying stimuli for this study of risk perception. Target populations were high-school students and adults ( n=462). Using these data, we discuss threat knowledge as an influence on risk perception, and perception as a driving mechanism for preparedness. Threat knowledge and perception of risk were found to be low to moderate. On average, fewer than two-thirds of the residents were aware of the most recent eruptions that impacted Kona, and a minority felt that Mauna Loa and Hualālai could ever erupt again. Furthermore, only about one-third were aware that lava flows could reach the coast in Kona in less than 3 h. Lava flows and ash fall were perceived to be among the least likely hazards to affect the respondent's community within the next 10 years, whereas vog (volcanic smog) was ranked the most likely. Less than 18% identified volcanic hazards as amongst the most likely hazards to affect them at home, school, or work. Not surprisingly, individual preparedness measures were found on average to be limited to simple tasks of value in frequently occurring domestic emergencies, whereas measures specific to infrequent hazard events such as volcanic eruptions were seldom adopted. Furthermore, our data show that respondents exhibit an 'unrealistic optimism bias' and infer that responsibility for community preparedness for future eruptions primarily rests with officials. We infer that these respondents may be less likely to attend to hazard information, react to warnings as

The perception of volcanic risk in Kona communities from Mauna Loa and Hualālai volcanoes, Hawai'i

USGS Publications Warehouse

Gregg, Chris E.; Houghton, Bruce F.; Johnston, David M.; Paton, Douglas; Swanson, D.A.

2004-01-01

Volcanic hazards in Kona (i.e. the western side of the island of Hawai'i) stem primarily from Mauna Loa and Huala??lai volcanoes. The former has erupted 39 times since 1832. Lava flows were emplaced in Kona during seven of these eruptions and last impacted Kona in 1950. Huala??lai last erupted in ca. 1800. Society's proximity to potential eruptive sources and the potential for relatively fast-moving lava flows, coupled with relatively long time intervals since the last eruptions in Kona, are the underlying stimuli for this study of risk perception. Target populations were high-school students and adults ( n =462). Using these data, we discuss threat knowledge as an influence on risk perception, and perception as a driving mechanism for preparedness. Threat knowledge and perception of risk were found to be low to moderate. On average, fewer than two-thirds of the residents were aware of the most recent eruptions that impacted Kona, and a minority felt that Mauna Loa and Huala??lai could ever erupt again. Furthermore, only about one-third were aware that lava flows could reach the coast in Kona in less than 3 h. Lava flows and ash fall were perceived to be among the least likely hazards to affect the respondent's community within the next 10 years, whereas vog (volcanic smog) was ranked the most likely. Less than 18% identified volcanic hazards as amongst the most likely hazards to affect them at home, school, or work. Not surprisingly, individual preparedness measures were found on average to be limited to simple tasks of value in frequently occurring domestic emergencies, whereas measures specific to infrequent hazard events such as volcanic eruptions were seldom adopted. Furthermore, our data show that respondents exhibit an 'unrealistic optimism bias' and infer that responsibility for community preparedness for future eruptions primarily rests with officials. We infer that these respondents may be less likely to attend to hazard information, react to warnings as

Investigations of interpolation errors of angle encoders for high precision angle metrology

NASA Astrophysics Data System (ADS)

Yandayan, Tanfer; Geckeler, Ralf D.; Just, Andreas; Krause, Michael; Asli Akgoz, S.; Aksulu, Murat; Grubert, Bernd; Watanabe, Tsukasa

2018-06-01

Interpolation errors at small angular scales are caused by the subdivision of the angular interval between adjacent grating lines into smaller intervals when radial gratings are used in angle encoders. They are often a major error source in precision angle metrology and better approaches for determining them at low levels of uncertainty are needed. Extensive investigations of interpolation errors of different angle encoders with various interpolators and interpolation schemes were carried out by adapting the shearing method to the calibration of autocollimators with angle encoders. The results of the laboratories with advanced angle metrology capabilities are presented which were acquired by the use of four different high precision angle encoders/interpolators/rotary tables. State of the art uncertainties down to 1 milliarcsec (5 nrad) were achieved for the determination of the interpolation errors using the shearing method which provides simultaneous access to the angle deviations of the autocollimator and of the angle encoder. Compared to the calibration and measurement capabilities (CMC) of the participants for autocollimators, the use of the shearing technique represents a substantial improvement in the uncertainty by a factor of up to 5 in addition to the precise determination of interpolation errors or their residuals (when compensated). A discussion of the results is carried out in conjunction with the equipment used.

Detection of EGFR Gene Mutation by Mutation-oriented LAMP Method.

PubMed

Matsumoto, Naoyuki; Kumasaka, Akira; Ando, Tomohiro; Komiyama, Kazuo

2018-04-01

Epidermal growth factor receptor (EGFR) is a target of molecular therapeutics for non-small cell lung cancer. EGFR gene mutations at codons 746-753 promote constitutive EGFR activation and result in worst prognosis. However, these mutations augment the therapeutic effect of EGFR-tyrosine kinase inhibitor. Therefore, the detection of EGFR gene mutations is important for determining treatment planning. The aim of the study was to establish a method to detect EGFR gene mutations at codons 746-753. EGFR gene mutation at codons 746-753 in six cancer cell lines were investigated. A loop-mediated isothermal amplification (LAMP)-based procedure was developed, that employed peptide nucleic acid to suppress amplification of the wild-type allele. This mutation-oriented LAMP can amplify the DNA fragment of the EGFR gene with codons 746-753 mutations within 30 min. Moreover, boiled cells can work as template resources. Mutation oriented-LAMP assay for EGFR gene mutation is sensitive on extracted DNA. This procedure would be capable of detecting EGFR gene mutation in sputum, pleural effusion, broncho-alveolar lavage fluid or trans-bronchial lung biopsy by chair side. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Angle performance on optima MDxt

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

David, Jonathan; Kamenitsa, Dennis

2012-11-06

Angle control on medium current implanters is important due to the high angle-sensitivity of typical medium current implants, such as halo implants. On the Optima MDxt, beam-to-wafer angles are controlled in both the horizontal and vertical directions. In the horizontal direction, the beam angle is measured through six narrow slits, and any angle adjustment is made by electrostatically steering the beam, while cross-wafer beam parallelism is adjusted by changing the focus of the electrostatic parallelizing lens (P-lens). In the vertical direction, the beam angle is measured through a high aspect ratio mask, and any angle adjustment is made by slightlymore » tilting the wafer platen prior to implant. A variety of tests were run to measure the accuracy and repeatability of Optima MDxt's angle control. SIMS profiles of a high energy, channeling sensitive condition show both the cross-wafer angle uniformity, along with the small-angle resolution of the system. Angle repeatability was quantified by running a channeling sensitive implant as a regular monitor over a seven month period and measuring the sheet resistance-to-angle sensitivity. Even though crystal cut error was not controlled for in this case, when attributing all Rs variation to angle changes, the overall angle repeatability was measured as 0.16 Degree-Sign (1{sigma}). A separate angle repeatability test involved running a series of V-curves tests over a four month period using low crystal cut wafers selected from the same boule. The results of this test showed the angle repeatability to be <0.1 Degree-Sign (1{sigma}).« less

Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations.

PubMed

Atik, Tahir; Aykut, Ayca; Hazan, Filiz; Onay, Huseyin; Goksen, Damla; Darcan, Sukran; Tukun, Ajlan; Ozkinay, Ferda

2016-06-01

To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations. In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed. Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes. By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations.

MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders.

PubMed

Ma, Wanlong; Zhang, Xi; Wang, Xiuqiang; Zhang, Zhong; Yeh, Chen-Hsiung; Uyeji, Jennifer; Albitar, Maher

2011-03-01

Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 V617F-negative chronic myeloproliferative disorders (MPDs). We evaluated the prevalence of MPL mutations relative to JAK2 mutations in patients with suspected MPDs. A total of 2790 patient samples submitted for JAK2 mutation analysis were tested using real-time polymerase chain reaction and bidirectional sequencing of plasma RNA. JAK2 V617F-negative samples were tested for JAK2 exons 12 to 14 mutations, and those with negative results were then tested for mutations in MPL exons 10 and 11. Of the 2790 patients, 529 (18.96%) had V617F, 12 (0.43%) had small insertions or deletions in exon 12, and 7 (0.25%) had other JAK2 mutations in exons 12 to 14. Of the 2242 JAK2 mutation-negative patients, 68 (3.03%) had MPL mutations. W515L was the predominant MPL mutation (n=46; 68%), and 10 (15%) patients had other W515 variants. The remaining MPL mutations (n=12, 17%) were detected at other locations in exons 10 and 11 and included 3 insertion/deletion mutations. The S505N mutation, associated with familial MPD, was detected in 3 patients. Overall, for every 100 V617F mutations in patients with suspected MPDs, there were 12.9 MPL mutations, 2.3 JAK2 exon 12 mutations, and 1.3 JAK2 exons 13 to 14 mutations. These findings suggest that MPL mutation screening should be performed before JAK2 exons 12 to 14 testing in JAK2 V617F-negative patients with suspected MPDs.

Detection of novel NF1 mutations and rapid mutation prescreening with Pyrosequencing.

PubMed

Brinckmann, Anja; Mischung, Claudia; Bässmann, Ingelore; Kühnisch, Jirko; Schuelke, Markus; Tinschert, Sigrid; Nürnberg, Peter

2007-12-01

Neurofibromatosis type 1 (NF1) is caused by mutations in the neurofibromin (NF1) gene. Mutation analysis of NF1 is complicated by its large size, the lack of mutation hotspots, pseudogenes and frequent de novo mutations. Additionally, the search for NF1 mutations on the mRNA level is often hampered by nonsense-mediated mRNA decay (NMD) of the mutant allele. In this study we searched for mutations in a cohort of 38 patients and investigated the relationship between mutation type and allele-specific transcription from the wild-type versus mutant alleles. Quantification of relative mRNA transcript numbers was done by Pyrosequencing, a novel real-time sequencing method whose signals can be quantified very accurately. We identified 21 novel mutations comprising various mutation types. Pyrosequencing detected a definite relationship between allelic NF1 transcript imbalance due to NMD and mutation type in 24 of 29 patients who all carried frame-shift or nonsense mutations. NMD was absent in 5 patients with missense and silent mutations, as well as in 4 patients with splice-site mutations that did not disrupt the reading frame. Pyrosequencing was capable of detecting NMD even when the effects were only moderate. Diagnostic laboratories could thus exploit this effect for rapid prescreening for NF1 mutations as more than 60% of the mutations in this gene disrupt the reading frame and are prone to NMD.

Molecular profiling and sequential somatic mutation shift in hypermutator tumours harbouring POLE mutations.

PubMed

Hatakeyama, Keiichi; Ohshima, Keiichi; Nagashima, Takeshi; Ohnami, Shumpei; Ohnami, Sumiko; Serizawa, Masakuni; Shimoda, Yuji; Maruyama, Koji; Akiyama, Yasuto; Urakami, Kenichi; Kusuhara, Masatoshi; Mochizuki, Tohru; Yamaguchi, Ken

2018-06-07

Defective DNA polymerase ε (POLE) proofreading leads to extensive somatic mutations that exhibit biased mutational properties; however, the characteristics of POLE-mutated tumours remain unclear. In the present study, we describe a molecular profile using whole exome sequencing based on the transition of somatic mutations in 10 POLE-mutated solid tumours that were obtained from 2,042 Japanese patients. The bias of accumulated variations in these mutants was quantified to follow a pattern of somatic mutations, thereby classifying the sequential mutation shift into three periods. During the period prior to occurrence of the aberrant POLE, bare accumulation of mutations in cancer-related genes was observed, whereas PTEN was highly mutated in conjunction with or subsequent to the event, suggesting that POLE and PTEN mutations were responsible for the development of POLE-mutated tumours. Furthermore, homologous recombination was restored following the occurrence of PTEN mutations. Our strategy for estimation of the footprint of somatic mutations may provide new insight towards the understanding of mutation-driven tumourigenesis.

Angle classification revisited 2: a modified Angle classification.

PubMed

Katz, M I

1992-09-01

Edward Angle, in his classification of malocclusions, appears to have made Class I a range of abnormality, not a point of ideal occlusion. Current goals of orthodontic treatment, however, strive for the designation "Class I occlusion" to be synonymous with the point of ideal intermeshing and not a broad range. If contemporary orthodontists are to continue to use Class I as a goal, then it is appropriate that Dr. Angle's century-old classification, be modified to be more precise.

[Spectral Study on the Effects of Angle-Tuned Filter Wedge Angle Parameter to Reflecting Characteristics].

PubMed

Yu, Kan; Huang, De-xiu; Yin, Juan-juan; Bao, Jia-qi

2015-08-01

Three-port tunable optical filter is a key device in the all-optic intelligent switching network and dense wavelength division multiplexing system. The characteristics of the reflecting spectrum, especially the reflectivity and the isolation degree are very important to the three-port filter. Angle-tuned thin film filter is widely used as a three-port tunable filter for its high rectangular degree and good temperature stability. The characteristics of the reflecting spectrum are greatly influenced not only by the incident angle, but also by the wedge angle parameter of the non-paralleled wedge thin film filter. In the present paper, the influences of the wedge angle parameter to the reflectivity and the half bandwidth are analyzed, and the reflecting spectrum characterstics are simulationed in different wedge angle parameter and polarity. The wedge angle-tuned thin film filter with 0.8° wedge angle parameter is fabricated. The experimental results show that keeping the wedge angle the same orientation to the incident angle will worsen the reflectivity and the rectangular degree of the reflecting spectrum. However, keeping the wedge angle orientation reverse to the incident angle will enhance the reflectivity and decrease the bandwidth, which will give higher reflectivity and isolation degree to the three-port filter than that of high parallel degree angle-tuned thin film filter.

Novel TMEM98 mutations in pedigrees with autosomal dominant nanophthalmos

PubMed Central

Khorram, David; Choi, Michael; Roos, Ben R.; Stone, Edwin M.; Kopel, Teresa; Allen, Richard; Alward, Wallace L.M.; Scheetz, Todd E.

2015-01-01

Purpose Autosomal dominant nanophthalmos is an inherited eye disorder characterized by a structurally normal but smaller eye. Patients with nanophthalmos have high hyperopia (far-sightedness), a greater incidence of angle-closure glaucoma, and increased risk of surgical complications. In this study, the clinical features and the genetic basis of nanophthalmos were investigated in two large autosomal dominant nanophthalmos pedigrees. Methods Fourteen members of a Caucasian pedigree from the United States and 15 members of a pedigree from the Mariana Islands enrolled in a genetic study of nanophthalmos and contributed DNA samples. Twenty of 29 family members underwent eye examinations that included measurement of axial eye length and/or refractive error. The genetic basis of nanophthalmos in the pedigrees was studied with linkage analysis, whole exome sequencing, and candidate gene (i.e., TMEM98) sequencing to identify the nanophthalmos-causing gene. Results Nine members of the pedigree from the United States and 11 members of the pedigree from the Mariana Islands were diagnosed with nanophthalmos that is transmitted as an autosomal dominant trait. The patients with nanophthalmos had abnormally short axial eye lengths, which ranged from 15.9 to 18.4 mm. Linkage analysis of the nanophthalmos pedigree from the United States identified nine large regions of the genome (greater than 10 Mbp) that were coinherited with disease in this family. Genes within these “linked regions” were examined for disease-causing mutations using exome sequencing, and a His196Pro mutation was detected in the TMEM98 gene, which was recently reported to be a nanophthalmos gene. Sanger sequencing subsequently showed that all other members of this pedigree with nanophthalmos also carry the His196Pro TMEM98 mutation. Testing the Mariana Islands pedigree for TMEM98 mutations identified a 34 bp heterozygous deletion that spans the 3′ end of exon 4 in all affected family members. Neither TMEM98

Novel TMEM98 mutations in pedigrees with autosomal dominant nanophthalmos.

PubMed

Khorram, David; Choi, Michael; Roos, Ben R; Stone, Edwin M; Kopel, Teresa; Allen, Richard; Alward, Wallace L M; Scheetz, Todd E; Fingert, John H

2015-01-01

Autosomal dominant nanophthalmos is an inherited eye disorder characterized by a structurally normal but smaller eye. Patients with nanophthalmos have high hyperopia (far-sightedness), a greater incidence of angle-closure glaucoma, and increased risk of surgical complications. In this study, the clinical features and the genetic basis of nanophthalmos were investigated in two large autosomal dominant nanophthalmos pedigrees. Fourteen members of a Caucasian pedigree from the United States and 15 members of a pedigree from the Mariana Islands enrolled in a genetic study of nanophthalmos and contributed DNA samples. Twenty of 29 family members underwent eye examinations that included measurement of axial eye length and/or refractive error. The genetic basis of nanophthalmos in the pedigrees was studied with linkage analysis, whole exome sequencing, and candidate gene (i.e., TMEM98) sequencing to identify the nanophthalmos-causing gene. Nine members of the pedigree from the United States and 11 members of the pedigree from the Mariana Islands were diagnosed with nanophthalmos that is transmitted as an autosomal dominant trait. The patients with nanophthalmos had abnormally short axial eye lengths, which ranged from 15.9 to 18.4 mm. Linkage analysis of the nanophthalmos pedigree from the United States identified nine large regions of the genome (greater than 10 Mbp) that were coinherited with disease in this family. Genes within these "linked regions" were examined for disease-causing mutations using exome sequencing, and a His196Pro mutation was detected in the TMEM98 gene, which was recently reported to be a nanophthalmos gene. Sanger sequencing subsequently showed that all other members of this pedigree with nanophthalmos also carry the His196Pro TMEM98 mutation. Testing the Mariana Islands pedigree for TMEM98 mutations identified a 34 bp heterozygous deletion that spans the 3' end of exon 4 in all affected family members. Neither TMEM98 mutation was detected in

The CDC Hemophilia B mutation project mutation list: a new online resource.

PubMed

Li, Tengguo; Miller, Connie H; Payne, Amanda B; Craig Hooper, W

2013-11-01

Hemophilia B (HB) is caused by mutations in the human gene F9. The mutation type plays a pivotal role in genetic counseling and prediction of inhibitor development. To help the HB community understand the molecular etiology of HB, we have developed a listing of all F9 mutations that are reported to cause HB based on the literature and existing databases. The Centers for Disease Control and Prevention (CDC) Hemophilia B Mutation Project (CHBMP) mutation list is compiled in an easily accessible format of Microsoft Excel and contains 1083 unique mutations that are reported to cause HB. Each mutation is identified using Human Genome Variation Society (HGVS) nomenclature standards. The mutation types and the predicted changes in amino acids, if applicable, are also provided. Related information including the location of mutation, severity of HB, the presence of inhibitor, and original publication reference are listed as well. Therefore, our mutation list provides an easily accessible resource for genetic counselors and HB researchers to predict inhibitors. The CHBMP mutation list is freely accessible at http://www.cdc.gov/hemophiliamutations.

TCOF1 mutation database: novel mutation in the alternatively spliced exon 6A and update in mutation nomenclature.

PubMed

Splendore, Alessandra; Fanganiello, Roberto D; Masotti, Cibele; Morganti, Lucas S C; Passos-Bueno, M Rita

2005-05-01

Recently, a novel exon was described in TCOF1 that, although alternatively spliced, is included in the major protein isoform. In addition, most published mutations in this gene do not conform to current mutation nomenclature guidelines. Given these observations, we developed an online database of TCOF1 mutations in which all the reported mutations are renamed according to standard recommendations and in reference to the genomic and novel cDNA reference sequences (www.genoma.ib.usp.br/TCOF1_database). We also report in this work: 1) results of the first screening for large deletions in TCOF1 by Southern blot in patients without mutation detected by direct sequencing; 2) the identification of the first pathogenic mutation in the newly described exon 6A; and 3) statistical analysis of pathogenic mutations and polymorphism distribution throughout the gene.

Angle Performance on Optima XE

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

David, Jonathan; Satoh, Shu

2011-01-07

Angle control on high energy implanters is important due to shrinking device dimensions, and sensitivity to channeling at high beam energies. On Optima XE, beam-to-wafer angles are controlled in both the horizontal and vertical directions. In the horizontal direction, the beam angle is measured through a series of narrow slits, and any angle adjustment is made by steering the beam with the corrector magnet. In the vertical direction, the beam angle is measured through a high aspect ratio mask, and any angle adjustment is made by slightly tilting the wafer platen during implant.Using a sensitive channeling condition, we were ablemore » to quantify the angle repeatability of Optima XE. By quantifying the sheet resistance sensitivity to both horizontal and vertical angle variation, the total angle variation was calculated as 0.04 deg. (1{sigma}). Implants were run over a five week period, with all of the wafers selected from a single boule, in order to control for any crystal cut variation.« less

Manifold angles, the concept of self-similarity, and angle-enhanced bifurcation diagrams

PubMed Central

Beims, Marcus W.; Gallas, Jason A. C.

2016-01-01

Chaos and regularity are routinely discriminated by using Lyapunov exponents distilled from the norm of orthogonalized Lyapunov vectors, propagated during the temporal evolution of the dynamics. Such exponents are mean-field-like averages that, for each degree of freedom, squeeze the whole temporal evolution complexity into just a single number. However, Lyapunov vectors also contain a step-by-step record of what exactly happens with the angles between stable and unstable manifolds during the whole evolution, a big-data information permanently erased by repeated orthogonalizations. Here, we study changes of angles between invariant subspaces as observed during temporal evolution of Hénon’s system. Such angles are calculated numerically and analytically and used to characterize self-similarity of a chaotic attractor. In addition, we show how standard tools of dynamical systems may be angle-enhanced by dressing them with informations not difficult to extract. Such angle-enhanced tools reveal unexpected and practical facts that are described in detail. For instance, we present a video showing an angle-enhanced bifurcation diagram that exposes from several perspectives the complex geometrical features underlying the attractors. We believe such findings to be generic for extended classes of systems. PMID:26732416

Manifold angles, the concept of self-similarity, and angle-enhanced bifurcation diagrams

NASA Astrophysics Data System (ADS)

Beims, Marcus W.; Gallas, Jason A. C.

2016-01-01

Chaos and regularity are routinely discriminated by using Lyapunov exponents distilled from the norm of orthogonalized Lyapunov vectors, propagated during the temporal evolution of the dynamics. Such exponents are mean-field-like averages that, for each degree of freedom, squeeze the whole temporal evolution complexity into just a single number. However, Lyapunov vectors also contain a step-by-step record of what exactly happens with the angles between stable and unstable manifolds during the whole evolution, a big-data information permanently erased by repeated orthogonalizations. Here, we study changes of angles between invariant subspaces as observed during temporal evolution of Hénon’s system. Such angles are calculated numerically and analytically and used to characterize self-similarity of a chaotic attractor. In addition, we show how standard tools of dynamical systems may be angle-enhanced by dressing them with informations not difficult to extract. Such angle-enhanced tools reveal unexpected and practical facts that are described in detail. For instance, we present a video showing an angle-enhanced bifurcation diagram that exposes from several perspectives the complex geometrical features underlying the attractors. We believe such findings to be generic for extended classes of systems.

Automatic near-real-time detection of CMEs in Mauna Loa K-Cor coronagraph images

NASA Astrophysics Data System (ADS)

Thompson, W. T.; St Cyr, O. C.; Burkepile, J.; Posner, A.

2017-12-01

A simple algorithm has been developed to detect the onset of coronal massejections (CMEs), together with an estimate of their speed, in near-real-timeusing images of the linearly polarized white-light solar corona taken by theK-Cor telescope at the Mauna Loa Solar Observatory (MLSO). The algorithm usedis a variation on the Solar Eruptive Event Detection System (SEEDS) developedat George Mason University. The algorithm was tested against K-Cor data takenbetween 29 April 2014 and 20 February 2017, on days which the MLSO websitemarked as containing CMEs. This resulted in testing of 139 days worth of datacontaining 171 CMEs. The detection rate varied from close to 80% in 2014-2015when solar activity was high, down to as low as 20-30% in 2017 when activitywas low. The difference in effectiveness with solar cycle is attributed to thedifference in relative prevalance of strong CMEs between active and quietperiods. There were also twelve false detections during this time period,leading to an average false detection rate of 8.6% on any given day. However,half of the false detections were clustered into two short periods of a fewdays each when special conditions prevailed to increase the false detectionrate. The K-Cor data were also compared with major Solar Energetic Particle(SEP) storms during this time period. There were three SEP events detectedeither at Earth or at one of the two STEREO spacecraft where K-Cor wasobserving during the relevant time period. The K-Cor CME detection algorithmsuccessfully generated alerts for two of these events, with lead times of 1-3hours before the SEP onset at 1 AU. The third event was not detected by theautomatic algorithm because of the unusually broad width of the CME in positionangle.

Remote-controlled pan, tilt, zoom cameras at Kilauea and Mauna Loa Volcanoes, Hawai'i

USGS Publications Warehouse

Hoblitt, Richard P.; Orr, Tim R.; Castella, Frederic; Cervelli, Peter F.

2008-01-01

Lists of important volcano-monitoring disciplines usually include seismology, geodesy, and gas geochemistry. Visual monitoring - the essence of volcanology - is usually not mentioned. Yet, observations of the outward appearance of a volcano provide data that is equally as important as that provided by the other disciplines. The eye was almost certainly the first volcano monitoring-tool used by early man. Early volcanology was mostly descriptive and was based on careful visual observations of volcanoes. There is still no substitute for the eye of an experienced volcanologist. Today, scientific instruments replace or augment our senses as monitoring tools because instruments are faster and more sensitive, work tirelessly day and night, keep better records, operate in hazardous environments, do not generate lawsuits when damaged or destroyed, and in most cases are cheaper. Furthermore, instruments are capable of detecting phenomena that are outside the reach of our senses. The human eye is now augmented by the camera. Sequences of timed images provide a record of visual phenomena that occur on and above the surface of volcanoes. Photographic monitoring is a fundamental monitoring tool; image sequences can often provide the basis for interpreting other data streams. Monitoring data are most useful when they are generated and are available for analysis in real-time or near real-time. This report describes the current (as of 2006) system for real-time photograph acquisition and transmission from remote sites on Kilauea and Mauna Loa volcanoes to the U.S. Geological Survey Hawaiian Volcano Observatory (HVO). It also describes how the photographs are archived and analyzed. In addition to providing system documentation for HVO, we hope that the report will prove useful as a practical guide to the construction of a high-bandwidth network for the telemetry of real-time data from remote locations.

Comparison of Inflation Processes at the 1859 Mauna Loa Flow, HI, and the McCartys Flow Field, NM

NASA Technical Reports Server (NTRS)

Bleacher, Jacob E.; Garry, W. Brent; Zimbelman, James R.; Crumpler, Larry S.

2012-01-01

Basaltic lavas typically form channels or tubes during flow emplacement. However, the importance of sheet flow in the development of basalt ic terrains received recognition over the last 15 years. George Walke r?s research on the 1859 Mauna Loa Flow was published posthumously in 2009. In this paper he discusses the concept of endogenous growth, or inflation, for the distal portion of this otherwise channeldominated lava flow. We used this work as a guide when visiting the 1859 flow to help us better interpret the inflation history of the McCartys flow field in NM. Both well preserved flows display similar clues about the process of inflation. The McCartys lava flow field is among the you ngest (approx.3000 yrs) basaltic lava flows in the continental United States. It was emplaced over slopes of <1 degree, which is similar to the location within the 1859 flow where inflation occurred. Although older than the 1859 flow, the McCartys is located in an arid environ ment and is among the most pristine examples of sheet flow morphologies. At the meter scale the flow surface typically forms smooth, undula ting swales that create a polygonal terrain. The literature for simil ar features includes multiple explanatory hypotheses, original breakouts from adjacent lobes, or inflation related upwarping of crust or sa gging along fractures that enable gas release. It is not clear which of these processes is responsible for polygonal terrains, and it is po ssible that one explanation is not the sole cause of this morphology between all inflated flows. Often, these smooth surfaces within an inflated sheet display lineated surfaces and occasional squeeze-ups alon g swale contacts. We interpret the lineations to preserve original fl ow direction and have begun mapping these orientations to better interpret the emplacement history. At the scale of 10s to 100s of meters t he flow comprises multiple topographic plateaus and depressions. Some depressions display level floors with

Setting the magic angle for fast magic-angle spinning probes.

PubMed

Penzel, Susanne; Smith, Albert A; Ernst, Matthias; Meier, Beat H

2018-06-15

Fast magic-angle spinning, coupled with 1 H detection is a powerful method to improve spectral resolution and signal to noise in solid-state NMR spectra. Commercial probes now provide spinning frequencies in excess of 100 kHz. Then, one has sufficient resolution in the 1 H dimension to directly detect protons, which have a gyromagnetic ratio approximately four times larger than 13 C spins. However, the gains in sensitivity can quickly be lost if the rotation angle is not set precisely. The most common method of magic-angle calibration is to optimize the number of rotary echoes, or sideband intensity, observed on a sample of KBr. However, this typically uses relatively low spinning frequencies, where the spinning of fast-MAS probes is often unstable, and detection on the 13 C channel, for which fast-MAS probes are typically not optimized. Therefore, we compare the KBr-based optimization of the magic angle with two alternative approaches: optimization of the splitting observed in 13 C-labeled glycine-ethylester on the carbonyl due to the Cα-C' J-coupling, or optimization of the H-N J-coupling spin echo in the protein sample itself. The latter method has the particular advantage that no separate sample is necessary for the magic-angle optimization. Copyright © 2018. Published by Elsevier Inc.

A Different Angle on Perspective

ERIC Educational Resources Information Center

Frantz, Marc

2012-01-01

When a plane figure is photographed from different viewpoints, lengths and angles appear distorted. Hence it is often assumed that lengths, angles, protractors, and compasses have no place in projective geometry. Here we describe a sense in which certain angles are preserved by projective transformations. These angles can be constructed with…

A Comparison of Aircraft and Ground-Based Measurements at Mauna Loa Observatory, Hawaii, During GTE PEM-West and MLOPEX 2

NASA Technical Reports Server (NTRS)

Atlas, E.; Ridley, B.; Walega, J.; Greenberg, J.; Kok, G.; Staffelbach, T.; Schauffler, S.; Lind, J.; Huebler, G.; Norton, R.

1996-01-01

During October 19-20, 1991, one flight of the NASA Global Tropospheric Experiment (GTE) Pacific Exploratory Mission (PEM-West A) mission was conducted near Hawaii as an intercomparison with ground-based measurements of the Mauna Loa Observatory Photochemistry Experiment (MLOPEX 2) and the NOAA Climate Modeling and Diagnostics Laboratory (CMDL). Ozone, reactive nitrogen species, peroxides, hydrocarbons, and halogenated hydrocarbons were measured by investigators aboard the DC-8 aircraft and at the ground site. Lidar cross sections of ozone revealed a complex air mass structure near the island of Hawaii which was evidenced by large variation in some trace gas mixing ratios. This variation limited the time and spatial scales for direct measurement intercomparisons. Where differences occurred between measurements in the same air masses, the intercomparison suggested that biases for some trace gases was due to different calibration scales or, in some cases, instrumental or sampling biases. Relatively large uncertainties were associated with those trace gases present in the low parts per trillion by volume range. Trace gas correlations were used to expand the scope of the intercomparison to identify consistent trends between the different data sets.

The gonial angle stripper: an instrument for the treatment of prominent gonial angle.

PubMed

Kyutoku, S; Yanagida, A; Kusumoto, K; Ogawa, Y

1994-12-01

In the Orient, a prominent gonial angle, so-called benign masseteric hypertrophy, is rather common and considered unattractive. Therefore, its surgical correction is one of the most popular forms of facial skeletal contouring. For accurate and safe osteotomy of the mandibular angle region, a gonial angle stripper was specially invented. It has a small projection that will ease identification of the osteotomy line in a narrow operative field. The tool has been clinically used in eight patients to prove its usefulness, especially for a posteriorly developed mandibular angle.

Using Mauna Loa Atmospheric CO2 Data in Large General Education Geoscience Courses

NASA Astrophysics Data System (ADS)

Richardson, R. M.; Kapp, J. L.

2007-12-01

We have been using the Mauna Loa atmospheric CO2 dataset (http://scrippsco2.ucsd.edu/data/in_situ_co2/monthly_mlo.csv) in a large (up to 300) General Education Geoscience course, primarily in small breakout groups (30 students). The exercise is designed to address quantitative literacy including percentages, slopes and linear trends, issues of data completeness and bias, quality of extrapolations, as well as implications for climate change. We are significantly revising the course, which serves 600 students a semester, with help from a curriculum grant. A major goal is to improve student learning by incorporating inquiry based activities in the large lecture setting. Lectures now incorporate several activities throughout a given class period, in which students are asked to use critical thinking skills such as interpreting patterns in data and graphs, analyzing a scientific hypothesis for its coherence with the scientific method, and answering higher order synthesis questions in both verbal and written form. This differs from our past format where class periods were dominated by lecture, with a single short activity done individually about every other lecture. To test the effectiveness of the new course format we will give students the same atmospheric CO2 exercise in the lecture setting that they were given previously in breakout groups. Students will work in small groups in lecture after receiving a short introduction to the exercise by the instructor. They will plot CO2 concentrations, make extrapolations, and interpret patterns in the data. We will compare scores on the exercise with previous semesters. We expect that students will do better having had more experience with interpreting scientific data and practicing higher order thinking skills. We also expect working in small groups will foster better learning through peer teaching and discussion. We will incorporate responses from students who took part in the exercises from current and previous semesters. We

Formaldehyde methods comparison in the remote lower troposphere during the Mauna Loa Photochemistry Experiment 2

NASA Astrophysics Data System (ADS)

Heikes, B.; McCully, B.; Zhou, X.; Lee, Y.-N.; Mopper, K.; Chen, X.; Mackay, G.; Karecki, D.; Schiff, H.; Campos, T.; Atlas, E.

1996-06-01

Five methods for the measurement of CH2O vapor were compared under remote tropospheric conditions. The techniques included an aqueous-scrubber enzyme fluorescence method (URIcoil), TDLAS (UNI), 2,4-dinitrophenylhydrazine (DNPH) impregnated-cartridges (BNL/WSUcart), an aqueous-scrubber DNPH method (BNL/WSUcoil), and an unpublished aqueous-scrubber immobilized-enzyme fluorescence method (NCARbound). This was part of the Mauna Loa Observatory Photochemistry Experiment 2 (MLOPEX 2) which was performed in four ˜30-day intensives. In MLOPEX 2a (fall 1991), the URIcoil technique indicated higher concentrations relative to the BNL/WSUcoil which were higher than UNI. The limited number of NCARbound measurements for MLOPEX 2a were greater than the other measurements and least reliable. During MLOPEX 2b (winter 1992), URIcoil, UNI, BNL/WSUcoil, and NCAR-bound gave comparable measurements of CH2O with the latter again being consistently higher than the first three methods and its performance and reliability was improved over MLOPEX 2a. URIcoil and BNL/WSUcoil were comparable in MLOPEX 2c (spring 1992) and 2d (summer 1992), whereas BNL/WSUcart was consistently higher than both for these intensives. The major source of difference between techniques was ascribed to variations in the analytical-procedural field blanks. Calibration differences were the most likely cause of URIcoil being higher than BNL/WSUcoil and BNL/WSUcoil being higher than UNI during MLOPEX 2a. Lower free troposphere median concentrations were between 100 and 150 ppt for all seasons and without a seasonal trend. These values were a factor of 2 to 3 lower than model estimates for this study site and were in keeping with earlier work.

Angle-stable and compressed angle-stable locking for tibiotalocalcaneal arthrodesis with retrograde intramedullary nails. Biomechanical evaluation.

PubMed

Mückley, Thomas; Hoffmeier, Konrad; Klos, Kajetan; Petrovitch, Alexander; von Oldenburg, Geert; Hofmann, Gunther O

2008-03-01

Retrograde intramedullary nailing is an established procedure for tibiotalocalcaneal arthrodesis. The goal of this study was to evaluate the effects of angle-stable locking or compressed angle-stable locking on the initial stability of the nails and on the behavior of the constructs under cyclic loading conditions. Tibiotalocalcaneal arthrodesis was performed in fifteen third-generation synthetic bones and twenty-four fresh-frozen cadaver legs with use of retrograde intramedullary nailing with three different locking modes: a Stryker nail with compressed angle-stable locking, a Stryker nail with angle-stable locking, and a statically locked Biomet nail. Analyses were performed of the initial stability of the specimens (range of motion) and the laxity of the constructs (neutral zone) in dorsiflexion/plantar flexion, varus/valgus, and external rotation/internal rotation. Cyclic testing up to 100,000 cycles was also performed. The range of motion and the neutral zone in dorsiflexion/plantar flexion at specific cycle increments were determined. In both bone models, the intramedullary nails with compressed angle-stable locking and those with angle-stable locking were significantly superior, in terms of a smaller range of motion and neutral zone, to the statically locked nails. The compressed angle-stable nails were superior to the angle-stable nails only in the synthetic bone model, in external/internal rotation. Cyclic testing showed the nails with angle-stable locking and those with compressed angle-stable locking to have greater stability in both models. In the synthetic bone model, compressed angle-stable locking was significantly better than angle-stable locking; in the cadaver bone model, there was no significant difference between these two locking modes. During cyclic testing, five statically locked nails in the cadaver bone model failed, whereas one nail with angle-stable locking and one with compressed angle-stable locking failed. Regardless of the bone model

Survival and Growth of Cottonwood Clones After Angle Planting and Base Angle Treatments

Treesearch

W.K. Randall; Harvey E. Kennedy

1976-01-01

Presently, commercial cottonwood plantations in the lower Mississippi Valley are established using vertically planted, unrooted cuttings with a flat (90°) base. Neither survival nor first-year growth of a group of six Stoneville clones was improved by angle planting or cutting base angles diagonally. For one clone, survival was significantly better when base angle was...

Anaerobically Grown Escherichia coli Has an Enhanced Mutation Rate and Distinct Mutational Spectra

PubMed Central

Shewaramani, Sonal; Finn, Thomas J.; Kassen, Rees; Rainey, Paul B.

2017-01-01

Oxidative stress is a major cause of mutation but little is known about how growth in the absence of oxygen impacts the rate and spectrum of mutations. We employed long-term mutation accumulation experiments to directly measure the rates and spectra of spontaneous mutation events in Escherichia coli populations propagated under aerobic and anaerobic conditions. To detect mutations, whole genome sequencing was coupled with methods of analysis sufficient to identify a broad range of mutational classes, including structural variants (SVs) generated by movement of repetitive elements. The anaerobically grown populations displayed a mutation rate nearly twice that of the aerobic populations, showed distinct asymmetric mutational strand biases, and greater insertion element activity. Consistent with mutation rate and spectra observations, genes for transposition and recombination repair associated with SVs were up-regulated during anaerobic growth. Together, these results define differences in mutational spectra affecting the evolution of facultative anaerobes. PMID:28103245

Quality assurance of the UV irradiances of the UV-B Monitoring and Research Program: the Mauna Loa test case

NASA Astrophysics Data System (ADS)

Zempila, Melina Maria; Davis, John; Janson, George; Olson, Becky; Chen, Maosi; Durham, Bill; Simpson, Scott; Straube, Jonathan; Sun, Zhibin; Gao, Wei

2017-09-01

The USDA UV-B Monitoring and Research Program (UVMRP) is an ongoing effort aiming to establish a valuable, longstanding database of ground-based ultraviolet (UV) solar radiation measurements over the US. Furthermore, the program aims to achieve a better understanding of UV variations through time, and develop a UV climatology for the Northern American section. By providing high quality radiometric measurements of UV solar radiation, UVMRP is also focusing on advancing science for agricultural, forest, and range systems in order to mitigate climate impacts. Within these foci, the goal of the present study is to investigate, analyze, and validate the accuracy of the measurements of the UV multi-filter rotating shadowband radiometer (UV-MFRSR) and Yankee (YES) UVB-1 sensor at the high altitude, pristine site at Mauna Loa, Hawaii. The response-weighted irradiances at 7 UV channels of the UV-MFRSR along with the erythemal dose rates from the UVB-1 radiometer are discussed, and evaluated for the period 2006-2015. Uncertainties during the calibration procedures are also analyzed, while collocated groundbased measurements from a Brewer spectrophotometer along with model simulations are used as a baseline for the validation of the data. Besides this quantitative research, the limitations and merits of the existing UVMRP methods are considered and further improvements are introduced.

Photoelectric angle converter

NASA Astrophysics Data System (ADS)

Podzharenko, Volodymyr A.; Kulakov, Pavlo I.

2001-06-01

The photo-electric angle transmitter of rotation is offered, at which the output voltage is linear function of entering magnitude. In a transmitter the linear phototransducer is used on the basis of pair photo diode -- operating amplifier, which output voltage is linear function of the area of an illuminated photosensitive stratum, and modulator of a light stream of the special shape, which ensures a linear dependence of this area from an angle of rotation. The transmitter has good frequent properties and can be used for dynamic measurements of an angular velocity and angle of rotation, in systems of exact drives and systems of autocontrol.

Fiber orientation measurements by diffusion tensor imaging improve hydrogen-1 magnetic resonance spectroscopy of intramyocellular lipids in human leg muscles.

PubMed

Valaparla, Sunil K; Gao, Feng; Daniele, Giuseppe; Abdul-Ghani, Muhammad; Clarke, Geoffrey D

2015-04-01

Twelve healthy subjects underwent hydrogen-1 magnetic resonance spectroscopy ([Formula: see text]) acquisition ([Formula: see text]), diffusion tensor imaging (DTI) with a [Formula: see text]-value of [Formula: see text], and fat-water magnetic resonance imaging (MRI) using the Dixon method. Subject-specific muscle fiber orientation, derived from DTI, was used to estimate the lipid proton spectral chemical shift. Pennation angles were measured as 23.78 deg in vastus lateralis (VL), 17.06 deg in soleus (SO), and 8.49 deg in tibialis anterior (TA) resulting in a chemical shift between extramyocellular lipids (EMCL) and intramyocellular lipids (IMCL) of 0.15, 0.17, and 0.19 ppm, respectively. IMCL concentrations were [Formula: see text], [Formula: see text], and [Formula: see text] in SO, VL, and TA, respectively. Significant differences were observed in IMCL and EMCL pairwise comparisons in SO, VL, and TA ([Formula: see text]). Strong correlations were observed between total fat fractions from [Formula: see text] and Dixon MRI for VL ([Formula: see text]), SO ([Formula: see text]), and TA ([Formula: see text]). Bland-Altman analysis between fat fractions (FFMRS and FFMRI) showed good agreement with small limits of agreement (LoA): [Formula: see text] (LoA: [Formula: see text] to 0.69%) in VL, [Formula: see text] (LoA: [Formula: see text] to 1.33%) in SO, and [Formula: see text] (LoA: [Formula: see text] to 0.47%) in TA. The results of this study demonstrate the variation in muscle fiber orientation and lipid concentrations in these three skeletal muscle types.

Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations.

PubMed

Setia, Nitika; Saxena, Renu; Arora, Anjali; Verma, Ishwar C

2016-12-01

Homozygous familial hypercholesterolemia (FH) is a rare but serious, inherited disorder of lipid metabolism characterized by very high total and LDL cholesterol levels from birth. It presents as cutaneous and tendon xanthomas since childhood, with or without cardiac involvement. FH is commonly caused by mutations in three genes, i.e. LDL receptor (LDLR), apolipoprotein B (ApoB) and PCSK9. We aimed to determine the spectrum of mutations in cases of homozygous FH in Asian Indians and evaluate if there was any similarity to the mutations observed in Caucasians. Sixteen homozygous FH subjects from eleven families were analyzed for mutations by Sanger sequencing. Large rearrangements in LDLR gene were evaluated by multiplex ligation probe dependent amplification (MLPA) technique. Ten mutations were observed in LDLR gene, of which four mutations were novel. No mutation was detected in ApoB gene and common PCSK9 mutation (p.D374Y). Fourteen cases had homozygous mutations; one had compound heterozygous mutation, while no mutation was detected in one clinically homozygous case. We report an interesting "Triple hit" case with features of homozygous FH. The spectrum of mutations in the Asian Indian population is quite heterogeneous. Of the mutations identified, 40% were novel. No mutation was observed in exons 3, 9 and 14 of LDLR gene, which are considered to be hot spots in studies done on Asian Indians in South Africa. Early detection followed by aggressive therapy, and cascade screening of extended families has been initiated to reduce the morbidity and mortality in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The CDC Hemophilia A Mutation Project (CHAMP) Mutation List: a New Online Resource

PubMed Central

Payne, Amanda B.; Miller, Connie H.; Kelly, Fiona M.; Soucie, J. Michael; Hooper, W. Craig

2015-01-01

Genotyping efforts in hemophilia A (HA) populations in many countries have identified large numbers of unique mutations in the Factor VIII gene (F8). To assist HA researchers conducting genotyping analyses, we have developed a listing of F8 mutations including those listed in existing locus-specific databases as well as those identified in patient populations and reported in the literature. Each mutation was reviewed and uniquely identified using Human Genome Variation Society (HGVS) nomenclature standards for coding DNA and predicted protein changes as well as traditional nomenclature based on the mature, processed protein. Listings also include the associated hemophilia severity classified by International Society of Thrombosis and Haemostasis (ISTH) criteria, associations of the mutations with inhibitors, and reference information. The mutation list currently contains 2,537 unique mutations known to cause HA. HA severity caused by the mutation is available for 2,022 mutations (80%) and information on inhibitors is available for 1,816 mutations (72%). The CDC Hemophilia A Mutation Project (CHAMP) Mutation List is available at http://www.cdc.gov/hemophiliamutations for download and search and will be updated quarterly based on periodic literature reviews and submitted reports. PMID:23280990

Modulation of HIV Protease Flexibility by the T80N Mutation

PubMed Central

Zhou, Hao; Li, Shangyang; Badger, John; Nalivaika, Ellen; Cai, Yufeng; Foulkes-Murzycki, Jennifer; Schiffer, Celia; Makowski, Lee

2015-01-01

The flexibility of HIV protease plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80 which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle scattering (WAXS) data was measured for a series of HIV protease variants. Starting with a calculated WAXS pattern from a rigid atomic model, the modulations in the intensity distribution caused by structural fluctuations in the protein were predicted by simple analytic methods and compared to the experimental data. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. The effects of this single point mutation extend throughout the protein, so as to alter the mobility of amino acids in the enzymatic core. These results support the contentions that significant protein flexibility extends throughout HIV protease and is critical to catalytic function. PMID:25488402

The effects of mutational processes and selection on driver mutations across cancer types.

PubMed

Temko, Daniel; Tomlinson, Ian P M; Severini, Simone; Schuster-Böckler, Benjamin; Graham, Trevor A

2018-05-10

Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data from 11,336 cancers of various types to infer the independent effects of mutation and selection on the set of driver mutations in a cancer type. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes have a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates.

Parkin dosage mutations have greater pathogenicity in familial PD than simple sequence mutations

PubMed Central

Pankratz, N; Kissell, D K.; Pauciulo, M W.; Halter, C A.; Rudolph, A; Pfeiffer, R F.; Marder, K S.; Foroud, T; Nichols, W C.

2009-01-01

Objective: Mutations in both alleles of parkin have been shown to result in Parkinson disease (PD). However, it is unclear whether haploinsufficiency (presence of a mutation in only 1 of the 2 parkin alleles) increases the risk for PD. Methods: We performed comprehensive dosage and sequence analysis of all 12 exons of parkin in a sample of 520 independent patients with familial PD and 263 controls. We evaluated whether presence of a single parkin mutation, either a sequence (point mutation or small insertion/deletion) or dosage (whole exon deletion or duplication) mutation, was found at increased frequency in cases as compared with controls. We then compared the clinical characteristics of cases with 0, 1, or 2 parkin mutations. Results: We identified 55 independent patients with PD with at least 1 parkin mutation and 9 controls with a single sequence mutation. Cases and controls had a similar frequency of single sequence mutations (3.1% vs 3.4%, p = 0.83); however, the cases had a significantly higher rate of dosage mutations (2.6% vs 0%, p = 0.009). Cases with a single dosage mutation were more likely to have an earlier age at onset (50% with onset at ≤45 years) compared with those with no parkin mutations (10%, p = 0.00002); this was not true for cases with only a single sequence mutation (25% with onset at ≤45 years, p = 0.06). Conclusions: Parkin haploinsufficiency, specifically for a dosage mutation rather than a point mutation or small insertion/deletion, is a risk factor for familial PD and may be associated with earlier age at onset. GLOSSARY ADL = Activities of Daily Living; GDS = Geriatric Depression Scale; MLPA = multiplex ligation-dependent probe amplification; MMSE = Mini-Mental State Examination; PD = Parkinson disease; UPDRS = Unified Parkinson’s Disease Rating Scale. PMID:19636047

Sharper angle, higher risk? The effect of cutting angle on knee mechanics in invasion sport athletes.

PubMed

Schreurs, Mervin J; Benjaminse, Anne; Lemmink, Koen A P M

2017-10-03

Cutting is an important skill in team-sports, but unfortunately is also related to non-contact ACL injuries. The purpose was to examine knee kinetics and kinematics at different cutting angles. 13 males and 16 females performed cuts at different angles (45°, 90°, 135° and 180°) at maximum speed. 3D kinematics and kinetics were collected. To determine differences across cutting angles (45°, 90°, 135° and 180°) and sex (female, male), a 4×2 repeated measures ANOVA was conducted followed by post hoc comparisons (Bonferroni) with alpha level set at α≤0.05a priori. At all cutting angles, males showed greater knee flexion angles than females (p<0.01). Also, where males performed all cutting angles with no differences in the amount of knee flexion -42.53°±8.95°, females decreased their knee flexion angle from -40.6°±7.2° when cutting at 45° to -36.81°±9.10° when cutting at 90°, 135° and 180° (p<0.01). Knee flexion moment decreased for both sexes when cutting towards sharper angles (p<0.05). At 90°, 135° and 180°, males showed greater knee valgus moments than females. For both sexes, knee valgus moment increased towards the sharper cutting angles and then stabilized compared to the 45° cutting angle (p<0.01). Both females and males showed smaller vGRF when cutting to sharper angles (p<0.01). It can be concluded that different cutting angles demand different knee kinematics and kinetics. Sharper cutting angles place the knee more at risk. However, females and males handle this differently, which has implications for injury prevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer

PubMed Central

Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L.

2016-01-01

The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. PMID:26590264

Behavior of Tilted Angle Shear Connectors.

PubMed

Khorramian, Koosha; Maleki, Shervin; Shariati, Mahdi; Ramli Sulong, N H

2015-01-01

According to recent researches, angle shear connectors are appropriate to transfer longitudinal shear forces across the steel-concrete interface. Angle steel profile has been used in different positions as L-shaped or C-shaped shear connectors. The application of angle shear connectors in tilted positions is of interest in this study. This study investigates the behaviour of tilted-shaped angle shear connectors under monotonic loading using experimental push out tests. Eight push-out specimens are tested to investigate the effects of different angle parameters on the ultimate load capacity of connectors. Two different tilted angles of 112.5 and 135 degrees between the angle leg and steel beam are considered. In addition, angle sizes and lengths are varied. Two different failure modes were observed consisting of concrete crushing-splitting and connector fracture. By increasing the size of connector, the maximum load increased for most cases. In general, the 135 degrees tilted angle shear connectors have a higher strength and stiffness than the 112.5 degrees type.

The R403Q Myosin Mutation Implicated in Familial Hypertrophic Cardiomyopathy Causes Disorder at the Actomyosin Interface

PubMed Central

Volkmann, Niels; Lui, HongJun; Hazelwood, Larnele; Trybus, Kathleen M.; Lowey, Susan; Hanein, Dorit

2007-01-01

Background Mutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC). Mutations in the β-myosin heavy chain (MHC) remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype. Principal Findings Here we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1), whose kinetic features have much in common with slow β-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP) and absence (apo) of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface. Significance These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state. PMID:17987111

AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance.

PubMed

Spanakis, Elias; Milord, Edrice; Gragnoli, Claudia

2008-12-01

Almost 90% of nephrogenic diabetes insipidus (NDI) is due to mutations in the arginine-vasopressin receptor 2 gene (AVPR2). We retrospectively examined all the published mutations/variants in AVPR2. We planned to perform a comprehensive review of all the AVPR2 mutations/variants and to test whether any amino acid change causing a missense mutation is significantly more or less common than others. We performed a Medline search and collected detailed information regarding all AVPR2 mutations and variants. We performed a frequency comparison between mutated and wild-type amino acids and codons. We predicted the mutation effect or reported it based on published in vitro studies. We also reported the ethnicity of each mutation/variant carrier. In summary, we identified 211 AVPR2 mutations which cause NDI in 326 families and 21 variants which do not cause NDI in 71 NDI families. We described 15 different types of mutations including missense, frameshift, inframe deletion, deletion, insertion, nonsense, duplication, splicing and combined mutations. The missense mutations represent the 55.83% of all the NDI published families. Arginine and tyrosine are significantly (P = 4.07E-08 and P = 3.27E-04, respectively) the AVPR2 most commonly mutated amino acids. Alanine and glutamate are significantly (P = 0.009 and P = 0.019, respectively) the least mutated AVPR2 amino acids. The spectrum of mutations varies from rare gene variants or polymorphisms not causing NDI to rare mutations causing NDI, among which arginine and tyrosine are the most common missense. The AVPR2 mutations are spread world-wide. Our study may serve as an updated review, comprehensive of all AVPR2 variants and specific gene locations. J. Cell. Physiol. 217: 605-617, 2008. (c) 2008 Wiley-Liss, Inc.

Mutations, mutation rates, and evolution at the hypervariable VNTR loci of Yersinia pestis.

PubMed

Vogler, Amy J; Keys, Christine E; Allender, Christopher; Bailey, Ira; Girard, Jessica; Pearson, Talima; Smith, Kimothy L; Wagner, David M; Keim, Paul

2007-03-01

VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing approximately 96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database.

Mechanisms of viral mutation.

PubMed

Sanjuán, Rafael; Domingo-Calap, Pilar

2016-12-01

The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.

MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer.

PubMed

Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L

2016-01-04

The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population

PubMed Central

Millá, Elena; Mañé, Begoña; Duch, Susana; Hernan, Imma; Borràs, Emma; Planas, Ester; Dias, Miguel de Sousa; Carballo, Miguel

2013-01-01

Purpose To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). Methods Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. Results We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). Conclusions The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1. PMID:23922489

Growth Angle - a Microscopic View

NASA Technical Reports Server (NTRS)

Mazurak, K.; Volz, M. P.; Croll, A.

2017-01-01

The growth angle that is formed between the side of the growing crystal and the melt meniscus is an important parameter in the detached Bridgman crystal growth method, where it determines the extent of the crystal-crucible wall gap, and in the Czochralski and float zone methods, where it influences the size and stability of the crystals. The growth angle is a non-equilibrium parameter, defined for the crystal growth process only. For a melt-crystal interface translating towards the crystal (melting), there is no specific angle defined between the melt and the sidewall of the solid. In this case, the corner at the triple line becomes rounded, and the angle between the sidewall and the incipience of meniscus can take a number of values, depending on the position of the triple line. In this work, a microscopic model is developed in which the fluid interacts with the solid surface through long range van der Waals or Casimir dispersive forces. This growth angle model is applied to Si and Ge and compared with the macroscopic approach of Herring. In the limit of a rounded corner with a large radius of curvature, the wetting of the melt on the crystal is defined by the contact angle. The proposed microscopic approach addresses the interesting issue of the transition from a contact angle to a growth angle as the radius of curvature decreases.

Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation

PubMed Central

Fedyna, Alison; Drayna, Dennis; Kang, Changsoo

2010-01-01

Stuttering is a disorder which affects the fluency of speech. It has been shown to have high heritability, and has recently been linked to mutations in the GNPTAB gene. One such mutation, Glu1200Lys, has been repeatedly observed in unrelated families and individual cases. Eight unrelated individuals carrying this mutation were analyzed in an effort to distinguish whether these arise from repeated mutation at the same site, or whether they represent a founder mutation with a single origin. Results show that all 12 chromosomes carrying this mutation share a common haplotype in this region, indicating it is a founder mutation. Further analysis estimated the age of this allele to be ~572 generations. Construction of a cladogram tracing the mutation through our study sample also supports the founder mutation hypothesis. PMID:20944643

Behavior of Tilted Angle Shear Connectors

PubMed Central

Khorramian, Koosha; Maleki, Shervin; Shariati, Mahdi; Ramli Sulong, N. H.

2015-01-01

According to recent researches, angle shear connectors are appropriate to transfer longitudinal shear forces across the steel-concrete interface. Angle steel profile has been used in different positions as L-shaped or C-shaped shear connectors. The application of angle shear connectors in tilted positions is of interest in this study. This study investigates the behaviour of tilted-shaped angle shear connectors under monotonic loading using experimental push out tests. Eight push-out specimens are tested to investigate the effects of different angle parameters on the ultimate load capacity of connectors. Two different tilted angles of 112.5 and 135 degrees between the angle leg and steel beam are considered. In addition, angle sizes and lengths are varied. Two different failure modes were observed consisting of concrete crushing-splitting and connector fracture. By increasing the size of connector, the maximum load increased for most cases. In general, the 135 degrees tilted angle shear connectors have a higher strength and stiffness than the 112.5 degrees type. PMID:26642193

Monoallelic mutation analysis (MAMA) for identifying germline mutations.

PubMed

Papadopoulos, N; Leach, F S; Kinzler, K W; Vogelstein, B

1995-09-01

Dissection of germline mutations in a sensitive and specific manner presents a continuing challenge. In dominantly inherited diseases, mutations occur in only one allele and are often masked by the normal allele. Here we report the development of a sensitive and specific diagnostic strategy based on somatic cell hybridization termed MAMA (monoallelic mutation analysis). We have demonstrated the utility of this strategy in two different hereditary colorectal cancer syndromes, one caused by a defective tumour suppressor gene on chromosome 5 (familial adenomatous polyposis, FAP) and the other caused by a defective mismatch repair gene on chromosome 2 (hereditary non-polyposis colorectal cancer, HNPCC).

View angle effect in LANDSAT imagery

NASA Technical Reports Server (NTRS)

Kaneko, T.; Engvall, J. L.

1977-01-01

The view angle effect in LANDSAT 2 imagery was investigated. The LANDSAT multispectral scanner scans over a range of view angles of -5.78 to 5.78 degrees. The view angle effect, which is caused by differing view angles, could be studied by comparing data collected at different view angles over a fixed location at a fixed time. Since such LANDSAT data is not available, consecutive day acquisition data were used as a substitute: they were collected over the same geographical location, acquired 24 hours apart, with a view angle change of 7 to 8 degrees at a latitude of 35 to 45 degrees. It is shown that there is approximately a 5% reduction in the average sensor response on the second-day acquisitions as compared with the first-day acquisitions, and that the view angle effect differs field to field and crop to crop. On false infrared color pictures the view angle effect causes changes primarily in brightness and to a lesser degree in color (hue and saturation). An implication is that caution must be taken when images with different view angles are combined for classification and a signature extension technique needs to take the view angle effect into account.

An application of the lottery competition model to a montane rainforest community of two canopy trees, ohia (Metrosideros polymorpha) and koa (Acacia koa) on Mauna Loa, Hawaii

USGS Publications Warehouse

Hatfield, J.S.; Link, W.A.; Dawson, D.K.; Lindquist, E.L.

1992-01-01

This rainforest occurs on Mauna Loa at 1500-2000 m elevation. Earthwatch volunteers, studying the habitat of 8 native forest bird species (3 endangered), identified 2382 living canopy trees, and 99 dead trees, on 68 study plots, 400 m2 each. Ohia made up 88% of the canopy; koa was 12%. The two-species lottery competition model, a stochastic model in which coexistence of species results from variation in recruitment and death rates, predicts a quadratic-beta distribution for the proportion of space occupied by one species. A discrete version was fit to the live tree data and a likelihood ratio test (p=0.02) was used to test if the mean death rates were equal. This test was corroborated by a contingency table analysis (p=0.03) based on dead trees. Parameter estimates from the two analyses were similar.

Demonstration of angle widening using EyeCam after laser peripheral iridotomy in eyes with angle closure.

PubMed

Perera, Shamira A; Quek, Desmond T; Baskaran, Mani; Tun, Tin A; Kumar, Rajesh S; Friedman, David S; Aung, Tin

2010-06-01

To evaluate EyeCam in detecting changes in angle configuration after laser peripheral iridotomy (LPI) in comparison to gonioscopy, the reference standard. Prospective comparative study. Twenty-four subjects (24 eyes) with primary angle-closure glaucoma (PACG) were recruited. Gonioscopy and EyeCam (Clarity Medical Systems) imaging of all 4 angle quadrants were performed, before and 2 weeks after LPI. Images were graded according to angle structures visible by an observer masked to clinical data or the status of LPI, and were performed in a random order. Angle closure in a quadrant was defined as the inability to visualize the posterior trabecular meshwork. We determined the number of quadrants with closed angles and the mean number of clock hours of angle closure before and after LPI in comparison to gonioscopy. Using EyeCam, all 24 eyes showed at least 1 quadrant of angle widening after LPI. The mean number of clock hours of angle closure decreased significantly, from 8.15 +/- 3.47 clock hours before LPI to 1.75 +/- 2.27 clock hours after LPI (P < .0001, Wilcoxon signed rank test). Overall, gonioscopy showed 1.0 +/- 1.41 (95% CI, 0.43-1.57) quadrants opening from closed to open after LPI compared to 2.0 +/- 1.28 (95% CI, 1.49-2.51, P = .009) quadrants with EyeCam. Intra-observer reproducibility of grading the extent of angle closure in clock hours in EyeCam images was moderate to good (intraclass correlation coefficient 0.831). EyeCam may be used to document changes in angle configuration after LPI in eyes with PACG. Copyright 2010 Elsevier Inc. All rights reserved.

Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer.

PubMed

Yu, Jun; Wu, William K K; Li, Xiangchun; He, Jun; Li, Xiao-Xing; Ng, Simon S M; Yu, Chang; Gao, Zhibo; Yang, Jie; Li, Miao; Wang, Qiaoxiu; Liang, Qiaoyi; Pan, Yi; Tong, Joanna H; To, Ka F; Wong, Nathalie; Zhang, Ning; Chen, Jie; Lu, Youyong; Lai, Paul B S; Chan, Francis K L; Li, Yingrui; Kung, Hsiang-Fu; Yang, Huanming; Wang, Jun; Sung, Joseph J Y

2015-04-01

Characterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication. To identify recurrent somatic mutations with prognostic significance in patients with CRC. Exome sequencing was performed to identify somatic mutations in tumour tissues of 22 patients with CRC, followed by validation of 187 recurrent and pathway-related genes using targeted capture sequencing in additional 160 cases. Seven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6-14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. For prognostication, a five-gene-signature (CDH10, COL6A3, SMAD4, TMEM132D, VCAN) was devised, in which mutation(s) in one or more of these genes was significantly associated with better overall survival independent of tumor-node-metastasis (TNM) staging. The median survival time was 80.4 months in the mutant group versus 42.4 months in the wild type group (p=0.0051). The prognostic significance of this signature was successfully verified using the data set from the Cancer Genome Atlas study. The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Bilateral mandibular angle fractures: clinical considerations.

PubMed

Boffano, Paolo; Roccia, Fabio

2010-03-01

The mandibular angle is a frequent site of fracture. It is a weak zone that is more exposed to fractures than other areas of the mandibular bone. The presence of incompletely erupted third molars is associated with a further increased risk of angle fractures. Our objective was to evaluate and discuss the surgical outcomes of a group of patients with bilateral mandibular angle fractures.In our study, patients with bilateral mandibular angle fractures surgically treated from January 1, 2001, to June 30, 2009, at the Division of Maxillofacial Surgery of the University of Turin were retrospectively analyzed. A combined transbuccal and intraoral approach or an intraoral approach only was adopted.Eight patients (7 men and 1 woman) underwent surgery for bilateral mandibular angle fractures. Good to satisfactory reduction of the fractures was obtained with both surgical techniques. Good to fair restored occlusion was observed postoperatively in all patients.Successful treatment of bilateral mandibular angle fractures may be achieved via different techniques. Superficially impacted third molars seem to be associated with an increased risk of angle fractures. Bilateral angle fractures are an ideal model to study the biomechanical pathogenesis of angle fractures.

Reading angles in maps.

PubMed

Izard, Véronique; O'Donnell, Evan; Spelke, Elizabeth S

2014-01-01

Preschool children can navigate by simple geometric maps of the environment, but the nature of the geometric relations they use in map reading remains unclear. Here, children were tested specifically on their sensitivity to angle. Forty-eight children (age 47:15-53:30 months) were presented with fragments of geometric maps, in which angle sections appeared without any relevant length or distance information. Children were able to read these map fragments and compare two-dimensional to three-dimensional angles. However, this ability appeared both variable and fragile among the youngest children of the sample. These findings suggest that 4-year-old children begin to form an abstract concept of angle that applies both to two-dimensional and three-dimensional displays and that serves to interpret novel spatial symbols. © 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.

Anterior Segment Imaging for Angle Closure.

PubMed

Chansangpetch, Sunee; Rojanapongpun, Prin; Lin, Shan C

2018-04-01

To summarize the role of anterior segment imaging (AS-imaging) in angle closure diagnosis and management, and the possible advantages over the current standard of gonioscopy. Literature review and perspective. Review of the pertinent publications with interpretation and perspective in relation to the use of AS-imaging in angle closure assessment focusing on anterior segment optical coherence tomography and ultrasound biomicroscopy. Several limitations have been encountered with the reference standard of gonioscopy for angle assessment. AS-imaging has been shown to have performance in angle closure detection compared to gonioscopy. Also, imaging has greater reproducibility and serves as better documentation for long-term follow-up than conventional gonioscopy. The qualitative and quantitative information obtained from AS-imaging enables better understanding of the underlying mechanisms of angle closure and provides useful parameters for risk assessment and possible prediction of the response to laser and surgical intervention. The latest technologies-including 3-dimensional imaging-have allowed for the assessment of the angle that simulates the gonioscopic view. These advantages suggest that AS-imaging has a potential to be a reference standard for the diagnosis and monitoring of angle closure disease in the future. Although gonioscopy remains the primary method of angle assessment, AS-imaging has an increasing role in angle closure screening and management. The test should be integrated into clinical practice as an adjunctive tool for angle assessment. It is arguable that AS-imaging should be considered first-line screening for patients at risk for angle closure. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevalence of pox-like lesions and malaria in forest bird communitites on leeward Mauna Loa volcano, Hawaii

USGS Publications Warehouse

Atkinson, C.T.; Lease, J.K.; Dusek, Robert J.; Samuel, M.D.

2005-01-01

Introduced avian pox virus and malaria have had devastating impacts on native Hawaiian forest birds, yet little has been published about their prevalence and distribution in forest bird communities outside of windward Hawaii Island. We surveyed native and non-native forest birds for these two diseases at three different elevations on leeward Mauna Loa Volcano at the Kona Forest Unit of Hakalau Forest National Wildlife Refuge. Prevalence of malaria by both serology and microscopy varied by elevation and ranged from 28% at 710 m to 13% at 1830 m. Prevalence of pox-like lesions also varied by altitude, ranging in native species from 10% at 710 m to 2% at 1830 m. Native species at all elevations had the highest prevalence of malarial antibody and pox-like lesions. By contrast, pox-like lesions were not detected in individuals of four non-native species and only 5% of Japanese White-eye (Zosterops japonicus) was positive for malaria. A significantly high proportion of birds with pox-like lesions also had serological evidence of concurrent, chronic malarial infections, suggesting an interaction between these diseases, dual transmission of both diseases by the primary mosquito vector (Culex quinquefasciatus) or complete recovery of some pox-infected birds without loss of toes. Results from this study document high prevalence of malaria and pox at this refuge. Development of effective disease control strategies will be important for restoration of remnant populations of the endangered 'Akiapola'au (Hemignathus munroi), Hawaii Creeper (Oreomystis mana), and Hawaii 'Akepa (Loxops coccineus coccineus) that still occur on the refuge.

iMARS--mutation analysis reporting software: an analysis of spontaneous cII mutation spectra.

PubMed

Morgan, Claire; Lewis, Paul D

2006-01-31

The sensitivity of any mutational assay is determined by the level at which spontaneous mutations occur in the corresponding untreated controls. Establishing the type and frequency at which mutations occur naturally within a test system is essential if one is to draw scientifically sound conclusions regarding chemically induced mutations. Currently, mutation-spectra analysis is laborious and time-consuming. Thus, we have developed iMARS, a comprehensive mutation-spectrum analysis package that utilises routinely used methodologies and visualisation tools. To demonstrate the use and capabilities of iMARS, we have analysed the distribution, types and sequence context of spontaneous base substitutions derived from the cII gene mutation assay in transgenic animals. Analysis of spontaneous mutation spectra revealed variation both within and between the transgenic rodent test systems Big Blue Mouse, MutaMouse and Big Blue Rat. The most common spontaneous base substitutions were G:C-->A:T transitions and G:C-->T:A transversions. All Big Blue Mouse spectra were significantly different from each other by distribution and nearly all by mutation type, whereas the converse was true for the other test systems. Twenty-eight mutation hotspots were observed across all spectra generally occurring in CG, GA/TC, GG and GC dinucleotides. A mutation hotspot at nucleotide 212 occurred at a higher frequency in MutaMouse and Big Blue Rat. In addition, CG dinucleotides were the most mutable in all spectra except two Big Blue Mouse spectra. Thus, spontaneous base-substitution spectra showed more variation in distribution, type and sequence context in Big Blue Mouse relative to spectra derived from MutaMouse and Big Blue Rat. The results of our analysis provide a baseline reference for mutation studies utilising the cII gene in transgenic rodent models. The potential differences in spontaneous base-substitution spectra should be considered when making comparisons between these test systems

Angle-Ply Weaving

NASA Technical Reports Server (NTRS)

Farley, Gary L.

1990-01-01

Bias-direction or angle-ply weaving is proposed new process for weaving fibers along bias in conventional planar fabric or in complicated three-dimensional multilayer fabric preform of fiber-reinforced composite structure. Based upon movement of racks of needles and corresponding angle yarns across fabric as fabric being formed. Fibers woven along bias increases shear stiffness and shear strength of preform, increasing value of preform as structural member.

Wafer scale oblique angle plasma etching

DOEpatents

Burckel, David Bruce; Jarecki, Jr., Robert L.; Finnegan, Patrick Sean

2017-05-23

Wafer scale oblique angle etching of a semiconductor substrate is performed in a conventional plasma etch chamber by using a fixture that supports a multiple number of separate Faraday cages. Each cage is formed to include an angled grid surface and is positioned such that it will be positioned over a separate one of the die locations on the wafer surface when the fixture is placed over the wafer. The presence of the Faraday cages influences the local electric field surrounding each wafer die, re-shaping the local field to be disposed in alignment with the angled grid surface. The re-shaped plasma causes the reactive ions to follow a linear trajectory through the plasma sheath and angled grid surface, ultimately impinging the wafer surface at an angle. The selected geometry of the Faraday cage angled grid surface thus determines the angle at with the reactive ions will impinge the wafer.

Spinning angle optical calibration apparatus

DOEpatents

Beer, Stephen K.; Pratt, II, Harold R.

1991-01-01

An optical calibration apparatus is provided for calibrating and reproducing spinning angles in cross-polarization, nuclear magnetic resonance spectroscopy. An illuminated magnifying apparatus enables optical setting an accurate reproducing of spinning "magic angles" in cross-polarization, nuclear magnetic resonance spectroscopy experiments. A reference mark scribed on an edge of a spinning angle test sample holder is illuminated by a light source and viewed through a magnifying scope. When the "magic angle" of a sample material used as a standard is attained by varying the angular position of the sample holder, the coordinate position of the reference mark relative to a graduation or graduations on a reticle in the magnifying scope is noted. Thereafter, the spinning "magic angle" of a test material having similar nuclear properties to the standard is attained by returning the sample holder back to the originally noted coordinate position.

Agreement between fiber optic and optoelectronic systems for quantifying sagittal plane spinal curvature in sitting.

PubMed

Cloud, Beth A; Zhao, Kristin D; Breighner, Ryan; Giambini, Hugo; An, Kai-Nan

2014-07-01

Spinal posture affects how individuals function from a manual wheelchair. There is a need to directly quantify spinal posture in this population to ultimately improve function. A fiber optic system, comprised of an attached series of sensors, is promising for measuring large regions of the spine in individuals sitting in a wheelchair. The purpose of this study was to determine the agreement between fiber optic and optoelectronic systems for measuring spinal curvature, and describe the range of sagittal plane spinal curvatures in natural sitting. Able-bodied adults (n = 26, 13 male) participated. Each participant assumed three sitting postures: natural, slouched (accentuated kyphosis), and extension (accentuated lordosis) sitting. Fiber optic (ShapeTape) and optoelectronic (Optotrak) systems were applied to the skin over spinous processes from S1 to C7 and used to measure sagittal plane spinal curvature. Regions of kyphosis and lordosis were identified. A Cobb angle-like method was used to quantify lordosis and kyphosis. Generalized linear model and Bland-Altman analyses were used to assess agreement. A strong correlation exists between curvature values obtained with Optotrak and ShapeTape (R(2) = 0.98). The mean difference between Optotrak and ShapeTape for kyphosis in natural, extension, and slouched postures was 4.30° (95% LOA: -3.43 to 12.04°), 3.64° (95% LOA: -1.07 to 8.36°), and 4.02° (95% LOA: -2.80 to 10.84°), respectively. The mean difference for lordosis, when present, in natural and extension postures was 2.86° (95% LOA: -1.18 to 6.90°) and 2.55° (95% LOA: -3.38 to 8.48°), respectively. In natural sitting, the mean ± SD of kyphosis values was 35.07 ± 6.75°. Lordosis was detected in 8/26 participants: 11.72 ± 7.32°. The fiber optic and optoelectronic systems demonstrate acceptable agreement for measuring sagittal plane thoracolumbar spinal curvature. Copyright © 2014 Elsevier B.V. All rights reserved.

Agreement between Fiber Optic and Optoelectronic Systems for Quantifying Sagittal Plane Spinal Curvature in Sitting

PubMed Central

Cloud, Beth A.; Zhao, Kristin D.; Breighner, Ryan; Giambini, Hugo; An, Kai-Nan

2014-01-01

Spinal posture affects how individuals function from a manual wheelchair. There is a need to directly quantify spinal posture in this population to ultimately improve function. A fiber optic system, comprised of an attached series of sensors, is promising for measuring large regions of the spine in individuals sitting in a wheelchair. The purpose of this study was to determine the agreement between fiber optic and optoelectronic systems for measuring spinal curvature, and describe the range of sagittal plane spinal curvatures in natural sitting. Able-bodied adults (n=26, 13 male) participated. Each participant assumed three sitting postures: natural, slouched (accentuated kyphosis), and extension (accentuated lordosis) sitting. Fiber optic (ShapeTape) and optoelectronic (Optotrak) systems were applied to the skin over spinous processes from S1 to C7 and used to measure sagittal plane spinal curvature. Regions of kyphosis and lordosis were identified. A Cobb angle-like method was used to quantify lordosis and kyphosis. Generalized linear model and Bland-Altman analyses were used to assess agreement. A strong correlation exists between curvature values obtained with Optotrak and ShapeTape (R2=0.98). The mean difference between Optotrak and ShapeTape for kyphosis in natural, extension, and slouched postures was 4.30° (95%LOA: −3.43-12.04°), 3.64° (95%LOA: −1.07-8.36°), and 4.02° (95%LOA: −2.80-10.84°), respectively. The mean difference for lordosis, when present, in natural and extension postures is 2.86° (95%LOA: −1.18-6.90°) and 2.55° (95%LOA: −3.38-8.48°), respectively. In natural sitting, the mean±SD of kyphosis values was 35.07± 6.75°. Lordosis was detected in 8/26 participants: 11.72±7.32°. The fiber optic and optoelectronic systems demonstrate acceptable agreement for measuring sagittal plane thoracolumbar spinal curvature. PMID:24909579

Mutation rates among RNA viruses

PubMed Central

Drake, John W.; Holland, John J.

1999-01-01

The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often lacking. A previous analysis of mutation rates in RNA viruses (specifically in riboviruses rather than retroviruses) was constrained by the quality and quantity of available measurements and by the lack of a specific theoretical framework for converting mutation frequencies into mutation rates in this group of organisms. Here, we describe a simple relation between ribovirus mutation frequencies and mutation rates, apply it to the best (albeit far from satisfactory) available data, and observe a central value for the mutation rate per genome per replication of μg ≈ 0.76. (The rate per round of cell infection is twice this value or about 1.5.) This value is so large, and ribovirus genomes are so informationally dense, that even a modest increase extinguishes the population. PMID:10570172

Frequent somatic TERT promoter mutations and CTNNB1 mutations in hepatocellular carcinoma.

PubMed

Lee, Seung Eun; Chang, Seong-Hwan; Kim, Wook Youn; Lim, So Dug; Kim, Wan Seop; Hwang, Tea Sook; Han, Hye Seung

2016-10-25

Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma.

Exome-wide Sequencing Shows Low Mutation Rates and Identifies Novel Mutated Genes in Seminomas.

PubMed

Cutcutache, Ioana; Suzuki, Yuka; Tan, Iain Beehuat; Ramgopal, Subhashini; Zhang, Shenli; Ramnarayanan, Kalpana; Gan, Anna; Lee, Heng Hong; Tay, Su Ting; Ooi, Aikseng; Ong, Choon Kiat; Bolthouse, Jonathan T; Lane, Brian R; Anema, John G; Kahnoski, Richard J; Tan, Patrick; Teh, Bin Tean; Rozen, Steven G

2015-07-01

Testicular germ cell tumors are the most common cancer diagnosed in young men, and seminomas are the most common type of these cancers. There have been no exome-wide examinations of genes mutated in seminomas or of overall rates of nonsilent somatic mutations in these tumors. The objective was to analyze somatic mutations in seminomas to determine which genes are affected and to determine rates of nonsilent mutations. Eight seminomas and matched normal samples were surgically obtained from eight patients. DNA was extracted from tissue samples and exome sequenced on massively parallel Illumina DNA sequencers. Single-nucleotide polymorphism chip-based copy number analysis was also performed to assess copy number alterations. The DNA sequencing read data were analyzed to detect somatic mutations including single-nucleotide substitutions and short insertions and deletions. The detected mutations were validated by independent sequencing and further checked for subclonality. The rate of nonsynonymous somatic mutations averaged 0.31 mutations/Mb. We detected nonsilent somatic mutations in 96 genes that were not previously known to be mutated in seminomas, of which some may be driver mutations. Many of the mutations appear to have been present in subclonal populations. In addition, two genes, KIT and KRAS, were affected in two tumors each with mutations that were previously observed in other cancers and are presumably oncogenic. Our study, the first report on exome sequencing of seminomas, detected somatic mutations in 96 new genes, several of which may be targetable drivers. Furthermore, our results show that seminoma mutation rates are five times higher than previously thought, but are nevertheless low compared to other common cancers. Similar low rates are seen in other cancers that also have excellent rates of remission achieved with chemotherapy. We examined the DNA sequences of seminomas, the most common type of testicular germ cell cancer. Our study identified 96

Spinning angle optical calibration apparatus

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

Beer, S.K.; Pratt, H.R. II.

1989-09-12

An optical calibration apparatus is provided for calibrating and reproducing spinning angles in cross-polarization, nuclear magnetic resonance spectroscopy. An illuminated magnifying apparatus enables optical setting and accurate reproducing of spinning magic angles in cross-polarization, nuclear magnetic resonance spectroscopy experiments. A reference mark scribed on an edge of a spinning angle test sample holder is illuminated by a light source and viewed through a magnifying scope. When the magic angle of a sample material used as a standard is attained by varying the angular position of the sample holder, the coordinate position of the reference mark relative to a graduation ormore » graduations on a reticle in the magnifying scope is noted. Thereafter, the spinning magic angle of a test material having similar nuclear properties to the standard is attained by returning the sample holder back to the originally noted coordinate position. 2 figs.« less

Growth Angle: A Microscopic View

NASA Technical Reports Server (NTRS)

Mazuruk, Konstantin; Croll, Arne; Volz, Martin P.

2017-01-01

A microscopic continuum mechanical model of the growth angle is proposed. It is based on the van der Waals type framework that is used for surface force phenomena. The obtained augmented Laplace type integro-differential equations are, in general, difficult to analyze. Here we focused primarily on the particular case of equal melt and crystal surface energies. We derived an approximate equation for the meniscus shape, and obtained an analytical relationship between the contact and the growth angle. Interestingly, the same result can be obtained using the macroscopic model of Herring. The case of a macroscopically sharp corner is also considered. For this case, the macroscopic angle is not defined and it can be any angle between the contact angles of both flat surfaces. The microscopic model yields the smooth shape for the meniscus that also is not unique, but depends on the initial position of the meniscus.

FLG mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics.

PubMed

Akiyama, M

2010-03-01

Filaggrin is a key protein involved in skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris and have been shown to be major predisposing factors for atopic eczema (AE), initially in European populations. Subsequently, FLG mutations were identified in Japanese, Chinese, Taiwanese and Korean populations. It was demonstrated that FLG mutations are closely associated with AE in the Japanese population. Notably, the same FLG mutations identified in the European population were rarely found in Asians. These results exemplify differences in filaggrin population genetics between Europe and Asia. For mutation screening, background information needs to be obtained on prevalent FLG mutations for each geographical population. It is therefore important to establish the global population genetics maps for FLG mutations. Mutations at any site within FLG, even mutations in C-terminal imperfect filaggrin repeats, cause significant reductions in amounts of profilaggrin/filaggrin peptide in patient epidermis as the C-terminal region is essential for proper processing of profilaggrin into filaggrin. Thus, no genotype-phenotype correlation has been observed in patients with FLG mutations. A restoration of the barrier function seems a feasible and promising strategy for treatment and prevention in individuals with filaggrin deficiency.

Pinatubo and pre-Pinatubo optical-depth spectra: Mauna Loa measurements, comparisons, inferred particle size distributions, radiative effects, and relationship to lidar data

NASA Technical Reports Server (NTRS)

Russell, P. B.; Livingston, J. M.; Dutton, E. G.; Pueschel, R. F.; Reagan, J. A.; Defoor, T. E.; Box, M. A.; Allen, D.; Pilewskie, P.; Herman, B. M.

1993-01-01

The Ames airborne tracking sunphotometer was operated at the National Oceanic and Atmospheric Administration (NOAA) Mauna Loa Observatory (MLO) in 1991 and 1992 along with the NOAA Climate Monitoring and Diagnostics Laboratory (CMDL) automated tracking sunphotometer and lidar. June 1991 measurements provided calibrations, optical-depth spectra, and intercomparisons under relatively clean conditions; later measurements provided spectra and comparisons for the Pinatubo cloud plus calibration checks. June 1991 results are similar to previous MLO springtime measurements, with midvisible particle optical depth at the near-background level of 0.012 +/- 0.006 and no significant wavelength dependence in the measured range (lambda = 0.38 to 1.06 micrometers). The arrival of the Pinatubo cloud in July 1991 increased midvisible particle optical depth by more than an order of magnitude and changed the spectral shape of to an approximate power law with an exponent of about -1.4. By clearly September 1991, the spectrum was broadly peaked near 0.5 micrometers, and by July 1992, it was peaked near 0.8 micrometers. Our optical-depth spectra include corrections for diffuse light. NOAA- and Ames Research Center (ARC)-measured spectra are in good agreement. Columnar size distributions inverted from the spectra show that the initial (July 1991) post-Pinatubo cloud was relatively rich in small particles (r less than 0.25 micrometers), which were progressively depleted in the August-September 1991 and July 1992 periods. Conversely, both of the later periods had more of the optically efficient medium-sized particles (0.25 less than r less than 1 micrometers) than did the fresh July 1991 cloud. These changes are consistent with particle growth by condensation and coagulation. Photometer-inferred column backscatter values agree with those measured by the CMDL lidar on nearby nights. Combining lidar-measured backscatter profiles with photometer-derived backscatter-to-area ratios gives peak

Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

PubMed

Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

2015-08-15

Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult

Angle closure in younger patients.

PubMed Central

Chang, Brian M; Liebmann, Jeffrey M; Ritch, Robert

2002-01-01

PURPOSE: Angle-closure glaucoma is rare in children and young adults. Only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients in our database aged 40 or younger with angle closure. METHODS: Our database was searched for patients with angle closure who were 40 years old or younger. Data recorded included age at initial consultation; age at the time of diagnosis; gender; results of slit-lamp examination, gonioscopy, and ultrasound biomicroscopy (from 1993 onward); clinical diagnosis; and therapy. Patients with previous incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. RESULTS: Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age (+/- SD) at the time of consultation was 34.4 +/- 9.4 years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients), iridociliary cysts (8 patients), retinopathy of prematurity (7 patients), uveitis (5 patients), isolated nanophthalmos (3 patients), relative pupillary block (2 patients), Weill-Marchesani syndrome (3 patients), and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. CONCLUSION: The etiology of angle closure in young persons is different from that in the older population and is typically associated with structural or developmental ocular anomalies rather than relative pupillary block. Following laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention. PMID:12545694

Are we ready for genetic testing for primary open-angle glaucoma?

PubMed

Khawaja, Anthony P; Viswanathan, Ananth C

2018-05-01

Following a dramatic reduction in the cost of genotyping technology in recent years, there have been significant advances in the understanding of the genetic basis of glaucoma. Glaucoma patients represent around a quarter of all outpatient activity in the UK hospital eye service and are a huge burden for the National Health Service. A potential benefit of genetic testing is personalised glaucoma management, allowing direction of our limited healthcare resources to the glaucoma patients who most need it. Our review aims to summarise recent discoveries in the field of glaucoma genetics and to discuss their potential clinical utility. While genome-wide association studies have now identified over ten genes associated with primary open-angle glaucoma (POAG), individually, variants in these genes are not predictive of POAG in populations. There are data suggesting some of these POAG variants are associated with conversion from ocular hypertension to POAG and visual field progression among POAG patients. However, these studies have not been replicated yet and such genetic testing is not currently justified in clinical care. In contrast, genetic testing for inherited early-onset disease in relatives of POAG patients with a known genetic mutation is of clear benefit; this can support either regular review to commence early treatment when the disease develops, or discharge from ophthalmology services of relatives who do not carry the mutation. Genetic testing for POAG at a population level is not currently justified.

SU-E-T-446: Group-Sparsity Based Angle Generation Method for Beam Angle Optimization

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

Gao, H

2015-06-15

Purpose: This work is to develop the effective algorithm for beam angle optimization (BAO), with the emphasis on enabling further improvement from existing treatment-dependent templates based on clinical knowledge and experience. Methods: The proposed BAO algorithm utilizes a priori beam angle templates as the initial guess, and iteratively generates angular updates for this initial set, namely angle generation method, with improved dose conformality that is quantitatively measured by the objective function. That is, during each iteration, we select “the test angle” in the initial set, and use group-sparsity based fluence map optimization to identify “the candidate angle” for updating “themore » test angle”, for which all the angles in the initial set except “the test angle”, namely “the fixed set”, are set free, i.e., with no group-sparsity penalty, and the rest of angles including “the test angle” during this iteration are in “the working set”. And then “the candidate angle” is selected with the smallest objective function value from the angles in “the working set” with locally maximal group sparsity, and replaces “the test angle” if “the fixed set” with “the candidate angle” has a smaller objective function value by solving the standard fluence map optimization (with no group-sparsity regularization). Similarly other angles in the initial set are in turn selected as “the test angle” for angular updates and this chain of updates is iterated until no further new angular update is identified for a full loop. Results: The tests using the MGH public prostate dataset demonstrated the effectiveness of the proposed BAO algorithm. For example, the optimized angular set from the proposed BAO algorithm was better the MGH template. Conclusion: A new BAO algorithm is proposed based on the angle generation method via group sparsity, with improved dose conformality from the given template. Hao Gao was partially supported by

Individualized optimal release angles in discus throwing.

PubMed

Leigh, Steve; Liu, Hui; Hubbard, Mont; Yu, Bing

2010-02-10

The purpose of this study was to determine individualized optimal release angles for elite discus throwers. Three-dimensional coordinate data were obtained for at least 10 competitive trials for each subject. Regression relationships between release speed and release angle, and between aerodynamic distance and release angle were determined for each subject. These relationships were linear with subject-specific characteristics. The subject-specific relationships between release speed and release angle may be due to subjects' technical and physical characteristics. The subject-specific relationships between aerodynamic distance and release angle may be due to interactions between the release angle, the angle of attack, and the aerodynamic distance. Optimal release angles were estimated for each subject using the regression relationships and equations of projectile motion. The estimated optimal release angle was different for different subjects, and ranged from 35 degrees to 44 degrees . The results of this study demonstrate that the optimal release angle for discus throwing is thrower-specific. The release angles used by elite discus throwers in competition are not necessarily optimal for all discus throwers, or even themselves. The results of this study provide significant information for understanding the biomechanics of discus throwing techniques. Copyright 2009 Elsevier Ltd. All rights reserved.

The Semiotic and Conceptual Genesis of Angle

ERIC Educational Resources Information Center

Tanguay, Denis; Venant, Fabienne

2016-01-01

In the present study, we try to understand how students at the end of primary school conceive of angle: Is an angle a magnitude for them or a geometric figure, and how do they manage to coordinate the two aspects in their understanding of the concepts of angle and of angle measurement? With the aim of better grasping the way "angle" is…

SU-E-I-56: Scan Angle Reduction for a Limited-Angle Intrafraction Verification (LIVE) System

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

Ren, L; Zhang, Y; Yin, F

Purpose: To develop a novel adaptive reconstruction strategy to further reduce the scanning angle required by the limited-angle intrafraction verification (LIVE) system for intrafraction verification. Methods: LIVE acquires limited angle MV projections from the exit fluence of the arc treatment beam or during gantry rotation between static beams. Orthogonal limited-angle kV projections are also acquired simultaneously to provide additional information. LIVE considers the on-board 4D-CBCT images as a deformation of the prior 4D-CT images, and solves the deformation field based on deformation models and data fidelity constraint. LIVE reaches a checkpoint after a limited-angle scan, and reconstructs 4D-CBCT for intrafractionmore » verification at the checkpoint. In adaptive reconstruction strategy, a larger scanning angle of 30° is used for the first checkpoint, and smaller scanning angles of 15° are used for subsequent checkpoints. The onboard images reconstructed at the previous adjacent checkpoint are used as the prior images for reconstruction at the current checkpoint. As the algorithm only needs to reconstruct the small deformation occurred between adjacent checkpoints, projections from a smaller scan angle provide enough information for the reconstruction. XCAT was used to simulate tumor motion baseline drift of 2mm along sup-inf direction at every subsequent checkpoint, which are 15° apart. Adaptive reconstruction strategy was used to reconstruct the images at each checkpoint using orthogonal 15° kV and MV projections. Results: Results showed that LIVE reconstructed the tumor volumes accurately using orthogonal 15° kV-MV projections. Volume percentage differences (VPDs) were within 5% and center of mass shifts (COMS) were within 1mm for reconstruction at all checkpoints. Conclusion: It's feasible to use an adaptive reconstruction strategy to further reduce the scan angle needed by LIVE to allow faster and more frequent intrafraction verification to

Spinning angle optical calibration apparatus

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

Beer, S.K.; Pratt, H.R.

1991-02-26

This patent describes an optical calibration apparatus provided for calibrating and reproducing spinning angles in cross-polarization, nuclear magnetic resonance spectroscopy. An illuminated magnifying apparatus enables optical setting an accurate reproducing of spinning magic angles in cross-polarization, nuclear magnetic resonance spectroscopy experiments. A reference mark scribed on an edge of a spinning angle test sample holder is illuminated by a light source and viewed through a magnifying scope. When the magic angle of a sample material used as a standard is attained by varying the angular position of the sample holder, the coordinate position of the reference mark relative to amore » graduation or graduations on a reticle in the magnifying scope is noted.« less

Northwest Angle, Minnesota

NASA Image and Video Library

2017-10-02

Minnesota's Northwest Angle is the northernmost point of the continental United States. The Angle became part of the US due to a map error during the 1783 Treaty of Paris. Located in the Lake of the Woods, driving there requires crossing the US-Canada border twice. The image was acquired September 22, 2013, covers an area of 40 by 55 km, and is located at 49.2 degrees north, 95.1 degrees west. https://photojournal.jpl.nasa.gov/catalog/PIA21997

Forecast, measurement, and modeling of an unprecedented polar ozone filament event over Mauna Loa Observatory, Hawaii

NASA Astrophysics Data System (ADS)

Tripathi, Om Prakash; Leblanc, Thierry; McDermid, I. Stuart; LefèVre, Frank; Marchand, Marion; Hauchecorne, Alain

2006-10-01

In mid-March 2005 the northern lower stratospheric polar vortex experienced a severe stretching episode, bringing a large polar filament far south of Alaska toward Hawaii. This meridional intrusion of rare extent, coinciding with the polar vortex final warming and breakdown, was followed by a zonal stretching in the wake of the easterly propagating subtropical main flow. This caused polar air to remain over Hawaii for several days before diluting into the subtropics. After being successfully forecasted to pass over Hawaii by the high-resolution potential vorticity advection model Modèle Isentrope du transport Méso-échelle de l'Ozone Stratosphérique par Advection (MIMOSA), the filament was observed on isentropic surfaces between 415 K and 455 K (17-20 km) by the Jet Propulsion Laboratory stratospheric ozone lidar measurements at Mauna Loa Observatory, Hawaii, between 16 and 19 March 2005. It was materialized as a thin layer of enhanced ozone peaking at 1.6 ppmv in a region where the climatological values usually average 1.0 ppmv. These values were compared to those obtained by the three-dimensional Chemistry-Transport Model MIMOSA-CHIM. Agreement between lidar and model was excellent, particularly in the similar appearance of the ozone peak near 435 K (18.5 km) on 16 March, and the persistence of this layer at higher isentropic levels for the following three days. Passive ozone, also modeled by MIMOSA-CHIM, was at about 3-4 ppmv inside the filament while above Hawaii. A detailed history of the modeled chemistry inside the filament suggests that the air mass was still polar ozone-depleted when passing over Hawaii. The filament quickly separated from the main vortex after its Hawaiian overpass. It never reconnected and, in less than 10 days, dispersed entirely in the subtropics.

Forecast, Measurement, and Modeling of an Unprecedented Polar Ozone Filament Event over Mauna Loa Observatory, Hawaii

NASA Technical Reports Server (NTRS)

Tripathi, Om Prakash; Leblanc, Thierry; McDermid, I. Stuart; Lefevre, Frank; Marchand, Marion; Hauchecorne, Alain

2006-01-01

In mid-March 2005 the northern lower stratospheric polar vortex experienced a severe stretching episode, bringing a large polar filament far south of Alaska toward Hawaii. This meridional intrusion of rare extent, coinciding with the polar vortex final warming and breakdown, was followed by a zonal stretching in the wake of the easterly propagating subtropical main flow. This caused polar air to remain over Hawaii for several days before diluting into the subtropics. After being successfully forecasted to pass over Hawaii by the high-resolution potential vorticity advection model Modele Isentrope du transport Meso-echelle de l'Ozone Stratospherique par Advection (MIMOSA), the filament was observed on isentropic surfaces between 415 K and 455 K (17-20 km) by the Jet Propulsion Laboratory stratospheric ozone lidar measurements at Mauna Loa Observatory, Hawaii, between 16 and 19 March 2005. It was materialized as a thin layer of enhanced ozone peaking at 1.6 ppmv in a region where the climatological values usually average 1.0 ppmv. These values were compared to those obtained by the three dimensional Chemistry-Transport Model MIMOSA-CHIM. Agreement between lidar and model was excellent, particularly in the similar appearance of the ozone peak near 435 K (18.5 km) on 16 March, and the persistence of this layer at higher isentropic levels for the following three days. Passive ozone, also modeled by MIMOSA-CHIM, was at about 3-4 ppmv inside the filament while above Hawaii. A detailed history of the modeled chemistry inside the filament suggests that the air mass was still polar ozone- depleted when passing over Hawaii. The filament quickly separated from the main vortex after its Hawaiian overpass. It never reconnected and, in less than 10 days, dispersed entirely in the subtropics.

Similar Mutation Rates but Highly Diverse Mutation Spectra in Ascomycete and Basidiomycete Yeasts.

PubMed

Long, Hongan; Behringer, Megan G; Williams, Emily; Te, Ronald; Lynch, Michael

2016-12-01

Yeast species are extremely diverse and not monophyletic. Because the majority of yeast research focuses on ascomycetes, the mutational determinants of genetic diversity across yeast species are not well understood. By combining mutation-accumulation techniques with whole-genome sequencing, we resolved the genomic mutation rate and spectrum of the oleaginous (oil-producing) ‘red yeast’ Rhodotorula toruloides, the first such study in the fungal phylum Basidiomycota. We find that the mutation spectrum is quite different from what has been observed in all other studied unicellular eukaryotes, but similar to that in most bacteria—a predominance of transitions relative to transversions. Rhodotorula toruloides has a significantly higher A:T→G:C transition rate—possibly elevated by the abundant flanking G/C nucleotides in the GC-rich genome, as well as a much lower G:C→T:A transversion rate. In spite of these striking differences, there are substantial consistencies between R. toruloides and the ascomycete model yeasts: a spontaneous base-substitution mutation rate of 1.90 × 10 −10 per site per cell division as well as an elevated mutation rate at non-methylated 5'CpG3' sites. These results imply the evolution of variable mutation spectra in the face of similar mutation rates in yeasts.

Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.

PubMed

Dehghanian, Fatemeh; Silawi, Mohammad; Tabei, Seyed M B

2017-02-01

Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. In this study, 13 unrelated classical PKU patients took part in the study detecting causative mutations. Mutations were identified by polymerase chain reaction (PCR) and direct sequencing in all patients. After that, haplotype analysis was performed by studying VNTR and PAHSTR markers (linked genetic markers of the PAH gene) through application of PCR and capillary electrophoresis (CE). Mutation analysis was performed successfully and the detected mutations were as follows: c.782G>A, c.754C>T, c.842C>G, c.113-115delTCT, c.688G>A, and c.696A>G. Additionally, PAHSTR/VNTR haplotypes were detected to discover haplotypes linked to each mutation. Mutation detection is the best approach for confirming PAH enzyme deficiency in PKU patients. Due to the relatively large size of the PAH gene and high cost of the direct sequencing in developing countries, haplotype analysis could be used before DNA sequencing and mutation detection for a faster and cheaper way via identifying probable mutated exons.

Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes.

PubMed

Supek, Fran; Lehner, Ben

2017-07-27

Many processes can cause the same nucleotide change in a genome, making the identification of the mechanisms causing mutations a difficult challenge. Here, we show that clustered mutations provide a more precise fingerprint of mutagenic processes. Of nine clustered mutation signatures identified from >1,000 tumor genomes, three relate to variable APOBEC activity and three are associated with tobacco smoking. An additional signature matches the spectrum of translesion DNA polymerase eta (POLH). In lymphoid cells, these mutations target promoters, consistent with AID-initiated somatic hypermutation. In solid tumors, however, they are associated with UV exposure and alcohol consumption and target the H3K36me3 chromatin of active genes in a mismatch repair (MMR)-dependent manner. These regions normally have a low mutation rate because error-free MMR also targets H3K36me3 chromatin. Carcinogens and error-prone repair therefore redistribute mutations to the more important regions of the genome, contributing a substantial mutation load in many tumors, including driver mutations. Copyright © 2017 Elsevier Inc. All rights reserved.

Rates of spontaneous mutation.

PubMed Central

Drake, J W; Charlesworth, B; Charlesworth, D; Crow, J F

1998-01-01

Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates. PMID:9560386

Deformation history of Mauna Loa (Hawaii) from 2003 to 2014 through InSAR data: understanding the shorter-term processes

NASA Astrophysics Data System (ADS)

La Marra, Daniele; Poland, Michael P.; Acocella, Valerio; Battaglia, Maurizio; Miklius, Asta

2016-04-01

Geodesy allows detecting the deformation of volcanoes, thus understanding magmatic processes. This becomes particularly efficient when time series are available and volcanoes can be monitored on the mean-term (decades), and not only during a specific event. Here we exploit the SBAS technique, using SAR images from ENVISAT (descending and ascending orbits; 2003 - 2010) and COSMO-SkyMed (descending and ascending orbits; 2012 - 2014), to study a decade of deformation at Mauna Loa (Hawaii). These data are merged time series data from 24 continuously operating GPS stations, which allows us to calibrate the InSAR time series. Our results show a long-term inflation of the volcano from 2003 to 2014, reaching a peak of ~11 cm/yr on the summit area between mid-2004 to mid-2005 and then slowing down. Within this frame, we were able to identify five main periods with approximately linear deformation behavior. The inversion of the deformation data in the first four periods suggests the repeated, though not constant, intrusion of one or more dikes below the summit caldera and the upper Southwest Rift Zone. Moreover, the dike intrusion coincides with minor acceleration of flank slip. Such a behavior is distinctive and, with the exception of the nearby Kilauea, has not been observed at any other volcano on the mean term. It is proposed that continuous, even though not constant flank instability of the SE flank may promote semi-continuous intrusions in a volcano with a ready magma supply.

Reading Angles in Maps

ERIC Educational Resources Information Center

Izard, Véronique; O'Donnell, Evan; Spelke, Elizabeth S.

2014-01-01

Preschool children can navigate by simple geometric maps of the environment, but the nature of the geometric relations they use in map reading remains unclear. Here, children were tested specifically on their sensitivity to angle. Forty-eight children (age 47:15-53:30 months) were presented with fragments of geometric maps, in which angle sections…

Mutation and premating isolation

NASA Technical Reports Server (NTRS)

Woodruff, R. C.; Thompson, J. N. Jr

2002-01-01

While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

Reliability of a smartphone-based goniometer for knee joint goniometry.

PubMed

Ferriero, Giorgio; Vercelli, Stefano; Sartorio, Francesco; Muñoz Lasa, Susana; Ilieva, Elena; Brigatti, Elisa; Ruella, Carolina; Foti, Calogero

2013-06-01

The aim of this study was to assess the reliability of a smartphone-based application developed for photographic-based goniometry, DrGoniometer (DrG), by comparing its measurement of the knee joint angle with that made by a universal goniometer (UG). Joint goniometry is a common mode of clinical assessment used in many disciplines, in particular in rehabilitation. One validated method is photographic-based goniometry, but the procedure is usually complex: the image has to be downloaded from the camera to a computer and then edited using dedicated software. This disadvantage may be overcome by the new generation of mobile phones (smartphones) that have computer-like functionality and an integrated digital camera. This validation study was carried out under two different controlled conditions: (i) with the participant to measure in a fixed position and (ii) with a battery of pictures to assess. In the first part, four raters performed repeated measurements with DrG and UG at different knee joint angles. Then, 10 other raters measured the knee at different flexion angles ranging 20-145° on a battery of 35 pictures taken in a clinical setting. The results showed that inter-rater and intra-rater correlations were always more than 0.958. Agreement with the UG showed a width of 18.2° [95% limits of agreement (LoA)=-7.5/+10.7°] and 14.1° (LoA=-6.6/+7.5°). In conclusion, DrG seems to be a reliable method for measuring knee joint angle. This mHealth application can be an alternative/additional method of goniometry, easier to use than other photographic-based goniometric assessments. Further studies are required to assess its reliability for the measurement of other joints.

Mutation testing in Treacher Collins Syndrome.

PubMed

Ellis, P E; Dawson, M; Dixon, M J

2002-12-01

To report on a study where 97 subjects were screened for mutations in the Treacher Collins syndrome (TCS) gene TCOF1. Ninety-seven subjects with a clinical diagnosis of TCS were screened for potential mutations in TCOF1, by means of single strand conformation polymorphism (SSCP) analysis. In those subjects where potential mutations were detected, sequence analysis was performed to determine the site and type of mutation present. Thirty-six TCS-specific mutations are reported including 27 deletions, six point mutations, two splice junction mutations, and one insertion/deletion. This brings the total number of mutations reported to date to 105. The importance of detection of these mutations is mainly in postnatal diagnosis and genetic counselling. Knowledge of the family specific mutation may also be used in prenatal diagnosis to confirm whether the foetus is affected or not, and give the parents the choice of whether to continue with the pregnancy.

Modeling of phonon scattering in n-type nanowire transistors using one-shot analytic continuation technique

NASA Astrophysics Data System (ADS)

Bescond, Marc; Li, Changsheng; Mera, Hector; Cavassilas, Nicolas; Lannoo, Michel

2013-10-01

We present a one-shot current-conserving approach to model the influence of electron-phonon scattering in nano-transistors using the non-equilibrium Green's function formalism. The approach is based on the lowest order approximation (LOA) to the current and its simplest analytic continuation (LOA+AC). By means of a scaling argument, we show how both LOA and LOA+AC can be easily obtained from the first iteration of the usual self-consistent Born approximation (SCBA) algorithm. Both LOA and LOA+AC are then applied to model n-type silicon nanowire field-effect-transistors and are compared to SCBA current characteristics. In this system, the LOA fails to describe electron-phonon scattering, mainly because of the interactions with acoustic phonons at the band edges. In contrast, the LOA+AC still well approximates the SCBA current characteristics, thus demonstrating the power of analytic continuation techniques. The limits of validity of LOA+AC are also discussed, and more sophisticated and general analytic continuation techniques are suggested for more demanding cases.

Predictable Phenotypes of Antibiotic Resistance Mutations.

PubMed

Knopp, M; Andersson, D I

2018-05-15

Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

Pitch Angles Of Artificially Redshifted Galaxies

NASA Astrophysics Data System (ADS)

Shields, Douglas W.; Davis, B.; Johns, L.; Berrier, J. C.; Kennefick, D.; Kennefick, J.; Seigar, M.

2012-05-01

We present the pitch angles of several galaxies that have been artificially redshifted using Barden et al’s FERENGI software. The (central black hole mass)-(spiral arm pitch angle) relation has been used on a statistically complete sample of local galaxies to determine the black hole mass function of local spiral galaxies. We now measure the pitch angles at increasing redshifts by operating on the images pixel-by-pixel. The results will be compared to the pitch angle function as measured in the GOODS field. This research was funded in part by NASA / EPScOR.

Detection of IDH1 R132H mutation in acute myeloid leukemia by mutation-specific immunohistochemistry.

PubMed

Byers, Richard; Hornick, Jason L; Tholouli, Eleni; Kutok, Jeffery; Rodig, Scott J

2012-01-01

IDH1 mutations are present but are uncommon in acute myeloid leukemia (AML) and although prognostically favorable in gliomas their clinical significance in AML is unclear. Some have associated IDH1 mutations with inferior outcome, whereas others found no association with prognosis. Complicating these analyses is the need to sequence IDH1 from leukemic blasts, which is technically challenging and not yet routine. Mutation-specific antibodies enable robust, cost-effective detection of mutations in routine biopsy samples. Immunohistochemistry for the R132H mutation-specific antibody was performed in a tissue microarray containing 159 cases of AML, detecting the R132H mutation in 7 cases (4.4%). Positivity was associated with intermediate risk cytogenetics. Our results demonstrate an association between the R132H IDH1 mutation and intermediate risk cytogenetics in AML, suggesting that R132H IDH1 mutation may be associated with improved clinical outcome and demonstrate the feasibility of using mutation-specific antibodies to genotype and subclassify AML.

Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern

PubMed Central

Hafner, Christian; López-Knowles, Elena; Luis, Nuno M.; Toll, Agustí; Baselga, Eulàlia; Fernández-Casado, Alex; Hernández, Silvia; Ribé, Adriana; Mentzel, Thomas; Stoehr, Robert; Hofstaedter, Ferdinand; Landthaler, Michael; Vogt, Thomas; Pujol, Ramòn M.; Hartmann, Arndt; Real, Francisco X.

2007-01-01

Activating mutations of the p110 α subunit of PI3K (PIK3CA) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown. Activating FGF receptor 3 (FGFR3) mutations are common in benign skin lesions, either as embryonic mutations in epidermal nevi (EN) or as somatic mutations in seborrheic keratoses (SK). FGFR3 mutations are also common in low-grade malignant bladder tumors, where they often occur in association with PIK3CA mutations. Therefore, we examined exons 9 and 20 of PIK3CA and FGFR3 hotspot mutations in EN (n = 33) and SK (n = 62), two proliferative skin lesions lacking malignant potential. Nine of 33 (27%) EN harbored PIK3CA mutations; all cases showed the E545G substitution, which is uncommon in cancers. In EN, R248C was the only FGFR3 mutation identified. By contrast, 10 of 62 (16%) SK revealed the typical cancer-associated PIK3CA mutations E542K, E545K, and H1047R. The same lesions displayed a wide range of FGFR3 mutations. Corresponding unaffected tissue was available for four EN and two mutant SK: all control samples displayed a WT sequence, confirming the somatic nature of the mutations found in lesional tissue. Forty of 95 (42%) lesions showed at least one mutation in either gene. PIK3CA and FGFR3 mutations displayed an independent distribution; 5/95 lesions harbored mutations in both genes. Our findings suggest that, in addition to their role in cancer, oncogenic PIK3CA mutations contribute to the pathogenesis of skin tumors lacking malignant potential. The remarkable genotype–phenotype correlation as observed in this study points to a distinct etiopathogenesis of the mutations in keratinocytes occuring either during fetal development or in adult life. PMID:17673550

Omni-Directional Viewing-Angle Switching through Control of the Beam Divergence Angle in a Liquid Crystal Panel

NASA Astrophysics Data System (ADS)

Baek, Jong-In; Kim, Ki-Han; Kim, Jae Chang; Yoon, Tae-Hoon

2010-01-01

This paper proposes a method of omni-directional viewing-angle switching by controlling the beam diverging angle (BDA) in a liquid crystal (LC) panel. The LCs aligned randomly by in-cell polymer structures diffuse the collimated backlight for the bright state of the wide viewing-angle mode. We align the LCs homogeneously by applying an in-plane field for the narrow viewing-angle mode. By doing this the scattering is significantly reduced so that the small BDA is maintained as it passes through the LC layer. The dark state can be obtained by aligning the LCs homeotropically with a vertical electric field. We demonstrated experimentally the omni-directional switching of the viewing-angle, without an additional panel or backlighting system.

Does the Angle of the Nail Matter for Pertrochanteric Fracture Reduction? Matching Nail Angle and Native Neck-Shaft Angle.

PubMed

Parry, Joshua A; Barrett, Ian; Schoch, Bradley; Yuan, Brandon; Cass, Joseph; Cross, William

2018-04-01

To determine whether fixation of pertrochanteric hip fractures with cephalomedullary nails (CMNs) with a neck-shaft angle (NSA) less than the native NSA affects reduction and lag screw cutout. Retrospective comparative study. Level I trauma center. Patients treated with a CMN for unstable pertrochanteric femur fractures (OTA/AO 31-A2.2 and 31-A2.3) between 2005 and 2014. CMN fixation. NSA reduction and lag screw cutout. Patients fixed with a nail angle less than their native NSA were less likely to have good reductions [17% vs. 60%, 95% confidence interval (CI), -63% to -18%; P = 0.0005], secondary to more varus reductions (41% vs. 10%, 95% CI, 9%-46%; P = 0.01) and more fractures with ≥4 mm of displacement (63% vs. 35%, 95% CI, 3%-49%; P = 0.03). The cutout was not associated with the use of a nail angle less than the native NSA (60% vs. 76%, 95% CI, -56% to 18%; P = 0.5), varus reductions (60% vs. 32%, 95% CI, -13% to 62%; P = 0.3), or poor reductions (20% vs. 17%, 95% CI, -24% to 44%; P = 1.0). The fixation of unstable pertrochanteric hip fractures with a nail angle less than the native NSA was associated with more varus reductions and fracture displacement but did not affect the lag screw cutout. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Angle amplifier based on multiplexed volume holographic gratings

NASA Astrophysics Data System (ADS)

Cao, Liangcai; Zhao, Yifei; He, Qingsheng; Jin, Guofan

2008-03-01

Angle amplifier of laser beam scanner is a widely used device in optical systems. Volume holographic optical elements can be applied in the angle amplifier. Compared with the traditional angle amplifier, it has the advantages of high angle resolution, high diffraction efficiency, small size, and high angle magnification and flexible design. Bragg anglewavelength- compensating recording method is introduced. Because of the Bragg compensatory relation between angle and wavelength, this device could be recorded at another wavelength. The design of the angle amplifier recording at the wavelength of 514.2nm for the working wavelength of 632.8nm is described. An optical setup for recording the angle amplifier device is designed and discussed. Experimental results in the photorefractive crystal Fe:LiNbO 3 demonstrate the feasibility of the angle amplifier scheme.

Targeted next-generation sequencing extends the phenotypic and mutational spectrums for EYS mutations

PubMed Central

Gu, Shun; Tian, Yuanyuan; Chen, Xue

2016-01-01

Purpose We aim to determine genetic lesions with a phenotypic correlation in four Chinese families with autosomal recessive retinitis pigmentosa (RP). Methods Medical histories were carefully reviewed. All patients received comprehensive ophthalmic evaluations. The next-generation sequencing (NGS) approach targeting a panel of 205 retinal disease–relevant genes and 15 candidate genes was selectively performed on probands from the four recruited families for mutation detection. Online predictive software and crystal structure modeling were also applied to test the potential pathogenic effects of identified mutations. Results Of the four families, two were diagnosed with RP sino pigmento (RPSP). Patients with RPSP claimed to have earlier RP age of onset but slower disease progression. Five mutations in the eyes shut homolog (EYS) gene, involving two novel (c.7228+1G>A and c.9248G>A) and three recurrent mutations (c.4957dupA, c.6416G>A and c.6557G>A), were found as RP causative in the four families. The missense variant c.5093T>C was determined to be a variant of unknown significance (VUS) due to the variant’s colocalization in the same allele with the reported pathogenic mutation c.6416G>A. The two novel variants were further confirmed absent in 100 unrelated healthy controls. Online predictive software indicated potential pathogenicity of the three missense mutations. Further, crystal structural modeling suggested generation of two abnormal hydrogen bonds by the missense mutation p.G2186E (c.6557G>A) and elongation of its neighboring β-sheet induced by p.G3083D (c.9248G>A), which could alter the tertiary structure of the eys protein and thus interrupt its physicochemical properties. Conclusions Taken together, with the targeted NGS approach, we reveal novel EYS mutations and prove the efficiency of targeted NGS in the genetic diagnoses of RP. We also first report the correlation between EYS mutations and RPSP. The genotypic-phenotypic relationship in all

Targeted next-generation sequencing extends the phenotypic and mutational spectrums for EYS mutations.

PubMed

Gu, Shun; Tian, Yuanyuan; Chen, Xue; Zhao, Chen

2016-01-01

We aim to determine genetic lesions with a phenotypic correlation in four Chinese families with autosomal recessive retinitis pigmentosa (RP). Medical histories were carefully reviewed. All patients received comprehensive ophthalmic evaluations. The next-generation sequencing (NGS) approach targeting a panel of 205 retinal disease-relevant genes and 15 candidate genes was selectively performed on probands from the four recruited families for mutation detection. Online predictive software and crystal structure modeling were also applied to test the potential pathogenic effects of identified mutations. Of the four families, two were diagnosed with RP sino pigmento (RPSP). Patients with RPSP claimed to have earlier RP age of onset but slower disease progression. Five mutations in the eyes shut homolog (EYS) gene, involving two novel (c.7228+1G>A and c.9248G>A) and three recurrent mutations (c.4957dupA, c.6416G>A and c.6557G>A), were found as RP causative in the four families. The missense variant c.5093T>C was determined to be a variant of unknown significance (VUS) due to the variant's colocalization in the same allele with the reported pathogenic mutation c.6416G>A. The two novel variants were further confirmed absent in 100 unrelated healthy controls. Online predictive software indicated potential pathogenicity of the three missense mutations. Further, crystal structural modeling suggested generation of two abnormal hydrogen bonds by the missense mutation p.G2186E (c.6557G>A) and elongation of its neighboring β-sheet induced by p.G3083D (c.9248G>A), which could alter the tertiary structure of the eys protein and thus interrupt its physicochemical properties. Taken together, with the targeted NGS approach, we reveal novel EYS mutations and prove the efficiency of targeted NGS in the genetic diagnoses of RP. We also first report the correlation between EYS mutations and RPSP. The genotypic-phenotypic relationship in all Chinese patients carrying mutations in the EYS

Fitness change in relation to mutation number in spontaneous mutation accumulation lines of Chlamydomonas reinhardtii

PubMed Central

Kraemer, Susanne A.; Böndel, Katharina B.; Ness, Robert W.; Keightley, Peter D.; Colegrave, Nick

2017-01-01

Abstract Although all genetic variation ultimately stems from mutations, their properties are difficult to study directly. Here, we used multiple mutation accumulation (MA) lines derived from five genetic backgrounds of the green algae Chlamydomonas reinhardtii that have been previously subjected to whole genome sequencing to investigate the relationship between the number of spontaneous mutations and change in fitness from a nonevolved ancestor. MA lines were on average less fit than their ancestors and we detected a significantly negative correlation between the change in fitness and the total number of accumulated mutations in the genome. Likewise, the number of mutations located within coding regions significantly and negatively impacted MA line fitness. We used the fitness data to parameterize a maximum likelihood model to estimate discrete categories of mutational effects, and found that models containing one to two mutational effect categories (one neutral and one deleterious category) fitted the data best. However, the best‐fitting mutational effects models were highly dependent on the genetic background of the ancestral strain. PMID:28884790

The correlation between calcaneal valgus angle and asymmetrical thoracic-lumbar rotation angles in patients with adolescent scoliosis.

PubMed

Park, Jaeyong; Lee, Sang Gil; Bae, Jongjin; Lee, Jung Chul

2015-12-01

[Purpose] This study aimed to provide a predictable evaluation method for the progression of scoliosis in adolescents based on quick and reliable measurements using the naked eye, such as the calcaneal valgus angle of the foot, which can be performed at public facilities such as schools. [Subjects and Methods] Idiopathic scoliosis patients with a Cobb's angle of 10° or more (96 females, 22 males) were included in this study. To identify relationships between factors, Pearson's product-moment correlation coefficient was computed. The degree of scoliosis was set as a dependent variable to predict thoracic and lumbar scoliosis using ankle angle and physique factors. Height, weight, and left and right calcaneal valgus angles were set as independent variables; thereafter, multiple regression analysis was performed. This study extracted variables at a significance level (α) of 0.05 by applying a stepwise method, and calculated a regression equation. [Results] Negative correlation (R=-0.266) was shown between lumbar lordosis and asymmetrical lumbar rotation angles. A correlation (R=0.281) was also demonstrated between left calcaneal valgus angles and asymmetrical thoracic rotation angles. [Conclusion] Prediction of scoliosis progress was revealed to be possible through ocular inspection of the calcaneus and Adams forward bending test and the use of a scoliometer.

Fiber orientation measurements by diffusion tensor imaging improve hydrogen-1 magnetic resonance spectroscopy of intramyocellular lipids in human leg muscles

PubMed Central

Valaparla, Sunil K.; Gao, Feng; Daniele, Giuseppe; Abdul-Ghani, Muhammad; Clarke, Geoffrey D.

2015-01-01

Abstract. Twelve healthy subjects underwent hydrogen-1 magnetic resonance spectroscopy (H1-MRS) acquisition (15×15×15  mm3), diffusion tensor imaging (DTI) with a b-value of 600  s mm−2, and fat-water magnetic resonance imaging (MRI) using the Dixon method. Subject-specific muscle fiber orientation, derived from DTI, was used to estimate the lipid proton spectral chemical shift. Pennation angles were measured as 23.78 deg in vastus lateralis (VL), 17.06 deg in soleus (SO), and 8.49 deg in tibialis anterior (TA) resulting in a chemical shift between extramyocellular lipids (EMCL) and intramyocellular lipids (IMCL) of 0.15, 0.17, and 0.19 ppm, respectively. IMCL concentrations were 8.66±1.24  mmol kg−1, 6.12±0.77  mmol kg−1, and 2.33±0.19  mmol kg−1 in SO, VL, and TA, respectively. Significant differences were observed in IMCL and EMCL pairwise comparisons in SO, VL, and TA (p<0.05). Strong correlations were observed between total fat fractions from H1-MRS and Dixon MRI for VL (r=0.794), SO (r=0.655), and TA (r=0.897). Bland-Altman analysis between fat fractions (FFMRS and FFMRI) showed good agreement with small limits of agreement (LoA): bias=−0.21% (LoA: −1.12% to 0.69%) in VL, bias=0.025% (LoA: −1.28% to 1.33%) in SO, and bias=−0.13% (LoA: −0.74% to 0.47%) in TA. The results of this study demonstrate the variation in muscle fiber orientation and lipid concentrations in these three skeletal muscle types. PMID:26158115

Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication

PubMed Central

Shinbrot, Eve; Henninger, Erin E.; Weinhold, Nils; Covington, Kyle R.; Göksenin, A. Yasemin; Schultz, Nikolaus; Chao, Hsu; Doddapaneni, HarshaVardhan; Muzny, Donna M.; Gibbs, Richard A.; Sander, Chris; Pursell, Zachary F.

2014-01-01

Tumors with somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) exhibit a novel mutator phenotype, with markedly elevated TCT→TAT and TCG→TTG mutations and overall mutation frequencies often exceeding 100 mutations/Mb. Here, we identify POLE-exo* tumors in numerous cancers and classify them into two groups, A and B, according to their mutational properties. Group A mutants are found only in POLE, whereas Group B mutants are found in POLE and POLD1 and appear to be nonfunctional. In Group A, cell-free polymerase assays confirm that mutations in the exonuclease domain result in high mutation frequencies with a preference for C→A mutation. We describe the patterns of amino acid substitutions caused by POLE-exo* and compare them to other tumor types. The nucleotide preference of POLE-exo* leads to increased frequencies of recurrent nonsense mutations in key tumor suppressors such as TP53, ATM, and PIK3R1. We further demonstrate that strand-specific mutation patterns arise from some of these POLE-exo* mutants during genome duplication. This is the first direct proof of leading strand-specific replication by human POLE, which has only been demonstrated in yeast so far. Taken together, the extremely high mutation frequency and strand specificity of mutations provide a unique identifier of eukaryotic origins of replication. PMID:25228659

The androgen receptor gene mutations database.

PubMed

Patterson, M N; Hughes, I A; Gottlieb, B; Pinsky, L

1994-09-01

The androgen receptor gene mutations database is a comprehensive listing of mutations published in journals and meetings proceedings. The majority of mutations are point mutations identified in patients with androgen insensitivity syndrome. Information is included regarding the phenotype, the nature and location of the mutations, as well as the effects of the mutations on the androgen binding activity of the receptor. The current version of the database contains 149 entries, of which 114 are unique mutations. The database is available from EMBL (NetServ@EMBL-Heidelberg.DE) or as a Macintosh Filemaker file (mc33001@musica.mcgill.ca).

Anterior Segment Imaging Predicts Incident Gonioscopic Angle Closure.

PubMed

Baskaran, Mani; Iyer, Jayant V; Narayanaswamy, Arun K; He, Yingke; Sakata, Lisandro M; Wu, Renyi; Liu, Dianna; Nongpiur, Monisha E; Friedman, David S; Aung, Tin

2015-12-01

To investigate the incidence of gonioscopic angle closure after 4 years in subjects with gonioscopically open angles but varying degrees of angle closure detected on anterior segment optical coherence tomography (AS OCT; Visante; Carl Zeiss Meditec, Dublin, CA) at baseline. Prospective, observational study. Three hundred forty-two subjects, mostly Chinese, 50 years of age or older, were recruited, of whom 65 were controls with open angles on gonioscopy and AS OCT at baseline, and 277 were cases with baseline open angles on gonioscopy but closed angles (1-4 quadrants) on AS OCT scans. All subjects underwent gonioscopy and AS OCT at baseline (horizontal and vertical single scans) and after 4 years. The examiner performing gonioscopy was masked to the baseline and AS OCT data. Angle closure in a quadrant was defined as nonvisibility of the posterior trabecular meshwork by gonioscopy and visible iridotrabecular contact beyond the scleral spur in AS OCT scans. Gonioscopic angle closure in 2 or 3 quadrants after 4 years. There were no statistically significant differences in age, ethnicity, or gender between cases and controls. None of the control subjects demonstrated gonioscopic angle closure after 4 years. Forty-eight of the 277 subjects (17.3%; 95% confidence interval [CI], 12.8-23; P < 0.0001) with at least 1 quadrant of angle closure on AS OCT at baseline demonstrated gonioscopic angle closure in 2 or more quadrants, whereas 28 subjects (10.1%; 95% CI, 6.7-14.6; P < 0.004) demonstrated gonioscopic angle closure in 3 or more quadrants after 4 years. Individuals with more quadrants of angle closure on baseline AS OCT scans had a greater likelihood of gonioscopic angle closure developing after 4 years (P < 0.0001, chi-square test for trend for both definitions of angle closure). Anterior segment OCT imaging at baseline predicts incident gonioscopic angle closure after 4 years among subjects who have gonioscopically open angles and iridotrabecular contact on AS OCT at

Exploring the common molecular basis for the universal DNA mutation bias: Revival of Loewdin mutation model

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

Fu, Liang-Yu; Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070; Wang, Guang-Zhong

2011-06-10

Highlights: {yields} There exists a universal G:C {yields} A:T mutation bias in three domains of life. {yields} This universal mutation bias has not been sufficiently explained. {yields} A DNA mutation model proposed by Loewdin 40 years ago offers a common explanation. -- Abstract: Recently, numerous genome analyses revealed the existence of a universal G:C {yields} A:T mutation bias in bacteria, fungi, plants and animals. To explore the molecular basis for this mutation bias, we examined the three well-known DNA mutation models, i.e., oxidative damage model, UV-radiation damage model and CpG hypermutation model. It was revealed that these models cannot providemore » a sufficient explanation to the universal mutation bias. Therefore, we resorted to a DNA mutation model proposed by Loewdin 40 years ago, which was based on inter-base double proton transfers (DPT). Since DPT is a fundamental and spontaneous chemical process and occurs much more frequently within GC pairs than AT pairs, Loewdin model offers a common explanation for the observed universal mutation bias and thus has broad biological implications.« less

Influence of Contact Angle, Growth Angle and Melt Surface Tension on Detached Solidification of InSb

NASA Technical Reports Server (NTRS)

Wang, Yazhen; Regel, Liya L.; Wilcox, William R.

2000-01-01

We extended the previous analysis of detached solidification of InSb based on the moving meniscus model. We found that for steady detached solidification to occur in a sealed ampoule in zero gravity, it is necessary for the growth angle to exceed a critical value, the contact angle for the melt on the ampoule wall to exceed a critical value, and the melt-gas surface tension to be below a critical value. These critical values would depend on the material properties and the growth parameters. For the conditions examined here, the sum of the growth angle and the contact angle must exceed approximately 130, which is significantly less than required if both ends of the ampoule are open.

Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice.

PubMed

Safdar, Adeel; Khrapko, Konstantin; Flynn, James M; Saleem, Ayesha; De Lisio, Michael; Johnston, Adam P W; Kratysberg, Yevgenya; Samjoo, Imtiaz A; Kitaoka, Yu; Ogborn, Daniel I; Little, Jonathan P; Raha, Sandeep; Parise, Gianni; Akhtar, Mahmood; Hettinga, Bart P; Rowe, Glenn C; Arany, Zoltan; Prolla, Tomas A; Tarnopolsky, Mark A

2016-01-01

Human genetic disorders and transgenic mouse models have shown that mitochondrial DNA (mtDNA) mutations and telomere dysfunction instigate the aging process. Epidemiologically, exercise is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of exercise are well established, the molecular mechanisms instigating these observations remain unclear. Endurance exercise reduces mtDNA mutation burden, alleviates multisystem pathology, and increases lifespan of the mutator mice, with proofreading deficient mitochondrial polymerase gamma (POLG1). We report evidence for a POLG1-independent mtDNA repair pathway mediated by exercise, a surprising notion as POLG1 is canonically considered to be the sole mtDNA repair enzyme. Here, we show that the tumor suppressor protein p53 translocates to mitochondria and facilitates mtDNA mutation repair and mitochondrial biogenesis in response to endurance exercise. Indeed, in mutator mice with muscle-specific deletion of p53, exercise failed to prevent mtDNA mutations, induce mitochondrial biogenesis, preserve mitochondrial morphology, reverse sarcopenia, or mitigate premature mortality. Our data establish a new role for p53 in exercise-mediated maintenance of the mtDNA genome and present mitochondrially targeted p53 as a novel therapeutic modality for diseases of mitochondrial etiology.

Modified Angle's Classification for Primary Dentition.

PubMed

Chandranee, Kaushik Narendra; Chandranee, Narendra Jayantilal; Nagpal, Devendra; Lamba, Gagandeep; Choudhari, Purva; Hotwani, Kavita

2017-01-01

This study aims to propose a modification of Angle's classification for primary dentition and to assess its applicability in children from Central India, Nagpur. Modification in Angle's classification has been proposed for application in primary dentition. Small roman numbers i/ii/iii are used for primary dentition notation to represent Angle's Class I/II/III molar relationships as in permanent dentition, respectively. To assess applicability of modified Angle's classification a cross-sectional preschool 2000 children population from central India; 3-6 years of age residing in Nagpur metropolitan city of Maharashtra state were selected randomly as per the inclusion and exclusion criteria. Majority 93.35% children were found to have bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half cusp Class iii molar relationships as per the modified Angle's classification for primary dentition. About 3.75% children had various combinations of Class ii relationships and 0.2% children were having Class iii subdivision relationship. Modification of Angle's classification for application in primary dentition has been proposed. A cross-sectional investigation using new classification revealed various 6.25% Class ii and 0.4% Class iii molar relationships cases in preschool children population in a metropolitan city of Nagpur. Application of the modified Angle's classification to other population groups is warranted to validate its routine application in clinical pediatric dentistry.

Modified Angle's Classification for Primary Dentition

PubMed Central

Chandranee, Kaushik Narendra; Chandranee, Narendra Jayantilal; Nagpal, Devendra; Lamba, Gagandeep; Choudhari, Purva; Hotwani, Kavita

2017-01-01

Aim: This study aims to propose a modification of Angle's classification for primary dentition and to assess its applicability in children from Central India, Nagpur. Methods: Modification in Angle's classification has been proposed for application in primary dentition. Small roman numbers i/ii/iii are used for primary dentition notation to represent Angle's Class I/II/III molar relationships as in permanent dentition, respectively. To assess applicability of modified Angle's classification a cross-sectional preschool 2000 children population from central India; 3–6 years of age residing in Nagpur metropolitan city of Maharashtra state were selected randomly as per the inclusion and exclusion criteria. Results: Majority 93.35% children were found to have bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half cusp Class iii molar relationships as per the modified Angle's classification for primary dentition. About 3.75% children had various combinations of Class ii relationships and 0.2% children were having Class iii subdivision relationship. Conclusions: Modification of Angle's classification for application in primary dentition has been proposed. A cross-sectional investigation using new classification revealed various 6.25% Class ii and 0.4% Class iii molar relationships cases in preschool children population in a metropolitan city of Nagpur. Application of the modified Angle's classification to other population groups is warranted to validate its routine application in clinical pediatric dentistry. PMID:29326514

Angle detector

NASA Technical Reports Server (NTRS)

Parra, G. T. (Inventor)

1978-01-01

An angle detector for determining a transducer's angular disposition to a capacitive pickup element is described. The transducer comprises a pendulum mounted inductive element moving past the capacitive pickup element. The capacitive pickup element divides the inductive element into two parts L sub 1 and L sub 2 which form the arms of one side of an a-c bridge. Two networks R sub 1 and R sub 2 having a plurality of binary weighted resistors and an equal number of digitally controlled switches for removing resistors from the networks form the arms of the other side of the a-c bridge. A binary counter, controlled by a phase detector, balances the bridge by adjusting the resistance of R sub 1 and R sub 2. The binary output of the counter is representative of the angle.

Hong's grading for evaluating anterior chamber angle width.

PubMed

Kim, Seok Hwan; Kang, Ja Heon; Park, Ki Ho; Hong, Chul

2012-11-01

To compare Hong's grading method with anterior segment optical coherence tomography (AS-OCT), gonioscopy, and the dark-room prone-position test (DRPT) for evaluating anterior chamber width. The anterior chamber angle was graded using Hong's grading method, and Hong's angle width was calculated from the arctangent of Hong's grades. The correlation between Hong's angle width and AS-OCT parameters was analyzed. The area under the receiver operating characteristic curve (AUC) for Hong's grading method when discriminating between narrow and open angles as determined by gonioscopy was calculated. Correlation analysis was performed between Hong's angle width and intraocular pressure (IOP) changes determined by DRPT. A total of 60 subjects were enrolled. Of these subjects, 53.5 % had a narrow angle. Hong's angle width correlated significantly with the AS-OCT parameters (r = 0.562-0.719, P < 0.01). A Bland-Altman plot showed relatively good agreement between Hong's angle width and the angle width obtained by AS-OCT. The ability of Hong's grading method to discriminate between open and narrow angles was good (AUC = 0.868, 95 % CI 0.756-0.942). A significant linear correlation was found between Hong's angle width and IOP change determined by DRPT (r = -0.761, P < 0.01). Hong's grading method is useful for detecting narrow angles. Hong's grading correlated well with AS-OCT parameters and DRPT.

Genomic mutation consequence calculator.

PubMed

Major, John E

2007-11-15

The genomic mutation consequence calculator (GMCC) is a tool that will reliably and quickly calculate the consequence of arbitrary genomic mutations. GMCC also reports supporting annotations for the specified genomic region. The particular strength of the GMCC is it works in genomic space, not simply in spliced transcript space as some similar tools do. Within gene features, GMCC can report on the effects on splice site, UTR and coding regions in all isoforms affected by the mutation. A considerable number of genomic annotations are also reported, including: genomic conservation score, known SNPs, COSMIC mutations, disease associations and others. The manual interface also offers link outs to various external databases and resources. In batch mode, GMCC returns a csv file which can easily be parsed by the end user. GMCC is intended to support the many tumor resequencing efforts, but can be useful to any study investigating genomic mutations.

Contact angle hysteresis on superhydrophobic stripes.

PubMed

Dubov, Alexander L; Mourran, Ahmed; Möller, Martin; Vinogradova, Olga I

2014-08-21

We study experimentally and discuss quantitatively the contact angle hysteresis on striped superhydrophobic surfaces as a function of a solid fraction, ϕS. It is shown that the receding regime is determined by a longitudinal sliding motion of the deformed contact line. Despite an anisotropy of the texture the receding contact angle remains isotropic, i.e., is practically the same in the longitudinal and transverse directions. The cosine of the receding angle grows nonlinearly with ϕS. To interpret this we develop a theoretical model, which shows that the value of the receding angle depends both on weak defects at smooth solid areas and on the strong defects due to the elastic energy of the deformed contact line, which scales as ϕS(2)lnϕS. The advancing contact angle was found to be anisotropic, except in a dilute regime, and its value is shown to be determined by the rolling motion of the drop. The cosine of the longitudinal advancing angle depends linearly on ϕS, but a satisfactory fit to the data can only be provided if we generalize the Cassie equation to account for weak defects. The cosine of the transverse advancing angle is much smaller and is maximized at ϕS ≃ 0.5. An explanation of its value can be obtained if we invoke an additional energy due to strong defects in this direction, which is shown to be caused by the adhesion of the drop on solid sectors and is proportional to ϕS(2). Finally, the contact angle hysteresis is found to be quite large and generally anisotropic, but it becomes isotropic when ϕS ≤ 0.2.

Impacts of low-molecular-weight organic acids on aquatic behavior of graphene nanoplatelets and their induced algal toxicity and antioxidant capacity.

PubMed

Wang, Zhuang; Gao, Yucheng; Wang, Se; Fang, Hao; Xu, Defu; Zhang, Fan

2016-06-01

Knowledge of the interaction between graphene-based materials and low-molecular-weight organic acids (LOAs) is essential to understand fate and effects of graphene-based materials in the aquatic environment, but this interaction remains poorly elucidated. In this study, the effects of LOAs on the physicochemical properties of graphene nanoplatelets (GNPs) in an aqueous medium and on the GNP toxicity to algae were studied. The unicellular green alga Scenedesmus obliquus was exposed to GNP suspensions in the presence of benzoic acid or gallic acid at various concentrations. The GNPs had smaller hydrodynamic sizes and the GNP suspensions were more stable and had higher or lower surface zeta potentials in the presence of LOAs than when LOAs were not present. The toxic effects in S. obliquus cultures incubated with GNP suspensions containing LOAs were related to the LOA concentration, and the presence of LOAs caused three effects: stimulation, alleviation, and synergistic inhibition. The intensities of the effects mainly correlated with the LOA concentration, the extent of agglomeration, and particle-induced oxidative stress. The results indicate that the environmental fates and toxicities of GNPs are strongly affected by the binding of GNPs to LOAs.

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

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

Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations

PubMed Central

Kunz, Anjali N.; Begum, Afrin A.; Wu, Hong; D'Ambrozio, Jonathan A.; Robinson, James M.; Shafer, William M.; Bash, Margaret C.; Jerse, Ann E.

2012-01-01

Background. Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA91/95 and parC86 mutations on gonococcal fitness. Methods. Mutant gyrA91/95 and parC86 alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR−79 mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection. Results. In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA91/95 mutation conferred an in vivo fitness benefit to wild-type and mtrR−79 mutant gonococci. The gyrA91/95, parC86 mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA91/95, parC86, mtrR−79 mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (CipR) mutant was selected during infection with the gyrA91/95, parC86, mtrR−79 mutant in which the mtrR−79 mutation was repaired and the gyrA91 mutation was altered. This in vivo–selected mutant grew as well as the wild-type strain in vitro. Conclusions. gyrA91/95 mutations may contribute to the spread of QRNG. Further acquisition of a parC86 mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain CipR. PMID:22492860

An angle-by-angle approach to predicting broadband high-frequency sound fields in rectangular enclosures with experimental comparison.

PubMed

Franzoni, Linda P; Elliott, Christopher M

2003-10-01

Experiments were performed on an elongated rectangular acoustic enclosure with different levels of absorptive material placed on side walls and an end wall. The acoustic source was a broadband high-frequency sound from a loudspeaker flush-mounted to an end wall of the enclosure. Measurements of sound-pressure levels were averaged in cross sections of the enclosure and then compared to theoretical results. Discrepancies between the experimental results and theoretical predictions that treated all incidence angles as equally probable led to the development of an angle-by-angle approach. The new approach agrees well with the experimentally obtained values. In addition, treating the absorptive material as bulk reacting rather than point reacting was found to significantly change the theoretical value for the absorption coefficient and to improve agreement with experiment. The new theory refines an earlier theory based on power conservation and locally diffuse assumptions. Furthermore, the new theory includes both the angle of incidence effects on the resistive and reactive properties of the absorptive material, and the effects of angle filtering, i.e., that reflecting waves associated with shallow angles become relatively stronger than those associated with steep angles as a function of distance from the source.

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma

NASA Astrophysics Data System (ADS)

Jalbert, Llewellyn E.; Elkhaled, Adam; Phillips, Joanna J.; Neill, Evan; Williams, Aurelia; Crane, Jason C.; Olson, Marram P.; Molinaro, Annette M.; Berger, Mitchel S.; Kurhanewicz, John; Ronen, Sabrina M.; Chang, Susan M.; Nelson, Sarah J.

2017-03-01

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

A Ruby in the Rubbish: Beneficial Mutations, Deleterious Mutations and the Evolution of Sex

PubMed Central

Peck, J. R.

1994-01-01

This study presents a mathematical model in which a single beneficial mutation arises in a very large population that is subject to frequent deleterious mutations. The results suggest that, if the population is sexual, then the deleterious mutations will have little effect on the ultimate fate of the beneficial mutation. However, if most offspring are produced asexually, then the probability that the beneficial mutation will be lost from the population may be greatly enhanced by the deleterious mutations. Thus, sexual populations may adapt much more quickly than populations where most reproduction is asexual. Some of the results were produced using computer simulation methods, and a technique was developed that allows treatment of arbitrarily large numbers of individuals in a reasonable amount of computer time. This technique may be of prove useful for the analysis of a wide variety of models, though there are some constraints on its applicability. For example, the technique requires that reproduction can be described by Poisson processes. PMID:8070669

Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.

PubMed

Choi, Min Chul; Heo, Jin-Hyung; Jang, Ja-Hyun; Jung, Sang Geun; Park, Hyun; Joo, Won Duk; Lee, Chan; Lee, Je Ho; Lee, Jun Mo; Hwang, Yoon Young; Kim, Seung Jo

2015-10-01

To investigate and analyze the BRCA mutations in Korean ovarian cancer patients with or without family history and to find founder mutations in this group. One hundred two patients who underwent a staging operation for pathologically proven epithelial cancer between January 2013 and December 2014 were enrolled. Thirty-two patients declined to analyze BRCA1/2 gene alterations after genetic counseling and pedigree analysis. Lymphocyte specimens from peripheral blood were assessed for BRCA1/2 by direct sequencing. BRCA genetic test results of 70 patients were available. Eighteen BRCA1/2 mutations and 17 unclassified variations (UVs) were found. Five of the BRCA1/2 mutations and 4 of the UVs were not reported in the Breast Cancer Information Core database. One BRCA2 UV (8665_8667delGGA) was strongly suspicious to be a deleterious mutation. BRCA1/2 mutations were identified in 11 (61.1%) of 18 patients with a family history and in 7 (13.5%) of 52 patients without a family history.Candidates for founder mutations in Korean ovarian cancer patients were assessed among 39 BRCA1/2 mutations from the present study and from literature reviews. The analysis showed that 1041_1043delAGCinsT (n = 4; 10.2%) and 3746insA (n = 4; 10.2%) were possible BRCA1 founder mutations. Only one of the BRCA2 mutations (5804_5807delTTAA) was repeated twice (n = 2; 5.1%). The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.

Mutation rate evolution in replicator dynamics.

PubMed

Allen, Benjamin; Rosenbloom, Daniel I Scholes

2012-11-01

The mutation rate of an organism is itself evolvable. In stable environments, if faithful replication is costless, theory predicts that mutation rates will evolve to zero. However, positive mutation rates can evolve in novel or fluctuating environments, as analytical and empirical studies have shown. Previous work on this question has focused on environments that fluctuate independently of the evolving population. Here we consider fluctuations that arise from frequency-dependent selection in the evolving population itself. We investigate how the dynamics of competing traits can induce selective pressure on the rates of mutation between these traits. To address this question, we introduce a theoretical framework combining replicator dynamics and adaptive dynamics. We suppose that changes in mutation rates are rare, compared to changes in the traits under direct selection, so that the expected evolutionary trajectories of mutation rates can be obtained from analysis of pairwise competition between strains of different rates. Depending on the nature of frequency-dependent trait dynamics, we demonstrate three possible outcomes of this competition. First, if trait frequencies are at a mutation-selection equilibrium, lower mutation rates can displace higher ones. Second, if trait dynamics converge to a heteroclinic cycle-arising, for example, from "rock-paper-scissors" interactions-mutator strains succeed against non-mutators. Third, in cases where selection alone maintains all traits at positive frequencies, zero and nonzero mutation rates can coexist indefinitely. Our second result suggests that relatively high mutation rates may be observed for traits subject to cyclical frequency-dependent dynamics.

Use of mutation spectra analysis software.

PubMed

Rogozin, I; Kondrashov, F; Glazko, G

2001-02-01

The study and comparison of mutation(al) spectra is an important problem in molecular biology, because these spectra often reflect on important features of mutations and their fixation. Such features include the interaction of DNA with various mutagens, the function of repair/replication enzymes, and properties of target proteins. It is known that mutability varies significantly along nucleotide sequences, such that mutations often concentrate at certain positions, called "hotspots," in a sequence. In this paper, we discuss in detail two approaches for mutation spectra analysis: the comparison of mutation spectra with a HG-PUBL program, (FTP: sunsite.unc.edu/pub/academic/biology/dna-mutations/hyperg) and hotspot prediction with the CLUSTERM program (www.itba.mi.cnr.it/webmutation; ftp.bionet.nsc.ru/pub/biology/dbms/clusterm.zip). Several other approaches for mutational spectra analysis, such as the analysis of a target protein structure, hotspot context revealing, multiple spectra comparisons, as well as a number of mutation databases are briefly described. Mutation spectra in the lacI gene of E. coli and the human p53 gene are used for illustration of various difficulties of such analysis. Copyright 2001 Wiley-Liss, Inc.

Effects of diurnal, lighting, and angle-of-incidence variation on anterior segment optical coherence tomography (AS-OCT) angle metrics.

PubMed

Akil, Handan; Dastiridou, Anna; Marion, Kenneth; Francis, Brian A; Chopra, Vikas

2017-03-23

First reported study to assess the effect of diurnal variation on anterior chamber angle measurements, as well as, to re-test the effects of lighting and angle-of-incidence variation on anterior chamber angle (ACA) measurements acquired by time-domain anterior segment optical coherence tomography (AS-OCT). A total of 30 eyes from 15 healthy, normal subjects underwent anterior chamber imaging using a Visante time-domain AS-OCT according to an IRB-approved protocol. For each eye, the inferior angle was imaged twice in the morning (8 am - 10 am) and then again in the afternoon (3 pm - 5 pm), under light meter-controlled conditions with ambient room lighting 'ON' and lights 'OFF', and at 5° angle of incidence increments. The ACA metrics measured for each eye were: angle opening distance (AOD, measured 500 and 750 μm anterior from scleral spur), the trabecular-iris-space area (TISA, measured 500 and 750 μm anterior from scleral spur), and scleral spur angle. Measurements were performed by masked, certified Reading Center graders using the Visante's Internal Measurement Tool. Differences in measurements between morning and afternoon, lighting variations, and angle of incidence were compared. Mean age of the participants was 31.2 years (range 23-58). Anterior chamber angle metrics did not differ significantly from morning to afternoon imaging, or when the angle of incidence was offset by 5° in either direction away from the inferior angle 6 o'clock position. (p-value 0.13-0.93). Angle metrics at the inferior corneal limbus, 6 o'clock position (IC270), with room lighting 'OFF', showed a significant decrease (p < 0.05) compared to room lighting 'ON'. There does not appear to be significant diurnal variation in AS-OCT parameters in normal individuals, but lighting conditions need to be strictly controlled since variation in lighting led to significant variability in AS-OCT parameters. No changes in ACA parameters were noted by varying the angle

Screening for duplications, deletions and a common intronic mutation detects 35% of second mutations in patients with USH2A monoallelic mutations on Sanger sequencing.

PubMed

Steele-Stallard, Heather B; Le Quesne Stabej, Polona; Lenassi, Eva; Luxon, Linda M; Claustres, Mireille; Roux, Anne-Francoise; Webster, Andrew R; Bitner-Glindzicz, Maria

2013-08-08

Usher Syndrome is the leading cause of inherited deaf-blindness. It is divided into three subtypes, of which the most common is Usher type 2, and the USH2A gene accounts for 75-80% of cases. Despite recent sequencing strategies, in our cohort a significant proportion of individuals with Usher type 2 have just one heterozygous disease-causing mutation in USH2A, or no convincing disease-causing mutations across nine Usher genes. The purpose of this study was to improve the molecular diagnosis in these families by screening USH2A for duplications, heterozygous deletions and a common pathogenic deep intronic variant USH2A: c.7595-2144A>G. Forty-nine Usher type 2 or atypical Usher families who had missing mutations (mono-allelic USH2A or no mutations following Sanger sequencing of nine Usher genes) were screened for duplications/deletions using the USH2A SALSA MLPA reagent kit (MRC-Holland). Identification of USH2A: c.7595-2144A>G was achieved by Sanger sequencing. Mutations were confirmed by a combination of reverse transcription PCR using RNA extracted from nasal epithelial cells or fibroblasts, and by array comparative genomic hybridisation with sequencing across the genomic breakpoints. Eight mutations were identified in 23 Usher type 2 families (35%) with one previously identified heterozygous disease-causing mutation in USH2A. These consisted of five heterozygous deletions, one duplication, and two heterozygous instances of the pathogenic variant USH2A: c.7595-2144A>G. No variants were found in the 15 Usher type 2 families with no previously identified disease-causing mutations. In 11 atypical families, none of whom had any previously identified convincing disease-causing mutations, the mutation USH2A: c.7595-2144A>G was identified in a heterozygous state in one family. All five deletions and the heterozygous duplication we report here are novel. This is the first time that a duplication in USH2A has been reported as a cause of Usher syndrome. We found that 8 of

Beyond Euler angles: exploiting the angle-axis parametrization in a multipole expansion of the rotation operator.

PubMed

Siemens, Mark; Hancock, Jason; Siminovitch, David

2007-02-01

Euler angles (alpha,beta,gamma) are cumbersome from a computational point of view, and their link to experimental parameters is oblique. The angle-axis {Phi, n} parametrization, especially in the form of quaternions (or Euler-Rodrigues parameters), has served as the most promising alternative, and they have enjoyed considerable success in rf pulse design and optimization. We focus on the benefits of angle-axis parameters by considering a multipole operator expansion of the rotation operator D(Phi, n), and a Clebsch-Gordan expansion of the rotation matrices D(MM')(J)(Phi, n). Each of the coefficients in the Clebsch-Gordan expansion is proportional to the product of a spherical harmonic of the vector n specifying the axis of rotation, Y(lambdamu)(n), with a fixed function of the rotation angle Phi, a Gegenbauer polynomial C(2J-lambda)(lambda+1)(cosPhi/2). Several application examples demonstrate that this Clebsch-Gordan expansion gives easy and direct access to many of the parameters of experimental interest, including coherence order changes (isolated in the Clebsch-Gordan coefficients), and rotation angle (isolated in the Gegenbauer polynomials).

Simple Map in Action-Angle Coordinates.

NASA Astrophysics Data System (ADS)

Kerwin, Olivia; Punjabi, Alkesh; Ali, Halima

2008-04-01

The simple map is the simplest map that has the topology of a divertor tokamak. The simple map has three canonical representations: (i) the natural coordinates - toroidal magnetic flux and poloidal angle (ψ,θ), (ii) the physical coordinates - the physical variables (R,Z) or (X,Y), and (iii) the action-angle coordinates - (J,θ) or magnetic coordinates (ψ, θ). All three are canonical coordinates for field lines. The simple map in the (X,Y) representation has been studied extensively ^1, 2. Here we analytically calculate the action-angle coordinates and safety factor q for the simple map. We construct the equilibrium generating function for the simple map in action-angle coordinates. We derive the simple map in action-angle representation, and calculate the stochastic broadening of the ideal separatrix due to topological noise in action-angle representation. We also show how the geometric effects such as elongation, the height, and width of the ideal separatrix surface can be investigated using a slight modification of the simple map in action-angle representation. This work is supported by the following grants US Department of Energy - OFES DE-FG02-01ER54624 and DE-FG02-04ER54793 and National Science Foundation - HRD-0630372 and 0411394. [1] A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys Lett A, 364 140-145 (2007). [2] A. Punjabi, A. Verma, and A. Boozer, Phys.Rev. Lett. 69, 3322 (1992).

Ethnic differences in primary angle-closure glaucoma.

PubMed

Yip, Jennifer L Y; Foster, Paul J

2006-04-01

Observational studies from different countries have shown that populations of East Asian origin have a higher frequency of primary angle-closure glaucoma compared with those of European or African descent. As half of all cases of glaucoma reside in Asia, and with primary angle-closure glaucoma carrying a higher rate of visual morbidity, primary angle-closure glaucoma poses an important public health problem; however, the inconsistent use of techniques and definitions to detect and diagnose primary angle-closure glaucoma has resulted in difficulties in interpreting the accuracy and comparability of such data. Therefore it is important to review these studies in the light of a consistent classification system. There are increasing reports that support previous findings on the incidence and prevalence of primary angle-closure glaucoma in different ethnic groups. There have also been further investigations into the mechanism and natural history of primary angle-closure glaucoma in Asian populations. International investigations into primary angle-closure glaucoma have demonstrated reproducible evidence that ethnic variations do exist. Cross-sectional studies in this area have also suggested that differences in anterior chamber depth, together with its association with peripheral anterior synechiae, may be part of the underlying mechanism behind these differences. The ideas generated need to be further explored with longitudinal data of changes in anterior chamber depth and peripheral anterior synechiae in different populations. The detailed mechanisms behind the development of angle-closure and primary angle-closure glaucoma should also be investigated.

Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.

PubMed

Vincent, John B; Kolozsvari, Debbie; Roberts, Wendy S; Bolton, Patrick F; Gurling, Hugh M D; Scherer, Stephen W

2004-08-15

Autism, a childhood neuropsychiatric disorder with a strong genetic component, is currently the focus of considerable attention within the field of human genetics as well many other medical-related disciplines. A recent study has implicated two X-chromosomal neuroligin genes, NLGN3 and NLGN4, as having an etiological role in autism, having identified a frameshift mutation in one gene and a substitution mutation in the other, segregating in multiplex autism spectrum families (Jamain et al. [2003: Nat Genet 34:27-29]). The function of neuroligin as a trigger for synapse formation would suggest that such mutations would likely result in some form of pathological manifestation. Our own study, screening a larger sample of 196 autism probands, failed to identify any mutations that would affect the coding regions of these genes. Our findings suggest that mutations in these two genes are infrequent in autism. Copyright 2004 Wiley-Liss, Inc.

Two Comments on Bond Angles

NASA Astrophysics Data System (ADS)

Glaister, P.

1997-09-01

Tetrahedral Bond Angle from Elementary Trigonometry The alternative approach of using the scalar (or dot) product of vectors enables the determination of the bond angle in a tetrahedral molecule in a simple way. There is, of course, an even more straightforward derivation suitable for students who are unfamiliar with vectors, or products thereof, but who do know some elementary trigonometry. The starting point is the figure showing triangle OAB. The point O is the center of a cube, and A and B are at opposite corners of a face of that cube in which fits a regular tetrahedron. The required bond angle alpha = AÔB; and using Pythagoras' theorem, AB = 2(square root 2) is the diagonal of a face of the cube. Hence from right-angled triangle OEB, tan(alpha/2) = (square root 2) and therefore alpha = 2tan-1(square root 2) is approx. 109° 28' (see Fig. 1).

A novel missense-mutation-related feature extraction scheme for 'driver' mutation identification.

PubMed

Tan, Hua; Bao, Jiguang; Zhou, Xiaobo

2012-11-15

It becomes widely accepted that human cancer is a disease involving dynamic changes in the genome and that the missense mutations constitute the bulk of human genetic variations. A multitude of computational algorithms, especially the machine learning-based ones, has consequently been proposed to distinguish missense changes that contribute to the cancer progression ('driver' mutation) from those that do not ('passenger' mutation). However, the existing methods have multifaceted shortcomings, in the sense that they either adopt incomplete feature space or depend on protein structural databases which are usually far from integrated. In this article, we investigated multiple aspects of a missense mutation and identified a novel feature space that well distinguishes cancer-associated driver mutations from passenger ones. An index (DX score) was proposed to evaluate the discriminating capability of each feature, and a subset of these features which ranks top was selected to build the SVM classifier. Cross-validation showed that the classifier trained on our selected features significantly outperforms the existing ones both in precision and robustness. We applied our method to several datasets of missense mutations culled from published database and literature and obtained more reasonable results than previous studies. The software is available online at http://www.methodisthealth.com/software and https://sites.google.com/site/drivermutationidentification/. xzhou@tmhs.org. Supplementary data are available at Bioinformatics online.

Effect of laser peripheral iridotomy on anterior chamber angle anatomy in primary angle closure spectrum eyes

PubMed Central

Kansara, Seema; Blieden, Lauren S.; Chuang, Alice Z.; Baker, Laura A.; Bell, Nicholas P.; Mankiewicz, Kimberly A.; Feldman, Robert M.

2015-01-01

Purpose To evaluate the change in trabecular-iris circumference volume (TICV) after laser peripheral iridotomy (LPI) in primary angle closure (PAC) spectrum eyes Patients and Methods Forty-two chronic PAC spectrum eyes from 24 patients were enrolled. Eyes with anterior chamber abnormalities affecting angle measurement were excluded. Intraocular pressure, slit lamp exam, and gonioscopy were recorded at each visit. Anterior segment optical coherence tomography (ASOCT) with 3D mode angle analysis scans were taken with the CASIA SS-1000 (Tomey Corp., Nagoya, Japan) before and after LPI. Forty-two pre-LPI ASOCT scans and 34 post-LPI ASOCT scans were analyzed using the Anterior Chamber Analysis and Interpretation (ACAI, Houston, TX) software. A mixed-effect model analysis was used to compare the trabecular-iris space area (TISA) changes among 4 quadrants, as well as to identify potential factors affecting TICV. Results There was a significant increase in all average angle parameters after LPI (TISA500, TISA750, TICV500, and TICV750). The magnitude of change in TISA500 in the superior angle was significantly less than the other angles. The changes in TICV500 and TICV750 were not associated with any demographic or ocular characteristics. Conclusion TICV is a useful parameter to quantitatively measure the effectiveness of LPI in the treatment of eyes with PAC spectrum disease. PMID:26066504

Using Digital Technology to See Angles from Different Angles. Part 2: Openings and Turns

ERIC Educational Resources Information Center

Host, Erin; Baynham, Emily; McMaster, Heather

2015-01-01

Ever wondered how to use technology to teach angles? This article follows on from an earlier article published last year, providing a range of ideas for integrating technology and concrete materials with the teaching of angle concepts. The authors also provide a comprehensive list of free online games and learning objects that can be used to teach…

Single-Point Mutation with a Rotamer Library Toolkit: Toward Protein Engineering.

PubMed

Pottel, Joshua; Moitessier, Nicolas

2015-12-28

Protein engineers have long been hard at work to harness biocatalysts as a natural source of regio-, stereo-, and chemoselectivity in order to carry out chemistry (reactions and/or substrates) not previously achieved with these enzymes. The extreme labor demands and exponential number of mutation combinations have induced computational advances in this domain. The first step in our virtual approach is to predict the correct conformations upon mutation of residues (i.e., rebuilding side chains). For this purpose, we opted for a combination of molecular mechanics and statistical data. In this work, we have developed automated computational tools to extract protein structural information and created conformational libraries for each amino acid dependent on a variable number of parameters (e.g., resolution, flexibility, secondary structure). We have also developed the necessary tool to apply the mutation and optimize the conformation accordingly. For side-chain conformation prediction, we obtained overall average root-mean-square deviations (RMSDs) of 0.91 and 1.01 Å for the 18 flexible natural amino acids within two distinct sets of over 3000 and 1500 side-chain residues, respectively. The commonly used dihedral angle differences were also evaluated and performed worse than the state of the art. These two metrics are also compared. Furthermore, we generated a family-specific library for kinases that produced an average 2% lower RMSD upon side-chain reconstruction and a residue-specific library that yielded a 17% improvement. Ultimately, since our protein engineering outlook involves using our docking software, Fitted/Impacts, we applied our mutation protocol to a benchmarked data set for self- and cross-docking. Our side-chain reconstruction does not hinder our docking software, demonstrating differences in pose prediction accuracy of approximately 2% (RMSD cutoff metric) for a set of over 200 protein/ligand structures. Similarly, when docking to a set of over 100

Particle chaos and pitch angle scattering

NASA Technical Reports Server (NTRS)

Burkhart, G. R.; Dusenbery, P. B.; Speiser, T. W.

1995-01-01

Pitch angle scattering is a factor that helps determine the dawn-to-dusk current, controls particle energization, and it has also been used as a remote probe of the current sheet structure. Previous studies have interpreted their results under the exception that randomization will be greatest when the ratio of the two timescales of motion (gyration parallel to and perpendicular to the current sheet) is closet to one. Recently, the average expotential divergence rate (AEDR) has been calculated for particle motion in a hyperbolic current sheet (Chen, 1992). It is claimed that this AEDR measures the degree of chaos and therefore may be thought to measure the randomization. In contrast to previous expectations, the AEDR is not maximized when Kappa is approximately equal to 1 but instead increases with decreasing Kappa. Also contrary to previous expectations, the AEDR is dependent upon the parameter b(sub z). In response to the challenge to previous expectations that has been raised by this calculation of the AEDR, we have investigated the dependence of a measure of particle pitch angle scattering on both the parameters Kappa and b(sub z). We find that, as was previously expected, particle pitch angle scattering is maximized near Kappa = 1 provided that Kappa/b(sub z) greater than 1. In the opposite regime, Kappa/b(sub z) less than 1, we find that particle pitch angle scattering is still largest when the two timescales are equal, but the ratio of the timescales is proportional to b(sub z). In this second regime, particle pitch angle scattering is not due to randomization, but is instead due to a systematic pitch angle change. This result shows that particle pitch angle scattering need not be due to randomization and indicates how a measure of pitch angle scattering can exhibit a different behavior than a measure of chaos.

AIP mutations and gigantism.

PubMed

Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F; Beckers, Albert

2017-06-01

AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated pituitary adenoma (FIPA) kindreds, and patients with macroadenomas who are diagnosed ≤30 years). AIP mutations are most prevalent in patients with pituitary gigantism (29% of this group were found to have mutations in AIP gene). These data support targeted genetic screening for AIP mutations/deletions in these groups of pituitary adenoma patients. Earlier diagnosis of AIP-related acromegaly-gigantism cases enables timely clinical evaluation and treatment, thereby improving outcomes in terms of excessive linear growth and acromegaly comorbidities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations.

PubMed

Chen, Ying; Guo, Luo; Li, Chen-Long; Shan, Jing; Xu, Hai-Song; Li, Jie-Ying; Sun, Shan; Hao, Shao-Juan; Jin, Lei; Chai, Gang; Zhang, Tian-Yu

2018-04-01

Treacher Collins syndrome (TCS) (OMIM 154500) is a rare congenital craniofacial disorder with an autosomal dominant manner of inheritance in most cases. To date, three pathogenic genes (TCOF1, POLR1D and POLR1C) have been identified. In this study, we conducted mutational analysis on Chinese TCS patients to reveal a mutational spectrum of known causative genes and show phenotype-genotype data to provide more information for gene counselling and future studies on the pathogenesis of TCS. Twenty-two TCS patients were recruited from two tertiary referral centres, and Sanger sequencing for the coding exons and exon-intron boundaries of TCOF1, POLR1D and POLR1C was performed. For patients without small variants, further copy number variations (CNVs) analysis was conducted using high-density SNP array platforms. The Sanger sequencing overall mutation detection rate was as high as 86.3% (19/22) for our cohort. Fifteen TCOF1 pathogenic variants, including ten novel mutations, were identified in nineteen patients. No causative mutations in POLR1D and POLR1C genes and no CNVs mutations were detected. A suspected autosomal dominant inheritance case that implies germinal mosaicism was described. Our study confirmed that TCOF1 was the main disease-causing gene for the Chinese TCS population and revealed its mutation spectrum. We also addressed the need for more studies of mosaicism in TCS cases, which could explain the mechanism of autosomal dominant inheritance in TCS cases and benefit the prevention of TCS.

Pitch angle of galactic spiral arms

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

Michikoshi, Shugo; Kokubo, Eiichiro, E-mail: michiko@mail.doshisha.ac.jp, E-mail: kokubo@th.nao.ac.jp

2014-06-01

One of the key parameters that characterizes spiral arms in disk galaxies is a pitch angle that measures the inclination of a spiral arm to the direction of galactic rotation. The pitch angle differs from galaxy to galaxy, which suggests that the rotation law of galactic disks determines it. In order to investigate the relation between the pitch angle of spiral arms and the shear rate of galactic differential rotation, we perform local N-body simulations of pure stellar disks. We find that the pitch angle increases with the epicycle frequency and decreases with the shear rate and obtain the fittingmore » formula. This dependence is explained by the swing amplification mechanism.« less

Gonioscopy in primary angle closure glaucoma.

PubMed

Bruno, Christina A; Alward, Wallace L M

2002-06-01

Primary angle closure is a condition characterized by obstruction to aqueous humor outflow by the peripheral iris, and results in changes in the iridocorneal angle that are visible through gonioscopic examination. Gonioscopy in these eyes, however, can be difficult. This chapter discusses techniques that might help in the examination. These include beginning the examination with the inferior angle, methods to help in looking over the iris, cycloplegia, locating the corneal wedge, indentation, van Herick estimation, examining the other eye, and topical glycerin. Finally, there is a discussion about the pathology associated with the closed angle, with emphasis on the appearance of iris bombé, plateau iris, and the distinction between iris processes and peripheral anterior synechiae.

Contact angle distribution of particles at fluid interfaces.

PubMed

Snoeyink, Craig; Barman, Sourav; Christopher, Gordon F

2015-01-27

Recent measurements have implied a distribution of interfacially adsorbed particles' contact angles; however, it has been impossible to measure statistically significant numbers for these contact angles noninvasively in situ. Using a new microscopy method that allows nanometer-scale resolution of particle's 3D positions on an interface, we have measured the contact angles for thousands of latex particles at an oil/water interface. Furthermore, these measurements are dynamic, allowing the observation of the particle contact angle with high temporal resolution, resulting in hundreds of thousands of individual contact angle measurements. The contact angle has been found to fit a normal distribution with a standard deviation of 19.3°, which is much larger than previously recorded. Furthermore, the technique used allows the effect of measurement error, constrained interfacial diffusion, and particle property variation on the contact angle distribution to be individually evaluated. Because of the ability to measure the contact angle noninvasively, the results provide previously unobtainable, unique data on the dynamics and distribution of the adsorbed particles' contact angle.

Correlations between Preoperative Angle Parameters and Postoperative Unpredicted Refractive Errors after Cataract Surgery in Open Angle Glaucoma (AOD 500).

PubMed

Lee, Wonseok; Bae, Hyoung Won; Lee, Si Hyung; Kim, Chan Yun; Seong, Gong Je

2017-03-01

To assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors. This study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors. In patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (β=-2.925, R²=0.404). Clinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors.

Optimum take-off angle in the long jump.

PubMed

Linthorne, Nicholas P; Guzman, Maurice S; Bridgett, Lisa A

2005-07-01

In this study, we found that the optimum take-off angle for a long jumper may be predicted by combining the equation for the range of a projectile in free flight with the measured relations between take-off speed, take-off height and take-off angle for the athlete. The prediction method was evaluated using video measurements of three experienced male long jumpers who performed maximum-effort jumps over a wide range of take-off angles. To produce low take-off angles the athletes used a long and fast run-up, whereas higher take-off angles were produced using a progressively shorter and slower run-up. For all three athletes, the take-off speed decreased and the take-off height increased as the athlete jumped with a higher take-off angle. The calculated optimum take-off angles were in good agreement with the athletes' competition take-off angles.

HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium.

PubMed

Pillai, Rathi N; Behera, Madhusmita; Berry, Lynne D; Rossi, Mike R; Kris, Mark G; Johnson, Bruce E; Bunn, Paul A; Ramalingam, Suresh S; Khuri, Fadlo R

2017-11-01

Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2-directed therapies. A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%-4%). One patient had a concurrent mesenchymal-epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never-smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2-targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy. HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed therapies should be investigated in this subgroup of patients. Cancer 2017;123:4099-4105. © 2017 American Cancer Society. © 2017 American Cancer Society.

Ring magnet firing angle control

DOEpatents

Knott, M.J.; Lewis, L.G.; Rabe, H.H.

1975-10-21

A device is provided for controlling the firing angles of thyratrons (rectifiers) in a ring magnet power supply. A phase lock loop develops a smooth ac signal of frequency equal to and in phase with the frequency of the voltage wave developed by the main generator of the power supply. A counter that counts from zero to a particular number each cycle of the main generator voltage wave is synchronized with the smooth AC signal of the phase lock loop. Gates compare the number in the counter with predetermined desired firing angles for each thyratron and with coincidence the proper thyratron is fired at the predetermined firing angle.

Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.

PubMed

Anandapadamanaban, Madhanagopal; Pilstål, Robert; Andresen, Cecilia; Trewhella, Jill; Moche, Martin; Wallner, Björn; Sunnerhagen, Maria

2016-08-02

MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 Å) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members. Copyright © 2016 Elsevier Ltd. All rights reserved.

A thermodynamic model of contact angle hysteresis.

PubMed

Makkonen, Lasse

2017-08-14

When a three-phase contact line moves along a solid surface, the contact angle no longer corresponds to the static equilibrium angle but is larger when the liquid is advancing and smaller when the liquid is receding. The difference between the advancing and receding contact angles, i.e., the contact angle hysteresis, is of paramount importance in wetting and capillarity. For example, it determines the magnitude of the external force that is required to make a drop slide on a solid surface. Until now, fundamental origin of the contact angle hysteresis has been controversial. Here, this origin is revealed and a quantitative theory is derived. The theory is corroborated by the available experimental data for a large number of solid-liquid combinations. The theory is applied in modelling the contact angle hysteresis on a textured surface, and these results are also in quantitative agreement with the experimental data.

Analysis and implications of mutational variation.

PubMed

Keightley, Peter D; Halligan, Daniel L

2009-06-01

Variation from new mutations is important for several questions in quantitative genetics. Key parameters are the genomic mutation rate and the distribution of effects of mutations (DEM), which determine the amount of new quantitative variation that arises per generation from mutation (V(M)). Here, we review methods and empirical results concerning mutation accumulation (MA) experiments that have shed light on properties of mutations affecting quantitative traits. Surprisingly, most data on fitness traits from laboratory assays of MA lines indicate that the DEM is platykurtic in form (i.e., substantially less leptokurtic than an exponential distribution), and imply that most variation is produced by mutations of moderate to large effect. This finding contrasts with results from MA or mutagenesis experiments in which mutational changes to the DNA can be assayed directly, which imply that the vast majority of mutations have very small phenotypic effects, and that the distribution has a leptokurtic form. We compare these findings with recent approaches that attempt to infer the DEM for fitness based on comparing the frequency spectra of segregating nucleotide polymorphisms at putatively neutral and selected sites in population samples. When applied to data for humans and Drosophila, these analyses also indicate that the DEM is strongly leptokurtic. However, by combining the resultant estimates of parameters of the DEM with estimates of the mutation rate per nucleotide, the predicted V(M) for fitness is only a tiny fraction of V(M) observed in MA experiments. This discrepancy can be explained if we postulate that a few deleterious mutations of large effect contribute most of the mutational variation observed in MA experiments and that such mutations segregate at very low frequencies in natural populations, and effectively are never seen in population samples.

Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation

PubMed Central

Mehta, Gautam U.; Feldman, Michael J.; Wang, Herui; Ding, Dale; Chittiboina, Prashant

2016-01-01

The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I–V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene. PMID:26848914

Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation.

PubMed

Mehta, Gautam U; Feldman, Michael J; Wang, Herui; Ding, Dale; Chittiboina, Prashant

2016-12-01

The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I-V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene.

Solar cell angle of incidence corrections

NASA Technical Reports Server (NTRS)

Burger, Dale R.; Mueller, Robert L.

1995-01-01

Literature on solar array angle of incidence corrections was found to be sparse and contained no tabular data for support. This lack along with recent data on 27 GaAs/Ge 4 cm by 4 cm cells initiated the analysis presented in this paper. The literature cites seven possible contributors to angle of incidence effects: cosine, optical front surface, edge, shadowing, UV degradation, particulate soiling, and background color. Only the first three are covered in this paper due to lack of sufficient data. The cosine correction is commonly used but is not sufficient when the incident angle is large. Fresnel reflection calculations require knowledge of the index of refraction of the coverglass front surface. The absolute index of refraction for the coverglass front surface was not known nor was it measured due to lack of funds. However, a value for the index of refraction was obtained by examining how the prediction errors varied with different assumed indices and selecting the best fit to the set of measured values. Corrections using front surface Fresnel reflection along with the cosine correction give very good predictive results when compared to measured data, except there is a definite trend away from predicted values at the larger incident angles. This trend could be related to edge effects and is illustrated by a use of a box plot of the errors and by plotting the deviation of the mean against incidence angle. The trend is for larger deviations at larger incidence angles and there may be a fourth order effect involved in the trend. A chi-squared test was used to determine if the measurement errors were normally distributed. At 10 degrees the chi-squared test failed, probably due to the very small numbers involved or a bias from the measurement procedure. All other angles showed a good fit to the normal distribution with increasing goodness-of-fit as the angles increased which reinforces the very small numbers hypothesis. The contributed data only went to 65 degrees

MUTATIONS INDUCED BY URBAN AIR AND DRINKING WATER: DO THEY LEAVE A MUTATIONAL SIGNATURE IN HUMAN TUMORS?

EPA Science Inventory

Mutations Induced by Urban Air and Drinking Water: Do They Leave a Mutational Signature in Human Tumors?

Mutation spectra of complex environmental mixtures have been determined thus far only in Salmonella. We have determined mutation spectra for the particulate organics ...

Spectral data of specular reflectance, narrow-angle transmittance and angle-resolved surface scattering of materials for solar concentrators.

PubMed

Good, Philipp; Cooper, Thomas; Querci, Marco; Wiik, Nicolay; Ambrosetti, Gianluca; Steinfeld, Aldo

2016-03-01

The spectral specular reflectance of conventional and novel reflective materials for solar concentrators is measured with an acceptance angle of 17.5 mrad over the wavelength range 300-2500 nm at incidence angles 15-60° using a spectroscopic goniometry system. The same experimental setup is used to determine the spectral narrow-angle transmittance of semi-transparent materials for solar collector covers at incidence angles 0-60°. In addition, the angle-resolved surface scattering of reflective materials is recorded by an area-scan CCD detector over the spectral range 350-1050 nm. A comprehensive summary, discussion, and interpretation of the results are included in the associated research article "Spectral reflectance, transmittance, and angular scattering of materials for solar concentrators" in Solar Energy Materials and Solar Cells.

Test-retest reliability of sit-to-stand and stand-to-sit analysis in people with and without chronic non-specific low back pain.

PubMed

Pourahmadi, Mohammad Reza; Ebrahimi Takamjani, Ismail; Jaberzadeh, Shapour; Sarrafzadeh, Javad; Sanjari, Mohammad Ali; Bagheri, Rasool; Jannati, Elham

2018-06-01

Sit-to-stand (STD) and stand-to-sit (SIT) analysis can provide information on functional independence in daily activities in patients with low back pain (LBP). However, in order for measurements to be clinically useful, data on psychometric properties should be available. The main purpose was to investigate intra-rater reliability of STD and SIT tasks in participants with and without chronic non-specific LBP (CNLBP). The second purpose was to detect any differences in lumbar spine and hips sagittal plane kinematics and coordination between asymptomatic individuals and CNLBP patients during STD and SIT. Cross-sectional study. Twenty-three CNLBP patients and 23 demographically-matched controls were recruited. Ten markers were placed on specific anatomical landmarks. Participants were asked to perform STD and SIT at a preferred speed. Peak flexion angles, mean angular velocities, lumbar to hip movement ratios, and relative phase angles were measured. The procedure was repeated after 2 h and 6-8 days. Differences between two groups were analyzed using independent t-test. Intraclass correlation coefficient (ICC 3,k), standard error of measurement (SEM), and limits of agreement (LOAs) were also estimated. The ICC values showed moderate to excellent intra-rater reliability, with relatively low SEM values (≤10.17°). The 95% LOAs demonstrated that there were no differences between the measured parameters. Furthermore, CNLBP patients had limited sagittal plane angles, smaller angular velocities, and lumbar-hip dis-coordination compared to asymptomatic participants. The results indicated moderate to excellent test-retest reliability of STD and SIT analysis. Moreover, CNLBP patients had altered kinematics during STD and its reverse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deflection angle detecting system for the large-angle and high-linearity fast steering mirror using quadrant detector

NASA Astrophysics Data System (ADS)

Ni, Yingxue; Wu, Jiabin; San, Xiaogang; Gao, Shijie; Ding, Shaohang; Wang, Jing; Wang, Tao

2018-02-01

A deflection angle detecting system (DADS) using a quadrant detector (QD) is developed to achieve the large deflection angle and high linearity for the fast steering mirror (FSM). The mathematical model of the DADS is established by analyzing the principle of position detecting and error characteristics of the QD. Based on this mathematical model, the method of optimizing deflection angle and linearity of FSM is demonstrated, which is proved feasible by simulation and experimental results. Finally, a QD-based FSM is designed and tested. The results show that it achieves 0.72% nonlinearity, ±2.0 deg deflection angle, and 1.11-μrad resolution. Therefore, the application of this method will be beneficial to design the FSM.

Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy

PubMed Central

Correa, Bruna R.; Bettoni, Fabiana; Koyama, Fernanda C.; Navarro, Fabio C.P.; Perez, Rodrigo O.; Mariadason, John; Sieber, Oliver M.; Strausberg, Robert L.; Simpson, Andrew J.G.; Jardim, Denis L.F.; Reis, Luiz Fernando L.; Parmigiani, Raphael B.; Galante, Pedro A.F.; Camargo, Anamaria A.

2014-01-01

We carried out a mutational analysis of 3,594 genes coding for cell surface proteins (Surfaceome) in 23 colorectal cancer cell lines, searching for new altered pathways, druggable mutations and mutated epitopes for targeted therapy in colorectal cancer. A total of 3,944 somatic non-synonymous substitutions and 595 InDels, occurring in 2,061 (57%) Surfaceome genes were catalogued. We identified 48 genes not previously described as mutated in colorectal tumors in the TCGA database, including genes that are mutated and expressed in >10% of the cell lines (SEMA4C, FGFRL1, PKD1, FAM38A, WDR81, TMEM136, SLC36A1, SLC26A6, IGFLR1). Analysis of these genes uncovered important roles for FGF and SEMA4 signaling in colorectal cancer with possible therapeutic implications. We also found that cell lines express on average 11 druggable mutations, including frequent mutations (>20%) in the receptor tyrosine kinases AXL and EPHA2, which have not been previously considered as potential targets for colorectal cancer. Finally, we identified 82 cell surface mutated epitopes, however expression of only 30% of these epitopes was detected in our cell lines. Notwithstanding, 92% of these epitopes were expressed in cell lines with the mutator phenotype, opening new venues for the use of “general” immune checkpoint drugs in this subset of patients. PMID:25193853

A gallery approach for off-angle iris recognition

NASA Astrophysics Data System (ADS)

Karakaya, Mahmut; Yoldash, Rashiduddin; Boehnen, Christopher

2015-05-01

It has been proven that hamming distance score between frontal and off-angle iris images of same eye differs in iris recognition system. The distinction of hamming distance score is caused by many factors such as image acquisition angle, occlusion, pupil dilation, and limbus effect. In this paper, we first study the effect of the angle variations between iris plane and the image acquisition systems. We present how hamming distance changes for different off-angle iris images even if they are coming from the same iris. We observe that increment in acquisition angle of compared iris images causes the increment in hamming distance. Second, we propose a new technique in off-angle iris recognition system that includes creating a gallery of different off-angle iris images (such as, 0, 10, 20, 30, 40, and 50 degrees) and comparing each probe image with these gallery images. We will show the accuracy of the gallery approach for off-angle iris recognition.

Population Heterogeneity in Mutation Rate Increases the Frequency of Higher-Order Mutants and Reduces Long-Term Mutational Load

PubMed Central

Alexander, Helen K.; Mayer, Stephanie I.; Bonhoeffer, Sebastian

2017-01-01

Abstract Mutation rate is a crucial evolutionary parameter that has typically been treated as a constant in population genetic analyses. However, the propensity to mutate is likely to vary among co-existing individuals within a population, due to genetic polymorphisms, heterogeneous environmental influences, and random physiological fluctuations. We review the evidence for mutation rate heterogeneity and explore its consequences by extending classic population genetic models to allow an arbitrary distribution of mutation rate among individuals, either with or without inheritance. With this general new framework, we rigorously establish the effects of heterogeneity at various evolutionary timescales. In a single generation, variation of mutation rate about the mean increases the probability of producing zero or many simultaneous mutations on a genome. Over multiple generations of mutation and selection, heterogeneity accelerates the appearance of both deleterious and beneficial multi-point mutants. At mutation-selection balance, higher-order mutant frequencies are likewise boosted, while lower-order mutants exhibit subtler effects; nonetheless, population mean fitness is always enhanced. We quantify the dependencies on moments of the mutation rate distribution and selection coefficients, and clarify the role of mutation rate inheritance. While typical methods of estimating mutation rate will recover only the population mean, analyses assuming mutation rate is fixed to this mean could underestimate the potential for multi-locus adaptation, including medically relevant evolution in pathogenic and cancerous populations. We discuss the potential to empirically parameterize mutation rate distributions, which have to date hardly been quantified. PMID:27836985

Comparison of next-generation sequencing mutation profiling with BRAF and IDH1 mutation-specific immunohistochemistry.

PubMed

Jabbar, Kausar J; Luthra, Rajalakshmi; Patel, Keyur P; Singh, Rajesh R; Goswami, Rashmi; Aldape, Ken D; Medeiros, L Jeffrey; Routbort, Mark J

2015-04-01

Mutation-specific antibodies for BRAF V600E and IDH1 R132H offer convenient immunohistochemical (IHC) assays to detect these mutations in tumors. Previous studies using these antibodies have shown high sensitivity and specificity, but use in routine diagnosis with qualitative assessment has not been well studied. In this retrospective study, we reviewed BRAF and IDH1 mutation-specific IHC results compared with separately obtained clinical next-generation sequencing results. For 67 tumors with combined IDH1 IHC and mutation data, IHC was unequivocally reported as positive or negative in all cases. Sensitivity of IHC for IDH1 R132H was 98% and specificity was 100% compared with mutation status. Four IHC-negative samples showed non-R132H IDH1 mutations including R132C, R132G, and P127T. For 128 tumors with combined BRAF IHC and mutation data, IHC was positive in 33, negative in 82, and equivocal in 13 tumors. The sensitivity of IHC was 97% and specificity was 99% when including only unequivocally positive or negative results. If equivocal IHC cases were included in the analysis as negative, sensitivity fell to 81%. If equivocal cases were classified as positive, specificity dropped to 91%. Eight IHC-negative samples showed non-V600E BRAF mutations including V600K, N581I, V600M, and K601E. We conclude that IHC for BRAF V600E and IDH1 R132H is relatively sensitive and specific, but there is a discordance rate that is not trivial. In addition, a significant proportion of patients harbor BRAF non-V600E or IDH1 non-R132H mutations not detectable by IHC, potentially limiting utility of IHC screening for BRAF and IDH1 mutations.

The Dual-Angle Method for Fast, Sensitive T1 Measurement in Vivo with Low-Angle Adiabatic Pulses

NASA Astrophysics Data System (ADS)

Bottomley, P. A.; Ouwerkerk, R.

A new method for measuring T1 based on a measurement of the ratio, R, of the steady-state partially saturated NMR signals acquired at two fixed low flip angles (<90°) and a single sequence-repetition period, TR, is presented, The flip angles are chosen to optimize both the signal-to-noise ratio per unit time relative to the best possible Ernst-angle performance and the sensitivity with which a measurement of R can resolve differences in T1. A flip-angle pair at of around (60°, 15°) yields 70-79% of the maximum achievable Ernst-angle signal-to-noise ratio and a near-linear dependence of R on TR/ T1 with gradient of about 2:1 over the range 0.1 ≤ TR/ T1 ≤ 1. Errors in hip-angle and excitation-field ( B1) inhomogeneity result in roughly proportionate errors in the apparent T1. The method is best implemented with adiabatic low-angle pulses such as B1-independent rotation (BIR-4) or BIR-4 phase-cycled (BIRP) pulses, which permit measurements with surface coils. Experimental validation was obtained at 2 T by comparison of unlocalized inversion-recovery and dual-angle proton ( 1H) and phosphorus ( 31P) measurements from vials containing doped water with 0.04 ≤ T1 ≤ 2.8 s and from the metabolites in the calf muscles of eight human volunteers. Calf muscle values of 6 ± 0.5 s for phosphocreatine and around 3.7 ± 0.8 s for the adenosine triphosphates (ATP) were in good agreement with inversion-recovery T1 values and values from the literature. Use of the dual-angle method accelerated T1 measurement time by about fivefold over inversion recovery. The dual-angle method was implemented in a one-dimensional localized surface-coil 31P spectroscopy sequence, producing consistent T1 measurements from phantoms, the calf muscle, and the human liver. 31P T1 values of ATP in the livers of six volunteers were about 0.5 ± 0.1 to 0.6 ± 0.2 s: the total exam times were about 35 minutes per subject. The method is ideally suited to low-sensitivity and/or low

Correlations between Preoperative Angle Parameters and Postoperative Unpredicted Refractive Errors after Cataract Surgery in Open Angle Glaucoma (AOD 500)

PubMed Central

Lee, Wonseok; Bae, Hyoung Won; Lee, Si Hyung; Kim, Chan Yun

2017-01-01

Purpose To assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors. Materials and Methods This study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors. Results In patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (β=-2.925, R2=0.404). Conclusion Clinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors. PMID:28120576

Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing.

PubMed

Stattin, Eva-Lena; Boström, Ida Maria; Winbo, Annika; Cederquist, Kristina; Jonasson, Jenni; Jonsson, Björn-Anders; Diamant, Ulla-Britt; Jensen, Steen M; Rydberg, Annika; Norberg, Anna

2012-10-25

Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort. Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT). In total, a disease-causing mutation was identified in 103 of the 200 (52%) index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%), whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death. In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the mutations and 3 of 36 selected cases (8%) harboured a mutation in the

Simultaneous mutation detection of three homoeologous genes in wheat by High Resolution Melting analysis and Mutation Surveyor.

PubMed

Dong, Chongmei; Vincent, Kate; Sharp, Peter

2009-12-04

TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful tool for reverse genetics, combining traditional chemical mutagenesis with high-throughput PCR-based mutation detection to discover induced mutations that alter protein function. The most popular mutation detection method for TILLING is a mismatch cleavage assay using the endonuclease CelI. For this method, locus-specific PCR is essential. Most wheat genes are present as three similar sequences with high homology in exons and low homology in introns. Locus-specific primers can usually be designed in introns. However, it is sometimes difficult to design locus-specific PCR primers in a conserved region with high homology among the three homoeologous genes, or in a gene lacking introns, or if information on introns is not available. Here we describe a mutation detection method which combines High Resolution Melting (HRM) analysis of mixed PCR amplicons containing three homoeologous gene fragments and sequence analysis using Mutation Surveyor software, aimed at simultaneous detection of mutations in three homoeologous genes. We demonstrate that High Resolution Melting (HRM) analysis can be used in mutation scans in mixed PCR amplicons containing three homoeologous gene fragments. Combining HRM scanning with sequence analysis using Mutation Surveyor is sensitive enough to detect a single nucleotide mutation in the heterozygous state in a mixed PCR amplicon containing three homoeoloci. The method was tested and validated in an EMS (ethylmethane sulfonate)-treated wheat TILLING population, screening mutations in the carboxyl terminal domain of the Starch Synthase II (SSII) gene. Selected identified mutations of interest can be further analysed by cloning to confirm the mutation and determine the genomic origin of the mutation. Polyploidy is common in plants. Conserved regions of a gene often represent functional domains and have high sequence similarity between homoeologous loci. The method described here

Anterior chamber angle assessment using gonioscopy and ultrasound biomicroscopy.

PubMed

Narayanaswamy, Arun; Vijaya, Lingam; Shantha, B; Baskaran, Mani; Sathidevi, A V; Baluswamy, Sukumar

2004-01-01

Comparison of anterior chamber angle measurements using ultrasound biomicroscopy (UBM) and gonioscopy. Five hundred subjects were evaluated for grading of angle width by the Shaffer method. UBM was done in the same group to document angle width, angle opening distance (AOD 500), and anterior chamber depth. Biometric parameters were documented in all subjects. UBM and gonioscopic findings were compared. A study was conducted in 282 men and 218 women with a mean age of 57.32 +/- 12.48 years. Gonioscopic grading was used to segregate occludable (slit-like, grades 1 and 2) from nonoccludable (grades 3 and 4) angles. Subjective assessment by gonioscopy resulted in an overestimation of angle width within the occludable group when compared with values obtained by UBM. This did not affect the segregation of occludable versus nonoccludable angles by gonioscopy. Biometric parameters in eyes with occludable angles were significantly lower in comparison with eyes with nonoccludable angles, except for lens thickness. AOD 500 correlated well with angle width. We concluded that clinical segregation into occludable and nonoccludable angles by an experienced observer using gonioscopy is fairly accurate. However, UBM is required for objective quantification of angles, and AOD 500 can be a reliable and standard parameter to grade angle width.

[Visual cuing effect for haptic angle judgment].

PubMed

Era, Ataru; Yokosawa, Kazuhiko

2009-08-01

We investigated whether visual cues are useful for judging haptic angles. Participants explored three-dimensional angles with a virtual haptic feedback device. For visual cues, we use a location cue, which synchronizes haptic exploration, and a space cue, which specifies the haptic space. In Experiment 1, angles were judged more correctly with both cues, but were overestimated with a location cue only. In Experiment 2, the visual cues emphasized depth, and overestimation with location cues occurred, but space cues had no influence. The results showed that (a) when both cues are presented, haptic angles are judged more correctly. (b) Location cues facilitate only motion information, and not depth information. (c) Haptic angles are apt to be overestimated when there is both haptic and visual information.

Analytical validation of BRAF mutation testing from circulating free DNA using the amplification refractory mutation testing system.

PubMed

Aung, Kyaw L; Donald, Emma; Ellison, Gillian; Bujac, Sarah; Fletcher, Lynn; Cantarini, Mireille; Brady, Ged; Orr, Maria; Clack, Glen; Ranson, Malcolm; Dive, Caroline; Hughes, Andrew

2014-05-01

BRAF mutation testing from circulating free DNA (cfDNA) using the amplification refractory mutation testing system (ARMS) holds potential as a surrogate for tumor mutation testing. Robust assay validation is needed to establish the optimal clinical matrix for measurement and cfDNA-specific mutation calling criteria. Plasma- and serum-derived cfDNA samples from 221 advanced melanoma patients were analyzed for BRAF c.1799T>A (p.V600E) mutation using ARMS in two stages in a blinded fashion. cfDNA-specific mutation calling criteria were defined in stage 1 and validated in stage 2. cfDNA concentrations in serum and plasma, and the sensitivities and specificities of BRAF mutation detection in these two clinical matrices were compared. Sensitivity of BRAF c.1799T>A (p.V600E) mutation detection in cfDNA was increased by using mutation calling criteria optimized for cfDNA (these criteria were adjusted from those used for archival tumor biopsies) without compromising specificity. Sensitivity of BRAF mutation detection in serum was 44% (95% CI, 35% to 53%) and in plasma 52% (95% CI, 43% to 61%). Specificity was 96% (95% CI, 90% to 99%) in both matrices. Serum contains significantly higher total cfDNA than plasma, whereas the proportion of tumor-derived mutant DNA was significantly higher in plasma. Using mutation calling criteria optimized for cfDNA improves sensitivity of BRAF c.1799T>A (p.V600E) mutation detection. The proportion of tumor-derived cfDNA in plasma was significantly higher than in serum. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Frequent PIK3CA Mutations in Colorectal and Endometrial Cancer with Double Somatic Mismatch Repair Mutations

PubMed Central

Cohen, Stacey A.; Turner, Emily H.; Beightol, Mallory B.; Jacobson, Angela; Gooley, Ted A.; Salipante, Stephen J.; Haraldsdottir, Sigurdis; Smith, Christina; Scroggins, Sheena; Tait, Jonathan F.; Grady, William M.; Lin, Edward H.; Cohn, David E.; Goodfellow, Paul J.; Arnold, Mark W.; de la Chapelle, Albert; Pearlman, Rachel; Hampel, Heather; Pritchard, Colin C.

2016-01-01

Background & Aims Double somatic mutations in mismatch repair (MMR) genes have recently been described in colorectal and endometrial cancers with microsatellite instability (MSI) not attributable to MLH1 hypermethylation or germline mutation. We sought to define the molecular phenotype of this newly recognized tumor subtype. Methods From two prospective Lynch syndrome screening studies, we identified patients with colorectal and endometrial tumors harboring ≥2 somatic MMR mutations, but normal germline MMR testing (“double somatic”). We determined the frequencies of tumor PIK3CA, BRAF, KRAS, NRAS, and PTEN mutations by targeted next-generation sequencing and used logistic-regression models to compare them to: Lynch syndrome, MLH1 hypermethylated, and microsatellite stable (MSS) tumors. We validated our findings using independent datasets from The Cancer Genome Atlas (TCGA). Results Among colorectal cancer cases, we found that 14/21 (67%) of double somatic cases had PIK3CA mutations vs. 4/18 (22%) Lynch syndrome, 2/10 (20%) MLH1 hypermethylated, and 12/78 (15%) MSS tumors; p<0.0001. PIK3CA mutations were detected in 100% of 13 double somatic endometrial cancers (p=0.04). BRAF mutations were absent in double somatic and Lynch syndrome colorectal tumors. We found highly similar results in a validation cohort from TCGA (113 colorectal, 178 endometrial cancer), with 100% of double somatic cases harboring a PIK3CA mutation (p<0.0001). Conclusions PIK3CA mutations are present in double somatic mutated colorectal and endometrial cancers at substantially higher frequencies than other MSI subgroups. PIK3CA mutation status may better define an emerging molecular entity in colorectal and endometrial cancers, with the potential to inform screening and therapeutic decision making. PMID:27302833

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

PubMed

Rebbeck, Timothy R; Friebel, Tara M; Friedman, Eitan; Hamann, Ute; Huo, Dezheng; Kwong, Ava; Olah, Edith; Olopade, Olufunmilayo I; Solano, Angela R; Teo, Soo-Hwang; Thomassen, Mads; Weitzel, Jeffrey N; Chan, T L; Couch, Fergus J; Goldgar, David E; Kruse, Torben A; Palmero, Edenir Inêz; Park, Sue Kyung; Torres, Diana; van Rensburg, Elizabeth J; McGuffog, Lesley; Parsons, Michael T; Leslie, Goska; Aalfs, Cora M; Abugattas, Julio; Adlard, Julian; Agata, Simona; Aittomäki, Kristiina; Andrews, Lesley; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Asseryanis, Ella; Auerbach, Leo; Azzollini, Jacopo; Balmaña, Judith; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Benitez, Javier; Berger, Andreas; Berger, Raanan; Blanco, Amie M; Blazer, Kathleen R; Blok, Marinus J; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caldes, Trinidad; Caliebe, Almuth; Caligo, Maria A; Campbell, Ian; Caputo, Sandrine M; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Collée, J Margriet; Cook, Jackie; Davidson, Rosemarie; de la Hoya, Miguel; De Leeneer, Kim; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Ding, Yuan Chun; Ditsch, Nina; Domchek, Susan M; Dorfling, Cecilia M; Velazquez, Carolina; Dworniczak, Bernd; Eason, Jacqueline; Easton, Douglas F; Eeles, Ros; Ehrencrona, Hans; Ejlertsen, Bent; Engel, Christoph; Engert, Stefanie; Evans, D Gareth; Faivre, Laurence; Feliubadaló, Lidia; Ferrer, Sandra Fert; Foretova, Lenka; Fowler, Jeffrey; Frost, Debra; Galvão, Henrique C R; Ganz, Patricia A; Garber, Judy; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Gesta, Paul; Giannini, Giuseppe; Giraud, Sophie; Glendon, Gord; Godwin, Andrew K; Greene, Mark H; Gronwald, Jacek; Gutierrez-Barrera, Angelica; Hahnen, Eric; Hauke, Jan; Henderson, Alex; Hentschel, Julia; Hogervorst, Frans B L; Honisch, Ellen; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Kaczmarek, Katarzyna; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Kim, Sung-Won; Konstantopoulou, Irene; Korach, Jacob; Laitman, Yael; Lasa, Adriana; Lasset, Christine; Lázaro, Conxi; Lee, Annette; Lee, Min Hyuk; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lindor, Noralane M; Longy, Michel; Loud, Jennifer T; Lu, Karen H; Lubinski, Jan; Machackova, Eva; Manoukian, Siranoush; Mari, Véronique; Martínez-Bouzas, Cristina; Matrai, Zoltan; Mebirouk, Noura; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Mensenkamp, Arjen R; Mickys, Ugnius; Miller, Austin; Montagna, Marco; Moysich, Kirsten B; Mulligan, Anna Marie; Musinsky, Jacob; Neuhausen, Susan L; Nevanlinna, Heli; Ngeow, Joanne; Nguyen, Huu Phuc; Niederacher, Dieter; Nielsen, Henriette Roed; Nielsen, Finn Cilius; Nussbaum, Robert L; Offit, Kenneth; Öfverholm, Anna; Ong, Kai-Ren; Osorio, Ana; Papi, Laura; Papp, Janos; Pasini, Barbara; Pedersen, Inge Sokilde; Peixoto, Ana; Peruga, Nina; Peterlongo, Paolo; Pohl, Esther; Pradhan, Nisha; Prajzendanc, Karolina; Prieur, Fabienne; Pujol, Pascal; Radice, Paolo; Ramus, Susan J; Rantala, Johanna; Rashid, Muhammad Usman; Rhiem, Kerstin; Robson, Mark; Rodriguez, Gustavo C; Rogers, Mark T; Rudaitis, Vilius; Schmidt, Ane Y; Schmutzler, Rita Katharina; Senter, Leigha; Shah, Payal D; Sharma, Priyanka; Side, Lucy E; Simard, Jacques; Singer, Christian F; Skytte, Anne-Bine; Slavin, Thomas P; Snape, Katie; Sobol, Hagay; Southey, Melissa; Steele, Linda; Steinemann, Doris; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tan, Yen Y; Teixeira, Manuel R; Terry, Mary Beth; Teulé, Alex; Thomas, Abigail; Thull, Darcy L; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Topka, Sabine; Trainer, Alison H; Tung, Nadine; van Asperen, Christi J; van der Hout, Annemieke H; van der Kolk, Lizet E; van der Luijt, Rob B; Van Heetvelde, Mattias; Varesco, Liliana; Varon-Mateeva, Raymonda; Vega, Ana; Villarreal-Garza, Cynthia; von Wachenfeldt, Anna; Walker, Lisa; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weber, Bernhard H F; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Zanzottera, Cristina; Zidan, Jamal; Zorn, Kristin K; Hutten Selkirk, Christina G; Hulick, Peter J; Chenevix-Trench, Georgia; Spurdle, Amanda B; Antoniou, Antonis C; Nathanson, Katherine L

2018-05-01

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations. © 2018 Wiley Periodicals, Inc.

Angle imaging: Advances and challenges

PubMed Central

Quek, Desmond T L; Nongpiur, Monisha E; Perera, Shamira A; Aung, Tin

2011-01-01

Primary angle closure glaucoma (PACG) is a major form of glaucoma in large populous countries in East and South Asia. The high visual morbidity from PACG is related to the destructive nature of the asymptomatic form of the disease. Early detection of anatomically narrow angles is important and the subsequent prevention of visual loss from PACG depends on an accurate assessment of the anterior chamber angle (ACA). This review paper discusses the advantages and limitations of newer ACA imaging technologies, namely ultrasound biomicroscopy, Scheimpflug photography, anterior segment optical coherence tomography and EyeCam, highlighting the current clinical evidence comparing these devices with each other and with clinical dynamic indentation gonioscopy, the current reference standard. PMID:21150037

Understanding Angle and Angle Measure: A Design-Based Research Study Using Context Aware Ubiquitous Learning

ERIC Educational Resources Information Center

Crompton, Helen

2015-01-01

Mobile technologies are quickly becoming tools found in the educational environment. The researchers in this study use a form of mobile learning to support students in learning about angle concepts. Design-based research is used in this study to develop an empirically-substantiated local instruction theory about students' develop of angle and…

Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort.

PubMed

Soylemezoglu, Oguz; Kandur, Yasar; Duzova, Ali; Ozkaya, Ozan; Kasapcopur, Ozgür; Baskin, Esra; Fidan, Kibriya; Yalcinkaya, Fatos

2015-01-01

Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations. We retrospectively reviewed the medical records of FMF patients with a single allele mutation who were followed up between 2008 and 2013 in six centres. We compared the patients with rare and common mutations for disease severity score, frequent exacerbations ( >1 attack per month), long attack period (>3 day), symptoms, age at the onset of symptoms, gender, consanguinity, and family history. Two hundred and seventeen patients (M/F=101/116) with the diagnosis of FMF and single mutation were included. Heterozygote mutations were defined as common (M694V, V726A, M68OI) and rare mutations (A744S, P369S, K695R, R761H, F479L). Sixty-seven patients (27 males, 40 females) had one single rare mutation and 150 (74 males, 76 females) had one single common mutation. No difference was found between the rare and common mutations with respect to the disease severity score. There was no significant difference between common and rare heterozygote form of mutations in terms of disease severity. Patients with typical characteristics of FMF, with some rare mutations (A744S, P369S) should be treated in the same manner as patients with a common mutation.

Definition, transformation-formulae and measurements of tipvane angles

NASA Astrophysics Data System (ADS)

Bruining, A.

1987-10-01

The theoretical background of different angle systems used to define tipvane attitude in 3-D space is outlined. Different Euler equations are used for the various, wind tunnel, towing tank, and full scale tipvane models. The influence of rotor blade flapping angle on tipvane angles is described. The tipvane attitude measuring method is outlined in relationship to the Euler angle system. Side effects on the angle of attack of the tipvane due to rotation, translation, and curving of the tipvane are described.

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression

PubMed Central

Poole, William; Leinonen, Kalle; Shmulevich, Ilya

2017-01-01

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C. PMID:28170390

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression.

PubMed

Poole, William; Leinonen, Kalle; Shmulevich, Ilya; Knijnenburg, Theo A; Bernard, Brady

2017-02-01

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C.

Determining Mutation Rates in Bacterial Populations

PubMed Central

Rosche, William A.; Foster, Patricia L.

2010-01-01

When properly determined, spontaneous mutation rates are a more accurate and biologically meaningful reflection of the underlying mutagenic mechanism than are mutation frequencies. Because bacteria grow exponentially and mutations arise stochastically, methods to estimate mutation rates depend on theoretical models that describe the distribution of mutant numbers among parallel cultures, as in the original Luria-Delbrück fluctuation analysis. An accurate determination of mutation rate depends on understanding the strengths and limitations of these methods, and how to design fluctuation assays to optimize a given method. In this paper we describe a number of methods to estimate mutation rates, give brief accounts of their derivations, and discuss how they behave under various experimental conditions. PMID:10610800

Physiological response of wild rainbow trout to angling: Impact of angling duration, fish size, body condition, and temperature

USGS Publications Warehouse

Meka, Julie M.; McCormick, S.D.

2005-01-01

This study evaluated the immediate physiological response of wild rainbow trout to catch-and-release angling in the Alagnak River, southwest Alaska. Information was recorded on individual rainbow trout (n = 415) captured by angling including landing time and the time required to remove hooks (angling duration), the time to anesthetize fish in clove oil and withdraw blood, fish length and weight, and water temperature at capture locations. Plasma cortisol, glucose, ions (sodium, potassium, chloride), and lactate were analyzed to determine the effects of angling duration, fish size, body condition, and temperature. Levels of plasma ions did not change significantly during the observed physiological response and levels of plasma glucose were sometimes influenced by length (2000, 2001), body condition (2001), or temperature (2001). Levels of plasma cortisol and lactate in extended capture fish (angling duration greater than 2 min) were significantly higher than levels in rapid capture fish (angling duration less than 2 min). Rapid capture fish were significantly smaller than extended capture fish, reflecting that fish size influenced landing and handling times. Fish size was related to cortisol and lactate in 2002, which corresponded to the year when larger fish were captured and there were longer landing times. Body condition (i.e., weight/length regression residuals index), was significantly related to lactate in 2000 and 2001. Water temperatures were higher in 2001 (mean temperature ± S.E., 13 ± 2oC) than in 2002 (10 ± 2oC), and fish captured in 2001 had significantly higher cortisol and lactate concentrations than fish captured in 2002. The pattern of increase in plasma cortisol and lactate was due to the amount of time fish were angled, and the upper limit of the response was due to water temperature. The results of this study indicate the importance of minimizing the duration of angling in order to reduce the sublethal physiological disturbances in wild

An MRPS12 mutation modifies aminoglycoside sensitivity caused by 12S rRNA mutations

PubMed Central

Emperador, Sonia; Pacheu-Grau, David; Bayona-Bafaluy, M. Pilar; Garrido-Pérez, Nuria; Martín-Navarro, Antonio; López-Pérez, Manuel J.; Montoya, Julio; Ruiz-Pesini, Eduardo

2015-01-01

Several homoplasmic pathologic mutations in mitochondrial DNA, such as those causing Leber hereditary optic neuropathy or non-syndromic hearing loss, show incomplete penetrance. Therefore, other elements must modify their pathogenicity. Discovery of these modifying factors is not an easy task because in multifactorial diseases conventional genetic approaches may not always be informative. Here, we have taken an evolutionary approach to unmask putative modifying factors for a particular homoplasmic pathologic mutation causing aminoglycoside-induced and non-syndromic hearing loss, the m.1494C>T transition in the mitochondrial DNA. The mutation is located in the decoding site of the mitochondrial ribosomal RNA. We first looked at mammalian species that had fixed the human pathologic mutation. These mutations are called compensated pathogenic deviations because an organism carrying one must also have another that suppresses the deleterious effect of the first. We found that species from the primate family Cercopithecidae (old world monkeys) harbor the m.1494T allele even if their auditory function is normal. In humans the m.1494T allele increases the susceptibility to aminoglycosides. However, in primary fibroblasts from a Cercopithecidae species, aminoglycosides do not impair cell growth, respiratory complex IV activity and quantity or the mitochondrial protein synthesis. Interestingly, this species also carries a fixed mutation in the mitochondrial ribosomal protein S12. We show that the expression of this variant in a human m.1494T cell line reduces its susceptibility to aminoglycosides. Because several mutations in this human protein have been described, they may possibly explain the absence of pathologic phenotype in some pedigree members with the most frequent pathologic mutations in mitochondrial ribosomal RNA. PMID:25642242

Parkinsonism Associated with Glucocerebrosidase Mutation

PubMed Central

Sunwoo, Mun-Kyung; Kim, Seung-Min; Lee, Sarah

2011-01-01

Background Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations. Case Report A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. 18F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen. Conclusions This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation. PMID:21779299

Gimbal-Angle Vectors of the Nonredundant CMG Cluster

NASA Astrophysics Data System (ADS)

Lee, Donghun; Bang, Hyochoong

2018-05-01

This paper deals with the method using the preferred gimbal angles of a control moment gyro (CMG) cluster for controlling spacecraft attitude. To apply the method to the nonredundant CMG cluster, analytical gimbal-angle solutions for the zero angular momentum state are derived, and the gimbal-angle vectors for the nonzero angular momentum states are studied by a numerical method. It will be shown that the number of the gimbal-angle vectors is determined from the given skew angle and the angular momentum state of the CMG cluster. Through numerical examples, it is shown that the method using the preferred gimbal-angle is an efficient approach to avoid internal singularities for the nonredundant CMG cluster.

Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience

PubMed Central

Dias-Santagata, Dora; Wistuba, Ignacio I.; Chen, Heidi; Fujimoto, Junya; Kugler, Kelly; Franklin, Wilbur A.; Iafrate, A. John; Ladanyi, Marc; Kris, Mark G.; Johnson, Bruce E.; Bunn, Paul A.; Minna, John D.; Kwiatkowski, David J.

2015-01-01

Introduction Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing, and clinicopathologic correlations are presented. Methods Mutation testing in at least one of 8 genes (EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing +/− PNA and/or sizing assays, along with ALK and/or MET FISH were performed in 6 labs on 1007 patients from 14 institutions. Results 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared to 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22, 25, 8.5, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never smoking status, and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK or MET. Conclusion Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations. PMID:25738220

Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations.

PubMed

Szpurka, Hadrian; Jankowska, Anna M; Makishima, Hideki; Bodo, Juraj; Bejanyan, Nelli; Hsi, Eric D; Sekeres, Mikkael A; Maciejewski, Jaroslaw P

2010-08-01

While a majority of patients with refractory anemia with ring sideroblasts and thrombocytosis harbor JAK2V617F and rarely MPLW515L, JAK2/MPL-negative cases constitute a diagnostic problem. 23 RARS-T cases were investigated applying immunohistochemical phospho-STAT5, sequencing and SNP-A-based karyotyping. Based on the association of TET2/ASXL1 mutations with MDS/MPN we studied molecular pattern of these genes. Two patients harbored ASXL1 and another 2 TET2 mutations. Phospho-STAT5 activation was present in one mutated TET2 and ASXL1 case. JAK2V617F/MPLW515L mutations were absent in TET2/ASXL1 mutants, indicating that similar clinical phenotype can be produced by various MPN-associated mutations and that additional unifying lesions may be present in RARS-T. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Ocular Biometrics of Myopic Eyes With Narrow Angles.

PubMed

Chong, Gabriel T; Wen, Joanne C; Su, Daniel Hsien-Wen; Stinnett, Sandra; Asrani, Sanjay

2016-02-01

The purpose of this study was to compare the ocular biometrics between myopic patients with and without narrow angles. Patients with a stable myopic refraction (myopia worse than -1.00 D spherical equivalent) were prospectively recruited. Angle status was assessed using gonioscopy and biometric measurements were performed using an anterior segment optical coherence tomography and an IOLMaster. A total of 29 patients (58 eyes) were enrolled with 13 patients (26 eyes) classified as having narrow angles and 16 patients (32 eyes) classified as having open angles. Baseline demographics of age, sex, and ethnicity did not differ significantly between the 2 groups. The patients with narrow angles were on average older than those with open angles but the difference did not reach statistical significance (P=0.12). The central anterior chamber depth was significantly less in the eyes with narrow angles (P=0.05). However, the average lens thickness, although greater in the eyes with narrow angles, did not reach statistical significance (P=0.10). Refractive error, axial lengths, and iris thicknesses did not differ significantly between the 2 groups (P=0.32, 0.47, 0.15). Narrow angles can occur in myopic eyes. Routine gonioscopy is therefore recommended for all patients regardless of refractive error.

Wide-angle imaging system with fiberoptic components providing angle-dependent virtual material stops

NASA Technical Reports Server (NTRS)

Vaughan, Arthur H. (Inventor)

1993-01-01

A strip imaging wide angle optical system is provided. The optical system is provided with a 'virtual' material stop to avoid aberrational effects inherent in wide angle optical systems. The optical system includes a spherical mirror section for receiving light from a 180 deg strip or arc of a target image. Light received by the spherical mirror section is reflected to a frustoconical mirror section for subsequent rereflection to a row of optical fibers. Each optical fiber transmits a portion of the received light to a detector. The optical system exploits the narrow cone of acceptance associated with optical fibers to substantially eliminate vignetting effects inherent in wide angle systems. Further, the optical system exploits the narrow cone of acceptance of the optical fibers to substantially limit spherical aberration. The optical system is ideally suited for any application wherein a 180 deg strip image need be detected, and is particularly well adapted for use in hostile environments such as in planetary exploration.

Rare beneficial mutations can halt Muller's ratchet

NASA Astrophysics Data System (ADS)

Balick, Daniel; Goyal, Sidhartha; Jerison, Elizabeth; Neher, Richard; Shraiman, Boris; Desai, Michael

2012-02-01

In viral, bacterial, and other asexual populations, the vast majority of non-neutral mutations are deleterious. This motivates the application of models without beneficial mutations. Here we show that the presence of surprisingly few compensatory mutations halts fitness decay in these models. Production of deleterious mutations is balanced by purifying selection, stabilizing the fitness distribution. However, stochastic vanishing of fitness classes can lead to slow fitness decay (i.e. Muller's ratchet). For weakly deleterious mutations, production overwhelms purification, rapidly decreasing population fitness. We show that when beneficial mutations are introduced, a stable steady state emerges in the form of a dynamic mutation-selection balance. We argue this state is generic for all mutation rates and population sizes, and is reached as an end state as genomes become saturated by either beneficial or deleterious mutations. Assuming all mutations have the same magnitude selective effect, we calculate the fraction of beneficial mutations necessary to maintain the dynamic balance. This may explain the unexpected maintenance of asexual genomes, as in mitochondria, in the presence of selection. This will affect in the statistics of genetic diversity in these populations.

Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer

PubMed Central

2010-01-01

Background Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients. PMID:21167064

[Gene mutation analysis of X-linked hypophosphatemic rickets].

PubMed

Song, Ying; Ma, Hong-Wei; Li, Fang; Hu, Man; Ren, Shuang; Yu, Ya-Fen; Zhao, Gui-Jie

2013-11-01

To investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype. Clinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated. PHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000). Missense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH.

Timing, rates and spectra of human germline mutation.

PubMed

Rahbari, Raheleh; Wuster, Arthur; Lindsay, Sarah J; Hardwick, Robert J; Alexandrov, Ludmil B; Turki, Saeed Al; Dominiczak, Anna; Morris, Andrew; Porteous, David; Smith, Blair; Stratton, Michael R; Hurles, Matthew E

2016-02-01

Germline mutations are a driving force behind genome evolution and genetic disease. We investigated genome-wide mutation rates and spectra in multi-sibling families. The mutation rate increased with paternal age in all families, but the number of additional mutations per year differed by more than twofold between families. Meta-analysis of 6,570 mutations showed that germline methylation influences mutation rates. In contrast to somatic mutations, we found remarkable consistency in germline mutation spectra between the sexes and at different paternal ages. In parental germ line, 3.8% of mutations were mosaic, resulting in 1.3% of mutations being shared by siblings. The number of these shared mutations varied significantly between families. Our data suggest that the mutation rate per cell division is higher during both early embryogenesis and differentiation of primordial germ cells but is reduced substantially during post-pubertal spermatogenesis. These findings have important consequences for the recurrence risks of disorders caused by de novo mutations.

Clock-like mutational processes in human somatic cells

PubMed Central

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

2016-01-01

During the course of a lifetime somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell’s genome. Some processes generate mutations throughout life at a constant rate in all individuals and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operative in human somatic cells. PMID:26551669

The hallux valgus angle of the margo medialis pedis as an alternative to the measurement of the metatarsophalangeal hallux valgus angle.

PubMed

Klein, Christian; Kinz, Wieland; Zembsch, Alexander; Groll-Knapp, Elisabeth; Kundi, Michael

2014-04-21

Currently, the metatarsophalangeal angle (hallux valgus angle) is measured based on radiographic images. However, using X-ray examinations for epidemiological or screening purposes would be unethical, especially in children. For this reason it is discussed to measure the hallux valgus angle of the margo medialis pedis (medial border of the foot) documented on foot outline drawings or foot scans. As a first step on the way to prove the validity of those approaches this study assesses the hallux valgus angle measured on the margo medialis pedis based on the same x-ray pictures as the metatarsophalangeal hallux valgus. Radiographic images of the foot were obtained from patients with symptomatic hallux valgus malformation. Twelve sets of contact copies of the 63 originals were made, and were marked and measured according to three different methods, each one performed by two observers and with two repeated measurements. Thus, data sets from 756 individual assessments were entered into the multifactorial statistical analysis.Comparisons were made between the angle of the margo medialis pedis and the metatarsophalangeal angle, which was determined by two different methods. To determine the inter- and intraobserver reliability of the different methods, each assessment was conducted by two independent experts and repeated after a period of several weeks. The correlations between the hallux valgus angles determined by the three different methods were all above r=0.89 (p<0.001) and thus highly significant. The values obtained by measuring the margo medialis pedis angle, however, were on average 4.8 degrees smaller than the metatarsophalangeal angles. No significant differences were found between the observers. No systematic deviations for any observer between repeated measurements were detected. Measurements of the radiographic hallux angle of the margo medialis pedis are reliable and show high correlation with the metatarsophalangeal angle. Because the hallux valgus angles

The hallux valgus angle of the margo medialis pedis as an alternative to the measurement of the metatarsophalangeal hallux valgus angle

PubMed Central

2014-01-01

Background Currently, the metatarsophalangeal angle (hallux valgus angle) is measured based on radiographic images. However, using X-ray examinations for epidemiological or screening purposes would be unethical, especially in children. For this reason it is discussed to measure the hallux valgus angle of the margo medialis pedis (medial border of the foot) documented on foot outline drawings or foot scans. As a first step on the way to prove the validity of those approaches this study assesses the hallux valgus angle measured on the margo medialis pedis based on the same x-ray pictures as the metatarsophalangeal hallux valgus. Methods Radiographic images of the foot were obtained from patients with symptomatic hallux valgus malformation. Twelve sets of contact copies of the 63 originals were made, and were marked and measured according to three different methods, each one performed by two observers and with two repeated measurements. Thus, data sets from 756 individual assessments were entered into the multifactorial statistical analysis. Comparisons were made between the angle of the margo medialis pedis and the metatarsophalangeal angle, which was determined by two different methods. To determine the inter- and intraobserver reliability of the different methods, each assessment was conducted by two independent experts and repeated after a period of several weeks. Results The correlations between the hallux valgus angles determined by the three different methods were all above r = 0.89 (p < 0.001) and thus highly significant. The values obtained by measuring the margo medialis pedis angle, however, were on average 4.8 degrees smaller than the metatarsophalangeal angles. No significant differences were found between the observers. No systematic deviations for any observer between repeated measurements were detected. Conclusions Measurements of the radiographic hallux angle of the margo medialis pedis are reliable and show high correlation with the

Channel overflows of the Pōhue Bay flow, Mauna Loa, Hawai'i: examples of the contrast between surface and interior lava

NASA Astrophysics Data System (ADS)

Jurado-Chichay, Zinzuni; Rowland, Scott K.

1995-04-01

A number of overflows from a large lava channel and tube system on the southwest rift zone of Mauna Loa were studied. Initial overflows were very low viscosity gas-rich pāhoehoe evidenced by flow-unit aspect ratios and vesicle sizes and contents. Calculated volumetric flow-rates in the channel range between 80 and 890 m3/s, and those of the overflows between 35 and 110 m3/s. After traveling tens to hundreds of meters the tops of these sheet-like overflows were disrupted into a surface composed of clinker and pāhoehoe fragments. After these 'a'ā overflows came to rest, lava from the interiors was able to break out on to the surface as pāhoehoe. The surface structure of a lava flow records the interaction between the differential shear rate (usually correlated with the volumetric flow-rate) and viscosity-induced resistance to flow. However, the interior of a flow, being better insulated, may react differently or record a later set of emplacement conditions. Clefts of toothpaste lava occurring within fields of clinker on proximal-type 'a'ā flows also record different shear rates during different times of flow emplacement. The interplay between viscosity and shear rate determines the final morphological lava type, and although no specific portion of lava ever makes a transition from 'a'ā back to pāhoehoe, parts of a flow can appear to do so.

Analysis of gene mutations among South Indian patients with maple syrup urine disease: identification of four novel mutations.

PubMed

Narayanan, M P; Menon, Krishnakumar N; Vasudevan, D M

2013-10-01

Maple syrup urine disease (MSUD) is predominantly caused by mutations in the BCKDHA, BCKDHB and DBT genes, which encode for the E1alpha, E1beta and E2 subunits of the branched-chain alpha-keto acid dehydrogenase complex, respectively. Because disease causing mutations play a major role in the development of the disease, prenatal diagnosis at gestational level may have significance in making decisions by parents. Thus, this study was aimed to screen South Indian MSUD patients for mutations and assess the genotype-phenotype correlation. Thirteen patients diagnosed with MSUD by conventional biochemical screening such as urine analysis by DNPH test, thin layer chromatography for amino acids and blood amino acid quantification by HPLC were selected for mutation analysis. The entire coding regions of the BCKDHA, BCKDHB and DBT genes were analyzed for mutations by PCR-based direct DNA sequencing. BCKDHA and BCKDHB mutations were seen in 43% of the total ten patients, while disease-causing DBT gene mutation was observed only in 14%. Three patients displayed no mutations. Novel mutations were c.130C>T in BCKDHA gene, c. 599C>T and c.121_122delAC in BCKDHB gene and c.190G>A in DBT gene. Notably, patients harbouring these mutations were non-responsive to thiamine supplementation and other treatment regimens and might have a worse prognosis as compared to the patients not having such mutations. Thus, identification of these mutations may have a crucial role in the treatment as well as understanding the molecular mechanisms in MSUD.

Tachometer Derived From Brushless Shaft-Angle Resolver

NASA Technical Reports Server (NTRS)

Howard, David E.; Smith, Dennis A.

1995-01-01

Tachometer circuit operates in conjunction with brushless shaft-angle resolver. By performing sequence of straightforward mathematical operations on resolver signals and utilizing simple trigonometric identity, generates voltage proportional to rate of rotation of shaft. One advantage is use of brushless shaft-angle resolver as main source of rate signal: no brushes to wear out, no brush noise, and brushless resolvers have proven robustness. No switching of signals to generate noise. Another advantage, shaft-angle resolver used as shaft-angle sensor, tachometer input obtained without adding another sensor. Present circuit reduces overall size, weight, and cost of tachometer.

Epilepsy caused by CDKL5 mutations.

PubMed

Castrén, Maija; Gaily, Eija; Tengström, Carola; Lähdetie, Jaana; Archer, Hayley; Ala-Mello, Sirpa

2011-01-01

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been identified in female patients with early onset epileptic encephalopathy and severe mental retardation with a Rett-like phenotype. Subsequently CDKL5 mutations were shown to be associated with more diverse phenotypes including mild epilepsy and autism without epilepsy. Furthermore, CDKL5 mutations were found in patients with Angelman-like phenotype. The severity of epilepsy associated with CDKL5 mutations was recently shown to correlate with the type of CDKL5 mutations and epilepsy was identified to involve three distinct sequential stages. Here, we describe the phenotype of a severe form of neurodevelopmental disease in a female patient with a de novo nonsense mutation of the CDKL5 gene c.175C > T (p.R59X) affecting the catalytic domain of CDKL5 protein. Mutations in the CDKL5 gene are less common in males and can be associated with a genomic deletion as found in our male patient with a deletion of 0.3 Mb at Xp22.13 including the CDKL5 gene. We review phenotypes associated with CDKL5 mutations and examine putative relationships between the clinical epilepsy phenotype and the type of the mutation in the CDKL5 gene. © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Mutational Signatures in Cancer (MuSiCa): a web application to implement mutational signatures analysis in cancer samples.

PubMed

Díaz-Gay, Marcos; Vila-Casadesús, Maria; Franch-Expósito, Sebastià; Hernández-Illán, Eva; Lozano, Juan José; Castellví-Bel, Sergi

2018-06-14

Mutational signatures have been proved as a valuable pattern in somatic genomics, mainly regarding cancer, with a potential application as a biomarker in clinical practice. Up to now, several bioinformatic packages to address this topic have been developed in different languages/platforms. MutationalPatterns has arisen as the most efficient tool for the comparison with the signatures currently reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. However, the analysis of mutational signatures is nowadays restricted to a small community of bioinformatic experts. In this work we present Mutational Signatures in Cancer (MuSiCa), a new web tool based on MutationalPatterns and built using the Shiny framework in R language. By means of a simple interface suited to non-specialized researchers, it provides a comprehensive analysis of the somatic mutational status of the supplied cancer samples. It permits characterizing the profile and burden of mutations, as well as quantifying COSMIC-reported mutational signatures. It also allows classifying samples according to the above signature contributions. MuSiCa is a helpful web application to characterize mutational signatures in cancer samples. It is accessible online at http://bioinfo.ciberehd.org/GPtoCRC/en/tools.html and source code is freely available at https://github.com/marcos-diazg/musica .

Multiple incidence angle SIR-B experiment over Argentina

NASA Technical Reports Server (NTRS)

Cimino, Jobea; Casey, Daren; Wall, Stephen; Brandani, Aldo; Domik, Gitta; Leberl, Franz

1986-01-01

The Shuttle Imaging Radar (SIR-B), the second synthetic aperture radar (SAR) to fly aboard a shuttle, was launched on October 5, 1984. One of the primary goals of the SIR-B experiment was to use multiple incidence angle radar images to distinguish different terrain types through the use of their characteristic backscatter curves. This goal was accomplished in several locations including the Chubut Province of southern Argentina. Four descending image acquisitions were collected providing a multiple incidence angle image set. The data were first used to assess stereo-radargrammetric techniques. A digital elevation model was produced using the optimum pair of multiple incidence angle images. This model was then used to determine the local incidence angle of each picture element to generate curves of relative brightness vs. incidence angle. Secondary image products were also generated using the multi-angle data. The results of this work indicate that: (1) various forest species and various structures of a single species may be discriminated using multiple incidence angle radar imagery, and (2) it is essential to consider the variation in backscatter due to a variable incidence angle when analyzing and comparing data collected at varying frequencies and polarizations.

Identification of proteins that interact with TANK binding kinase 1 and testing for mutations associated with glaucoma.

PubMed

Seo, Seongjin; Solivan-Timpe, Frances; Roos, Ben R; Robin, Alan L; Stone, Edwin M; Kwon, Young H; Alward, Wallace L M; Fingert, John H

2013-02-01

Copy number variations (duplications) of TANK binding kinase 1 (TBK1) have been associated with normal tension glaucoma (NTG), a common cause of blindness worldwide. Mutations in other genes involved in autophagy (TLR4 and OPTN) have been associated with NTG. Here we report searching for additional proteins involved in autophagy that may also have roles in NTG. HEK-293T cells were transfected to produce synthetic TBK1 protein with FLAG and S tags. Proteins that associate with TBK1 were isolated from HEK-293T lysates using tandem affinity purification (TAP) and polyacrylamide gel electrophoresis (PAGE). Isolated proteins were identified with mass spectrometry. A cohort of 148 NTG patients and 77 controls from Iowa were tested for glaucoma-causing mutations in genes that encode identified proteins that interact with TBK1 using high resolution melt (HRM) analysis and DNA sequencing. TAP studies show that three proteins expressed in HEK-293T cells (NAP1, TANK and TBKBP1) interact with TBK1. Testing cohorts of NTG and normal controls for disease-causing mutations in TANK, identified a total of nine unique variants including three non-synonymous changes, one synonymous changes and five intronic changes. When analyzed alone or as a group, the non-synonymous TBK1 coding sequence changes were not associated with either NTG or primary open angle glaucoma. TAP showed that NAP1, TANK and TBKBP1 interact with TBK1 and are good candidates for contributing to NTG. A mutation screen of TANK detected three non-synonymous variants. Although, it remains possible that one or more of these TANK mutations may have a role in NTG, the data in this report do not provide statistical support for an association between TANK variants and NTG.

Mutation induction by heavy ions

NASA Astrophysics Data System (ADS)

Kiefer, J.; Stoll, U.; Schneider, E.

1994-10-01

Mutation induction by heavy ions is compared in yeast and mammalian cells. Since mutants can only be recovered in survivors the influence of inactivation cross sections has to be taken into account. It is shown that both the size of the sensitive cellular site as well as track structure play an important role. Another parameter which influences the probability of mutation induction is repair: Contrary to naive assumptions primary radiation damage does not directly lead to mutations but requires modification to reconstitute the genetic machinery so that mutants can survive. The molecular structure of mutations was analyzed after exposure to deuterons by amplification with the aid of polymerase chain reaction. The results-although preliminary-demonstrate that even with densely ionizing particles a large fraction does not carry big deletions which suggests that point mutations may also be induced by heavy ions.

Phase-angle controller for Stirling engines

NASA Technical Reports Server (NTRS)

Mcdougal, A. R. (Inventor)

1980-01-01

An actuator includes a restraint link adapted to be connected with a pivotal carrier arm for a force transfer gear interposed between the crankshaft for an expander portion of a Stirling engine and a crankshaft for the displacer portion of the engine. The restraint link is releasably trapped hydraulic fluid for selectively establishing a phase angle relationship between the crankshaft. A second embodiment incorporates a hydraulic coupler for use in varying the phase angle of gear-coupled crank fpr a Stirling engine whereby phase angle changes are obtainable.

Preferred nasolabial angle in Middle Eastern population.

PubMed

Alharethy, Sami

2017-05-01

To define the preferred nasolabial angle measurement in Middle Eastern population. An observational study was conducted from January 2012 to January 2016 at the Department of Otolaryngology, Head and Neck Surgery, King Abdulaziz University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. A total of 1027 raters, 506 males, and 521 females were asked to choose the most ideal nasolabial angle for 5 males and 5 females lateral photographs whose nasolabial angle were modified with Photoshop into the following angles (85°, 90°, 95°, 100°, 105°, and 110°). Male raters preferred the angle of 89.5° ± 3.5° (mean ± SD) for males and 90.8° ± 5.6° for females. While female raters preferred the angle of 89.3° ± 3.8° for males and 90.5° ± 4.8° for females. ANOVA test compare means among groups: p: 0.342, and there is no statistically significant difference between groups. The results of our study showed an even more acute angles than degrees found in the literature. It shows that what young generation in our region prefers and clearly reflects that what could be explained as under rotation of the nasal tip in other cultures is just the ideal for some Middle Eastern population.

A quantitative analysis of phenotypic variations of Metrosideros polymorpha within and across populations along environmental gradients on Mauna Loa, Hawaii.

PubMed

Tsujii, Yuki; Onoda, Yusuke; Izuno, Ayako; Isagi, Yuji; Kitayama, Kanehiro

2016-04-01

Metrosideros polymorpha, a dominant tree species in the Hawaiian Islands, shows an extreme phenotypic polymorphism both across gradients of climatic/edaphic conditions and within populations, making it a potentially useful model species for evolutionary study. In order to understand how the phenotypic diversity is maintained within populations as well as across populations, we examined the diversities of several leaf and stem functional traits across five elevations and two soil substrates on the volcanic mountain of Mauna Loa, on the island of Hawaii. Leaf dry mass per area (LMA), a key leaf functional trait, was particularly focused on and analyzed in relation to its underlying components-namely, tissue LMA and trichome LMA (LMA = tissue LMA + trichome LMA). Across populations, tissue LMA increased linearly with elevation while trichome LMA showed unimodal patterns with elevation, which were better correlated with temperature and rainfall, respectively. Substantial phenotypic variations were also found within populations. Interestingly, the variations of tissue LMA were often negatively correlated to trichome LMA within populations, which contrasts with the cross-populations pattern, where a strong positive correlation between tissue LMA and trichome LMA was found. This suggests that phenotypic variations within populations were substantially influenced by local ecological processes. Soil depth (an indicator of local water availability) and tree size (an indicator of colonized timing) modestly explained the within-population variations, implying other local environmental factors and/or random processes are also important in local phenotypic diversity. This study provides an insight about how phenotypic diversity of plant species is maintained from local to landscape levels.

Normal Q-angle in an adult Nigerian population.

PubMed

Omololu, Bade B; Ogunlade, Olusegun S; Gopaldasani, Vinod K

2009-08-01

The Q-angle has been studied among the adult Caucasian population with the establishment of reference values. Scientists are beginning to accept the concept of different human races. Physical variability exists between various African ethnic groups and Caucasians as exemplified by differences in anatomic features such as a flat nose compared with a pointed nose, wide rather than narrow faces, and straight rather than curly hair. Therefore, we cannot assume the same Q-angle values will be applicable to Africans and Caucasians. We established a baseline reference value for normal Q-angles among asymptomatic Nigerian adults. The Q-angles of the left and right knees were measured using a goniometer in 477 Nigerian adults (354 males; 123 females) in the supine and standing positions. The mean Q-angles for men were 10.7 degrees +/- 2.2 degrees in the supine position and 12.3 degrees +/- 2.2 degrees in the standing position in the right knee. The left knee Q-angles in men were 10.5 degrees +/- 2.6 degrees in the supine position and 11.7 degrees +/- 2.8 degrees in the standing position. In women, the mean Q-angles for the right knee were 21 degrees +/- 4.8 degrees in the supine position and 22.8 degrees +/- 4.7 degrees in the standing position. The mean Q-angles for the left knee in women were 20.9 degrees +/- 4.6 degrees in the supine position and 22.7 degrees +/- 4.6 degrees in the standing position. We observed a difference in Q-angles in the supine and standing positions for all participants. The Q-angle in adult Nigerian men is comparable to that of adult Caucasian men, but the Q-angle of Nigerian women is greater than that of their Caucasian counterparts.

A dystroglycan mutation (p.Cys667Phe) associated to muscle-eye-brain disease with multicystic leucodystrophy results in ER-retention of the mutant protein.

PubMed

Signorino, Giulia; Covaceuszach, Sonia; Bozzi, Manuela; Hübner, Wolfgang; Mönkemöller, Viola; Konarev, Petr V; Cassetta, Alberto; Brancaccio, Andrea; Sciandra, Francesca

2018-02-01

Dystroglycan (DG) is a cell adhesion complex composed by two subunits, the highly glycosylated α-DG and the transmembrane β-DG. In skeletal muscle, DG is involved in dystroglycanopathies, a group of heterogeneous muscular dystrophies characterized by a reduced glycosylation of α-DG. The genes mutated in secondary dystroglycanopathies are involved in the synthesis of O-mannosyl glycans and in the O-mannosylation pathway of α-DG. Mutations in the DG gene (DAG1), causing primary dystroglycanopathies, destabilize the α-DG core protein influencing its binding to modifying enzymes. Recently, a homozygous mutation (p.Cys699Phe) hitting the β-DG ectodomain has been identified in a patient affected by muscle-eye-brain disease with multicystic leucodystrophy, suggesting that other mechanisms than hypoglycosylation of α-DG could be implicated in dystroglycanopathies. Herein, we have characterized the DG murine mutant counterpart by transfection in cellular systems and high-resolution microscopy. We observed that the mutation alters the DG processing leading to retention of its uncleaved precursor in the endoplasmic reticulum. Accordingly, small-angle X-ray scattering data, corroborated by biochemical and biophysical experiments, revealed that the mutation provokes an alteration in the β-DG ectodomain overall folding, resulting in disulfide-associated oligomerization. Our data provide the first evidence of a novel intracellular mechanism, featuring an anomalous endoplasmic reticulum-retention, underlying dystroglycanopathy. © 2017 Wiley Periodicals, Inc.

Can orbital angle morphology distinguish dogs from wolves?

PubMed

Janssens, Luc; Spanoghe, Inge; Miller, Rebecca; Van Dongen, Stefan

For more than a century, the orbital angle has been studied by many authors to distinguish dog skulls from their progenitor, the wolf. In early studies, the angle was reported to be different between dogs (49°-55°) and wolves (39°-46°). This clear difference was, however, questioned in a more recent Scandinavian study that shows some overlap. It is clear that in all studies several methodological issues were unexplored or unclear and that group sizes and the variety of breeds and wolf subspecies were small. Archaeological dog skulls had also not been studied. Our goal was to test larger and more varied groups and add archaeological samples as they are an evolutionary stage between wolves and modern dogs. We also tested the influence of measuring methods, intra- and inter-reliability, angle symmetry, the influence of variations in skull position and the possibility of measuring and comparing this angle on 3D CT scan images. Our results indicate that there is about 50 % overlap between the angle range in wolves and modern dogs. However, skulls with a very narrow orbital angle were only found in wolves and those with a very wide angle only in dogs. Archaeological dogs have a mean angle very close to the one of the wolves. Symmetry is highest in wolves and lowest in archaeological dogs. The measuring method is very reliable, for both inter- and intra-reliability (0.99-0.97), and most skull position changes have no statistical influence on the angle measured. Three-dimensional CT scan images can be used to measure OA, but the angles differ from direct measuring and cannot be used for comparison. Evolutionary changes in dog skulls responsible for the wider OA compared to wolf skulls are mainly the lateralisation of the zygomatic process of the frontal bone. Our conclusion is that the orbital angle can be used as an additional morphological measuring method to discern wolves from recent and archaeological dogs. Angles above 60° are certainly from recent dogs. Angles

Mutation spectrum of RB1 mutations in retinoblastoma cases from Singapore with implications for genetic management and counselling.

PubMed

Tomar, Swati; Sethi, Raman; Sundar, Gangadhara; Quah, Thuan Chong; Quah, Boon Long; Lai, Poh San

2017-01-01

Retinoblastoma (RB) is a rare childhood malignant disorder caused by the biallelic inactivation of RB1 gene. Early diagnosis and identification of carriers of heritable RB1 mutations can improve disease outcome and management. In this study, mutational analysis was conducted on fifty-nine matched tumor and peripheral blood samples from 18 bilateral and 41 unilateral unrelated RB cases by a combinatorial approach of Multiplex Ligation-dependent Probe Amplification (MLPA) assay, deletion screening, direct sequencing, copy number gene dosage analysis and methylation assays. Screening of both blood and tumor samples yielded a mutation detection rate of 94.9% (56/59) while only 42.4% (25/59) of mutations were detected if blood samples alone were analyzed. Biallelic mutations were observed in 43/59 (72.9%) of tumors screened. There were 3 cases (5.1%) in which no mutations could be detected and germline mutations were detected in 19.5% (8/41) of unilateral cases. A total of 61 point mutations were identified, of which 10 were novel. There was a high incidence of previously reported recurrent mutations, occurring at 38.98% (23/59) of all cases. Of interest were three cases of mosaic RB1 mutations detected in the blood from patients with unilateral retinoblastoma. Additionally, two germline mutations previously reported to be associated with low-penetrance phenotypes: missense-c.1981C>T and splice variant-c.607+1G>T, were observed in a bilateral and a unilateral proband, respectively. These findings have implications for genetic counselling and risk prediction for the affected families. This is the first published report on the spectrum of mutations in RB patients from Singapore and shows that further improved mutation screening strategies are required in order to provide a definitive molecular diagnosis for every case of RB. Our findings also underscore the importance of genetic testing in supporting individualized disease management plans for patients and asymptomatic

Mutation spectrum of RB1 mutations in retinoblastoma cases from Singapore with implications for genetic management and counselling

PubMed Central

Tomar, Swati; Sethi, Raman; Sundar, Gangadhara; Quah, Thuan Chong; Quah, Boon Long; Lai, Poh San

2017-01-01

Retinoblastoma (RB) is a rare childhood malignant disorder caused by the biallelic inactivation of RB1 gene. Early diagnosis and identification of carriers of heritable RB1 mutations can improve disease outcome and management. In this study, mutational analysis was conducted on fifty-nine matched tumor and peripheral blood samples from 18 bilateral and 41 unilateral unrelated RB cases by a combinatorial approach of Multiplex Ligation-dependent Probe Amplification (MLPA) assay, deletion screening, direct sequencing, copy number gene dosage analysis and methylation assays. Screening of both blood and tumor samples yielded a mutation detection rate of 94.9% (56/59) while only 42.4% (25/59) of mutations were detected if blood samples alone were analyzed. Biallelic mutations were observed in 43/59 (72.9%) of tumors screened. There were 3 cases (5.1%) in which no mutations could be detected and germline mutations were detected in 19.5% (8/41) of unilateral cases. A total of 61 point mutations were identified, of which 10 were novel. There was a high incidence of previously reported recurrent mutations, occurring at 38.98% (23/59) of all cases. Of interest were three cases of mosaic RB1 mutations detected in the blood from patients with unilateral retinoblastoma. Additionally, two germline mutations previously reported to be associated with low-penetrance phenotypes: missense-c.1981C>T and splice variant-c.607+1G>T, were observed in a bilateral and a unilateral proband, respectively. These findings have implications for genetic counselling and risk prediction for the affected families. This is the first published report on the spectrum of mutations in RB patients from Singapore and shows that further improved mutation screening strategies are required in order to provide a definitive molecular diagnosis for every case of RB. Our findings also underscore the importance of genetic testing in supporting individualized disease management plans for patients and asymptomatic

Clock-like mutational processes in human somatic cells

DOE PAGES

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; ...

2015-11-09

During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutationmore » rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.« less

Thailand mutation and variation database (ThaiMUT).

PubMed

Ruangrit, Uttapong; Srikummool, Metawee; Assawamakin, Anunchai; Ngamphiw, Chumpol; Chuechote, Suparat; Thaiprasarnsup, Vilasinee; Agavatpanitch, Gallissara; Pasomsab, Ekawat; Yenchitsomanus, Pa-Thai; Mahasirimongkol, Surakameth; Chantratita, Wasun; Palittapongarnpim, Prasit; Uyyanonvara, Bunyarit; Limwongse, Chanin; Tongsima, Sissades

2008-08-01

With the completion of the human genome project, novel sequencing and genotyping technologies had been utilized to detect mutations. Such mutations have continually been produced at exponential rate by researchers in various communities. Based on the population's mutation spectra, occurrences of Mendelian diseases are different across ethnic groups. A proportion of Mendelian diseases can be observed in some countries at higher rates than others. Recognizing the importance of mutation effects in Thailand, we established a National and Ethnic Mutation Database (NEMDB) for Thai people. This database, named Thailand Mutation and Variation database (ThaiMUT), offers a web-based access to genetic mutation and variation information in Thai population. This NEMDB initiative is an important informatics tool for both research and clinical purposes to retrieve and deposit human variation data. The mutation data cataloged in ThaiMUT database were derived from journal articles available in PubMed and local publications. In addition to collected mutation data, ThaiMUT also records genetic polymorphisms located in drug related genes. ThaiMUT could then provide useful information for clinical mutation screening services for Mendelian diseases and pharmacogenomic researches. ThaiMUT can be publicly accessed from http://gi.biotec.or.th/thaimut.

Dosage Mutator Genes in Saccharomyces cerevisiae: A Novel Mutator Mode-of-Action of the Mph1 DNA Helicase.

PubMed

Ang, J Sidney; Duffy, Supipi; Segovia, Romulo; Stirling, Peter C; Hieter, Philip

2016-11-01

Mutations that cause genome instability are considered important predisposing events that contribute to initiation and progression of cancer. Genome instability arises either due to defects in genes that cause an increased mutation rate (mutator phenotype), or defects in genes that cause chromosome instability (CIN). To extend the catalog of genome instability genes, we systematically explored the effects of gene overexpression on mutation rate, using a forward-mutation screen in budding yeast. We screened ∼5100 plasmids, each overexpressing a unique single gene, and characterized the five strongest mutators, MPH1 (mutator phenotype 1), RRM3, UBP12, PIF1, and DNA2 We show that, for MPH1, the yeast homolog of Fanconi Anemia complementation group M (FANCM), the overexpression mutator phenotype is distinct from that of mph1Δ. Moreover, while four of our top hits encode DNA helicases, the overexpression of 48 other DNA helicases did not cause a mutator phenotype, suggesting this is not a general property of helicases. For Mph1 overexpression, helicase activity was not required for the mutator phenotype; in contrast Mph1 DEAH-box function was required for hypermutation. Mutagenesis by MPH1 overexpression was independent of translesion synthesis (TLS), but was suppressed by overexpression of RAD27, a conserved flap endonuclease. We propose that binding of DNA flap structures by excess Mph1 may block Rad27 action, creating a mutator phenotype that phenocopies rad27Δ. We believe this represents a novel mutator mode-of-action and opens up new prospects to understand how upregulation of DNA repair proteins may contribute to mutagenesis. Copyright © 2016 by the Genetics Society of America.

Activating PIK3CA mutations coexist with BRAF or NRAS mutations in a limited fraction of melanomas.

PubMed

Manca, Antonella; Lissia, Amelia; Capone, Mariaelena; Ascierto, Paolo A; Botti, Gerardo; Caracò, Corrado; Stanganelli, Ignazio; Colombino, Maria; Sini, MariaCristina; Cossu, Antonio; Palmieri, Giuseppe

2015-01-28

Activated PI3K-AKT pathway may contribute to decrease sensitivity to inhibitors of key pathogenetic effectors (mutated BRAF, active NRAS or MEK) in melanoma. Functional alterations are deeply involved in PI3K-AKT activation, with a minimal role reported for mutations in PIK3CA, the catalytic subunit of the PI3K gene. We here assessed the prevalence of the coexistence of BRAF/NRAS and PIK3CA mutations in a series of melanoma samples. A total of 245 tumor specimens (212 primary melanomas and 33 melanoma cell lines) was screened for mutations in BRAF, NRAS, and PIK3CA genes by automated direct sequencing. Overall, 110 (44.9%) samples carried mutations in BRAF, 26 (10.6%) in NRAS, and 24 (9.8%) in PIK3CA. All identified PIK3CA mutations have been reported to induce PI3K activation; those detected in cultured melanomas were investigated for their interference with the antiproliferative activity of the BRAF-mutant inhibitor vemurafenib. A reduced suppression in cell growth was observed in treated cells carrying both BRAF and PIK3CA mutations as compared with those presenting a mutated BRAF only. Among the analysed melanomas, 12/245 (4.9%) samples presented the coexistence of PIK3CA and BRAF/NRAS mutations. Our study further suggests that PIK3CA mutations account for a small fraction of PI3K pathway activation and have a limited impact in interfering with the BRAF/NRAS-driven growth in melanoma.

Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline

PubMed Central

Giannoulatou, Eleni; McVean, Gilean; Taylor, Indira B.; McGowan, Simon J.; Maher, Geoffrey J.; Iqbal, Zamin; Pfeifer, Susanne P.; Turner, Isaac; Burkitt Wright, Emma M. M.; Shorto, Jennifer; Itani, Aysha; Turner, Karen; Gregory, Lorna; Buck, David; Rajpert-De Meyts, Ewa; Looijenga, Leendert H. J.; Kerr, Bronwyn; Wilkie, Andrew O. M.; Goriely, Anne

2013-01-01

The RAS proto-oncogene Harvey rat sarcoma viral oncogene homolog (HRAS) encodes a small GTPase that transduces signals from cell surface receptors to intracellular effectors to control cellular behavior. Although somatic HRAS mutations have been described in many cancers, germline mutations cause Costello syndrome (CS), a congenital disorder associated with predisposition to malignancy. Based on the epidemiology of CS and the occurrence of HRAS mutations in spermatocytic seminoma, we proposed that activating HRAS mutations become enriched in sperm through a process akin to tumorigenesis, termed selfish spermatogonial selection. To test this hypothesis, we quantified the levels, in blood and sperm samples, of HRAS mutations at the p.G12 codon and compared the results to changes at the p.A11 codon, at which activating mutations do not occur. The data strongly support the role of selection in determining HRAS mutation levels in sperm, and hence the occurrence of CS, but we also found differences from the mutation pattern in tumorigenesis. First, the relative prevalence of mutations in sperm correlates weakly with their in vitro activating properties and occurrence in cancers. Second, specific tandem base substitutions (predominantly GC>TT/AA) occur in sperm but not in cancers; genomewide analysis showed that this same mutation is also overrepresented in constitutional pathogenic and polymorphic variants, suggesting a heightened vulnerability to these mutations in the germline. We developed a statistical model to show how both intrinsic mutation rate and selfish selection contribute to the mutational burden borne by the paternal germline. PMID:24259709

Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline.

PubMed

Giannoulatou, Eleni; McVean, Gilean; Taylor, Indira B; McGowan, Simon J; Maher, Geoffrey J; Iqbal, Zamin; Pfeifer, Susanne P; Turner, Isaac; Burkitt Wright, Emma M M; Shorto, Jennifer; Itani, Aysha; Turner, Karen; Gregory, Lorna; Buck, David; Rajpert-De Meyts, Ewa; Looijenga, Leendert H J; Kerr, Bronwyn; Wilkie, Andrew O M; Goriely, Anne

2013-12-10

The RAS proto-oncogene Harvey rat sarcoma viral oncogene homolog (HRAS) encodes a small GTPase that transduces signals from cell surface receptors to intracellular effectors to control cellular behavior. Although somatic HRAS mutations have been described in many cancers, germline mutations cause Costello syndrome (CS), a congenital disorder associated with predisposition to malignancy. Based on the epidemiology of CS and the occurrence of HRAS mutations in spermatocytic seminoma, we proposed that activating HRAS mutations become enriched in sperm through a process akin to tumorigenesis, termed selfish spermatogonial selection. To test this hypothesis, we quantified the levels, in blood and sperm samples, of HRAS mutations at the p.G12 codon and compared the results to changes at the p.A11 codon, at which activating mutations do not occur. The data strongly support the role of selection in determining HRAS mutation levels in sperm, and hence the occurrence of CS, but we also found differences from the mutation pattern in tumorigenesis. First, the relative prevalence of mutations in sperm correlates weakly with their in vitro activating properties and occurrence in cancers. Second, specific tandem base substitutions (predominantly GC>TT/AA) occur in sperm but not in cancers; genomewide analysis showed that this same mutation is also overrepresented in constitutional pathogenic and polymorphic variants, suggesting a heightened vulnerability to these mutations in the germline. We developed a statistical model to show how both intrinsic mutation rate and selfish selection contribute to the mutational burden borne by the paternal germline.

Can a surgeon drill accurately at a specified angle?

PubMed Central

Brioschi, Valentina; Cook, Jodie; Arthurs, Gareth I

2016-01-01

Objectives To investigate whether a surgeon can drill accurately a specified angle and whether surgeon experience, task repetition, drill bit size and perceived difficulty influence drilling angle accuracy. Methods The sample population consisted of final-year students (n=25), non-specialist veterinarians (n=22) and board-certified orthopaedic surgeons (n=8). Each participant drilled a hole twice in a horizontal oak plank at 30°, 45°, 60°, 80°, 85° and 90° angles with either a 2.5  or a 3.5 mm drill bit. Participants then rated the perceived difficulty to drill each angle. The true angle of each hole was measured using a digital goniometer. Results Greater drilling accuracy was achieved at angles closer to 90°. An error of ≤±4° was achieved by 84.5 per cent of participants drilling a 90° angle compared with approximately 20 per cent of participants drilling a 30–45° angle. There was no effect of surgeon experience, task repetition or drill bit size on the mean error for intended versus achieved angle. Increased perception of difficulty was associated with the more acute angles and decreased accuracy, but not experience level. Clinical significance This study shows that surgeon ability to drill accurately (within ±4° error) is limited, particularly at angles ≤60°. In situations where drill angle is critical, use of computer-assisted navigation or custom-made drill guides may be preferable. PMID:27547423

Angle closure glaucoma in congenital ectropion uvea.

PubMed

Wang, Grace M; Thuente, Daniel; Bohnsack, Brenda L

2018-06-01

Congenital ectropion uvea is a rare anomaly, which is associated with open, but dysplastic iridocorneal angles that cause childhood glaucoma. Herein, we present 3 cases of angle-closure glaucoma in children with congenital ectropion uvea. Three children were initially diagnosed with unilateral glaucoma secondary to congenital ectropion uvea at 7, 8 and 13 years of age. The three cases showed 360° of ectropion uvea and iris stromal atrophy in the affected eye. In one case, we have photographic documentation of progression to complete angle closure, which necessitated placement of a glaucoma drainage device 3 years after combined trabeculotomy and trabeculectomy. The 2 other cases, which presented as complete angle closure, also underwent glaucoma drainage device implantation. All three cases had early glaucoma drainage device encapsulation (within 4 months) and required additional surgery (cycloablation or trabeculectomy). Congenital ectropion uvea can be associated with angle-closure glaucoma, and placement of glaucoma drainage devices in all 3 of our cases showed early failure due to plate encapsulation. Glaucoma in congenital ectropion uvea requires attention to angle configuration and often requires multiple surgeries to obtain intraocular pressure control.

Advances in computational approaches for prioritizing driver mutations and significantly mutated genes in cancer genomes.

PubMed

Cheng, Feixiong; Zhao, Junfei; Zhao, Zhongming

2016-07-01

Cancer is often driven by the accumulation of genetic alterations, including single nucleotide variants, small insertions or deletions, gene fusions, copy-number variations, and large chromosomal rearrangements. Recent advances in next-generation sequencing technologies have helped investigators generate massive amounts of cancer genomic data and catalog somatic mutations in both common and rare cancer types. So far, the somatic mutation landscapes and signatures of >10 major cancer types have been reported; however, pinpointing driver mutations and cancer genes from millions of available cancer somatic mutations remains a monumental challenge. To tackle this important task, many methods and computational tools have been developed during the past several years and, thus, a review of its advances is urgently needed. Here, we first summarize the main features of these methods and tools for whole-exome, whole-genome and whole-transcriptome sequencing data. Then, we discuss major challenges like tumor intra-heterogeneity, tumor sample saturation and functionality of synonymous mutations in cancer, all of which may result in false-positive discoveries. Finally, we highlight new directions in studying regulatory roles of noncoding somatic mutations and quantitatively measuring circulating tumor DNA in cancer. This review may help investigators find an appropriate tool for detecting potential driver or actionable mutations in rapidly emerging precision cancer medicine. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The Effect of Suture Anchor Insertion Angle on Calcaneus Pullout Strength: Challenging the Deadman's Angle.

PubMed

Weiss, William M; Saucedo, Ramon P; Robinson, John D; Lo, Chung-Chieh Jason; Morris, Randal P; Panchbhavi, Vinod K

2017-10-01

Refractory cases of Achilles tendinopathy amenable to surgery may include reattachment of the tendon using suture anchors. However, there is paucity of information describing the optimal insertion angle to maximize the tendon footprint and anchor stability in the calcaneus. The purpose of this investigation is to compare the fixation strength of suture anchors inserted at 90° and 45° (the Deadman's angle) relative to the primary compressive trabeculae of the calcaneus. A total of 12 matched pairs of adult cadaveric calcanei were excised and potted to approximate their alignment in vivo. Each pair was implanted with 5.5-mm bioabsorbable suture anchors placed either perpendicular (90°) or oblique (45°) to the primary compressive trabeculae. A tensile load was applied until failure of anchor fixation. Differences in failure load and stiffness between anchor fixation angles were determined by paired t-tests. No significant differences were detected between perpendicular and oblique suture anchor insertion relative to primary compressive trabeculae in terms of load to failure or stiffness. This investigation suggests that the fixation strength of suture anchors inserted perpendicular to the primary compression trabeculae and at the Deadman's angle are possibly comparable. Biomechanical comparison study.

Computer programs for calculation of sting pitch and roll angles required to obtain angles of attack and sideslip on wind tunnel models

NASA Technical Reports Server (NTRS)

Peterson, John B., Jr.

1988-01-01

Two programs have been developed to calculate the pitch and roll angles of a wind-tunnel sting drive system that will position a model at the desired angle of attack and and angle of sideslip in the wind tunnel. These programs account for the effects of sting offset angles, sting bending angles and wind-tunnel stream flow angles. In addition, the second program incorporates inputs from on-board accelerometers that measure model pitch and roll with respect to gravity. The programs are presented in the report and a description of the numerical operation of the programs with a definition of the variables used in the programs is given.

RaptorX-Angle: real-value prediction of protein backbone dihedral angles through a hybrid method of clustering and deep learning.

PubMed

Gao, Yujuan; Wang, Sheng; Deng, Minghua; Xu, Jinbo

2018-05-08

Protein dihedral angles provide a detailed description of protein local conformation. Predicted dihedral angles can be used to narrow down the conformational space of the whole polypeptide chain significantly, thus aiding protein tertiary structure prediction. However, direct angle prediction from sequence alone is challenging. In this article, we present a novel method (named RaptorX-Angle) to predict real-valued angles by combining clustering and deep learning. Tested on a subset of PDB25 and the targets in the latest two Critical Assessment of protein Structure Prediction (CASP), our method outperforms the existing state-of-art method SPIDER2 in terms of Pearson Correlation Coefficient (PCC) and Mean Absolute Error (MAE). Our result also shows approximately linear relationship between the real prediction errors and our estimated bounds. That is, the real prediction error can be well approximated by our estimated bounds. Our study provides an alternative and more accurate prediction of dihedral angles, which may facilitate protein structure prediction and functional study.

Mutations affecting gyrase in Haemophilus influenzae.

PubMed Central

Setlow, J K; Cabrera-Juárez, E; Albritton, W L; Spikes, D; Mutschler, A

1985-01-01

Mutants separately resistant to novobiocin, coumermycin, nalidixic acid, and oxolinic acid contained gyrase activity as measured in vitro that was resistant to the antibiotics, indicating that the mutations represented structural alterations of the enzyme. One Novr mutant contained an altered B subunit of the enzyme, as judged by the ability of a plasmid, pNov1, containing the mutation to complement a temperature-sensitive gyrase B mutation in Escherichia coli and to cause novobiocin resistance in that strain. Three other Novr mutations did not confer antibiotic resistance to the gyrase but appeared to increase the amount of active enzyme in the cell. One of these, novB1, could only act in cis, whereas a new mutation, novC, could act in trans. An RNA polymerase mutation partially substituted for the novB1 mutation, suggesting that novB1 may be a mutation in a promoter region for the B subunit gene. Growth responses of strains containing various combinations of mutations on plasmids or on the chromosome indicated that low-level resistance to novobiocin or coumermycin may have resulted from multiple copies of wild-type genes coding for the gyrase B subunit, whereas high-level resistance required a structural change in the gyrase B gene and was also dependent on alteration in a regulatory region. When there was mismatch at the novB locus, with the novB1 mutation either on a plasmid or the chromosome, and the corresponding wild-type gene present in trans, chromosome to plasmid recombination during transformation was much higher than when the genes matched, probably because plasmid to chromosome recombination, eliminating the plasmid, was inhibited by the mismatch. PMID:2997115

BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.

PubMed

Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L; El-Deiry, Wafik S

2017-06-20

Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P < 0.0001) in BRCA2. Of 1104 profiled CRCs from a second cohort (COSMIC), MSH2/MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P < 0.0000001). BRCA2 mutations in MSH2/MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P < 0.0000001). Approximately 15% of EGFR mutations found may be actionable through TKI therapy, including N700D, G719D, T725M, T790M, and E884K. NTRK gene mutations were identified in MSH2/MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.

Myeloid neoplasms with germline DDX41 mutation.

PubMed

Cheah, Jesse J C; Hahn, Christopher N; Hiwase, Devendra K; Scott, Hamish S; Brown, Anna L

2017-08-01

Recently, DDX41 mutations have been identified both as germline and acquired somatic mutations in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. The majority of germline mutations are frameshift mutations suggesting loss of function with DDX41 acting as a tumor suppressor, and there is a common somatic missense mutation found in a majority of germline mutated tumors. Clinically, DDX41 mutations lead to development of high-risk MDS at an age similar to that observed in sporadic cohorts, presenting a unique challenge to hematologists in recognizing the familial context. Functionally, DDX41 has been shown to contribute to multiple pathways and processes including mRNA splicing, innate immunity and rRNA processing. Mutations in DDX41 result in aberrations to each of these in ways that could potentially impact on tumorigenesis-initiation, maintenance or progression. This review discusses the various molecular, clinical and biological aspects of myeloid malignancy predisposition due to DDX41 mutation and highlights how each of these suggest potential therapeutic opportunities through the use of pathway-specific inhibitors.

A Landscape of Driver Mutations in Melanoma

PubMed Central

Hodis, Eran; Watson, Ian R.; Kryukov, Gregory V.; Arold, Stefan T.; Imielinski, Marcin; Theurillat, Jean-Philippe; Nickerson, Elizabeth; Auclair, Daniel; Li, Liren; Place, Chelsea; DiCara, Daniel; Ramos, Alex H.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey; Voet, Douglas; Saksena, Gordon; Stransky, Nicolas; Onofrio, Robert C.; Winckler, Wendy; Ardlie, Kristin; Wagle, Nikhil; Wargo, Jennifer; Chong, Kelly; Morton, Donald L.; Stemke-Hale, Katherine; Chen, Guo; Noble, Michael; Meyerson, Matthew; Ladbury, John E.; Davies, Michael A.; Gershenwald, Jeffrey E.; Wagner, Stephan N.; Hoon, Dave S.B.; Schadendorf, Dirk; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Garraway, Levi A.; Chin, Lynda

2012-01-01

SUMMARY Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic ultraviolet (UV) light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19 and ARID2), three of which - RAC1, PPP6C and STK19 - harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis. PMID:22817889

The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients.

PubMed

Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, Miho; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

2014-09-01

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.

GATA2 mutations in patients with acute myeloid leukemia-paired samples analyses show that the mutation is unstable during disease evolution.

PubMed

Hou, Hsin-An; Lin, Yun-Chu; Kuo, Yuan-Yeh; Chou, Wen-Chien; Lin, Chien-Chin; Liu, Chieh-Yu; Chen, Chien-Yuan; Lin, Liang-In; Tseng, Mei-Hsuan; Huang, Chi-Fei; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Tang, Jih-Luh; Yao, Ming; Huang, Shang-Yi; Ko, Bor-Sheng; Hsu, Szu-Chun; Wu, Shang-Ju; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

2015-02-01

Recently, mutations of the GATA binding protein 2 (GATA2) gene were identified in acute myeloid leukemia (AML) patients with CEBPA double mutations (CEBPA (double-mut)), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, 14 different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal zinc finger 1 domain, were identified in 27.4, 6.7, and 1 % of patients with CEBPA (double-mut), CEBPA (single-mut), and CEBPA wild type, respectively. All but one patient with GATA2 mutation had concurrent CEBPA mutation. GATA2 mutations were closely associated with younger age, FAB M1 subtype, intermediate-risk cytogenetics, expression of HLA-DR, CD7, CD15, or CD34 on leukemic cells, and CEBPA mutation, but negatively associated with FAB M4 subtype, favorable-risk cytogenetics, and NPM1 mutation. Patients with GATA2 mutation had significantly better overall survival and relapse-free survival than those without GATA2 mutation. Sequential analysis showed that the original GATA2 mutations might be lost during disease progression in GATA2-mutated patients, while novel GATA2 mutations might be acquired at relapse in GATA2-wild patients. In conclusion, AML patients with GATA2 mutations had distinct clinic-biological features and a favorable prognosis. GATA2 mutations might be lost or acquired at disease progression, implying that it was a second hit in the leukemogenesis of AML, especially those with CEBPA mutation.

Adaptive mutation: has the unicorn landed?

PubMed

Foster, P L

1998-04-01

Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution.

Adaptive mutation: has the unicorn landed?

PubMed Central

Foster, P L

1998-01-01

Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution. PMID:9560365

Wide-angle vision for road views

NASA Astrophysics Data System (ADS)

Huang, F.; Fehrs, K.-K.; Hartmann, G.; Klette, R.

2013-03-01

The field-of-view of a wide-angle image is greater than (say) 90 degrees, and so contains more information than available in a standard image. A wide field-of-view is more advantageous than standard input for understanding the geometry of 3D scenes, and for estimating the poses of panoramic sensors within such scenes. Thus, wide-angle imaging sensors and methodologies are commonly used in various road-safety, street surveillance, street virtual touring, or street 3D modelling applications. The paper reviews related wide-angle vision technologies by focusing on mathematical issues rather than on hardware.

Diversity of ARSACS mutations in French-Canadians.

PubMed

Thiffault, I; Dicaire, M J; Tetreault, M; Huang, K N; Demers-Lamarche, J; Bernard, G; Duquette, A; Larivière, R; Gehring, K; Montpetit, A; McPherson, P S; Richter, A; Montermini, L; Mercier, J; Mitchell, G A; Dupré, N; Prévost, C; Bouchard, J P; Mathieu, J; Brais, B

2013-01-01

The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability. Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin. A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin. The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.

Biomarkers in primary open angle glaucoma.

PubMed

Kokotas, Haris; Kroupis, Christos; Chiras, Dimitrios; Grigoriadou, Maria; Lamnissou, Klea; Petersen, Michael B; Kitsos, George

2012-12-01

Glaucoma, a leading cause of blindness worldwide, is currently defined as a disturbance of the structural or functional integrity of the optic nerve that causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. This disturbance usually can be arrested or diminished by adequate lowering of intraocular pressure (IOP). Glaucoma can be divided roughly into two main categories, ‘ open angle ’ and ‘ closed angle ’ glaucoma.Open angle, chronic glaucoma tends to progress at a slower rate and patients may not notice loss of vision until the disease has progressed significantly. Primary open angle glaucoma(POAG) is described distinctly as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibers. Such loss develops in the presence of open anterior chamber angles, characteristic visual field abnormalities, and IOP that is too high for the healthy eye. It manifests by cupping and atrophy of the optic disc, in the absence of other known causes of glaucomatous disease. Several biological markers have been implicated with the disease. The purpose of this study was to summarize the current knowledge regarding the non-genetic molecular markers which have been predicted to have an association with POAG but have not yet been validated.

Apparatus and method for variable angle slant hole collimator

DOEpatents

Lee, Seung Joon; Kross, Brian J.; McKisson, John E.

2017-07-18

A variable angle slant hole (VASH) collimator for providing collimation of high energy photons such as gamma rays during radiological imaging of humans. The VASH collimator includes a stack of multiple collimator leaves and a means of quickly aligning each leaf to provide various projection angles. Rather than rotate the detector around the subject, the VASH collimator enables the detector to remain stationary while the projection angle of the collimator is varied for tomographic acquisition. High collimator efficiency is achieved by maintaining the leaves in accurate alignment through the various projection angles. Individual leaves include unique angled cuts to maintain a precise target collimation angle. Matching wedge blocks driven by two actuators with twin-lead screws accurately position each leaf in the stack resulting in the precise target collimation angle. A computer interface with the actuators enables precise control of the projection angle of the collimator.

Mutations in Lettuce Improvement.

USDA-ARS?s Scientific Manuscript database

Mutations can make profound impact on the evolution and improvement of a self-pollinated crop such as lettuce. Since it is nontransgenic, mutation breeding is more acceptable to consumers. Combined with genomic advances in new technologies like TILLING, mutagenesis is becoming an even more powerfu...

Chloroplast mutations induced by 9-aminoacridine hydrochloride are independent of the plastome mutator in Oenothera.

PubMed

GuhaMajumdar, M; Baldwin, S; Sears, B B

2004-02-01

Oenothera plants homozygous for the recessive plastome mutator allele ( pm) show chloroplast DNA (cpDNA) mutation frequencies that are about 1,000-fold higher than spontaneous levels. The pm-encoded gene product has been hypothesized to have a function in cpDNA replication, repair and/or mutation avoidance. Previous chemical mutagenesis experiments with the alkylating agent nitroso-methyl urea (NMU) showed a synergistic effect of NMU on the induction of mutations in the pm line, suggesting an interaction between the pm-encoded gene product and one of the repair systems that corrects alkylation damage. The goal of the experiments described here was to examine whether the pm activity extends to the repair of damage caused by non-alkylating mutagens. To this end, the intercalating mutagen, 9-aminoacridine hydrochloride (9AA) was tested for synergism with the plastome mutator. A statistical analysis of the data reported here indicates that the pm-encoded gene product is not involved in the repair of the 9AA-induced mutations. However, the recovery of chlorotic sectors in plants derived from the mutagenized seeds shows that 9AA can act as a mutagen of the chloroplast genome.

Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms.

PubMed

Zahorakova, Daniela; Rosipal, Robert; Hadac, Jan; Zumrova, Alena; Bzduch, Vladimir; Misovicova, Nadezda; Baxova, Alice; Zeman, Jiri; Martasek, Pavel

2007-01-01

Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Here we report mutation analysis of the MECP2 gene in 87 patients with RTT from the Czech and Slovak Republics, and Ukraine. The patients, all girls, with classical RTT were investigated for mutations using bi-directional DNA sequencing and conformation sensitive gel electrophoresis analysis of the coding sequence and exon/intron boundaries of the MECP2 gene. Restriction fragment length polymorphism analysis was performed to confirm the mutations that cause the creation or abolition of the restriction site. Mutation-negative cases were subsequently examined by multiple ligation-dependent probe amplification (MLPA) to identify large deletions. Mutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms. Six mutations have not been previously published: two point mutations (323T>A, 904C>T), three deletions (189_190delGA, 816_832del17, 1069delAGC) and one deletion/inversion (1063_1236del174;1189_1231inv43). MLPA analysis revealed large deletions in two patients. The detection rate was 78.16%. Our results confirm the high frequency of MECP2 mutations in females with RTT and provide data concerning the mutation heterogeneity in the Slavic population.

In situ assessment of the contact angles of nanoparticles adsorbed at fluid interfaces by multiple angle of incidence ellipsometry.

PubMed

Stocco, Antonio; Su, Ge; Nobili, Maurizio; In, Martin; Wang, Dayang

2014-09-28

Here multiple angle of incidence ellipsometry was successfully applied to in situ assess the contact angle and surface coverage of gold nanoparticles as small as 18 nm, coated with stimuli-responsive polymers, at water-oil and water-air interfaces in the presence of NaCl and NaOH, respectively. The interfacial adsorption of the nanoparticles was found to be very slow and took days to reach a fairly low surface coverage. For water-oil interfaces, in situ nanoparticle contact angles agree with the macroscopic equilibrium contact angles of planar gold surfaces with the same polymer coatings, whilst for water-air interfaces, significant differences have been observed.

Age-related mutations and chronic myelomonocytic leukemia

PubMed Central

Mason, CC; Khorashad, JS; Tantravahi, SK; Kelley, TW; Zabriskie, MS; Yan, D; Pomicter, AD; Reynolds, KR; Eiring, AM; Kronenberg, Z; Sherman, RL; Tyner, JW; Dalley, BK; Dao, K-H; Yandell, M; Druker, BJ; Gotlib, J; O’Hare, T; Deininger, MW

2016-01-01

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy nearly confined to the elderly. Previous studies to determine incidence and prognostic significance of somatic mutations in CMML have relied on candidate gene sequencing, although an unbiased mutational search has not been conducted. As many of the genes commonly mutated in CMML were recently associated with age-related clonal hematopoiesis (ARCH) and aged hematopoiesis is characterized by a myelomonocytic differentiation bias, we hypothesized that CMML and aged hematopoiesis may be closely related. We initially established the somatic mutation landscape of CMML by whole exome sequencing followed by gene-targeted validation. Genes mutated in ⩾ 10% of patients were SRSF2, TET2, ASXL1, RUNX1, SETBP1, KRAS, EZH2, CBL and NRAS, as well as the novel CMML genes FAT4, ARIH1, DNAH2 and CSMD1. Most CMML patients (71%) had mutations in ⩾ 2 ARCH genes and 52% had ⩾ 7 mutations overall. Higher mutation burden was associated with shorter survival. Age-adjusted population incidence and reported ARCH mutation rates are consistent with a model in which clinical CMML ensues when a sufficient number of stochastically acquired age-related mutations has accumulated, suggesting that CMML represents the leukemic conversion of the myelomonocytic-lineage-biased aged hematopoietic system. PMID:26648538

A deletion mutation in GJB6 cooperating with a GJB2 mutation in trans in non-syndromic deafness: A novel founder mutation in Ashkenazi Jews.

PubMed

Lerer, I; Sagi, M; Ben-Neriah, Z; Wang, T; Levi, H; Abeliovich, D

2001-11-01

A deletion of at least 140 kb starting approximately 35kb upstream (telomeric) to the GJB2 (CX26) gene was identified in 7 patients from 4 unrelated Jewish Ashkenazi families with non-syndromic hearing loss. These patients were heterozygous for one of the common mutations 167delT or 35delG in the GJB2 gene in trans to the deletion. The deletion started at 5' side of the GJB6 (CX30) gene including the first exon and it did not affect the integrity of the GJB2 gene. The deletion mutation segregated together with the hearing loss, and was not found in a control group of 100 Ashkenazi individuals. We suggest that the deletion is a recessive mutation causing hearing loss in individuals that are double heterozygous for the deletion and for a mutation in the GJB2 gene. The effect of the deletion mutation could be due to a digenic mode of inheritance of GJB2 and GJB6 genes that encode two different connexins; connexin 26 and connexin 30, or it may abolish control elements that are important in the expression of the GJB2 gene in the cochlea. Regardless which of the options is valid, it is apparent that the deletion mutation provides a new insight into connexin function in the auditory system. The deletion mutation was on the same haplotypic background in all the families, and therefore is a founder mutation that increases the impact of GJB2 in the etiology of prelingual recessive non-syndromic hearing loss in the Ashkenazi population. Copyright 2001 Wiley-Liss, Inc.

Trabecular Meshwork Height in Primary Open-Angle Glaucoma Versus Primary Angle-Closure Glaucoma.

PubMed

Masis, Marisse; Chen, Rebecca; Porco, Travis; Lin, Shan C

2017-11-01

To determine if trabecular meshwork (TM) height differs between primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) eyes. Prospective, cross-sectional clinical study. Adult patients were consecutively recruited from glaucoma clinics at the University of California, San Francisco, from January 2012 to July 2015. Images were obtained from spectral-domain optical coherence tomography (Cirrus OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA). Univariate and multivariate linear mixed models comparing TM height and glaucoma type were performed to assess the relationship between TM height and glaucoma subtype. Mixed-effects regression was used to adjust for the use of both eyes in some subjects. The study included 260 eyes from 161 subjects, composed of 61 men and 100 women. Mean age was 70 years (SD 11.77). There were 199 eyes (123 patients) in the POAG group and 61 eyes (38 patients) in the PACG group. Mean TM heights in the POAG and PACG groups were 812 ± 13 μm and 732 ± 27 μm, respectively, and the difference was significant in univariate analysis (P = .004) and in multivariate analysis (β = -88.7 [24.05-153.5]; P = .008). In this clinic-based population, trabecular meshwork height is shorter in PACG patients compared to POAG patients. This finding may provide insight into the pathophysiology of angle closure and provide assistance in future diagnosis, prevention, and management of the angle-closure spectrum of disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

NORAD LOOK ANGLES AND PIO SATELLITE PACKAGE

NASA Technical Reports Server (NTRS)

ANONYMOUS

1994-01-01

This program package consists of two programs. First is the NORAD Look Angles Program, which computes satellite look angles (azimuth, elevation, and range) as well as the subsatellite points (latitude, longitude, and height). The second program in this package is the PIO Satellite Program, which computes sighting directions, visibility times, and the maximum elevation angle attained during each pass of an earth-orbiting satellite. Computations take into consideration the observing location and the effect of the earth's shadow on the satellite visibility. Input consists of a magnetic tape prepared by the NORAD Look Angles Program and punched cards containing reference Julian date, right ascension, declination, mean sidereal time at zero hours universal time of the reference date, and daily changes of these quantities. Output consists of a tabulated listing of the satellite's rise and set times, direction, and the maximum elevation angle visible from each observing location. This program has been implemented on the GE 635. The program Assembler code can easily be replaced by FORTRAN statements.

Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific.

PubMed

Chehade, Rania; Pettapiece-Phillips, Rachael; Salmena, Leonardo; Kotlyar, Max; Jurisica, Igor; Narod, Steven A; Akbari, Mohammad R; Kotsopoulos, Joanne

2016-08-17

BRCA1 mutation carriers face a high lifetime risk of developing both breast and ovarian cancer. Haploinsufficiency is thought to predispose these women to cancer by reducing the pool of available BRCA1 transcript and protein, thereby compromising BRCA1 function. Whether or not cancer-free BRCA1 mutation carriers have lower messenger (m)RNA transcript levels in peripheral blood leukocytes has not been evaluated. The primary aim of this study was to characterize an association between BRCA1 mutation status and BRCA1 mRNA leukocyte expression levels among healthy women with a BRCA1 mutation. RNA was extracted from freshly isolated peripheral blood leukocytes of 58 cancer-free, female participants (22 BRCA1 mutation carriers and 36 non-carriers). The expression levels of 236 cancer-associated genes, including BRCA1, were quantified using the Human Cancer Reference gene panel from the Nanostring Technologies nCounter Analysis System. Multivariate modeling demonstrated that carrying a BRCA1 mutation was the most significant predictor of BRCA1 mRNA levels. BRCA1 mRNA levels were significantly lower in BRCA1 mutation carriers compared to non-carriers (146.7 counts vs. 175.1 counts; P = 0.002). Samples with BRCA1 mutations within exon 11 had lower BRCA1 mRNA levels than samples with mutations within the 5' and 3' regions of the BRCA1 gene (122.1 counts vs. 138.9 and 168.6 counts, respectively; P = 0.003). Unsupervised hierarchical clustering of gene expression profiles from freshly isolated blood leukocytes revealed that BRCA1 mutation carriers cluster more closely with other BRCA1 mutation carriers than with BRCA1 wild-type samples. Moreover, a set of 17 genes (including BRCA1) previously shown to be involved in carcinogenesis, were differentially expressed between BRCA1 mutation carriers and non-carriers. Overall, these findings support the concept of BRCA1 haploinsufficiency wherein a specific mutation results in dosage-dependent alteration of BRCA1 at the

Rapid evolution of the human mutation spectrum

PubMed Central

Harris, Kelley; Pritchard, Jonathan K

2017-01-01

DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely related populations. Close examination of one signal, an increased TCC→TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate. Our results suggest that mutation rates can evolve markedly over short evolutionary timescales and suggest the possibility of mapping mutational modifiers. DOI: http://dx.doi.org/10.7554/eLife.24284.001 PMID:28440220

Deep learning methods for protein torsion angle prediction.

PubMed

Li, Haiou; Hou, Jie; Adhikari, Badri; Lyu, Qiang; Cheng, Jianlin

2017-09-18

Deep learning is one of the most powerful machine learning methods that has achieved the state-of-the-art performance in many domains. Since deep learning was introduced to the field of bioinformatics in 2012, it has achieved success in a number of areas such as protein residue-residue contact prediction, secondary structure prediction, and fold recognition. In this work, we developed deep learning methods to improve the prediction of torsion (dihedral) angles of proteins. We design four different deep learning architectures to predict protein torsion angles. The architectures including deep neural network (DNN) and deep restricted Boltzmann machine (DRBN), deep recurrent neural network (DRNN) and deep recurrent restricted Boltzmann machine (DReRBM) since the protein torsion angle prediction is a sequence related problem. In addition to existing protein features, two new features (predicted residue contact number and the error distribution of torsion angles extracted from sequence fragments) are used as input to each of the four deep learning architectures to predict phi and psi angles of protein backbone. The mean absolute error (MAE) of phi and psi angles predicted by DRNN, DReRBM, DRBM and DNN is about 20-21° and 29-30° on an independent dataset. The MAE of phi angle is comparable to the existing methods, but the MAE of psi angle is 29°, 2° lower than the existing methods. On the latest CASP12 targets, our methods also achieved the performance better than or comparable to a state-of-the art method. Our experiment demonstrates that deep learning is a valuable method for predicting protein torsion angles. The deep recurrent network architecture performs slightly better than deep feed-forward architecture, and the predicted residue contact number and the error distribution of torsion angles extracted from sequence fragments are useful features for improving prediction accuracy.

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

Detection of a novel silent deletion, a missense mutation and a nonsense mutation in TCOF1.

PubMed

Fujioka, Hirotaka; Ariga, Tadashi; Horiuchi, Katsumi; Ishikiriyama, Satoshi; Oyama, Kimie; Otsu, Makoto; Kawashima, Kunihiro; Yamamoto, Yuhei; Sugihara, Tsuneki; Sakiyama, Yukio

2008-12-01

Treacher Collins syndrome (TCS) is a disorder of craniofacial development, that is caused by mutations in the TCOF1 gene. TCS is inherited as an autosomal dominant trait, and haploinsufficiency of the TCOF1 gene product treacle is proposed to be etiologically involved. Mutational analysis of the TCOF1 gene was done in 10 patients diagnosed with TCS using single-strand conformation polymorphism and direct sequencing. Among these 10 patients, a novel 9 bp deletion was found, together with a previously reported 2 bp deletion, a novel missense mutation and a novel nonsense mutation in three different families. Familial studies allowed judgment of whether these abnormal findings were responsible for the TCS phenotype, or not. The 9 bp deletion of three amino acids Lys-Glu-Lys (1378-1380), which was located in the nuclear localization domain of treacle, seemed not essential for the treacle function. In contrast, the novel mutation of Ala26Val is considered to affect the LisH domain, an important domain of treacle. All of the mutations thus far detected in exon 5 have resulted in frameshift, but a nonsense mutation was detected (Lys159Stop). The information obtained in the present study provides additional insights into the functional domains of treacle.

Metric analysis of basal sphenoid angle in adult human skulls

PubMed Central

Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

2014-01-01

Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

Limbus Impact on Off-angle Iris Degradation

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

Karakaya, Mahmut; Barstow, Del R; Santos-Villalobos, Hector J

The accuracy of iris recognition depends on the quality of data capture and is negatively affected by several factors such as angle, occlusion, and dilation. Off-angle iris recognition is a new research focus in biometrics that tries to address several issues including corneal refraction, complex 3D iris texture, and blur. In this paper, we present an additional significant challenge that degrades the performance of the off-angle iris recognition systems, called the limbus effect . The limbus is the region at the border of the cornea where the cornea joins the sclera. The limbus is a semitransparent tissue that occludes amore » side portion of the iris plane. The amount of occluded iris texture on the side nearest the camera increases as the image acquisition angle increases. Without considering the role of the limbus effect, it is difficult to design an accurate off-angle iris recognition system. To the best of our knowledge, this is the first work that investigates the limbus effect in detail from a biometrics perspective. Based on results from real images and simulated experiments with real iris texture, the limbus effect increases the hamming distance score between frontal and off-angle iris images ranging from 0.05 to 0.2 depending upon the limbus height.« less

Effects of clinically relevant MPL mutations in the transmembrane domain revealed at the atomic level through computational modeling.

PubMed

Lee, Tai-Sung; Kantarjian, Hagop; Ma, Wanlong; Yeh, Chen-Hsiung; Giles, Francis; Albitar, Maher

2011-01-01

Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures. Modern computational biology techniques were utilized to explore the mechanisms of MPL protein activation due to various mutations. Transmembrane (TM) domain predictions, homology modeling, ab initio protein structure prediction, and molecular dynamics (MD) simulations were used to build structural dynamic models of wild-type and four clinically observed mutants of MPL. The simulation results suggest that S505 and W515 are important in keeping the TM domain in its correct position within the membrane. Mutations at either of these two positions cause movement of the TM domain, altering the conformation of the nearby intracellular domain in unexpected ways, and may cause the unwanted constitutive activation of MPL's kinase partner, JAK2. Our findings represent the first full-scale molecular dynamics simulations of the wild-type and clinically observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT signaling pathway. In contrast to usual explanations for the activation mechanism that are based on the relative translational movement between rigid domains of MPL, our results suggest that mutations within the TM region could result in conformational changes including tilt and rotation (azimuthal) angles along the membrane axis. Such changes may significantly alter the conformation of the adjacent and intrinsically flexible intracellular domain. Hence, caution should be exercised when interpreting experimental evidence based on rigid models of cytokine receptors or similar systems.

Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation.

PubMed

Raveendran, Sureshkumar; Sarojam, Santhi; Vijay, Sangeetha; Geetha, Aswathy Chandran; Sreedharan, Jayadevan; Narayanan, Geetha; Sreedharan, Hariharan

2015-01-01

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.