WorldWideScience

Sample records for huntington canyon generating

  1. High prevalence of diabetes mellitus in a five-generation Chinese family with Huntington's disease.

    Science.gov (United States)

    Hu, Yueqing; Liang, Jingyao; Yu, Shengyuan

    2014-01-01

    Huntington's disease (HD) is associated with diabetes mellitus (DM) in population studies, but no case has been reported in a large HD family. We report a case of a five-generation Chinese family who is afflicted by both HD and DM. The prevalence of DM in HD of this family was high (72.7%). The diagnosis of HD in 11 family members was confirmed by the genetic test of the proband who had 42 CAG repeats. Furthermore, the proband's daughter had abnormal locus at G3460T in MT-ND1 among mtDNA genome. Our case report suggests a genetic link between HD and DM.

  2. Probabilistic Hazard of Tsunamis Generated by Submarine Landslides in the Cook Strait Canyon (New Zealand)

    Science.gov (United States)

    Lane, Emily M.; Mountjoy, Joshu J.; Power, William L.; Mueller, Christof

    2016-12-01

    Cook Strait Canyon is a submarine canyon that lies within ten kilometres of Wellington, the capital city of New Zealand. The canyon walls are covered with scars from previous landslides which could have caused local tsunamis. Palaeotsunami evidence also points to past tsunamis in the Wellington region. Furthermore, the canyon's location in Cook Strait means that there is inhabited land in the path of both forward- and backward-propagating waves. Tsunamis induced by these submarine landslides pose hazard to coastal communities and infrastructure but major events are very uncommon and the historical record is not extensive enough to quantify this hazard. The combination of infrequent but potentially very consequential events makes realistic assessment of the hazard challenging. However, information on both magnitude and frequency is very important for land use planning and civil defence purposes. We use a multidisciplinary approach bringing together geological information with modelling to construct a Probabilistic Tsunami Hazard Assessment of submarine landslide-generated tsunami. Although there are many simplifying assumptions used in this assessment, it suggests that the Cook Strait open coast is exposed to considerable hazard due to submarine landslide-generated tsunamis. We emphasise the uncertainties involved and present opportunities for future research.

  3. Huntington's Disease

    Science.gov (United States)

    Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of ...

  4. Conditions for generation of fire-related debris flows, Capulin Canyon, New Mexico

    Science.gov (United States)

    Cannon, S.H.; Reneau, S.L.

    2000-01-01

    Comparison of the responses of three drainage basins burned by the Dome fire of 1996 in New Mexico is used to identify the hillslope, channel and fire characteristics that indicate a susceptibility specifically to wildfire-related debris flow. Summer thunderstorms generated three distinct erosive responses from each of three basins. The Capulin Canyon basin showed widespread erosive sheetwash and rilling from hillslopes, and severe flooding occurred in the channel; the North Tributary basin exhibited extensive erosion of the mineral soil to a depth of 5 cm and downslope movement of up to boulder-sized material, and at least one debris flow occurred in the channel; negligible surface runoff was observed in the South Tributary basin. The negligible surface runoff observed in the South Tributary basin is attributed to the limited extent and severity of the fire in that basin. The factors that best distinguish between debris-flow producing and flood-producing drainages are drainage basin morphology and lithology. A rugged drainage basin morphology, an average 12 per cent channel gradient, and steep, rough hillslopes coupled with colluvium and soil weathered from volcaniclastic and volcanic rocks promoted the generation of debris flows. A less rugged basin morphology, an average gradient of 5 per cent, and long, smooth slopes mantled with pumice promoted flooding. Flood and debris-flow responses were produced without the presence of water-repellent soils. The continuity and severity of the burn mosaic, the condition of the riparian vegetation, the condition of the fibrous root mat, accumulations of dry ravel and colluvial material in the channel and on hillslopes, and past debris-flow activity, appeared to have little bearing on the distinctive responses of the basins. Published in 2000 by John Wiley and Sons, Ltd.

  5. Genomic Instability Associated with p53 Knockdown in the Generation of Huntington's Disease Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Tidball, Andrew M; Neely, M Diana; Chamberlin, Reed; Aboud, Asad A; Kumar, Kevin K; Han, Bingying; Bryan, Miles R; Aschner, Michael; Ess, Kevin C; Bowman, Aaron B

    2016-01-01

    Alterations in DNA damage response and repair have been observed in Huntington's disease (HD). We generated induced pluripotent stem cells (iPSC) from primary dermal fibroblasts of 5 patients with HD and 5 control subjects. A significant fraction of the HD iPSC lines had genomic abnormalities as assessed by karyotype analysis, while none of our control lines had detectable genomic abnormalities. We demonstrate a statistically significant increase in genomic instability in HD cells during reprogramming. We also report a significant association with repeat length and severity of this instability. Our karyotypically normal HD iPSCs also have elevated ATM-p53 signaling as shown by elevated levels of phosphorylated p53 and H2AX, indicating either elevated DNA damage or hypersensitive DNA damage signaling in HD iPSCs. Thus, increased DNA damage responses in the HD genotype is coincidental with the observed chromosomal aberrations. We conclude that the disease causing mutation in HD increases the propensity of chromosomal instability relative to control fibroblasts specifically during reprogramming to a pluripotent state by a commonly used episomal-based method that includes p53 knockdown.

  6. Huntington's disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia

    2011-01-01

    In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient...

  7. Huntington disease

    Science.gov (United States)

    ... President of the Florida Society of Neurology (FSN). Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Huntington's Disease Read more Latest Health News Read more Health ...

  8. Learning about Huntington's Disease

    Science.gov (United States)

    ... Mouse Models Of Huntington's Disease 1998 News Release Learning About Huntington's Disease What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Huntington's Outreach ...

  9. Was the 1531 Lisbon tsunami generated by a landslide along the Cascais Canyon? Geologic inferences and tsunami simulation

    Science.gov (United States)

    Lo Iacono, C.; Masson, D. G.; Glimsdal, S.; Huvenne, V. A. I.; Wynn, R. B.; Harbitz, C. B.

    2015-12-01

    In 1531, a 6.5 magnitude earthquake with an epicentre inland of Lisbon caused severe damage to the city, rendering a third of its buildings uninhabitable, with its intensity comparable or even greater than the 1755 Lisbon earthquake. This event was followed by a destructive tsunami of slightly smaller size than the 1755 and, in contrast to the latter, it was only observed locally along the entire Tagus estuary and in coastal belt surroundings the mouth of the Tagus River. For the 1531 tsunami, a satisfactory mechanism for its generation has yet to be found, but the inland earthquake epicentre and the absence of large submarine scarps tend to rule out fault-related seabed displacement in and out of the Tagus estuary. An alternative possibility is that the 1531 tsunami was caused by a submarine landslide triggered by the earthquake. Here we describe a submarine landslide along the Cascais Canyon, whose head faces the Tagus estuary, which may have caused the 1531 tsunami. At a depth of around 2000 m, up to 150 m across and 45 m high bocks, erosional furrows and possible gravel waves have been imaged over an area of at least 15 km2 using 30 kHz deep-towed sidescan sonar, suggesting a geologically recent large-scale flow event. High-resolution bathymetry and seafloor photographs acquired at around 4000 m using a remotely operated vehicle (ROV) in the blocky landslide area show boulders at the seafloor, mantled with a thin sediment cover, again suggestive of a recent landslide. Radiocarbon dates from collected cores show that this landslide is likely to have been generated during the 16th century, suggesting a cause-effect relationship with the 1531 earthquake. Preliminary tsunami models suggest that a landslide potentially fitting the characteristics of the Cascais landslide is able to generate a near-field tsunami wave reaching the Lisbon coast but not crossing the whole Tagus estuary. Recognising that the 1531 Lisbon tsunami may have been generated by a submarine

  10. Proposed Wilderness Areas of Grand Canyon National Park, Arizona (Generated in 2003 by the Intermountain Region GIS Support Office)

    Data.gov (United States)

    National Park Service, Department of the Interior — This shapefile contains boundaries for Proposed Recommended Wilderness, Proposed Potential Wilderness, and Non-Wilderness in Grand Canyon National Park, Arizona....

  11. Psychopathology in Huntington's disease

    NARCIS (Netherlands)

    Duijn, Erik van

    2010-01-01

    Dit proefschrift begint met een overzichtsartikel van oorspronkelijke onderzoek naar psychopathologie bij mutatiedragers voor de ziekte van Huntington. Aansluitend worden de resultaten van een cohortstudie naar de aanwezigheid en ernst van psychopathologie bij mensen met de ziekte van Huntington in

  12. Psychopathology in Huntington's disease

    NARCIS (Netherlands)

    Duijn, Erik van

    2010-01-01

    Dit proefschrift begint met een overzichtsartikel van oorspronkelijke onderzoek naar psychopathologie bij mutatiedragers voor de ziekte van Huntington. Aansluitend worden de resultaten van een cohortstudie naar de aanwezigheid en ernst van psychopathologie bij mensen met de ziekte van Huntington in

  13. Monkey hybrid stem cells develop cellular features of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Lorthongpanich Chanchao

    2010-02-01

    Full Text Available Abstract Background Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research. Results To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1 was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development in vitro , and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events. Conclusions Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis.

  14. Impaired mitochondrial trafficking in Huntington's disease

    OpenAIRE

    Li, Xiao-Jiang; Orr, Adam L.; Li, Shihua

    2009-01-01

    Abstract Impaired mitochondrial function has been well documented in Huntington?s disease. Mutant huntingtin is found to affect mitochondria via various mechanisms including the dysregulation of gene transcription and impairment of mitochondrial function or trafficking. The lengthy and highly branched neuronal processes constitute complex neural networks in which there is a large demand for mitochondria-generated energy. Thus, the impaired mitochondria trafficking in neuronal cells...

  15. Huntington's disease phenocopy syndromes.

    Science.gov (United States)

    Wild, Edward J; Tabrizi, Sarah J

    2007-12-01

    Patients presenting with features of Huntington's disease but lacking the causative genetic expansion can be challenging diagnostically. The differential diagnosis of such Huntington's disease phenocopy syndromes has not recently been reviewed. Cohort studies have established the relative frequencies of known Huntington's disease phenocopy syndromes, whereas newly described ones have been characterized genetically, clinically, radiologically and pathologically. About 1% of suspected Huntington's disease cases emerge as phenocopy syndromes. Such syndromes are clinically important in their own right but may also shed light on the pathogenesis of Huntington's disease. Huntington's disease produces a range of clinical phenotypes, and the range of syndromes that may be responsible for Huntington's disease phenocopies is correspondingly wide. Cohort studies have established that, while the majority of phenocopy patients remain undiagnosed, in those patients where a genetic diagnosis is reached the commonest causes are SCA17, Huntington's disease-like syndrome 2 (HDL2), familial prion disease and Friedreich's ataxia. We review the features of the reported genetic causes of Huntington's disease phenocopy syndromes, including HDL1-3, SCA17, familial prion disease, spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, chorea-acanthocytosis and iron-accumulation disorders. We present an evidence-based framework for the genetic testing of Huntington's disease phenocopy cases.

  16. Antipsychotic drugs in Huntington's disease.

    Science.gov (United States)

    Unti, E; Mazzucchi, S; Palermo, G; Bonuccelli, U; Ceravolo, R

    2017-03-01

    The aim of this review is to overview the pharmacological features of neuroleptics experienced in the treatment of Huntington's disease (HD) symptoms. Despite a large number of case reports, randomized controlled trials (RCT) and drug comparison studies are lacking. Areas covered: After evaluating current guidelines and clinical unmet needs we searched PubMed for the term 'Huntington's disease' cross referenced with the terms 'Antipsychotic drugs' 'Neuroleptic drugs' and single drug specific names. Expert commentary: In clinical practice antipsychotics represent the first choice in the management of chorea in the presence of psychiatric symptoms, when poor compliance is suspected or when there is an increased risk of adverse events due to tetrabenazine. Antipsychotics are considered valid strategies, with the second generation preferred to reduce extrapyramidal adverse events, however they may cause more metabolic side effects. In the future 'dopamine stabilizers', such as pridopidine, could replace antipsychotics modulating dopamine transmission.

  17. Geomorphic process fingerprints in submarine canyons

    Science.gov (United States)

    Brothers, Daniel S.; ten Brink, Uri S.; Andrews, Brian D.; Chaytor, Jason D.; Twichell, David C.

    2013-01-01

    Submarine canyons are common features of continental margins worldwide. They are conduits that funnel vast quantities of sediment from the continents to the deep sea. Though it is known that submarine canyons form primarily from erosion induced by submarine sediment flows, we currently lack quantitative, empirically based expressions that describe the morphology of submarine canyon networks. Multibeam bathymetry data along the entire passive US Atlantic margin (USAM) and along the active central California margin near Monterey Bay provide an opportunity to examine the fine-scale morphology of 171 slope-sourced canyons. Log–log regression analyses of canyon thalweg gradient (S) versus up-canyon catchment area (A) are used to examine linkages between morphological domains and the generation and evolution of submarine sediment flows. For example, canyon reaches of the upper continental slope are characterized by steep, linear and/or convex longitudinal profiles, whereas reaches farther down canyon have distinctly concave longitudinal profiles. The transition between these geomorphic domains is inferred to represent the downslope transformation of debris flows into erosive, canyon-flushing turbidity flows. Over geologic timescales this process appears to leave behind a predictable geomorphic fingerprint that is dependent on the catchment area of the canyon head. Catchment area, in turn, may be a proxy for the volume of sediment released during geomorphically significant failures along the upper continental slope. Focused studies of slope-sourced submarine canyons may provide new insights into the relationships between fine-scale canyon morphology and down-canyon changes in sediment flow dynamics.

  18. Huntington's Disease and Mitochondria.

    Science.gov (United States)

    Jodeiri Farshbaf, Mohammad; Ghaedi, Kamran

    2017-06-21

    Huntington's disease (HD) as an inherited neurodegenerative disorder leads to neuronal loss in striatum. Progressive motor dysfunction, cognitive decline, and psychiatric disturbance are the main clinical symptoms of the HD. This disease is caused by expansion of the CAG repeats in exon 1 of the huntingtin which encodes Huntingtin protein (Htt). Various cellular and molecular events play role in the pathology of HD. Mitochondria as important organelles play crucial roles in the most of neurodegenerative disorders like HD. Critical roles of the mitochondria in neurons are ATP generation, Ca(2+) buffering, ROS generation, and antioxidant activity. Neurons as high-demand energy cells closely related to function, maintenance, and dynamic of mitochondria. In the most neurological disorders, mitochondrial activities and dynamic are disrupted which associate with high ROS level, low ATP generation, and apoptosis. Accumulation of mutant huntingtin (mHtt) during this disease may evoke mitochondrial dysfunction. Here, we review recent findings to support this hypothesis that mHtt could cause mitochondrial defects. In addition, by focusing normal huntingtin functions in neurons, we purpose mitochondria and Huntingtin association in normal condition. Moreover, mHtt affects various cellular signaling which ends up to mitochondrial biogenesis. So, it could be a potential candidate to decline ATP level in HD. We conclude how mitochondrial biogenesis plays a central role in the neuronal survival and activity and how mHtt affects mitochondrial trafficking, maintenance, integrity, function, dynamics, and hemostasis and makes neurons vulnerable to degeneration in HD.

  19. Examination of Huntington's disease in a Chinese family.

    Science.gov (United States)

    Yu, Mingxia; Li, Xiaogai; Wu, Sanyun; Shen, Ji; Tu, Jiancheng

    2014-02-15

    We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington's disease. Among 17 family members across three generations, four patients (II2, II6, III5, and III9) show typical Huntington's disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members (II2, II6, and III5). Moreover, genetic analysis identified abnormally amplified CAG sequence repeats (> 40) in two members (III5 and III9). Among borderline cases, with clinical symptoms and brain imaging features of Huntington's disease, two cases were identified (II2 and II6), but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington's disease. Our findings suggest that clinical diagnosis of Huntington's disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.

  20. The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity.

    Science.gov (United States)

    Camnasio, Stefano; Delli Carri, Alessia; Lombardo, Angelo; Grad, Iwona; Mariotti, Caterina; Castucci, Alessia; Rozell, Björn; Lo Riso, Pietro; Castiglioni, Valentina; Zuccato, Chiara; Rochon, Christelle; Takashima, Yasuhiro; Diaferia, Giuseppe; Biunno, Ida; Gellera, Cinzia; Jaconi, Marisa; Smith, Austin; Hovatta, Outi; Naldini, Luigi; Di Donato, Stefano; Feki, Anis; Cattaneo, Elena

    2012-04-01

    Neuronal disorders, like Huntington's disease (HD), are difficult to study, due to limited cell accessibility, late onset manifestations, and low availability of material. The establishment of an in vitro model that recapitulates features of the disease may help understanding the cellular and molecular events that trigger disease manifestations. Here, we describe the generation and characterization of a series of induced pluripotent stem (iPS) cells derived from patients with HD, including two rare homozygous genotypes and one heterozygous genotype. We used lentiviral technology to transfer key genes for inducing reprogramming. To confirm pluripotency and differentiation of iPS cells, we used PCR amplification and immunocytochemistry to measure the expression of marker genes in embryoid bodies and neurons. We also analyzed teratomas that formed in iPS cell-injected mice. We found that the length of the pathological CAG repeat did not increase during reprogramming, after long term growth in vitro, and after differentiation into neurons. In addition, we observed no differences between normal and mutant genotypes in reprogramming, growth rate, caspase activation or neuronal differentiation. However, we observed a significant increase in lysosomal activity in HD-iPS cells compared to control iPS cells, both during self-renewal and in iPS-derived neurons. In conclusion, we have established stable HD-iPS cell lines that can be used for investigating disease mechanisms that underlie HD. The CAG stability and lysosomal activity represent novel observations in HD-iPS cells. In the future, these cells may provide the basis for a powerful platform for drug screening and target identification in HD.

  1. Parcels and Land Ownership, Published in 2011, Huntington County Government.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Parcels and Land Ownership dataset as of 2011. The extent of these data is generally Huntington County, IN. This metadata was auto-generated through the Ramona...

  2. [The Henry E. Huntington Library.

    Science.gov (United States)

    Abraham, Terry

    The biographical sketch of Henry E. Huntington includes a description of the establishment of the Huntington Library and the purpose and scope of its collection. Although this is a free and public library, its use is restricted to qualified scholars having legitimate research needs. Photographic techniques were developed at the Huntington Library…

  3. Subinertial canyon resonance

    Science.gov (United States)

    Clarke, Allan J.; Van Gorder, Stephen

    2016-04-01

    Near the bottom of a narrow canyon currents that oscillate back and forth along the bottom slope hx in a stratified ocean of buoyancy frequency N do so with a natural internal gravitational frequency Nhx. From May 2012 to May 2013 Acoustic Doppler Current Profiler measurements were made at 715 m depth in the deep narrow part of the DeSoto Canyon south of Pensacola, Florida, in water with 2π/Nhx ≈ 2.5 days. Above the canyon the flow follows the large-scale isobaths, but beneath the canyon rim the current oscillates along the canyon axis with 2-3 day periodicity, and is much stronger than and uncorrelated with the overlying flow. A simple theoretical model explains the resonant response. Published observations from the Hudson and Gully canyons suggest that the strong subinertial current oscillations observed in these canyons occur close to the relevant local frequency Nhx, consistent with the proposed simple model physics.

  4. Flow dynamics around downwelling submarine canyons

    Directory of Open Access Journals (Sweden)

    J. M. Spurgin

    2014-05-01

    Full Text Available Flow dynamics around a downwelling submarine canyon were analysed with the Massachusetts Institute of Technology general circulation model. Blanes Canyon (Northwest Mediterranean was used for topographic and initial forcing conditions. Fourteen scenarios were modelled with varying forcing conditions. Rossby number and Burger number were used to determine the significance of Coriolis acceleration and stratification (respectively and their impacts on flow dynamics. A new non-dimensional parameter (χ was introduced to determine the significance of vertical variations in stratification. Some simulations do see brief periods of upwards displacement of water during the 10 day model period, however, the presence of the submarine canyon is found to enhance downwards advection of density in all model scenarios. High Burger numbers lead to negative vorticity and a trapped anticyclonic eddy within the canyon, as well as an increased density anomaly. Low Burger numbers lead to positive vorticity, cyclonic circulation and weaker density anomalies. Vertical variations in stratification affect zonal jet placement. Under the same forcing conditions, the zonal jet is pushed offshore in more uniformly stratified domains. Offshore jet location generates upwards density advection away from the canyon, while onshore jets generate downwards density advection everywhere within the model domain. Increasing Rossby values across the canyon axis, as well as decreasing Burger values, increase negative vertical flux at shelf break depth (150 m. Increasing Rossby numbers lead to stronger downwards advection of a passive tracer (nitrate as well as stronger vorticity within the canyon. Results from previous studies were explained within this new dynamic framework.

  5. Flow dynamics around downwelling submarine canyons

    Directory of Open Access Journals (Sweden)

    J. M. Spurgin

    2014-10-01

    Full Text Available Flow dynamics around a downwelling submarine canyon were analysed with the Massachusetts Institute of Technology general circulation model. Blanes Canyon (northwestern Mediterranean was used for topographic and initial forcing conditions. Fourteen scenarios were modelled with varying forcing conditions. Rossby and Burger numbers were used to determine the significance of Coriolis acceleration and stratification (respectively and their impacts on flow dynamics. A new non-dimensional parameter (χ was introduced to determine the significance of vertical variations in stratification. Some simulations do see brief periods of upwards displacement of water during the 10-day model period; however, the presence of the submarine canyon is found to enhance downwards advection of density in all model scenarios. High Burger numbers lead to negative vorticity and a trapped anticyclonic eddy within the canyon, as well as an increased density anomaly. Low Burger numbers lead to positive vorticity, cyclonic circulation, and weaker density anomalies. Vertical variations in stratification affect zonal jet placement. Under the same forcing conditions, the zonal jet is pushed offshore in more uniformly stratified domains. The offshore jet location generates upwards density advection away from the canyon, while onshore jets generate downwards density advection everywhere within the model domain. Increasing Rossby values across the canyon axis, as well as decreasing Burger values, increase negative vertical flux at shelf break depth (150 m. Increasing Rossby numbers lead to stronger downwards advection of a passive tracer (nitrate, as well as stronger vorticity within the canyon. Results from previous studies are explained within this new dynamic framework.

  6. Flow dynamics around downwelling submarine canyons

    Science.gov (United States)

    Spurgin, J. M.; Allen, S. E.

    2014-10-01

    Flow dynamics around a downwelling submarine canyon were analysed with the Massachusetts Institute of Technology general circulation model. Blanes Canyon (northwestern Mediterranean) was used for topographic and initial forcing conditions. Fourteen scenarios were modelled with varying forcing conditions. Rossby and Burger numbers were used to determine the significance of Coriolis acceleration and stratification (respectively) and their impacts on flow dynamics. A new non-dimensional parameter (χ) was introduced to determine the significance of vertical variations in stratification. Some simulations do see brief periods of upwards displacement of water during the 10-day model period; however, the presence of the submarine canyon is found to enhance downwards advection of density in all model scenarios. High Burger numbers lead to negative vorticity and a trapped anticyclonic eddy within the canyon, as well as an increased density anomaly. Low Burger numbers lead to positive vorticity, cyclonic circulation, and weaker density anomalies. Vertical variations in stratification affect zonal jet placement. Under the same forcing conditions, the zonal jet is pushed offshore in more uniformly stratified domains. The offshore jet location generates upwards density advection away from the canyon, while onshore jets generate downwards density advection everywhere within the model domain. Increasing Rossby values across the canyon axis, as well as decreasing Burger values, increase negative vertical flux at shelf break depth (150 m). Increasing Rossby numbers lead to stronger downwards advection of a passive tracer (nitrate), as well as stronger vorticity within the canyon. Results from previous studies are explained within this new dynamic framework.

  7. Impaired motor speech performance in Huntington's disease.

    Science.gov (United States)

    Skodda, Sabine; Schlegel, Uwe; Hoffmann, Rainer; Saft, Carsten

    2014-04-01

    Dysarthria is a common symptom of Huntington's disease and has been reported, besides other features, to be characterized by alterations of speech rate and regularity. However, data on the specific pattern of motor speech impairment and their relationship to other motor and neuropsychological symptoms are sparse. Therefore, the aim of the present study was to describe and objectively analyse different speech parameters with special emphasis on the aspect of speech timing of connected speech and non-speech verbal utterances. 21 patients with manifest Huntington's disease and 21 age- and gender-matched healthy controls had to perform a reading task and several syllable repetition tasks. Computerized acoustic analysis of different variables for the measurement of speech rate and regularity generated a typical pattern of impaired motor speech performance with a reduction of speech rate, an increase of pauses and a marked disability to steadily repeat single syllables. Abnormalities of speech parameters were more pronounced in the subgroup of patients with Huntington's disease receiving antidopaminergic medication, but were also present in the drug-naïve patients. Speech rate related to connected speech and parameters of syllable repetition showed correlations to overall motor impairment, capacity of tapping in a quantitative motor assessment and some score of cognitive function. After these preliminary data, further investigations on patients in different stages of disease are warranted to survey if the analysis of speech and non-speech verbal utterances might be a helpful additional tool for the monitoring of functional disability in Huntington's disease.

  8. Clinical neurogenetics: huntington disease.

    Science.gov (United States)

    Bordelon, Yvette M

    2013-11-01

    Huntington disease (HD) is an autosomal dominant, adult-onset, progressive neurodegenerative disease characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric problems. It is caused by an expanded CAG repeat in the gene encoding the protein huntingtin on chromosome 4 and causes progressive atrophy of the striatum as well as cortical and other extrastriatal structures. Genetic testing has been available since 1993 to confirm diagnosis in affected adults and for presymptomatic testing in at-risk individuals. This review covers HD signs, symptoms, and pathophysiology; current genetic testing issues; and current and future treatment strategies.

  9. Large genetic animal models of Huntington's Disease.

    Science.gov (United States)

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research.

  10. Tectonic activity and the evolution of submarine canyons: The Cook Strait Canyon system, New Zealand

    Science.gov (United States)

    Micallef, Aaron; Mountjoy, Joshu; Barnes, Philip; Canals, Miquel; Lastras, Galderic

    2016-04-01

    Submarine canyons are Earth's most dramatic erosional features, comprising steep-walled valleys that originate in the continental shelf and slope. They play a key role in the evolution of continental margins by transferring sediments into deep water settings and are considered important biodiversity hotspots, pathways for nutrients and pollutants, and analogues of hydrocarbon reservoirs. Although comprising only one third of continental margins worldwide, active margins host more than half of global submarine canyons. We still lack of thorough understanding of the coupling between active tectonics and submarine canyon processes, which is necessary to improve the modelling of canyon evolution in active margins and derive tectonic information from canyon morphology. The objectives of this study are to: (i) understand how tectonic activity influences submarine canyon morphology, processes, and evolution in an active margin, and (2) formulate a generalised model of canyon development in response to tectonic forcing based on morphometric parameters. We fulfil these objectives by analysing high resolution geophysical data and imagery from Cook Strait Canyon system, offshore New Zealand. Using these data, we demonstrate that tectonic activity, in the form of major faults and structurally-generated tectonic ridges, leaves a clear topographic signature on submarine canyon location and morphology, in particular their dendritic and sinuous planform shapes, steep and linear longitudinal profiles, and cross-sectional asymmetry and width. We also report breaks/changes in canyon longitudinal slope gradient, relief and slope-area regression models at the intersection with faults. Tectonic activity gives rise to two types of knickpoints in the Cook Strait Canyon. The first type consists of low slope gradient, rounded and diffusive knickpoints forming as a result of short wavelength folds or fault break outs and being restored to an equilibrium profile by upstream erosion and

  11. Flow in bedrock canyons.

    Science.gov (United States)

    Venditti, Jeremy G; Rennie, Colin D; Bomhof, James; Bradley, Ryan W; Little, Malcolm; Church, Michael

    2014-09-25

    Bedrock erosion in rivers sets the pace of landscape evolution, influences the evolution of orogens and determines the size, shape and relief of mountains. A variety of models link fluid flow and sediment transport processes to bedrock incision in canyons. The model components that represent sediment transport processes are increasingly well developed. In contrast, the model components being used to represent fluid flow are largely untested because there are no observations of the flow structure in bedrock canyons. Here we present a 524-kilometre, continuous centreline, acoustic Doppler current profiler survey of the Fraser Canyon in western Canada, which includes 42 individual bedrock canyons. Our observations of three-dimensional flow structure reveal that, as water enters the canyons, a high-velocity core follows the bed surface, causing a velocity inversion (high velocities near the bed and low velocities at the surface). The plunging water then upwells along the canyon walls, resulting in counter-rotating, along-stream coherent flow structures that diverge near the bed. The resulting flow structure promotes deep scour in the bedrock channel floor and undercutting of the canyon walls. This provides a mechanism for channel widening and ensures that the base of the walls is swept clear of the debris that is often deposited there, keeping the walls nearly vertical. These observations reveal that the flow structure in bedrock canyons is more complex than assumed in the models presently used. Fluid flow models that capture the essence of the three-dimensional flow field, using simple phenomenological rules that are computationally tractable, are required to capture the dynamic coupling between flow, bedrock erosion and solid-Earth dynamics.

  12. Ascension Submarine Canyon, California - Evolution of a multi-head canyon system along a strike-slip continental margin

    Science.gov (United States)

    Nagel, D.K.; Mullins, H.T.; Greene, H. Gary

    1986-01-01

    Ascension Submarine Canyon, which lies along the strike-slip (transform) dominated continental margin of central California, consists of two discrete northwestern heads and six less well defined southeastern heads. These eight heads coalesce to form a single submarine canyon near the 2700 m isobath. Detailed seismic stratigraphic data correlated with 19 rock dredge hauls from the walls of the canyon system, suggest that at least one of the two northwestern heads was initially eroded during a Pliocene lowstand of sea level ???3.8 m.y. B.P. Paleogeographic reconstructions indicate that at this time, northwestern Ascension Canyon formed the distal channel of nearby Monterey Canyon and has subsequently been offset by right-lateral, strike-slip faulting along the San Gregorio fault zone. Some of the six southwestern heads of Ascension Canyon may also have been initially eroded as the distal portions of Monterey Canyon during late Pliocene-early Pleistocene sea-level lowstands (???2.8 and 1.75 m.y. B.P.) and subsequently truncated and offset to the northwest. There have also been a minimum of two canyon-cutting episodes within the past 750,000 years, after the entire Ascension Canyon system migrated to the northwest past Monterey Canyon. We attribute these late Pleistocene erosional events to relative lowstands of sea level 750,000 and 18,000 yrs B.P. The late Pleistocene and Holocene evolution of the six southeastern heads also appears to have been controlled by structural uplift of the Ascension-Monterey basement high at the southeastern terminus of the Outer Santa Cruz Basin. We believe that uplift of this basement high sufficiently oversteepened submarine slopes to induce gravitational instability and generate mass movements that resulted in the erosion of the canyon heads. Most significantly, though, our results and interpretations support previous proposals that submarine canyons along strike-slip continental margins can originate by tectonic trunction and lateral

  13. Internal tide convergence and mixing in a submarine canyon

    Science.gov (United States)

    Waterhouse, Amy

    2016-11-01

    Observations from Eel Canyon, located on the north coast of California, show that elevated turbulence in the full water column arises from the convergence of remotely-generated internal wave energy. The incoming semidiurnal and bottom-trapped diurnal internal tides generate complex interference patterns. The semidiurnal internal tide sets up a partly standing wave within the canyon due to reflection at the canyon head, dissipating all of its energy within the canyon. Dissipation in the near-bottom is associated with the diurnal trapped tide, while midwater isopycnal shear and strain is associated with the semidiurnal tide. Dissipation is elevated up to 600 m off the bottom, in contrast to observations over flat continental shelf where dissipation occurs closer to the topography. Slope canyons are sinks for internal wave energy and may have important influences on the global distribution of tidally-driven mixing.

  14. Effects of canyon geometry on the distribution of traffic-related air pollution in a large urban area: Implications of a multi-canyon air pollution dispersion model

    Science.gov (United States)

    Fu, Xiangwen; Liu, Junfeng; Ban-Weiss, George A.; Zhang, Jiachen; Huang, Xin; Ouyang, Bin; Popoola, Olalekan; Tao, Shu

    2017-09-01

    Street canyons are ubiquitous in urban areas. Traffic-related air pollutants in street canyons can adversely affect human health. In this study, an urban-scale traffic pollution dispersion model is developed considering street distribution, canyon geometry, background meteorology, traffic assignment, traffic emissions and air pollutant dispersion. In the model, vehicle exhausts generated from traffic flows first disperse inside street canyons along the micro-scale wind field generated by computational fluid dynamics (CFD) model. Then, pollutants leave the street canyon and further disperse over the urban area. On the basis of this model, the effects of canyon geometry on the distribution of NOx and CO from traffic emissions were studied over the center of Beijing. We found that an increase in building height leads to heavier pollution inside canyons and lower pollution outside canyons at pedestrian level, resulting in higher domain-averaged concentrations over the area. In addition, canyons with highly even or highly uneven building heights on each side of the street tend to lower the urban-scale air pollution concentrations at pedestrian level. Further, increasing street widths tends to lead to lower pollutant concentrations by reducing emissions and enhancing ventilation simultaneously. Our results indicate that canyon geometry strongly influences human exposure to traffic pollutants in the populated urban area. Carefully planning street layout and canyon geometry while considering traffic demand as well as local weather patterns may significantly reduce inhalation of unhealthy air by urban residents.

  15. Huntington's disease presenting as amyotrophic lateral sclerosis.

    LENUS (Irish Health Repository)

    Phukan, Julie

    2010-08-01

    We present the clinical, electrophysiological and molecular genetic findings of a 58-year-old male with genetically confirmed Huntington\\'s disease (HD) and concurrent clinically definite ALS by El Escorial criteria. The patient presented with asymmetric upper limb amyotrophy and weakness, and subsequently developed chorea and cognitive change. Genetic testing confirmed the presence of expanded trinucleotide repeats in huntingtin, consistent with a diagnosis of Huntington\\'s disease. This case confirms the rare coexistence of Huntington\\'s disease and motor neuron degeneration.

  16. What is HD - Huntington's Disease?

    Science.gov (United States)

    ... the person less able to work at their customary level and less functional in their regular activities ... not is intensely personal and there is no "right" answer. The Huntington's Disease Society of America recommends ...

  17. Stages of Huntington's Disease (HD)

    Science.gov (United States)

    ... the person less able to work at their customary level and less functional in their regular activities ... not is intensely personal and there is no "right" answer. The Huntington's Disease Society of America recommends ...

  18. Natural history of Huntington disease.

    Science.gov (United States)

    Dorsey, E Ray; Beck, Christopher A; Darwin, Kristin; Nichols, Paige; Brocht, Alicia F D; Biglan, Kevin M; Shoulson, Ira

    2013-12-01

    Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials. To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls. Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n =4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease. Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs. Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P Huntington disease all declined in a monotonic manner. These data quantify the natural history of the disease and may inform the design of trials aimed at reducing its burden. clinicaltrials.gov Identifier: NCT00313495.

  19. Huntington's disease in children.

    Science.gov (United States)

    Letort, Derek; Gonzalez-Alegre, Pedro

    2013-01-01

    Huntington's disease (HD) is a dominantly inherited, fatal neurodegenerative disease. This incurable illness is characterized by a triad of a movement disorder, cognitive decline and psychiatric manifestations. Although most patients with HD have disease onset in the adult years, a small but significant proportion present with pediatric HD. It has been long known that patients with early-onset HD commonly exhibit prominent parkinsonism, known as the Westphal variant of HD. However, even among patients with pediatric HD there are differential clinical features depending on the age of onset, with younger patients frequently presenting diagnostic challenges. In his chapter, the characteristics of patients with childhood- and adolescence-onset HD are discussed, focusing on the differential clinical features that can aid the clinical reach a correct diagnosis, the indications and rational use of genetic testing and the currently available options for symptomatic treatment.

  20. Error processing in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Christian Beste

    Full Text Available BACKGROUND: Huntington's disease (HD is a genetic disorder expressed by a degeneration of the basal ganglia inter alia accompanied with dopaminergic alterations. These dopaminergic alterations are related to genetic factors i.e., CAG-repeat expansion. The error (related negativity (Ne/ERN, a cognitive event-related potential related to performance monitoring, is generated in the anterior cingulate cortex (ACC and supposed to depend on the dopaminergic system. The Ne is reduced in Parkinson's Disease (PD. Due to a dopaminergic deficit in HD, a reduction of the Ne is also likely. Furthermore it is assumed that movement dysfunction emerges as a consequence of dysfunctional error-feedback processing. Since dopaminergic alterations are related to the CAG-repeat, a Ne reduction may furthermore also be related to the genetic disease load. METHODOLOGY/PRINCIPLE FINDINGS: We assessed the error negativity (Ne in a speeded reaction task under consideration of the underlying genetic abnormalities. HD patients showed a specific reduction in the Ne, which suggests impaired error processing in these patients. Furthermore, the Ne was closely related to CAG-repeat expansion. CONCLUSIONS/SIGNIFICANCE: The reduction of the Ne is likely to be an effect of the dopaminergic pathology. The result resembles findings in Parkinson's Disease. As such the Ne might be a measure for the integrity of striatal dopaminergic output function. The relation to the CAG-repeat expansion indicates that the Ne could serve as a gene-associated "cognitive" biomarker in HD.

  1. Geologic Investigation of a Potential Site for a Next-Generation Reactor Neutrino Oscillation Experiment -- Diablo Canyon, San Luis Obispo County, CA

    Energy Technology Data Exchange (ETDEWEB)

    Onishi, Celia Tiemi; Dobson, Patrick; Nakagawa, Seiji; Glaser, Steven; Galic, Dom

    2004-06-11

    This report provides information on the geology and selected physical and mechanical properties of surface rocks collected at Diablo Canyon, San Luis Obispo County, California as part of the design and engineering studies towards a future reactor neutrino oscillation experiment. The main objective of this neutrino project is to study the process of neutrino flavor transformation or neutrino oscillation by measuring neutrinos produced in the fission reactions of a nuclear power plant. Diablo Canyon was selected as a candidate site because it allows the detectors to be situated underground in a tunnel close to the source of neutrinos (i.e., at a distance of several hundred meters from the nuclear power plant) while having suitable topography for shielding against cosmic rays. The detectors have to be located underground to minimize the cosmic ray-related background noise that can mimic the signal of reactor neutrino interactions in the detector. Three Pliocene-Miocene marine sedimentary units dominate the geology of Diablo Canyon: the Pismo Formation, the Monterey Formation, and the Obispo Formation. The area is tectonically active, located east of the active Hosgri Fault and in the southern limb of the northwest trending Pismo Syncline. Most of the potential tunnel for the neutrino detector lies within the Obispo Formation. Review of previous geologic studies, observations from a field visit, and selected physical and mechanical properties of rock samples collected from the site provided baseline geological information used in developing a preliminary estimate for tunneling construction cost. Gamma-ray spectrometric results indicate low levels of radioactivity for uranium, thorium, and potassium. Grain density, bulk density, and porosity values for these rock samples range from 2.37 to 2.86 g/cc, 1.41 to 2.57 g/cc, and 1.94 to 68.5 percent respectively. Point load, unconfined compressive strength, and ultrasonic velocity tests were conducted to determine rock

  2. Geologic Investigation of a Potential Site for a Next-Generation Reactor Neutrino Oscillation Experiment -- Diablo Canyon, San Luis Obispo County, CA

    Energy Technology Data Exchange (ETDEWEB)

    Onishi, Celia Tiemi; Dobson, Patrick; Nakagawa, Seiji; Glaser, Steven; Galic, Dom

    2004-08-01

    This report provides information on the geology and selected physical and mechanical properties of surface rocks collected at Diablo Canyon, San Luis Obispo County, California as part of the design and engineering studies towards a future reactor neutrino oscillation experiment. The main objective of this neutrino project is to study the process of neutrino flavor transformation--or neutrino oscillation--by measuring neutrinos produced in the fission reactions of a nuclear power plant. Diablo Canyon was selected as a candidate site because it allows the detectors to be situated underground in a tunnel close to the source of neutrinos (i.e., at a distance of several hundred meters from the nuclear power plant) while having suitable topography for shielding against cosmic rays. The detectors have to be located underground to minimize the cosmic ray-related background noise that can mimic the signal of reactor neutrino interactions in the detector. Three Pliocene-Miocene marine sedimentary units dominate the geology of Diablo Canyon: the Pismo Formation, the Monterey Formation, and the Obispo Formation. The area is tectonically active, located east of the active Hosgri Fault and in the southern limb of the northwest trending Pismo Syncline. Most of the potential tunnel for the neutrino detector lies within the Obispo Formation. Review of previous geologic studies, observations from a field visit, and selected physical and mechanical properties of rock samples collected from the site provided baseline geological information used in developing a preliminary estimate for tunneling construction cost. Gamma-ray spectrometric results indicate low levels of radioactivity for uranium, thorium, and potassium. Grain density, bulk density, and porosity values for these rock samples range from 2.37 to 2.86 g/cc, 1.41 to 2.57 g/cc, and 1.94 to 68.5% respectively. Point load, unconfined compressive strength, and ultrasonic velocity tests were conducted to determine rock mechanical

  3. PM10 emission factors for non-exhaust particles generated by road traffic in an urban street canyon and along a freeway in Switzerland

    Science.gov (United States)

    Bukowiecki, N.; Lienemann, P.; Hill, M.; Furger, M.; Richard, A.; Amato, F.; Prévôt, A. S. H.; Baltensperger, U.; Buchmann, B.; Gehrig, R.

    2010-06-01

    Recent studies have shown clear contributions of non-exhaust emissions to the traffic related PM10 load of the ambient air. These emissions consist of particles produced by abrasion from brakes, road wear, tire wear, as well as vehicle induced resuspension of deposited road dust. The main scope of the presented work was to identify and quantify the non-exhaust fraction of traffic related PM10 for two roadside locations in Switzerland with different traffic regimes. The two investigated locations, an urban street canyon with heavily congested traffic and an interurban freeway, are considered as being typical for Central Europe. Mass-relevant contributions from abrasion particles and resuspended road dust mainly originated from particles in the size range 1-10 μm. The results showed a major influence of vehicle induced resuspension of road dust. In the street canyon, the traffic related PM10 emissions (LDV: 24 ± 8 mg km -1 vehicle -1, HDV: 498 ± 86 mg km -1 vehicle -1) were assigned to 21% brake wear, 38% resuspended road dust and 41% exhaust emissions. Along the freeway (LDV: 50 ± 13 mg km -1 vehicle -1, HDV: 288 ± 72 mg km -1 vehicle -1), respective contributions were 3% brake wear, 56% resuspended road dust and 41% exhaust emissions. There was no indication for relevant contributions from tire wear and abrasion from undamaged pavements.

  4. Treatment of Huntington's disease.

    Science.gov (United States)

    Frank, Samuel

    2014-01-01

    Huntington's disease (HD) is a dominantly inherited progressive neurological disease characterized by chorea, an involuntary brief movement that tends to flow between body regions. HD is typically diagnosed based on clinical findings in the setting of a family history and may be confirmed with genetic testing. Predictive testing is available to family members at risk, but only experienced clinicians should perform the counseling and testing. Multiple areas of the brain degenerate, mainly involving the neurotransmitters dopamine, glutamate, and γ-aminobutyric acid. Although pharmacotherapies theoretically target these neurotransmitters, few well-conducted trials for symptomatic interventions have yielded positive results and current treatments have focused on the motor aspects of HD. Tetrabenazine is a dopamine-depleting agent that may be one of the more effective agents for reducing chorea, although it has a risk of potentially serious adverse effects. Some newer neuroleptic agents, such as olanzapine and aripiprazole, may have adequate efficacy with a more favorable adverse effect profile than older neuroleptic agents for treating chorea and psychosis. There are no current treatments to change the course of HD, but education and symptomatic therapies can be effective tools for clinicians to use with patients and families affected by HD.

  5. Dopamine and Huntington's disease.

    Science.gov (United States)

    Schwab, Laetitia C; Garas, Shady N; Garas, Shaady N; Drouin-Ouellet, Janelle; Mason, Sarah L; Stott, Simon R; Barker, Roger A

    2015-04-01

    Huntington's disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA receptors. It is, therefore, not surprising that the drug treatments most commonly used in HD are anti-dopaminergic agents. Their use is based primarily on the belief that the characteristic motor impairments are a result of overactivation of the central dopaminergic pathways. While this is a useful starting place, it is clear that the behavior of the central dopaminergic pathways is not fully understood in this condition and may change as a function of disease stage. In addition, how abnormalities in dopaminergic systems may underlie some of the non-motor features of HD has also been poorly investigated and this is especially important given the greater burden these place on the patients' and families' quality of life. In this review, we discuss what is known about central dopaminergic pathways in HD and how this informs us about the mechanisms of action of the dopaminergic therapies used to treat it. By doing so, we will highlight some of the paradoxes that exist and how solving them may reveal new insights for improved treatment of this currently incurable condition, including the possibility that such drugs may even have effects on disease progression and pathogenesis.

  6. Neuroimaging in Huntington's disease.

    Science.gov (United States)

    Niccolini, Flavia; Politis, Marios

    2014-06-28

    Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded trinucleotide CAG sequence in huntingtin gene (HTT) on chromosome 4. HD manifests with chorea, cognitive and psychiatric symptoms. Although advances in genetics allow identification of individuals carrying the HD gene, much is still unknown about the mechanisms underlying the development of overt clinical symptoms and the transitional period between premanifestation and manifestation of the disease. HD has no cure and patients rely only in symptomatic treatment. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have provided important advances in our understanding of HD. MRI provides information about structural and functional organization of the brain, while PET can detect molecular changes in the brain. MRI and PET are able to detect changes in the brains of HD gene carriers years ahead of the manifestation of the disease and have also proved to be powerful in assessing disease progression. However, no single technique has been validated as an optimal biomarker. An integrative multimodal imaging approach, which combines different MRI and PET techniques, could be recommended for monitoring potential neuroprotective and preventive therapies in HD. In this article we review the current neuroimaging literature in HD.

  7. Huntington Disease in Asia

    Institute of Scientific and Technical Information of China (English)

    Miao Xu; Zhi-Ying Wu

    2015-01-01

    Objective:The objective was to review the major differences of Huntington disease (HD) in Asian population from those in the Caucasian population.Data Sources:Data cited in this review were obtained from PubMed database and China National Knowledge Infrastructure (CNKI) from 1994 to 2014.All the papers were written in English or Chinese languages,with the terms of Asia/Asian,HD,genotype,epidemiology,phenotype,and treatment used for the literature search.Study Selection:From the PubMed database,we included the articles and reviews which contained the HD patients' data from Asian countries.From the CNKI,we excluded the papers which were not original research.Due to the language's restrictions,those data published in other languages were not included.Results:In total,50 papers were cited in this review,authors of which were from the mainland of China,Japan,India,Thailand,Taiwan (China),Korea,and western countries.Conclusions:The lower epidemiology in Asians can be partly explained by the less cytosine-adenine-guanine repeats,different haplotypes,and CCG polymorphisms.For the physicians,atypical clinical profiles such as the initial symptom of ataxia,movement abnormalities of Parkinsonism,dystonia,or tics need to be paid more attention to and suggest gene testing if necessary.Moreover,some pathogenesis studies may help progress some new advanced treatments.The clinicians in Asian especially in China should promote the usage of genetic testing and put more effects in rehabilitation,palliative care,and offer comfort of patients and their families.The unified HD rating scale also needs to be popularized in Asia to assist in evaluating the progression of HD.

  8. Mitochondrial dysfunction and Huntington disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

  9. Is Huntington's disease a tauopathy?

    Science.gov (United States)

    Gratuze, Maud; Cisbani, Giulia; Cicchetti, Francesca; Planel, Emmanuel

    2016-04-01

    Tauopathies are a subclass of neurodegenerative diseases typified by the deposition of abnormal microtubule-associated tau protein within the cerebral tissue. Alzheimer's disease, progressive supranuclear palsy, chronic traumatic encephalopathy and some fronto-temporal dementias are examples of the extended family of tauopathies. In the last decades, intermittent reports of cerebral tau pathology in individuals afflicted with Huntington's disease-an autosomal dominant neurodegenerative disorder that manifests by severe motor, cognitive and psychiatric problems in adulthood-have also begun to surface. These observations remained anecdotal until recently when a series of publications brought forward compelling evidence that this monogenic disorder may, too, be a tauopathy. Collectively, these studies reported that: (i) patients with Huntington's disease present aggregated tau inclusions within various structures of the brain; (ii) tau haplotype influences the cognitive function of Huntington's disease patients; and (iii) that the genetic product of the disease, the mutant huntingtin protein, could alter tau splicing, phosphorylation, oligomerization and subcellular localization. Here, we review the past and current evidence in favour of the postulate that Huntington's disease is a new member of the family of tauopathies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. The Whittard Canyon - A case study of submarine canyon processes

    Science.gov (United States)

    Amaro, T.; Huvenne, V. A. I.; Allcock, A. L.; Aslam, T.; Davies, J. S.; Danovaro, R.; De Stigter, H. C.; Duineveld, G. C. A.; Gambi, C.; Gooday, A. J.; Gunton, L. M.; Hall, R.; Howell, K. L.; Ingels, J.; Kiriakoulakis, K.; Kershaw, C. E.; Lavaleye, M. S. S.; Robert, K.; Stewart, H.; Van Rooij, D.; White, M.; Wilson, A. M.

    2016-08-01

    Submarine canyons are large geomorphological features that incise continental shelves and slopes around the world. They are often suggested to be biodiversity and biomass hotspots, although there is no consensus about this in the literature. Nevertheless, many canyons do host diverse faunal communities but owing to our lack of understanding of the processes shaping and driving this diversity, appropriate management strategies have yet to be developed. Here, we integrate all the current knowledge of one single system, the Whittard Canyon (Celtic Margin, NE Atlantic), including the latest research on its geology, sedimentology, geomorphology, oceanography, ecology, and biodiversity in order to address this issue. The Whittard Canyon is an active system in terms of sediment transport. The net suspended sediment transport is mainly up-canyon causing sedimentary overflow in some upper canyon areas. Occasionally sediment gravity flow events do occur, some possibly the result of anthropogenic activity. However, the role of these intermittent gravity flows in transferring labile organic matter to the deeper regions of the canyon appears to be limited. More likely, any labile organic matter flushed downslope in this way becomes strongly diluted with bulk material and is therefore of little food value for benthic fauna. Instead, the fresh organic matter found in the Whittard Channel mainly arrives through vertical deposition and lateral transport of phytoplankton blooms that occur in the area during spring and summer. The response of the Whittard Canyon fauna to these processes is different in different groups. Foraminiferal abundances are higher in the upper parts of the canyon and on the slope than in the lower canyon. Meiofaunal abundances in the upper and middle part of the canyon are higher than on adjacent slopes, but lower in the deepest part. Mega- and macrofauna abundances are higher in the canyon compared with the adjacent slope and are higher in the eastern than

  11. Neurodegenerative disorders: Parkinson's disease and Huntington's disease

    Science.gov (United States)

    Hague, S; Klaffke, S; Bandmann, O

    2005-01-01

    Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease. PMID:16024878

  12. Neurodegenerative disorders: Parkinson's disease and Huntington's disease.

    Science.gov (United States)

    Hague, S M; Klaffke, S; Bandmann, O

    2005-08-01

    Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease.

  13. Huntington's disease presenting as amyotrophic lateral sclerosis.

    Science.gov (United States)

    Phukan, Julie; Ali, Elfatih; Pender, Niall P; Molloy, Fiona; Hennessy, Michael; Walsh, Ronan J; Hardiman, Orla

    2010-08-01

    We present the clinical, electrophysiological and molecular genetic findings of a 58-year-old male with genetically confirmed Huntington's disease (HD) and concurrent clinically definite ALS by El Escorial criteria. The patient presented with asymmetric upper limb amyotrophy and weakness, and subsequently developed chorea and cognitive change. Genetic testing confirmed the presence of expanded trinucleotide repeats in huntingtin, consistent with a diagnosis of Huntington's disease. This case confirms the rare coexistence of Huntington's disease and motor neuron degeneration.

  14. Tidal motions and tidally induced fluxes through La Línea submarine canyon, western Alboran Sea

    Science.gov (United States)

    Lafuente, Jesús GarcíA.; Sarhan, Tarek; Vargas, Manuel; Vargas, Juan M.; Plaza, Francisco

    1999-02-01

    Detailed observations from two mooring lines deployed in La Línea submarine canyon, western Alboran Sea, are presented. This is a narrow canyon in the sense that its width is always less than the internal radius of deformation. Tidal currents within the canyon are polarized in the along-canyon direction according to its narrow nature. They have considerable amplitude (values of around 0.5 m/s are often observed) and are forced by the internal pressure gradients associated with the baroclinic tide that is generated in the surroundings. Subsequent amplification of onshore baroclinic currents within the canyon accounts for the large amplitude observed. Cross-shelf exchange through the canyon due to tidal motions is different from zero despite the close to zero mean of tidal currents. The explanation is based on the asymmetry of water properties flowing up-canyon and down-canyon (some sort of tidal rectification). Regarding the energy flux, the canyon seems to be an adequate conduit to carry energy to the shore. Estimations made from our observations indicate that energy input onto the shelf per unit length parallel to the shore at the canyon head is enough to maintain mixing on the shelf at intermediate depths.

  15. New York Canyon Stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Raemy, Bernard

    2012-06-21

    The New York Canyon Stimulation Project was to demonstrate the commercial application of Enhanced Geothermal System techniques in Buena Vista Valley area of Pershing County, Nevada. From October 2009 to early 2012, TGP Development Company aggressively implemented Phase I of Pre-Stimulation and Site/Wellbore readiness. This included: geological studies; water studies and analyses and procurement of initial permits for drilling. Oversubscription of water rights and lack of water needed for implementation of EGS were identified and remained primary obstacles. Despite extended efforts to find alternative solutions, the water supply circumstances could not be overcome and led TGP to determine a "No Go" decision and initiate project termination in April 2012.

  16. Huntington disease: DNA analysis in brazilian population

    Directory of Open Access Journals (Sweden)

    RASKIN SALMO

    2000-01-01

    Full Text Available Huntington disease (HD is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.

  17. Huntington Disease: Molecular Diagnostics Approach.

    Science.gov (United States)

    Bastepe, Murat; Xin, Winnie

    2015-10-06

    Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed.

  18. Cortical myoclonus in Huntington's disease.

    Science.gov (United States)

    Thompson, P D; Bhatia, K P; Brown, P; Davis, M B; Pires, M; Quinn, N P; Luthert, P; Honovar, M; O'Brien, M D; Marsden, C D

    1994-11-01

    We describe three patients with Huntington's disease, from two families, in whom myoclonus was the predominant clinical feature. The diagnosis was confirmed at autopsy in two cases and by DNA analysis in all three. These patients all presented before the age of 30 years and were the offspring of affected fathers. Neurophysiological studies documented generalised and multifocal action myoclonus of cortical origin that was strikingly stimulus sensitive, without enlargement of the cortical somatosensory evoked potential. The myoclonus improved with piracetam therapy in one patient and a combination of sodium valproate and clonazepam in the other two. Cortical reflex myoclonus is a rare but disabling component of the complex movement disorder of Huntington's disease, which may lead to substantial diagnostic difficulties.

  19. Molecular Imaging of Huntington's Disease.

    Science.gov (United States)

    Ciarmiello, Andrea; Giovacchini, Giampiero; Giovannini, Elisabetta; Lazzeri, Patrizia; Borsò, Elisa; Mannironi, Antonio; Mansi, Luigi

    2017-08-01

    The onset and the clinical progression of Huntington Disease (HD) is influenced by several events prompted by a genetic mutation that affects several organs tissues including different regions of the brain. In the last decades years, Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) helped to deepen the knowledge of neurodegenerative mechanisms that guide to clinical symptoms. Brain imaging with PET represents a tool to investigate the physiopathology occurring in the brain and it has been used to predict the age of onset of the disease and to evaluate the therapeutic efficacy of new drugs. This article reviews the contribution of PET and MRI in the research field on Huntington's disease, focusing in particular on some most relevant achievements that have helped recognize the molecular changes, the clinical symptoms and evolution of the disease. J. Cell. Physiol. 232: 1988-1993, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Big Canyon Creek Ecological Restoration Strategy.

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lynn; Richardson, Shannon

    2007-10-01

    then used data collected from the District's stream assessment and inventory, utilizing the Stream Visual Assessment Protocol (SVAP), to determine treatment necessary to bring 90% of reaches ranked Poor or Fair through the SVAP up to good or excellent. In 10 year's time, all reaches that were previously evaluated with SVAP will be reevaluated to determine progress and to adapt methods for continued success. Over 400 miles of stream need treatment in order to meet identified restoration goals. Treatments include practices which result in riparian habitat improvements, nutrient reductions, channel condition improvements, fish habitat improvements, invasive species control, water withdrawal reductions, improved hydrologic alterations, upland sediment reductions, and passage barrier removal. The Nez Perce Soil and Water Conservation District (District) and the Nez Perce Tribe Department of Fisheries Resource Management Watershed Division (Tribe) developed this document to guide restoration activities within the Big Canyon Creek watershed for the period of 2008-2018. This plan was created to demonstrate the ongoing need and potential for anadromous fish habitat restoration within the watershed and to ensure continued implementation of restoration actions and activities. It was developed not only to guide the District and the Tribe, but also to encourage cooperation among all stakeholders, including landowners, government agencies, private organizations, tribal governments, and elected officials. Through sharing information, skills, and resources in an active, cooperative relationships, all concerned parties will have the opportunity to join together to strengthen and maintain a sustainable natural resource base for present and future generations within the watershed. The primary goal of the strategy is to address aquatic habitat restoration needs on a watershed level for resident and anadromous fish species, promoting quality habitat within a self

  1. Neuropsychiatric Burden in Huntington's Disease.

    Science.gov (United States)

    Paoli, Ricardo Augusto; Botturi, Andrea; Ciammola, Andrea; Silani, Vincenzo; Prunas, Cecilia; Lucchiari, Claudio; Zugno, Elisa; Caletti, Elisabetta

    2017-06-16

    Huntington's disease is a disorder that results in motor, cognitive, and psychiatric problems. The symptoms often take different forms and the presence of disturbances of the psychic sphere reduces patients' autonomy and quality of life, also impacting patients' social life. It is estimated that a prevalence between 33% and 76% of the main psychiatric syndromes may arise in different phases of the disease, often in atypical form, even 20 years before the onset of chorea and dementia. We present a narrative review of the literature describing the main psychopathological patterns that may be found in Huntington's disease, searching for a related article in the main database sources (Medline, ISI Web of Knowledge, Scopus, and Medscape). Psychiatric conditions were classified into two main categories: affective and nonaffective disorders/symptoms; and anxiety and neuropsychiatric features such as apathy and irritability. Though the literature is extensive, it is not always convergent, probably due to the high heterogeneity of methods used. We summarize main papers for pathology and sample size, in order to present a synoptic vision of the argument. Since the association between Huntington's disease and psychiatric symptoms was demonstrated, we argue that the prevalent and more invalidating psychiatric components should be recognized as early as possible during the disease course in order to best address psychopharmacological therapy, improve quality of life, and also reduce burden on caregivers.

  2. H CANYON PROCESSING IN CORRELATION WITH FH ANALYTICAL LABS

    Energy Technology Data Exchange (ETDEWEB)

    Weinheimer, E.

    2012-08-06

    Management of radioactive chemical waste can be a complicated business. H Canyon and F/H Analytical Labs are two facilities present at the Savannah River Site in Aiken, SC that are at the forefront. In fact H Canyon is the only large-scale radiochemical processing facility in the United States and this processing is only enhanced by the aid given from F/H Analytical Labs. As H Canyon processes incoming materials, F/H Labs provide support through a variety of chemical analyses. Necessary checks of the chemical makeup, processing, and accountability of the samples taken from H Canyon process tanks are performed at the labs along with further checks on waste leaving the canyon after processing. Used nuclear material taken in by the canyon is actually not waste. Only a small portion of the radioactive material itself is actually consumed in nuclear reactors. As a result various radioactive elements such as Uranium, Plutonium and Neptunium are commonly found in waste and may be useful to recover. Specific processing is needed to allow for separation of these products from the waste. This is H Canyon's specialty. Furthermore, H Canyon has the capacity to initiate the process for weapons-grade nuclear material to be converted into nuclear fuel. This is one of the main campaigns being set up for the fall of 2012. Once usable material is separated and purified of impurities such as fission products, it can be converted to an oxide and ultimately turned into commercial fuel. The processing of weapons-grade material for commercial fuel is important in the necessary disposition of plutonium. Another processing campaign to start in the fall in H Canyon involves the reprocessing of used nuclear fuel for disposal in improved containment units. The importance of this campaign involves the proper disposal of nuclear waste in order to ensure the safety and well-being of future generations and the environment. As processing proceeds in the fall, H Canyon will have a substantial

  3. Huntington's disease: review and anesthetic case management.

    OpenAIRE

    Cangemi, C. F.; Miller, R. J.

    1998-01-01

    Huntington's disease is a dominantly inherited progressive autosomal disease that affects the basal ganglia. Symptoms appear later in life and manifest as progressive mental deterioration and involuntary choreiform movements. Patients with Huntington's disease develop a progressive but variable dementia. Dysphagia, the most significant related motor symptom, hinders nutrition intake and places the patient at risk for aspiration. The combination of involuntary choreoathetoid movements, depress...

  4. Drug-induced hyperthermia in Huntington's disease

    NARCIS (Netherlands)

    Gaasbeek, D; Naarding, Paul; Stor, T; Kremer, H P H

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic

  5. Drug-induced hyperthermia in Huntington's disease.

    NARCIS (Netherlands)

    Gaasbeek, D.; Naarding, P.; Stor, T.; Kremer, H.P.H.

    2004-01-01

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic

  6. Drug-induced hyperthermia in Huntington's disease.

    NARCIS (Netherlands)

    Gaasbeek, D.; Naarding, P.; Stor, T.; Kremer, H.P.H.

    2004-01-01

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic m

  7. Apathy is not depression in Huntington's disease

    NARCIS (Netherlands)

    Naarding, Paul; Janzing, Joost G E; Eling, Paul; van der Werf, Sieberen; Kremer, Berry

    2009-01-01

    Apathy and depression are common neuropsychiatric features of Huntington's disease. The authors studied a group of 34 Huntington's disease patients. In addition to the conventional classification according to DSM-IV criteria of depression, emphasis was put on a dimensional approach using scores on

  8. Association of Huntington's disease and schizophrenia-like psychosis in a Huntington's disease pedigree

    Directory of Open Access Journals (Sweden)

    Guimarães João

    2006-02-01

    Full Text Available Abstract Background Huntington's disease (HD is a dominantly inherited, neurodegenerative disorder due to expansion of a polymorphic trinucleotide repeat in the short arm of chromosome 4. Clinical manifestations consist of a triad of choreic movements, cognitive decline and psychiatric syndromes starting in the fourth to fifth decade. Psychiatric manifestations vary and may precede motor and cognitive changes. Personality changes and depression occur most commonly. Paranoid schizophrenia-like symptoms occur in 6% to 25% of cases. Case report We describe a 55 year-old woman with an 8 yearlong history of behavioural changes, multi-thematic delusions and auditory hallucinations. History and mental state examination were suggestive of paranoid schizophrenia. Neurological examination revealed discrete, involuntary movements affecting her arms and trunk. Genotyping detected an expanded allele (43 trinucleotide repeats. A three-generation-long family history of chorea and schizophrenia-like psychosis was found. Conclusion HD-families have been reported in which schizophrenia-like syndromes emerged in all or most HD-affected members long before they developed extra-pyramidal or cognitive changes. This has been attributed to more than mere coincidence. We hypothesise that in these families the HD gene is transmitted along with a low load of small-effect "psychosis genes" which, in the presence of the severe cognitive changes of HD, manifest as a schizophrenia-like phenotype. Further research is needed in order to clarify the links between genetic loading and the emergence of psychotic symptoms in Huntington's disease.

  9. Huntington's disease: clinical characteristics, pathogenesis and therapies.

    Science.gov (United States)

    Nakamura, Ken; Aminoff, Michael J

    2007-02-01

    Huntington's disease is a devastating disorder with no known cure. The disease results from an expanded sequence of CAG repeats in the huntingtin gene and leads to a movement disorder with associated cognitive and systemic deficits. Huntington's disease is diagnosed by genetic testing and disease progression can be followed with a variety of imaging modalities. The accumulation of aggregated huntingtin with associated striatal degeneration is evident at autopsy. The pathophysiology of Huntington's disease remains unknown, although protein aggregation, excitotoxicity, deficits in energy metabolism, transcriptional dysregulation and apoptosis may all be involved. Current pharmacologic therapy for Huntington's disease is limited and exclusively symptomatic. However, the disease is being heavily researched, and a wide range of disease-modifying therapies is currently under development. The efficacy of these therapies is being evaluated in transgenic models of Huntington's disease and in preliminary clinical trials.

  10. 2010 Pacific Gas and Electric Diablo Canyon Power Plant (DCPP): Diablo Canyon, CA Central Coast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Diablo Canyon Power Plant (DCPP) LiDAR and Imagery datasets are comprised of three separate LiDAR surveys: Diablo Canyon (2010), Diablo Canyon (2010), and San...

  11. Huntington's Disease: An Immune Perspective

    Directory of Open Access Journals (Sweden)

    Annapurna Nayak

    2011-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.

  12. Huntington disease: pathogenesis and treatment.

    Science.gov (United States)

    Dayalu, Praveen; Albin, Roger L

    2015-02-01

    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment.

  13. Psychiatric symptoms and CAG expansion in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

    1996-02-16

    The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

  14. [Molecular therapeutic strategies for Huntington's disease].

    Science.gov (United States)

    Milewski, Michał; Hoffman-Zacharska, Dorota; Ball, Jerzy

    2015-01-01

    Huntington's disease is a progressive neurodegenerative disorder of genetic origin that still lacks an effective treatment. Recently, a number of new attempts have been undertaken to develop a successful molecular therapy for this incurable condition. The novel approaches employ, among others, some new methods to selectively silence the mutated gene or to neutralize its toxic protein product. This paper reviews all major strategies that are currently considered for molecular therapy of Huntington's disease while discussing their potential effectiveness regarding the treatment of both the Huntington's disease and a large group of related neurodegenerative disorders associated with abnormal protein aggregation.

  15. Genetic modifiers of Huntington's disease.

    Science.gov (United States)

    Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

    2014-09-15

    Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs.

  16. Huntington's disease: review and anesthetic case management.

    Science.gov (United States)

    Cangemi, C F; Miller, R J

    1998-01-01

    Huntington's disease is a dominantly inherited progressive autosomal disease that affects the basal ganglia. Symptoms appear later in life and manifest as progressive mental deterioration and involuntary choreiform movements. Patients with Huntington's disease develop a progressive but variable dementia. Dysphagia, the most significant related motor symptom, hinders nutrition intake and places the patient at risk for aspiration. The combination of involuntary choreoathetoid movements, depression, and apathy leads to cachexia. Factors of considerable concern to the anesthesiologist who treats patients with Huntington's disease may include how to treat frail elderly people incapable of cooperation, how to treat patients suffering from malnourishment, and how to treat patients with an increased risk for aspiration or exaggerated responses to sodium thiopental and succinylcholine. The successful anesthetic management of a 65-yr-old woman with Huntington's disease who presented for full-mouth extractions is described.

  17. Huntington's Disease: Speech, Language and Swallowing

    Science.gov (United States)

    ... Disease Society of America Huntington's Disease Youth Organization Movement Disorder Society National Institute of Neurological Disorders and Stroke Typical Speech and Language Development Learning More Than One Language Adult Speech and Language Child Speech and Language Swallowing ...

  18. Deepwater Canyons 2013: Pathways to the Abyss

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Leg I focused on biological objectives in Norfolk Canyon, with some sampling in Baltimore Canyon. Leg II focused on archaeological targets in and around the Norfolk...

  19. Clinical presentation of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Ruocco Heloísa H.

    2006-01-01

    Full Text Available OBJECTIVE: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. METHOD: All patients were interviewed following a structured clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG repeat in the Huntington Disease gene. High resolution brain MRI was performed in all patients. RESULTS: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our Neurogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001 and reduced cerebral and cerebellum volumes (p=0.01. CONCLUSION: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were seizures and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.

  20. Ethical issues and Huntington's disease.

    Science.gov (United States)

    Kromberg, Jennifer G R; Wessels, Tina-Marié

    2013-10-11

    The practice of genetic counselling gives rise to many ethical dilemmas, and counsellors need to be familiar with the principles of biomedical ethics. The primary principles include respect for autonomy, beneficence, non-maleficence and justice. A case of identical twins at 50% risk for Huntington's disease, in which only one twin sought predictive testing for this dominantly inherited disease, created several ethical dilemmas. Another case where predictive testing was carried out on two young children, at high risk, by a laboratory at the request of an adoption agency and a doctor, with a view to giving information to the foster parents, also posed many ethical conundrums for the counsellor. The ethical issues that arose in these cases are discussed in this paper. 

  1. Cholesterol metabolism in Huntington disease.

    Science.gov (United States)

    Karasinska, Joanna M; Hayden, Michael R

    2011-09-06

    The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

  2. Juvenile Huntington disease in Argentina.

    Science.gov (United States)

    Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis; Sanguinetti, Ana; Cordi, Lorena; Binelli, Adrian; Persi, Gabriel; Squitieri, Ferdinando

    2016-01-01

    We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.

  3. Language impairment in Huntington's disease.

    Science.gov (United States)

    Azambuja, Mariana Jardim; Radanovic, Marcia; Haddad, Mônica Santoro; Adda, Carla Cristina; Barbosa, Egberto Reis; Mansur, Letícia Lessa

    2012-06-01

    Language alterations in Huntington's disease (HD) are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT). HD patients performed poorer in verbal fluency (poral comprehension (preading comprehension (p=0.034) and narrative writing (p<0.0001). There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively). Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.

  4. Huntington's disease: a clinical review

    Directory of Open Access Journals (Sweden)

    Roos Raymund AC

    2010-12-01

    Full Text Available Abstract Huntington disease (HD is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD. The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which

  5. Huntington's disease as caused by 34 CAG repeats.

    Science.gov (United States)

    Andrich, Jürgen; Arning, Larissa; Wieczorek, Stefan; Kraus, Peter H; Gold, Ralf; Saft, Carsten

    2008-04-30

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by an abnormal expansion of a polymorphic stretch of CAG repeats in the coding 5' part of the HD gene on chromosome 4p. Expansions of CAG blocks beyond 35 repeats are associated with the clinical presentation of HD. There is an intermediate range of rare alleles between 27 and 35 CAG repeats with a higher risk for further expansion in subsequent generations. Here, we report a 75-year-old male with clinical features of HD and 34 CAG repeat units.

  6. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  7. Regional economic impacts of Grand Canyon river runners.

    Science.gov (United States)

    Hjerpe, Evan E; Kim, Yeon-Su

    2007-10-01

    Economic impact analysis (EIA) of outdoor recreation can provide critical social information concerning the utilization of natural resources. Outdoor recreation and other non-consumptive uses of resources are viewed as environmentally friendly alternatives to extractive-type industries. While outdoor recreation can be an appropriate use of resources, it generates both beneficial and adverse socioeconomic impacts on rural communities. The authors used EIA to assess the regional economic impacts of rafting in Grand Canyon National Park. The Grand Canyon region of northern Arizona represents a rural US economy that is highly dependent upon tourism and recreational expenditures. The purpose of this research is twofold. The first is to ascertain the previously unknown regional economic impacts of Grand Canyon river runners. The second purpose is to examine attributes of these economic impacts in terms of regional multipliers, leakage, and types of employment created. Most of the literature on economic impacts of outdoor recreation has focused strictly on the positive economic impacts, failing to illuminate the coinciding adverse and constraining economic impacts. Examining the attributes of economic impacts can highlight deficiencies and constraints that limit the economic benefits of recreation and tourism. Regional expenditure information was obtained by surveying non-commercial boaters and commercial outfitters. The authors used IMPLAN input-output modeling to assess direct, indirect, and induced effects of Grand Canyon river runners. Multipliers were calculated for output, employment, and income. Over 22,000 people rafted on the Colorado River through Grand Canyon National Park in 2001, resulting in an estimated $21,100,000 of regional expenditures to the greater Grand Canyon economy. However, over 50% of all rafting-related expenditures were not captured by the regional economy and many of the jobs created by the rafting industry are lower-wage and seasonal. Policy

  8. Silencing Huntington's chorea: Is RNA Interference a Potential Cure?

    OpenAIRE

    Metz, Gerlinde A.; Whishaw, Ian Q.; Afra Foroud; Nafisa M Jadavji

    2006-01-01

    In 1872, George Huntington described Huntington's disease as characterized by motor, cognitive and psychiatric impairments. Huntington's disease is a dominant and autosomal mutation on chromosome 4 featuring the insertion of numerous CAG repeats. CAG codes for the amino acid, glutmanine that forms part of the Huntingtin protein (htt). Excess glutamine attachments make htt prone to accumulate in neurons. Three genes can be considered when developing therapies for Huntington's disease. They inc...

  9. Submarine canyons off Madras Coast

    Digital Repository Service at National Institute of Oceanography (India)

    Setty, M.G.A.P.

    Submarine canyons off the coast of Madras, Tamil Nadu, India were studied during cruise of @iINS Kistna@@ as part of the IIOE programme They consist of hill-like projections and V-shaped valleys Their other features are also reported...

  10. Big Canyon Creek Ecological Restoration Strategy.

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lynn; Richardson, Shannon

    2007-10-01

    then used data collected from the District's stream assessment and inventory, utilizing the Stream Visual Assessment Protocol (SVAP), to determine treatment necessary to bring 90% of reaches ranked Poor or Fair through the SVAP up to good or excellent. In 10 year's time, all reaches that were previously evaluated with SVAP will be reevaluated to determine progress and to adapt methods for continued success. Over 400 miles of stream need treatment in order to meet identified restoration goals. Treatments include practices which result in riparian habitat improvements, nutrient reductions, channel condition improvements, fish habitat improvements, invasive species control, water withdrawal reductions, improved hydrologic alterations, upland sediment reductions, and passage barrier removal. The Nez Perce Soil and Water Conservation District (District) and the Nez Perce Tribe Department of Fisheries Resource Management Watershed Division (Tribe) developed this document to guide restoration activities within the Big Canyon Creek watershed for the period of 2008-2018. This plan was created to demonstrate the ongoing need and potential for anadromous fish habitat restoration within the watershed and to ensure continued implementation of restoration actions and activities. It was developed not only to guide the District and the Tribe, but also to encourage cooperation among all stakeholders, including landowners, government agencies, private organizations, tribal governments, and elected officials. Through sharing information, skills, and resources in an active, cooperative relationships, all concerned parties will have the opportunity to join together to strengthen and maintain a sustainable natural resource base for present and future generations within the watershed. The primary goal of the strategy is to address aquatic habitat restoration needs on a watershed level for resident and anadromous fish species, promoting quality habitat within a self

  11. Exercise effects in Huntington disease.

    Science.gov (United States)

    Frese, Sebastian; Petersen, Jens A; Ligon-Auer, Maria; Mueller, Sandro Manuel; Mihaylova, Violeta; Gehrig, Saskia M; Kana, Veronika; Rushing, Elisabeth J; Unterburger, Evelyn; Kägi, Georg; Burgunder, Jean-Marc; Toigo, Marco; Jung, Hans H

    2017-01-01

    Huntington disease (HD) is a relentlessly progressive neurodegenerative disorder with symptoms across a wide range of neurological domains, including cognitive and motor dysfunction. There is still no causative treatment for HD but environmental factors such as passive lifestyle may modulate disease onset and progression. In humans, multidisciplinary rehabilitation has a positive impact on cognitive functions. However, a specific role for exercise as a component of an environmental enrichment effect has been difficult to demonstrate. We aimed at investigating whether endurance training (ET) stabilizes the progression of motor and cognitive dysfunction and ameliorates cardiovascular function in HD patients. Twelve male HD patients (mean ± SD, 54.8 ± 7.1 years) and twelve male controls (49.1 ± 6.8 years) completed 26 weeks of endurance training. Before and after the training intervention, clinical assessments, exercise physiological tests, and a body composition measurement were conducted and a muscle biopsy was taken from M. vastus lateralis. To examine the natural course of the disease, HD patients were additionally assessed 6 months prior to ET. During the ET period, there was a motor deficit stabilization as indicated by the Unified Huntington's Disease Rating Scale motor section score in HD patients (baseline: 18.6 ± 9.2, pre-training: 26.0 ± 13.7, post-training: 26.8 ± 16.4). Peak oxygen uptake ([Formula: see text]) significantly increased in HD patients (∆[Formula: see text] = +0.33 ± 0.28 l) and controls (∆[Formula: see text] = +0.29 ± 0.41 l). No adverse effects of the training intervention were reported. Our results confirm that HD patients are amenable to a specific exercise-induced therapeutic strategy indicated by an increased cardiovascular function and a stabilization of motor function.

  12. NUMERICAL STUDIES ON AIRFLOW AND POLLUTANT DISPERSION IN URBAN STREET CANYONS FORMED BY SLANTED ROOF BUILDINGS

    Institute of Scientific and Technical Information of China (English)

    HUANG Yuan-dong; JIN Ming-xia; SUN Ya-nan

    2007-01-01

    Based on the CFD technique, fifteen cases were evaluated for the airflows and pollutant dispersions inside urban street canyons formed by slanted roof buildings. The simulated wind fields and concentration contours show that W/H, W/h and h/H (where W is the street width, and H and h are the heights of buildings at the leeward and windward sides of the street, respectively) are the crucial factors in determining the vortex structure and pollutant distribution within a canyon. It is concluded that (1) in a symmetrical canyon, at W/H =0.5 two vortices (an upper clockwise vortex between the slanted roofs and a lower counter-clockwise one) are developed and pollutants accumulate on the windward side of the street, whereas at W/H=2.0 only one clockwise vortex is generated and thus pollution piles up on the leeward side, (2) in a step-up canyon with W/H =0.5 to 2.0 (at h/H =1.5 to 2.0)and a step-down canyon with W/h=1.0 (at h/H =0.5 to 0.667), the pollution level close to the lower building is higher than that close to the taller building since a clockwise vortex is generated in the step-up canyon and a counter-clockwise one in the step-down canyon, (3) in a narrow step-down canyon with W/h=0.5 (at h/H =0.667) very poor ventilation properties is detected, and inside a wider step-down canyon with W/h=2.0 the vortex structure and consequently pollutant distribution varies greatly with h/H.

  13. Near-inertial motions in the DeSoto Canyon during Hurricane Georges

    Science.gov (United States)

    Jordi, Antoni; Wang, Dong-Ping; Hamilton, Peter

    2016-09-01

    Hurricane Georges passed directly over an array of 13 moorings deployed in the DeSoto Canyon in the northern Gulf of Mexico on 27-28 September 1998. Current velocity data from the mooring array were analyzed together with a primitive-equation model simulation with realistic hurricane forcing, to characterize the generation and propagation of the hurricane-generated near-inertial waves. The model successfully reproduces the observed mean (sub-inertial) and near-inertial motions. The upper ocean response is strongly impacted by the canyon 'wall': a strong jet is formed along the slope, and the near-inertial motions on the shelf are rapidly suppressed. The model results moreover suggest that strong near-inertial waves in the mixed layer are mostly trapped in an energy flux recirculating gyre around the canyon. This gyre retains the near-inertial energy in the canyon region and enhances the transfer of near-inertial energy below the mixed layer. Additional simulations with idealized topographies show that the presence of a steep slope rather than the canyon is fundamental for the generation of this recirculating gyre. The near-inertial wave energy budget shows that during the study period the wind generated an input of 6.79 × 10-2 Wm-2 of which about 1/3, or 2.43 × 10-2 Wm-2, was transferred below the mixed layer. The horizontal energy flux into and out of the canyon region, in contrast, was relatively weak.

  14. Biochemical aspects of Huntington's chorea.

    Science.gov (United States)

    Caraceni, T; Calderini, G; Consolazione, A; Riva, E; Algeri, S; Girotti, F; Spreafico, R; Branciforti, A; Dall'olio, A; Morselli, P L

    1977-01-01

    Fifteen patients affected by Huntington's chorea were divided into two groups, 'slow' and 'fast', according to IQ scores on the Wechsler-Bellevue scale, and scores on some motor performance tests. A possible correlation was looked for between some biochemical data (cerebrospinal fluid (CSF), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5HIAA) levels, plasma dopamine-beta-hydroxylase (DBH), dopamine (DA) uptake by platelets), and clinical data (duration of illness, severity of symptoms, age of patients, IQ scores, 'slow' and 'fast' groups). The CSF, HVA, and 5HIAA levels were found to be significantly lowered in comparison with normal controls. DBH activity and DA uptake by platelets did not differ significantly from normal subjects. Treatment with haloperidol in all patients and with dipropylacetic acid in three patients did not appear to modify the CSF, HVA, and 5HIAA concentrations, the plasma DBH activity, or the DA uptake. There were no significant differences in the CSF, HVA, and 5HIAA contents between the two groups of patients, and there was no correlation between biochemical data and clinical features. PMID:143508

  15. Protein oxidation in Huntington disease.

    Science.gov (United States)

    Sorolla, M Alba; Rodríguez-Colman, María José; Vall-llaura, Núria; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

    2012-01-01

    Huntington disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG repeats in the huntingtin gene, affecting initially the striatum and progressively the cortex. Oxidative stress, and consequent protein oxidation, has been described as important to disease progression. This review focuses on recent advances in the field, with a particular emphasis on the identified target proteins and the role that their oxidation has or might have in the pathophysiology of HD. Oxidation and the resulting inactivation and/or degradation of important proteins can explain the impairment of several metabolic pathways in HD. Oxidation of enzymes involved in ATP synthesis can account for the energy deficiency observed. Impairment of protein folding and degradation can be due to oxidation of several heat shock proteins and Valosin-containing protein. Oxidation of two enzymes involved in the vitamin B6 metabolism could result in decreased availability of pyridoxal phosphate, which is a necessary cofactor in transaminations, the kynurenine pathway and the synthesis of glutathione, GABA, dopamine and serotonin, all of which have a key role in HD pathology. In addition, protein oxidation often contributes to oxidative stress, aggravating the molecular damage inside the cell. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  16. Predictive testing for Huntington's disease.

    Science.gov (United States)

    Tibben, Aad

    2007-04-30

    Worldwide, predictive testing for Huntington's disease has become an accepted clinical application that has allowed many individuals from HD-families to proceed with their life without the uncertainty of being at risk. International guidelines have extensively contributed to establishing counselling programmes of high quality, and have served as a model for other genetic disorders. Psychological follow-up studies have increased the insight into the far-reaching impact of test results for all individuals involved. Although the guidelines have served as a useful frame of reference, clinical experience has shown the importance of a case-by-case approach to do justice to the specific needs of the individual test candidate. Issues such as ambiguous test results, lack of awareness in a test candidate of early signs of the disease, non-compliance to the test protocol, or the test candidate's need for information on the relationship between age at onset and CAG-repeat require careful consideration. Receiving a test result is only one of the transition points in the life of an individual at risk; such result needs to be valued from a life-cycle perspective.

  17. Huntington's Disease and Striatal Signaling.

    Science.gov (United States)

    Roze, Emmanuel; Cahill, Emma; Martin, Elodie; Bonnet, Cecilia; Vanhoutte, Peter; Betuing, Sandrine; Caboche, Jocelyne

    2011-01-01

    Huntington's Disease (HD) is the most frequent neurodegenerative disease caused by an expansion of polyglutamines (CAG). The main clinical manifestations of HD are chorea, cognitive impairment, and psychiatric disorders. The transmission of HD is autosomal dominant with a complete penetrance. HD has a single genetic cause, a well-defined neuropathology, and informative pre-manifest genetic testing of the disease is available. Striatal atrophy begins as early as 15 years before disease onset and continues throughout the period of manifest illness. Therefore, patients could theoretically benefit from therapy at early stages of the disease. One important characteristic of HD is the striatal vulnerability to neurodegeneration, despite similar expression of the protein in other brain areas. Aggregation of the mutated Huntingtin (HTT), impaired axonal transport, excitotoxicity, transcriptional dysregulation as well as mitochondrial dysfunction, and energy deficits, are all part of the cellular events that underlie neuronal dysfunction and striatal death. Among these non-exclusive mechanisms, an alteration of striatal signaling is thought to orchestrate the downstream events involved in the cascade of striatal dysfunction.

  18. Therapeutic advances in Huntington's Disease.

    Science.gov (United States)

    Shannon, Kathleen M; Fraint, Avram

    2015-09-15

    Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease-modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later-stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD. © 2015 International Parkinson and Movement Disorder Society.

  19. Huntington's disease: a clinical review.

    Science.gov (United States)

    McColgan, Peter; Tabrizi, Sarah J

    2017-08-17

    Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100,000. It is characterised by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently underway. This may bring us one step closer to treating and potentially preventing this devastating condition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Movement sequencing in Huntington disease.

    Science.gov (United States)

    Georgiou-Karistianis, Nellie; Long, Jeffrey D; Lourens, Spencer G; Stout, Julie C; Mills, James A; Paulsen, Jane S

    2014-08-01

    To examine longitudinal changes in movement sequencing in prodromal Huntington's disease (HD) participants (795 prodromal HD; 225 controls) from the PREDICT-HD study. Prodromal HD participants were tested over seven annual visits and were stratified into three groups (low, medium, high) based on their CAG-Age Product (CAP) score, which indicates likely increasing proximity to diagnosis. A cued movement sequence task assessed the impact of advance cueing on response initiation and execution via three levels of advance information. Compared to controls, all CAP groups showed longer initiation and movement times across all conditions at baseline, demonstrating a disease gradient for the majority of outcomes. Across all conditions, the high CAP group had the highest mean for baseline testing, but also demonstrated an increase in movement time across the study. For initiation time, the high CAP group showed the highest mean baseline time across all conditions, but also faster decreasing rates of change over time. With progress to diagnosis, participants may increasingly use compensatory strategies, as evidenced by faster initiation. However, this occurred in conjunction with slowed execution times, suggesting a decline in effectively accessing control processes required to translate movement into effective execution.

  1. Language impairment in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mariana Jardim Azambuja

    2012-06-01

    Full Text Available Language alterations in Huntington's disease (HD are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT. HD patients performed poorer in verbal fluency (p<0.0001, oral comprehension (p<0.0001, repetition (p<0.0001, oral agility (p<0.0001, reading comprehension (p=0.034 and narrative writing (p<0.0001. There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively. Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.

  2. Mapping energy poverty in Huntington, West Virginia

    Science.gov (United States)

    Callicoat, Elizabeth Anne

    Energy poverty is a growing phenomenon culminating from the combination of low to mid household income, deteriorating housing structures and rising household energy costs. Energy prices are increasing for all households, but the burden is proportionally larger for those with low to mid income. These groups must sacrifice to afford energy, and are often unable or do not have the autonomy to make structural improvements, especially if they rent their home. Data on residential dwellings from the Cabell County Tax Assessor's Office was used within a geographic information system to map where energy poverty likely exists within the city limits of Huntington, WV. It was found that one fifth of Huntington households are at a high risk of energy poverty, primarily located across the northern section of the city and in the center, surrounding Marshall University, Downtown and Cabell Huntington Hospital.

  3. Unusual early-onset Huntingtons disease.

    Science.gov (United States)

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  4. Development of biomarkers for Huntington's disease.

    Science.gov (United States)

    Weir, David W; Sturrock, Aaron; Leavitt, Blair R

    2011-06-01

    Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is no disease-modifying treatment. By use of predictive genetic testing, it is possible to identify individuals who carry the gene defect before the onset of symptoms, providing a window of opportunity for intervention aimed at preventing or delaying disease onset. However, without robust and practical measures of disease progression (ie, biomarkers), the efficacy of therapeutic interventions in this premanifest Huntington's disease population cannot be readily assessed. Current progress in the development of biomarkers might enable evaluation of disease progression in individuals at the premanifest stage of the disease; these biomarkers could be useful in defining endpoints in clinical trials in this population. Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease.

  5. Maternal transmission in sporadic Huntington's disease.

    OpenAIRE

    Sánchez, A; Milà, M.; Castellví-Bel, S; Rosich, M; Jiménez, D; Badenas, C.; ESTIVILL, X.

    1997-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disorder caused by the expansion of a (CAG)n repeat in the IT15 gene. Three per cent of cases are sporadic and in those in which family studies have been performed, the origin of the mutation was always paternal. The first sporadic case of Huntington's disease is presented in which a premutated maternal allele of 37 CAG repeats was transmitted expanded to the proband (43 CAG repeats). Molecular analysis of the IT15 gene is extrem...

  6. SYCAMORE CANYON PRIMITIVE AREA, ARIZONA.

    Science.gov (United States)

    Huff, Lyman C.; Raabe, R.C.

    1984-01-01

    The Sycamore Canyon Primitive Area, which occupies about 74 sq mi, lies about 24 mi southwest of Flagstaff, Arizona. To help evaluate the area for mineral resources, sediment samples were collected along Sycamore Creek and its tributaries. These were analyzed for traces of the ore metals without finding any local concentrations. In addition, a scintillometer was used to test rocks in the area without finding any abnormal radioactivity.

  7. Submarine canyon morphologies and evolution on a modern carbonate system: the Northern Slope of Little Bahama Bank (Bahamas).

    Science.gov (United States)

    Tournadour, Elsa; Mulder, Thierry; Borgomano, Jean; Hanquiez, Vincent; Ducassou, Emmanuelle; Gillet, Hervé; Sorriaux, Patrick

    2013-04-01

    located 5 km upstream toward the upper slope. Indeed, upslope the canyon heads, the reflectivity map shows low backscatters characteristic of fine grained sediments within small elongated depressions (3-5 km long, 1-5 m deep) that are probably-formed by the flow of sediments coming the platform. These initial results allow a preliminary model of the canyon evolution to be proposed with two stages: (1) a first stage controlled by retrogressive erosion, generating several slides and collapses finally forming the amphitheater-shaped canyon heads, (2) a second stage of retrogressive erosion influenced on the upper slope by the sediment input from the platform along small erosional depressions located seaward of the carbonate bank. These small depressions can locally merge with the canyon heads.

  8. Pathogenic insights from Huntington's disease-like 2 and other Huntington's disease genocopies.

    Science.gov (United States)

    Margolis, Russell L; Rudnicki, Dobrila D

    2016-12-01

    Huntington's disease-like 2 (HDL2) is a rare, progressive, autosomal dominant neurodegenerative disorder that genetically, clinically, and pathologically closely resembles Huntington's disease. We review HDL2 pathogenic mechanisms and examine the implications of these mechanisms for Huntington's disease and related diseases. HDL2 is caused by a CTG/CAG repeat expansion in junctophilin-3. Available data from cell and animal models and human brain suggest that HDL2 is a complex disease in which transcripts and proteins expressed bidirectionally from the junctophilin-3 locus contribute to pathogenesis through both gain-and loss-of-function mechanisms. Recent advances indicate that the pathogenesis of Huntington's disease is equally complex, despite the emphasis on toxic gain-of-function properties of the mutant huntingtin protein. Studies examining in parallel the genetic, clinical, neuropathological, and mechanistic similarities between Huntington's disease and HDL2 have begun to identify points of convergence between the pathogenic pathways of the two diseases. Comparisons to other diseases that are phenotypically or genetically related to Huntington's disease and HDL2 will likely reveal additional common pathways. The ultimate goal is to identify shared therapeutic targets and eventually develop therapies that may, at least in part, be effective across multiple similar rare diseases, an essential approach given the scarcity of resources for basic and translational research.

  9. [Periodontitis determining the onset and progression of Huntington's disease: review of the literature].

    Science.gov (United States)

    Rodríguez Coyago, María Lourdes; Sánchez Temiño, Victoria Emilia

    2015-10-27

    Huntington's disease is a neurodegenerative disorder caused by the expansion of a CAG triplet in the huntingtin gene. It presents with physical, cognitive and psychiatric impairment at different ages in the adult, and has a fatal prognosis. Other than the number of triplet repetitions, there seem to be other factors that explain the onset of this disease at an earlier age. It is well known that neuroinflammation has a key role in neurodegenerative disorders; Huntington's disease is not an exception to that rule. Neuroinflammation exacerbates neuronal damage produced by mutation, by initiating aberrant activation of microglia cell, as well as astrocyte and dendritic cell dysfunction; also compromising the blood-brain barrier and activating the complement cascade. The latter as a direct and indirect effect of the mutation and other stimuli such as chronic infections. In this study, periodontitis is presented as a model of chronic oral infection and a systemic inflammation source. We hypothesize the potential role of periodontitis in Huntington's disease, and the mechanisms by which it contributes to the early onset and progress of the disease. We considered experimental studies, systematic reviews, meta-analyses, published in both Spanish and English, obtained from the PubMed and SciELO databases. There are various mechanisms that generate brain inflammation in these patients; mechanisms of innate immunity being especially prominent. Chronic oral-dental infections, such as periodontal disease, may be an exacerbating factor that adds to the neuroinflammation of Huntington'’s disease.

  10. Comprehensive care in Huntington's disease: a physician's perspective.

    Science.gov (United States)

    Nance, Martha A

    2007-04-30

    Huntington's disease is a slowly progressive neurodegenerative disorder with wide-ranging effects on affected individuals and their families. Until a cure is found for the disease, patients and their families will continue to need care over years, even generations. The ideal care for HD is provided by a team, led by a physician, with input from rehabilitation therapists, nurses, psychologists, genetic counselors, social workers, and other health care providers. The goals of care are to maximize the quality of life at all points through the course of the disease, in part by anticipating problems that are likely to arise at the next stage of the illness. We describe below an approach to comprehensive care, and introduce the concept of the "Huntington disease molecule", in which the patient, in the center, is surrounded by a shell of immediate and extended family members, with bonds extended in multiple directions to provider who can give appropriate medical care, education, crisis management, research opportunities, address family issues, maximize function, and prepare for the future.

  11. Destination and source memory in Huntington's disease

    NARCIS (Netherlands)

    El Haj, M.; Caillaud, M.; Verny, C.; Fasotti, L.; Allain, P.

    2016-01-01

    Destination memory refers to the recall of the destination of previously relayed information, and source memory refers to the recollection of the origin of received information. We compared both memory systems in Huntington's disease (HD) participants. For this, HD participants and healthy adults

  12. Kas Huntington oli prohvet? / Priit Simson

    Index Scriptorium Estoniae

    Simson Priit, 1977-

    2008-01-01

    Autor käsitleb Samuel Huntingtoni teese ning leiab, et tegelikult Huntington ei pakkunud õigustust islamiriikide ründamisele, vaid pigem hoiatas tsivilisatsioonide siseasjusse sekkumise, tekkida võiva ahelreaktsiooni eest, kus üks tsivilisatsiooni liige tõmbab sõtta ka teise

  13. Wearable Sensors in Huntington Disease: A Pilot Study.

    Science.gov (United States)

    Andrzejewski, Kelly L; Dowling, Ariel V; Stamler, David; Felong, Timothy J; Harris, Denzil A; Wong, Cynthia; Cai, Hang; Reilmann, Ralf; Little, Max A; Gwin, Joseph T; Biglan, Kevin M; Dorsey, E Ray

    2016-06-18

    The Unified Huntington's Disease Rating Scale (UHDRS) is the principal means of assessing motor impairment in Huntington disease but is subjective and generally limited to in-clinic assessments. To evaluate the feasibility and ability of wearable sensors to measure motor impairment in individuals with Huntington disease in the clinic and at home. Participants with Huntington disease and controls were asked to wear five accelerometer-based sensors attached to the chest and each limb for standardized, in-clinic assessments and for one day at home. A second chest sensor was worn for six additional days at home. Gait measures were compared between controls, participants with Huntington disease, and participants with Huntington disease grouped by UHDRS total motor score using Cohen's d values. Fifteen individuals with Huntington disease and five controls completed the study. Sensor data were successfully captured from 18 of the 20 participants at home. In the clinic, the standard deviation of step time (time between consecutive steps) was increased in Huntington disease (p Huntington disease, and participants with Huntington disease grouped by motor impairment.

  14. Silencing Huntington's chorea: Is RNA Interference a Potential Cure?

    Directory of Open Access Journals (Sweden)

    Gerlinde A. Metz

    2006-01-01

    Full Text Available In 1872, George Huntington described Huntington's disease as characterized by motor, cognitive and psychiatric impairments. Huntington's disease is a dominant and autosomal mutation on chromosome 4 featuring the insertion of numerous CAG repeats. CAG codes for the amino acid, glutmanine that forms part of the Huntingtin protein (htt. Excess glutamine attachments make htt prone to accumulate in neurons. Three genes can be considered when developing therapies for Huntington's disease. They include targeting the symptoms of the disease, the progression of the disease and the cause of the disease. By using RNA interference (RNAi, the cause of the disease can be targeted. RNAi is a method that could potentially silence the formation of abnormal htt. This paper will discuss how RNAi could potentially cure Huntington's disease, by describing the genetic and proteinomic basis of Huntington's disease, the function of RNAi in Huntington's disease and the problems of benefits of RNAi. Preliminary work using RNAi in transgenic mice has shown a decrease in the behavioural expression of the mutant Huntington gene. There are several limitations associated with using RNAi as a gene therapy. For example, the effects of RNAi are short lived. A transposition system such as Sleeping Beauty can be used to increase the integration of the gene, however, for patients who currently have Huntington's disease, RNAi may potentially be used in combination with drugs or other treatments to target both symptoms and the underlying cause of Huntington's disease. This combination could eventually alleviate many painful symptoms associated with Huntington's disease and could even stop the progressive neurodegeneration of Huntington's disease. This review concludes that a substantial amount of new research is still necessary before RNAi is directly applicable to human patients with Huntington's disease.

  15. A Metabolic Study of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Rajasree Nambron

    Full Text Available Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III and controls.Control (n = 15, premanifest (n = 14 and stage II/III (n = 13 participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a, fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine there is a suggestion (p values between 0.02 and 0.05 that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that

  16. Environmental assessment: Davis Canyon site, Utah

    Energy Technology Data Exchange (ETDEWEB)

    none,

    1986-05-01

    In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOE prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considering for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has found that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of five sites suitable for characterization.

  17. Environmental assessment: Davis Canyon site, Utah

    Energy Technology Data Exchange (ETDEWEB)

    none,

    1986-05-01

    In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high- level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOE prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has found that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of the five sites suitable for characterization.

  18. Primary Initiation of Submarine Canyons

    CERN Document Server

    Herndon, J Marvin

    2011-01-01

    The discovery of close-to-star gas-giant exo-planets lends support to the idea of Earth's origin as a Jupiter-like gas-giant and to the consequences of its compression, including whole-Earth decompression dynamics that gives rise, without requiring mantle convection, to the myriad measurements and observations whose descriptions are attributed to plate tectonics. I propose here another, unanticipated consequence of whole-Earth decompression dynamics: namely, a specific, dominant, non-erosion, underlying initiation-mechanism precursor for submarine canyons that follows as a direct consequence of Earth's early origin as a Jupiter-like gas-giant.

  19. H-Canyon Recovery Crawler

    Energy Technology Data Exchange (ETDEWEB)

    Kriikku, E. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hera, K. R. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Marzolf, A. D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Phillips, M. H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-08-01

    The Nuclear Material Disposition Project group asked the Savannah River National Lab (SRNL) Research and Development Engineering (R&DE) department to help procure, test, and deploy a remote crawler to recover the 2014 Inspection Crawler (IC) that tipped over in the H-Canyon Air Exhaust Tunnel. R&DE wrote a Procurement Specification for a Recovery Crawler (RC) and SRNS Procurement Department awarded the contract to Power Equipment Manufacturing Inc. (PEM). The PEM RC was based on their standard sewer inspection crawler with custom arms and forks added to the front. The arms and forks would be used to upright the 2014 Inspection Crawler. PEM delivered the RC and associated cable reel, 2014 Inspection Crawler mockup, and manuals in late April 2015. R&DE and the team tested the crawler in May of 2015 and made modifications based on test results and Savannah River Site (SRS) requirements. R&DE delivered the RC to H-Area at the end of May. The team deployed the RC on June 9, 10, and 11, 2015 in the H-Canyon Air Exhaust Tunnel. The RC struggled with some obstacles in the tunnel, but eventually made it to the IC. The team spent approximately five hours working to upright the IC and eventually got it on its wheels. The IC travelled approximately 20 feet and struggled to drive over debris on the air tunnel floor. Unfortunately the IC tripped over trying to pass this obstacle. The team decided to leave the IC in this location and inspect the tunnel with the RC. The RC passed the IC and inspected the tunnel as it travelled toward H-Canyon. The team turned the RC around when it was about 20 feet from the H-Canyon crossover tunnel. From that point, the team drove the RC past the manway towards the new sand filter and stopped approximately 20 feet from the new sand filter. The team removed the RC from the tunnel, decontaminated the RC, and stored it the manway building, 294-2H. The RC deployment confirmed the IC was not in a condition to perform useful tunnel inspections and

  20. A temporal and ecological analysis of the Huntington Beach Wetlands through an unmanned aerial system remote sensing perspective

    Science.gov (United States)

    Rafiq, Talha

    Wetland monitoring and preservation efforts have the potential to be enhanced with advanced remote sensing acquisition and digital image analysis approaches. Progress in the development and utilization of Unmanned Aerial Systems (UAS) and Unmanned Aerial Vehicles (UAV) as remote sensing platforms has offered significant spatial and temporal advantages over traditional aerial and orbital remote sensing platforms. Photogrammetric approaches to generate high spatial resolution orthophotos of UAV acquired imagery along with the UAV's low-cost and temporally flexible characteristics are explored. A comparative analysis of different spectral based land cover maps derived from imagery captured using UAV, satellite, and airplane platforms provide an assessment of the Huntington Beach Wetlands. This research presents a UAS remote sensing methodology encompassing data collection, image processing, and analysis in constructing spectral based land cover maps to augment the efforts of the Huntington Beach Wetlands Conservancy by assessing ecological and temporal changes at the Huntington Beach Wetlands.

  1. An experimental approach to submarine canyon evolution

    Science.gov (United States)

    Lai, Steven Y. J.; Gerber, Thomas P.; Amblas, David

    2016-03-01

    We present results from a sandbox experiment designed to investigate how sediment gravity flows form and shape submarine canyons. In the experiment, unconfined saline gravity flows were released onto an inclined sand bed bounded on the downstream end by a movable floor that was used to increase relief during the experiment. In areas unaffected by the flows, we observed featureless, angle-of-repose submarine slopes formed by retrogressive breaching processes. In contrast, areas influenced by gravity flows cascading across the shelf break were deeply incised by submarine canyons with well-developed channel networks. Normalized canyon long profiles extracted from successive high-resolution digital elevation models collapse to a single profile when referenced to the migrating shelf-slope break, indicating self-similar growth in the relief defined by the canyon and intercanyon profiles. Although our experimental approach is simple, the resulting canyon morphology and behavior appear similar in several important respects to that observed in the field.

  2. Molecular diagnostic analysis for Huntington's disease: a prospective evaluation.

    OpenAIRE

    MacMillan, J C; Davies, P.; Harper, P S

    1995-01-01

    The availability of mutation analysis for the CAG repeat expansion associated with Huntington's disease has prompted clinicians in various specialties to request testing of samples from patients displaying clinical features that might be attributable to Huntington's disease. A series of 38 cases presenting with clinical features thought possibly to be due to Huntington's disease were analysed prospectively. In 53% of such cases presenting initially with chorea and 62.5% with psychiatric sympt...

  3. Normal CAG and CCG repeats in the Huntington`s disease genes of Parkinson`s disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Rubinsztein, D.C.; Leggo, J.; Barton, D.E. [Cambridge Univ. (United Kingdom)] [and others

    1995-04-24

    The clinical features of Parkinson`s disease, particularly rigidity and bradykinesia and occasionally tremor, are seen in juvenile-onset Huntington`s disease. Therefore, the CAG and CCG repeats in the Huntington`s disease gene were investigated in 45 Parkinson`s disease patients and compared to 40 control individuals. All of the Parkinson`s disease chromosomes fell within the normal size ranges. In addition, the distributions of the two repeats in the Parkinson`s disease patients did not differ significantly from those of the control population. Therefore, abnormalities of these trinucleotide repeats in the Huntington`s disease gene are not likely to contribute to the pathogenesis of Parkinson`s disease. 12 refs., 2 figs.

  4. Prehistoric deforestation at Chaco Canyon?

    Science.gov (United States)

    Wills, W H; Drake, Brandon L; Dorshow, Wetherbee B

    2014-08-12

    Ancient societies are often used to illustrate the potential problems stemming from unsustainable land-use practices because the past seems rife with examples of sociopolitical "collapse" associated with the exhaustion of finite resources. Just as frequently, and typically in response to such presentations, archaeologists and other specialists caution against seeking simple cause-and effect-relationships in the complex data that comprise the archaeological record. In this study we examine the famous case of Chaco Canyon, New Mexico, during the Bonito Phase (ca. AD 860-1140), which has become a prominent popular illustration of ecological and social catastrophe attributed to deforestation. We conclude that there is no substantive evidence for deforestation at Chaco and no obvious indications that the depopulation of the canyon in the 13th century was caused by any specific cultural practices or natural events. Clearly there was a reason why these farming people eventually moved elsewhere, but the archaeological record has not yet produced compelling empirical evidence for what that reason might have been. Until such evidence appears, the legacy of Ancestral Pueblo society in Chaco should not be used as a cautionary story about socioeconomic failures in the modern world.

  5. Modern Genome Editing Technologies in Huntington's Disease Research.

    Science.gov (United States)

    Malankhanova, Tuyana B; Malakhova, Anastasia A; Medvedev, Sergey P; Zakian, Suren M

    2017-01-01

    The development of new revolutionary technologies for directed gene editing has made it possible to thoroughly model and study NgAgo human diseases at the cellular and molecular levels. Gene editing tools like ZFN, TALEN, CRISPR-based systems, NgAgo and SGN can introduce different modifications. In gene sequences and regulate gene expression in different types of cells including induced pluripotent stem cells (iPSCs). These tools can be successfully used for Huntington's disease (HD) modeling, for example, to generate isogenic cell lines bearing different numbers of CAG repeats or to correct the mutation causing the disease. This review presents common genome editing technologies and summarizes the progress made in using them in HD and other hereditary diseases. Furthermore, we will discuss prospects and limitations of genome editing in understanding HD pathology.

  6. Internal tides affect benthic community structure in an energetic submarine canyon off SW Taiwan

    Science.gov (United States)

    Liao, Jian-Xiang; Chen, Guan-Ming; Chiou, Ming-Da; Jan, Sen; Wei, Chih-Lin

    2017-07-01

    other hand, rebounded more rapidly due to their fast growth rate and short generation time and thus did not display bathymetric pattern in the canyon. To our knowledge, this is the first benthic ecological study in a submarine canyon connected to a high-sediment-yield SMR. The biological responses to extreme physical conditions in the GPSC could have broad implications on understanding the anthropogenic and climate change impacts in the deep-sea ecosystems.

  7. Revisiting the neuropsychiatry of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Antonio Lucio Teixeira

    Full Text Available ABSTRACT Huntington's disease (HD is an autosomal dominant neurodegenerative disease classified under the choreas. Besides motor symptoms, HD is marked by cognitive and behavioral symptoms, impacting patients' functional capacity. The progression of cognitive impairment and neuropsychiatric symptoms occur in parallel with neurodegeneration. The nature of these symptoms is very dynamic, and the major clinical challenges include executive dysfunction, apathy, depression and irritability. Herein, we provide a focused updated review on the cognitive and psychiatric features of HD.

  8. [Sporadic juvenile forms of Huntington's chorea].

    Science.gov (United States)

    Zinchenko, A P; Goncharov, V D; Burtianskii, D L; Zakhar'ev, Iu M

    1980-01-01

    Six patients with Huntington's chorea in the age of 15-24 years old, suffered from diffusive choreic hyperkynesis with slowly progressive dementia. The development of this disease in childhood and adolescence was atypical, as nobody in the family and in kin sufferred from it and it was difficult to diagnose the disease. Recognition of the disease was promoted by pneumoencephalography, electromyography and memory investigation.

  9. Clinical and genetic study of a juvenile-onset Huntington disease

    Directory of Open Access Journals (Sweden)

    HAO Ying

    2012-06-01

    Full Text Available Background Huntington's disease (HD is an autosomal dominant hereditary progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dementia, cognitive and affective impairment. There are selective neural cell loss and atrophy in the caudate and putamen. Dr. George Huntington firstly described the disease accurately and insightfully, which led to a widespread recognition of the inherited chorea that now bears his name. Huntington disease gene (IT15 locus on chromosome 4p16.3, and encompasses 67 exons with a trinucleotide repeat (CAG in the first exon. The CAG repeat length is highly polymorphic in the population and expanded on at least one chromosome of individuals with HD. Clinically, patient with HD are often onset in adulthood. Juvenile-onset HD is relatively rare. Adult-onset HD patients usually have a CAG expansion from 40 to 55 whereas those with juvenile-onset greater than 60 which are often inherited from the father. We investigated the clinical features of a juvenile-onset case with Huntington disease and dynamic mutation of his family. Methods The CAG repeats of IT15 gene were detected using polymerase chain reaction and capillary electrophoresis in 115 individuals with preliminary diagnosis as Huntington disease. The repeat numbers of some samples carried expanded or intermediate alleles were verified by the pMD18-T vector clone sequencing. Results Fragment analysis showed that one juvenile-onset case presenting with cognitive dysfunction and hypokinesis carried 15/68 CAG repeats of IT15. His father carried 17/37 and mother carried 15/17. Conclusion 1 The juvenile-onset case of HD presented with different clinical features compared with adult-onset cases. The typical signs of adult-onset cases include progressive chorea, rigidity and dementia. The most common sign of juvenile-onset Huntington disease is cognitive decline. 2 The dynamic mutation of IT15 gene expansion of the CAG repeats in the

  10. Altered cholesterol and fatty acid metabolism in Huntington disease.

    Science.gov (United States)

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  11. Arithmetic Word-Problem-Solving in Huntington's Disease

    Science.gov (United States)

    Allain, P.; Verny, C.; Aubin, G.; Pinon, K.; Bonneau, D.; Dubas, F.; Gall, D.L.

    2005-01-01

    The purpose of this study was to examine executive functioning in patients with Huntington's disease using an arithmetic word-problem-solving task including eight solvable problems of increasing complexity and four aberrant problems. Ten patients with Huntington's disease and 12 normal control subjects matched by age and education were tested.…

  12. Comprehension of Complex Discourse in Different Stages of Huntington's Disease

    Science.gov (United States)

    Saldert, Charlotta; Fors, Angelika; Stroberg, Sofia; Hartelius, Lena

    2010-01-01

    Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group…

  13. Contours--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents bathymetric contours for several seafloor maps of the Monterey Canyon and Vicinity map area, California. The raster data file is...

  14. Street canyon ventilation and atmospheric turbulence

    Science.gov (United States)

    Salizzoni, P.; Soulhac, L.; Mejean, P.

    Operational models for pollutant dispersion in urban areas require an estimate of the turbulent transfer between the street canyons and the overlying atmospheric flow. To date, the mechanisms that govern this process remain poorly understood. We have studied the mass exchange between a street canyon and the atmospheric flow above it by means of wind tunnel experiments. Fluid velocities were measured with a Particle Image Velocimetry system and passive scalar concentrations were measured using a Flame Ionisation Detector. The mass-transfer velocity between the canyon and the external flow has been estimated by measuring the cavity wash-out time. A two-box model, used to estimate the transfer velocity for varying dynamical conditions of the external flow, has been used to interpret the experimental data. This study sheds new light on the mechanisms which drive the ventilation of a street canyon and illustrates the influence of the external turbulence on the transfer process.

  15. Modelling Aerosol Dispersion in Urban Street Canyons

    Science.gov (United States)

    Tay, B. K.; Jones, D. P.; Gallagher, M. W.; McFiggans, G. B.; Watkins, A. P.

    2009-04-01

    Flow patterns within an urban street canyon are influenced by various micrometeorological factors. It also represents an environment where pollutants such as aerosols accumulate to high levels due to high volumes of traffic. As adverse health effects are being attributed to exposure to aerosols, an investigation of the dispersion of aerosols within such environments is of growing importance. In particular, one is concerned with the vertical structure of the aerosol concentration, the ventilation characteristics of the street canyon and the influence of aerosol microphysical processes. Due to the inherent heterogeneity of the aerosol concentrations within the street canyon and the lack of spatial resolution of measurement campaigns, these issues are an on-going debate. Therefore, a modelling tool is required to represent aerosol dispersion patterns to provide insights to results of past measurement campaigns. Computational Fluid Dynamics (CFD) models are able to predict detailed airflow patterns within urban geometries. This capability may be further extended to include aerosol dispersion, by an Euler-Euler multiphase approach. To facilitate the investigation, a two-dimensional, multiphase CFD tool coupled with the k-epsilon turbulence model and with the capability of modelling mixed convection flow regimes arising from both wind driven flows and buoyancy effects from heated walls was developed. Assuming wind blowing perpendicularly to the canyon axis and treating aerosols as a passive scalar, an attempt will be made to assess the sensitivities of aerosol vertical structure and ventilation characteristics to the various flow conditions. Numerical studies were performed using an idealized 10m by 10m canyon to represent a regular canyon and 10m by 5m to represent a deep one. An aerosol emission source was assigned on the centerline of the canyon to represent exhaust emissions. The vertical structure of the aerosols would inform future directives regarding the

  16. Habitat--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the habitat map of the seafloor of the Monterey Canyon and Vicinity map area, California. The vector data file is included in...

  17. Habitat--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the habitat map of the seafloor of the Monterey Canyon and Vicinity map area, California. The vector data file is included in...

  18. Contours--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents bathymetric contours for several seafloor maps of the Monterey Canyon and Vicinity map area, California. The raster data file is...

  19. Flow Structure in a Bedrock Canyon (Invited)

    Science.gov (United States)

    Venditti, J. G.; Rennie, C. D.; Church, M. A.; Bomhof, J.; Lin, M.

    2013-12-01

    Bedrock canyon incision is widely recognized as setting the pace of landscape evolution. A variety of models link flow and sediment transport processes to the bedrock canyon incision rate. The model components that represent sediment transport processes are quite well developed in some models. In contrast, the model components that represent fluid flow remain rudimentary. Part of the reason is that there have been relatively few observations of flow structure in a bedrock canyon. Here, we present observations of flow obtained using an array of three acoustic Doppler current profilers during a 524 km long continuous centerline traverse of the Fraser River, British Columbia, Canada as it passes through a series of bedrock canyons. Through this portion of the river, the channel alternates between gravel-bedded reaches that are deeply incised into semi-consolidated glacial deposits and solid bedrock-bound reaches. We present observations of flow through 41 bedrock bound reaches of the river, derived from our centerline traverses and more detailed three-dimensional mapping of the flow structure in 2 canyons. Our observations suggest that flow in the most well-defined canyons (deep, laterally constrained, completely bedrock bound) is far more complex than that in a simple prismatic channel. As flow enters the canyon, a high velocity core plunges from the surface to the bed, causing a velocity inversion (high velocities at the bed and low velocities at the surface). This plunging flow then upwells along the canyon wall, resulting in a three-dimensional flow with counter-rotating, along-stream eddies that diverge near the bed. We observe centerline ridges along the canyon floors that result from the divergence and large-scale surface boils caused by the upwelling. This flow structure causes deep scour in the bedrock channel floor, and ensures the base of the canyon walls are swept of debris that otherwise may be deposited due to lower shear stresses abutting the walls. The

  20. Structure of Flow in a Bedrock Canyon

    Science.gov (United States)

    Venditti, J. G.; Rennie, C. D.; Church, M. A.; Bomhof, J.; Lin, M.

    2012-12-01

    Bedrock canyon incision is widely recognized as setting the pace of landscape evolution. A variety of models link flow and sediment transport processes to the bedrock canyon incision rate. The model components that represent sediment transport processes are quite well developed in some models. In contrast, the model components that represent fluid flow remain rudimentary. Part of the reason is that there have been relatively few observations of flow structure in a bedrock canyon. Here, we present observations of flow obtained using an array of three acoustic Doppler current profilers during a 524 km long continuous centerline traverse of the Fraser River, British Columbia, Canada as it passes through a series of bedrock canyons. Through this portion of the river, the channel alternates between gravel-bedded reaches that are deeply incised into semi-consolidated glacial deposits and solid bedrock-bound reaches. We present observations of flow through 41 bedrock bound reaches of the river, derived from our centerline traverses and more detailed three-dimensional mapping of the flow structure in 2 canyons. Our observations suggest that flow in the most well-defined canyons (deep, laterally constrained, completely bedrock bound) is far more complex than that in a simple prismatic channel. As flow enters the canyon, a high velocity core plunges from the surface to the bed, causing a velocity inversion (high velocities at the bed and low velocities at the surface). This plunging flow then upwells along the canyon wall, resulting in a three-dimensional flow with counter-rotating, along-stream eddies that diverge near the bed. We observe centerline ridges along the canyon floors that result from the divergence and large-scale surface boils caused by the upwelling. This flow structure causes deep scour in the bedrock channel floor, and ensures the base of the canyon walls are swept of debris that otherwise may be deposited due to lower shear stresses abutting the walls. The

  1. Environmental assessment: Davis Canyon site, Utah

    Energy Technology Data Exchange (ETDEWEB)

    none,

    1986-05-01

    In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOE prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has fond that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of five sites suitable for characterization. 181 figs., 175 tabs.

  2. Different Views of the Grand Canyon

    Science.gov (United States)

    Elders, Wilfred A.

    Each year the spectacular scenery of the Grand Canyon of Arizona awes its more than 4,000,000 visitors. Just as its enormous scale dwarfs our human sense of space, its geology also dwarfs our human sense of time. Perhaps here, more than anywhere else on the planet, we can experience a sense of ``Deep Time.'' The colorful rocks exposed in the vertical walls of the canyon display a span of 1.8 billion years of Earth's history [Beus and Morales, 2003]. But wait! There is a different view! According to Vail [2003], this time span is only 6,000 years and the Grand Canyon and its rocks are a record of the Biblical 6 days of creation and Noah's flood. During a visit to Grand Canyon, in August 2003, I learned that Vail's book, Grand Canyon: A Different View, is being sold within the National Park. The author and compiler of Grand Canyon: A Different View is a Colorado River guide who is well acquainted with the Grand Canyon at river level. He has produced a book with an attractive layout and beautiful photographs. The book is remarkable because it has 23 co-authors, all male, who comprise a veritable ``Who's Who'' in creationism. For example, Henry Morris and John Whitcomb, the authors of the seminal young Earth creationist text, The Genesis Flood [Whitcomb and Morris, 1961], each contribute a brief introduction. Each chapter of Grand Canyon: A Different View begins with an overview by Vail, followed by brief comments by several contributors that ``have been peer reviewed to ensure a consistent and Biblical perspective.'' This perspective is strict Biblical literalism.

  3. Communication and Huntington's Disease: Qualitative Interviews and Focus Groups with Persons with Huntington's Disease, Family Members, and Carers

    Science.gov (United States)

    Hartelius, Lena; Jonsson, Maria; Rickeberg, Anneli; Laakso, Katja

    2010-01-01

    Background: As an effect of the cognitive, emotional and motor symptoms associated with Huntington's disease, communicative interaction is often dramatically changed. No study has previously included the subjective reports on this subject from individuals with Huntington's disease. Aims: To explore the qualitative aspects of how communication is…

  4. 3-NP-induced neurodegeneration studies in experimental models of Huntington's disease : apoptosis in Huntington's disease

    NARCIS (Netherlands)

    Vis, Johanna Catharina

    2005-01-01

    This thesis investigates the possible role of apoptosis, or programmed cell death, in Huntington's disease (HD). HD is caused by an expanded CAG repeat in the N-terminal region of the huntingtin protein leading to specific neostriatal neurodegeneration. The sequence of events that leads to this sele

  5. Characterization of conservative somatic instability of the CAG repeat region in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, F.V.; Calikoglu, A.S.; Whetsell, L.H. [H.A. Chapman Research Institute of Medical Genetics, Tulsa, OK (United States)

    1994-09-01

    Instability and enlargement of a CAG repeat region at the beginning of the huntingtin gene (IT-15) has been linked with Huntington`s disease. The CAG repeat size shows a highly significant correlation with age-of-onset of clinicial features in individuals with 40 or more repeats who have Huntington disease. The clinical status of nonsymptomatic individuals with 30 to 39 CAG repeats is considered ambiguous. In order to define more carefully the nature of the HD expansion instability, we examined patients in our HD population using a discriminating fluorescence-based PCR approach. The degree of somatic mutation increases with both earlier age of onset and the size of the inherited allele. A single prominent band one repeat larger than the index peak was typical in individuals with 40-41 CAG repeats. Three to four larger bands are typically discerned in individuals with 50 or more repeats. In an extreme example, an individual with approximately 95 repeats had at least 8 prominent bands. Plotting the degree of somatic mutation relative to the size of the HD allele shows somatic mutation activity increases with size. By this approach 40-60% of the alleles in a 40-41 CAG repeat HD loci is represented in the primary allele. In contrast, the primary allele represents a relatively minor proportion of the total alleles for expansions greater than 50 CAG repeats (10-20%). The limited range of somatic mutation suggest that the instability is restricted to very early stages of embryogenesis before tissue development diverges or that persistent somatic instability occurs at a slow rate. Therefore, the properties of somatic instability in Huntington`s disease have aspects that are both in common but also different from that found in other trinucleotide repeat expanding diseases such as myotonic muscular dystrophy and fragile X syndrome.

  6. Compilation of PRF Canyon Floor Pan Sample Analysis Results

    Energy Technology Data Exchange (ETDEWEB)

    Pool, Karl N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Minette, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wahl, Jon H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greenwood, Lawrence R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Coffey, Deborah S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McNamara, Bruce K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bryan, Samuel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Scheele, Randall D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Delegard, Calvin H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sinkov, Sergey I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Soderquist, Chuck Z. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fiskum, Sandra K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Brown, Garrett N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clark, Richard A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-06-30

    On September 28, 2015, debris collected from the PRF (236-Z) canyon floor, Pan J, was observed to exhibit chemical reaction. The material had been transferred from the floor pan to a collection tray inside the canyon the previous Friday. Work in the canyon was stopped to allow Industrial Hygiene to perform monitoring of the material reaction. Canyon floor debris that had been sealed out was sequestered at the facility, a recovery plan was developed, and drum inspections were initiated to verify no additional reactions had occurred. On October 13, in-process drums containing other Pan J material were inspected and showed some indication of chemical reaction, limited to discoloration and degradation of inner plastic bags. All Pan J material was sealed back into the canyon and returned to collection trays. Based on the high airborne levels in the canyon during physical debris removal, ETGS (Encapsulation Technology Glycerin Solution) was used as a fogging/lock-down agent. On October 15, subject matter experts confirmed a reaction had occurred between nitrates (both Plutonium Nitrate and Aluminum Nitrate Nonahydrate (ANN) are present) in the Pan J material and the ETGS fixative used to lower airborne radioactivity levels during debris removal. Management stopped the use of fogging/lock-down agents containing glycerin on bulk materials, declared a Management Concern, and initiated the Potential Inadequacy in the Safety Analysis determination process. Additional drum inspections and laboratory analysis of both reacted and unreacted material are planned. This report compiles the results of many different sample analyses conducted by the Pacific Northwest National Laboratory on samples collected from the Plutonium Reclamation Facility (PRF) floor pans by the CH2MHill’s Plateau Remediation Company (CHPRC). Revision 1 added Appendix G that reports the results of the Gas Generation Rate and methodology. The scope of analyses requested by CHPRC includes the determination of

  7. Canyon conditions impact carbon flows in food webs of three sections of the Nazare canyon

    NARCIS (Netherlands)

    van Oevelen, D.; Soetaert, K.; Garcia, R.; de Stigter, H.C.; Cunha, M.R.; Pusceddu, A.; Danovaro, R.; Garcia, R.

    2011-01-01

    Submarine canyons transport large amounts of sediment and organic matter (OM) from the continental shelf to the abyssal plain. Three carbon-based food web models were constructed for the upper (300-750 m water depth), middle (2700-3500 m) and lower section (4000-5000 m) of the Nazare canyon (eastern

  8. The Whittard Canyon – a case study of submarine canyon processes

    NARCIS (Netherlands)

    Amaro, T.; Huvenne, V.A.I.; Allcock, A.L.; Aslam, T.; Davies, J.S.; Danovaro, R.; de Stigter, H.C.; Duineveld, G.C.A.; Gambi, C.; Gooday, A.J.; Gunton, L.M.; Hall, R.; Howell, K.L.; Ingels, J.; Kiriakoulakis, K.; Kershaw, C.E.; Lavaleye, M.; Robert, K.; Stewart, H.; Van Rooij, D.; White, M.; Wilson, A.M.

    2016-01-01

    Submarine canyons are large geomorphological features that incise continental shelves and slopes around the world. They are often suggested to be biodiversity and biomass hotspots, although there is no consensus about this in the literature. Nevertheless, many canyons do host diverse faunal communit

  9. Altered Fractional Anisotropy in Early Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Silky Singh

    2013-02-01

    Full Text Available Huntington's disease (HD is a dominantly inherited neurodegenerative disease best known for chorea. The disorder includes numerous other clinical features including mood disorder, eye movement abnormalities, cognitive disturbance, pendular knee reflexes, motor impersistence, and postural instability. We describe a mild case of HD early in the disease course with depression and subtle neurological manifestations. In addition, we review MRI and diffusion tensor imaging features in this patient. The bicaudate ratio, a measure of caudate atrophy, was increased. Fractional anisotropy values of the bilateral caudate and putamen were increased, signifying neurodegeneration of these structures in HD.

  10. Huntingtin processing in pathogenesis of Huntington disease

    Institute of Scientific and Technical Information of China (English)

    Zhenghong QIN; Zhenlun GU

    2004-01-01

    Huntington's disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin.The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis.

  11. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington's disease.

    Science.gov (United States)

    Paul, Bindu D; Sbodio, Juan I; Xu, Risheng; Vandiver, M Scott; Cha, Jiyoung Y; Snowman, Adele M; Snyder, Solomon H

    2014-05-01

    Huntington's disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes. Huntington's disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington's disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine γ-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington's disease tissues, which may mediate Huntington's disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington's disease tissues and in intact mouse models of Huntington's disease, suggesting therapeutic potential.

  12. TRAFFIC EMISSION TRANSPORTATION IN STREET CANYONS

    Institute of Scientific and Technical Information of China (English)

    XIE Xiao-min; WANG Jia-song; HUANG Zhen

    2009-01-01

    Spatial distributions of traffic-related pollutants in street canyons were investigated by field measurements and Computational Fluid Dynamics(CFD).Two typical street canyons were selected for field monitoring,and a three-dimensional numerical model was built based on Reynolds-averaged Navier-Stokes equations equipped with the standard k-ε turbulence models for CFD simulations.The study shows that the pollutant concentrations of vehicle emission correlate well with the traffic volume variation,wind direction and wind speed.The wind direction and speed at the roof level determine overwhellmingly the flow field and the distributions of pollutant concentrations in the street canyon.When the wind speed is equal to zero,the pollutant concentrations on the breath height of the both sides of the street canyon are almost the same.When the wind direction is perpendicular to the street,one main vortex is formed with a shape depending on the building structure on both sides of the street,the pollutant is accumulated on the leeward side,and the pollutant concentrations at the breath height on the leeward side are 2 to 3 times as those at the breath height on the windward side.If the wind direction makes some angles with the street canyon,the pollutant concentration will be higher on the leeward side because one main vortex will also be formed in the vertical section of the canyon by the perpendicular component of the wind.But pollutant concentrations decrease in the canyon because pollutants are dispersed along the axis of the street.Pollutants at different heights of the vertical section decrease with height,i.e.there are concentration gradients in the vertical section,and the pollutant concentrations on the leeward side of the upstream building are much higher than those on the windward side of the downstream building.

  13. Peaks, plateaus, canyons, and craters: The complex geometry of simple mid-domain effect models

    DEFF Research Database (Denmark)

    Colwell, Robert K.; Gotelli, Nicholas J.; Rahbek, Carsten

    2009-01-01

    Background: Geographic ranges, randomly located within a bounded geographical domain, Geographic ranges, randomly located within a bounded geographical domain, produce a central hump of species richness (the mid-domain effect, MDE). The hump arises from geometric constraints on the location of ra...... of a uniform size generate more complex patterns, including peaks, plateaus, canyons, and craters of species richness....

  14. Unawareness of motor phenoconversion in Huntington disease.

    Science.gov (United States)

    McCusker, Elizabeth A; Gunn, David G; Epping, Eric A; Loy, Clement T; Radford, Kylie; Griffith, Jane; Mills, James A; Long, Jeffrey D; Paulsen, Jane S

    2013-09-24

    To determine whether Huntington disease (HD) mutation carriers have motor symptoms (complaints) when definite motor onset (motor phenoconversion) is diagnosed and document differences between the groups with and without unawareness of motor signs. We analyzed data from 550 HD mutation carriers participating in the multicenter PREDICT-HD Study followed through the HD prodrome. Data analysis included demographics, the Unified Huntington's Disease Rating Scale (UHDRS) and the Participant HD History of symptoms, self-report of progression, and cognitive, behavioral, and imaging measures. Unawareness was identified when no motor symptoms were self-reported but when definite motor HD was diagnosed. Of 38 (6.91%) with onset of motor HD, almost half (18/38 = 47.36%) had no motor symptoms despite signs of disease on the UHDRS motor rating and consistent with unawareness. A group with motor symptoms and signs was similar on a range of measures to the unaware group. Those with unawareness of HD signs reported less depression. Patients with symptoms had more striatal atrophy on imaging measures. Only half of the patients with newly diagnosed motor HD had motor symptoms. Unaware patients were less likely to be depressed. Self-report of symptoms may be inaccurate in HD at the earliest stage.

  15. High Protein Diet and Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Chiung-Mei Chen

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder caused by the huntingtin (HTT gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT exists in the liver and causes urea cycle deficiency. A low protein diet (17% restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories than in mice (~22%. We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein for 5 days, followed by a high protein diet (HPD, 26.3% protein for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington's Disease Rating Scale (UHDRS. The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378 in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

  16. Grand Canyon Humpback Chub Population Improving

    Science.gov (United States)

    Andersen, Matthew E.

    2007-01-01

    The humpback chub (Gila cypha) is a long-lived, freshwater fish found only in the Colorado River Basin. Physical adaptations-large adult body size, large predorsal hump, and small eyes-appear to have helped humpback chub evolve in the historically turbulent Colorado River. A variety of factors, including habitat alterations and the introduction of nonnative fishes, likely prompted the decline of native Colorado River fishes. Declining numbers propelled the humpback chub onto the Federal list of endangered species in 1967, and the species is today protected under the Endangered Species Act of 1973. Only six populations of humpback chub are currently known to exist, five in the Colorado River Basin above Lees Ferry, Ariz., and one in Grand Canyon, Ariz. The U.S. Geological Survey's Grand Canyon Monitoring and Research Center oversees monitoring and research activities for the Grand Canyon population under the auspices of the Glen Canyon Dam Adaptive Management Program (GCDAMP). Analysis of data collected through 2006 suggests that the number of adult (age 4+ years) humpback chub in Grand Canyon increased to approximately 6,000 fish in 2006, following an approximate 40-50 percent decline between 1989 and 2001. Increasing numbers of adult fish appear to be the result of steadily increasing numbers of juvenile fish reaching adulthood beginning in the mid- to late-1990s and continuing through at least 2002.

  17. Deciphering Outburst Flood Discharges from the Morphology of Hesperian Canyons

    Science.gov (United States)

    Lapotre, M. G. A.; Lamb, M. P.; Williams, R. M.

    2014-07-01

    We model the hydraulics of outburst floods over canyon escarpments. We show that canyons only maintain a constant width under a certain hydraulic regime. We combine the hydraulic model to an erosion law to constrain paleodischarges at Echus Chasma.

  18. Contemporary sediment-transport processes in submarine canyons.

    Science.gov (United States)

    Puig, Pere; Palanques, Albert; Martín, Jacobo

    2014-01-01

    Submarine canyons are morphological incisions into continental margins that act as major conduits of sediment from shallow- to deep-sea regions. However, the exact mechanisms involved in sediment transfer within submarine canyons are still a subject of investigation. Several studies have provided direct information about contemporary sedimentary processes in submarine canyons that suggests different modes of transport and various triggering mechanisms. Storm-induced turbidity currents and enhanced off-shelf advection, hyperpycnal flows and failures of recently deposited fluvial sediments, dense shelf-water cascading, canyon-flank failures, and trawling-induced resuspension largely dominate present-day sediment transfer through canyons. Additionally, internal waves periodically resuspend ephemeral deposits within canyons and contribute to dispersing particles or retaining and accumulating them in specific regions. These transport processes commonly deposit sediments in the upper- and middle-canyon reaches for decades or centuries before being completely or partially flushed farther down-canyon by large sediment failures.

  19. Association of Huntington's disease and schizophrenia-like psychosis in a Huntington's disease pedigree

    OpenAIRE

    Guimarães João; Xavier Miguel; Corrêa Bernardo

    2006-01-01

    Abstract Background Huntington's disease (HD) is a dominantly inherited, neurodegenerative disorder due to expansion of a polymorphic trinucleotide repeat in the short arm of chromosome 4. Clinical manifestations consist of a triad of choreic movements, cognitive decline and psychiatric syndromes starting in the fourth to fifth decade. Psychiatric manifestations vary and may precede motor and cognitive changes. Personality changes and depression occur most commonly. Paranoid schizophrenia-lik...

  20. O desenvolvimento político em Huntington e Fukuyama Huntington and Fukuyama on political development

    Directory of Open Access Journals (Sweden)

    Natália Nóbrega de Mello

    2010-01-01

    Full Text Available O artigo contrasta as teses de Huntington e Fukuyama sobre desenvolvimento político. As obras analisadas, Ordem política nas sociedades em mudança e O fim da história, inscrevem-se entre duas conjunturas decisivas - 1968 e 1989. Huntington desmontou a equivalência entre desenvolvimento político e modernização e Fukuyama reafirmou a democracia como o destino de todos os países e, desse modo, como o fim da história. Nesta comparação, dois eixos se sobressaem: o contexto de produção das obras e a alternância entre os polos teóricos da democracia e da estabilidade. Procura-se demonstrar como, apesar de reinserir a democracia no desenvolvimento político, a instabilidade continua a ser um foco privilegiado de análise no pensamento de Fukuyama.The article contrasts the theories of Huntington and Fukuyama on political development. The analyzed works, Political order in changing societies and The end of history, fall between two decisive historical moments - in 1968 and 1989. Huntington disassembled the equivalence between political development and modernization; Fukuyama reaffirmed democracy as the destiny of all countries and, as such, it is the end of history. In this comparison, two axes call our attention: the production context of these works and the alternation between the theoreticals poles of democracy and stability. The article shows how, although reenters democracy in the political development theory, instablility remains a prime focus of analysis in Fukuyama's thought.

  1. 27 CFR 9.152 - Malibu-Newton Canyon.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Malibu-Newton Canyon. 9... Malibu-Newton Canyon. (a) Name. The name of the viticultural area described in this petition is “Malibu-Newton Canyon.” (b) Approved maps. The appropriate map for determining the boundary of the...

  2. 78 FR 21415 - Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2013-04-10

    ... Bureau of Reclamation Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of Reclamation, Interior. ACTION: Notice of public meeting. SUMMARY: The Glen Canyon Dam Adaptive Management Work Group..., the AMWG, a technical work group, a Grand Canyon Monitoring and Research Center, and...

  3. 77 FR 43117 - Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2012-07-23

    ... Bureau of Reclamation Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of Reclamation, Interior. ACTION: Notice of public meeting. SUMMARY: The Glen Canyon Dam Adaptive Management Work Group... Federal advisory committee, the AMWG, a technical work group (TWG), a Grand Canyon Monitoring and...

  4. 77 FR 22801 - Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2012-04-17

    ... Bureau of Reclamation Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of Reclamation... Management Work Group (AMWG) makes recommendations to the Secretary of the Interior concerning Glen Canyon... AMP includes a Federal advisory committee, the AMWG, a technical work group, a Grand Canyon...

  5. 77 FR 9265 - Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2012-02-16

    ... Bureau of Reclamation Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of Reclamation, Interior. ACTION: Notice of public meeting. SUMMARY: The Glen Canyon Dam Adaptive Management Work Group... Federal advisory committee, the AMWG, a technical work group (TWG), a Grand Canyon Monitoring and...

  6. Américo Negrette and Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mariana Moscovich

    2011-08-01

    Full Text Available The authors present a historical review of the seminal clinical contribution of Professor Américo Negrette, a Venezuelan neurologist, to the evolution of scientific knowledge about Huntington's disease.

  7. 1H magnetic resonance spectroscopy in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, Joost C. H.; Sijens, Paul E.; Roos, Raymund A. C.; Leenders, Klaus L.

    2007-01-01

    Huntington disease (HD) is a hereditary brain disease, causing progressive deterioration after a preclinical phase. The pathophysiology of early brain abnormalities around disease onset is largely unknown. Some preclinical mutation carriers (PMC) show structural or metabolic changes on brain imaging

  8. Juvenile Huntington's disease: a case report and literature review.

    Science.gov (United States)

    Reyes Molón, L; Yáñez Sáez, R M; López-Ibor Alcocer, M I

    2010-01-01

    Huntington's disease is the most frequent neurodegenerative disease with a prevalence of fewer than 10 cases per 10,000 inhabitants; the juvenile form is responsible for less than 10% of all cases. Huntington's disease belongs to the group known as "triad syndromes," which evolve with cognitive, motor and neuropsychiatric manifestations. Around 30% of patients debut with behavioral symptoms, which are a major challenge for management by patients, families, and caregivers. Huntington's disease (HD) is reviewed and a case of juvenile onset is reported in this article. The characteristics of juvenile-onset Huntington's disease (HD) differ from those of adult-onset HD, as chorea does not occur, although bradykinesia, dystonia, and signs of cerebellar disorder, such as rigidity, are present, frequently in association with convulsive episodes and psychotic manifestations.

  9. Genetics Home Reference: Huntington disease-like syndrome

    Science.gov (United States)

    ... 21915. Citation on PubMed Wild EJ, Tabrizi SJ. Huntington's disease phenocopy syndromes. Curr Opin Neurol. 2007 Dec;20(6):681-7. Review. Citation on PubMed Reviewed : August 2008 Published : August ...

  10. Episodic Memory Decline in Huntington's Disease, A Binding Deficit?

    NARCIS (Netherlands)

    El Haj, M.; Caillaud, M.; Fasotti, L.; Verny, C.; Allain, P.

    2013-01-01

    Background: Huntington's disease (HD) is characterized by episodic memory deterioration. Objective: Our paper investigates the cognitive mechanisms that might underlie this decline. To this aim, we tested two executive hypotheses, the binding and the inhibition hypotheses. Methods: Fifteen HD patien

  11. O paradigma de Huntington e o realismo político Huntington's paradigm and political realism

    Directory of Open Access Journals (Sweden)

    José R. Novaes Chiappin

    1994-12-01

    Full Text Available Examina-se a proposta de Huntington de um novo paradigma da política internacional (centrado na idéia de "civilizações" em substituição ao paradigma do realismo. Demonstra-se que se trata, na realidade, de um subparadigma do realismo e, portanto, a ele subordinado. Aplica-se isso à mudança da concepção estratégica de "contenção", que passa a aplicar-se às civilizações não-ocidentais e não mais ao expansionismo soviético.Huntington's proposal of a new paradigm for international politics (focused on the idea of "civilizations", meant to replace the paradigm of realism, is examined. It is shown that the proposed new paradigm should in fact be viewed as as sub-paradigm of the realist one. In particular, it is pointed out that Huntington's proposal, in a realist vein, draws on the idea of "containment", which is now directed (instead of its former target, the soviet expansionism to non-Western civilizations.

  12. Subtle changes among presymptomatic carriers of the Huntington's disease gene

    OpenAIRE

    S. Kirkwood; Siemers, E.; Hodes, M; Conneally, P; Christian, J.; Foroud, T

    2000-01-01

    OBJECTIVES—To compare the neurological and psychometric characteristics of presymptomatic gene carriers and non-gene carriers who are at risk for developing Huntington's disease so as to characterise early signs of disease and to identify markers of neurological function that could be used to assess the impact of experimental therapies on the progression of disease, even among those who are clinically presymptomatic.
METHODS—A sample of people at risk for Huntington's dis...

  13. Samuel Huntington, Clash of Civilizations: A Book Review

    OpenAIRE

    Yrd. Doç. Dr. Cengiz Kartýn

    2015-01-01

    Samuel Huntington's The Clash of Civilizations was written in 1993 by him. Study is a work containing the article and the responses to this article. Work is composed of two main parts. Makes the important point of this study is the process that began with the September 11 attacks by some strategists that is exactly the way towards a world where it is hidden in Huntington's fictionalized articulate.

  14. Linking SNPs to CAG repeat length in Huntington's disease patients.

    Science.gov (United States)

    Liu, Wanzhao; Kennington, Lori A; Rosas, H Diana; Hersch, Steven; Cha, Jang-Ho; Zamore, Phillip D; Aronin, Neil

    2008-11-01

    Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.

  15. Neuropathological diagnosis and CAG repeat expansion in Huntington's disease.

    OpenAIRE

    Xuereb, J H; MacMillan, J C; Snell, R; Davies, P.; Harper, P S

    1996-01-01

    OBJECTIVE--To correlate the degree of CAG repeat expansion with neuropathological findings in Huntington's disease. METHODS--The CAG repeat polymorphism was analysed in a large series of brain samples from 268 patients with a clinical diagnosis of Huntington's disease in which full neuropathological data was available. RESULTS--Analysis by polymerase chain reaction was successful in 63% of samples (169 of 268). Repeat expansions were detected in 152 of 153 (99%) samples with a neuropathologic...

  16. Levodopa responsive parkinsonism in an adult with Huntington's disease

    OpenAIRE

    Racette, B.; Perlmutter, J

    1998-01-01

    A patient is reported on with Huntington's disease who, as an adult, first developed severe parkinsonism with bradykinesia, rigidity, postural instability and festinating gait. His clinical signs were similar to those of the Westphal variant of Huntington's disease except that he also had resting tremor and a supranuclear gaze palsy. Magnetic resonance imaging showed caudate and putamen atrophy. Genetic analysis disclosed 49 triple CAG repeats in allele 1 and 17 in allele 2 ...

  17. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O;

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development....

  18. [Olanzapine improves chorea in patients with Huntington's disease].

    Science.gov (United States)

    Jiménez-Jiménez, F J; de Toledo, M; Puertas, I; Barón, M; Zurdo, M; Barcenilla, B

    The main treatment for choreatic movements associated to Huntington s disease are the neuroleptic drugs, however, its use causes long term troubles. We describe two patients with a predominantly choreic Huntington s disease, who experience improvement of choreatic movements after introduction of olanzapine to their treatment, being this drug well tolerated. The improvement of chorea suggests that olanzapine has a dopaminergic D2 receptors blocking action.

  19. Reconstructing the Aliso Canyon natural gas leak incident

    Science.gov (United States)

    Duren, R. M.; Yadav, V.; Verhulst, K. R.; Thorpe, A. K.; Hopkins, F. M.; Prasad, K.; Kuai, L.; Thompson, D. R.; Wong, C.; Sander, S. P.; Mueller, K. L.; Nehrkorn, T.; Lee, M.; Hulley, G. C.; Johnson, W. R.; Aubrey, A. D.; Whetstone, J. R.; Miller, C. E.

    2016-12-01

    Natural gas is a key energy source and presents significant policy challenges including energy reliability and the potential for fugitive methane emissions. The well blowout reported in October 2015 at the Aliso Canyon underground gas storage facility near Porter Ranch, California and subsequent uncontrolled venting was the largest single anthropogenic methane source known to date. Multiple independent estimates indicate that this super-emitter source rivaled the normal methane flux of the entire South Coast Air Basin (SoCAB) for several months until the well was plugged. The complexity of the event and logistical challenges - particularly in the initial weeks - presented significant barriers to estimating methane losses. Additionally, accounting for total gas lost is necessary but not sufficient for understanding the sequence of events and the controlling physical processes. We used a tiered system of observations to assess methane emissions from the Aliso Canyon incident. To generate a complete flux time-series, we applied tracer-transport models and tracer-tracer techniques to persistent, multi-year atmospheric methane observations from a network of surface in-situ and remote-sensing instruments. To study the fine spatio-temporal structure of methane plumes and understand the changing source morphology, we conducted intensive mobile surface campaigns, deployed airborne imaging spectrometers, requested special observations from two satellites, and employed large eddy simulations. Through a synthesis analysis we assessed methane fluxes from Aliso Canyon before, during and after the reported incident. We compared our fine scale spatial data with bottom-up data and reports of activity at the facility to better understand the controlling processes. We coordinated with California stakeholder agencies to validate and interpret these results and to consider the potential broader implications on underground gas storage and future priorities for methane monitoring.

  20. Geo-hazard by sediment mass movements in submarine canyons

    Science.gov (United States)

    Ghaith, Afif; Fakhri, Milad; Ivaldi, Roberta; Ciavola, Paolo

    2017-04-01

    Submarine mass movements and their consequences are of major concern for coastal communities and infrastructures but also for the exploitation and the development of seafloor resources. Elevated awareness of the need for better understanding of the underwater mass movement is coupled with great advances in underwater mapping technologies over the past two decades. The seafloor in the Nahr Ibrahim and Saida regions (Lebanon) is characterized by deep canyons, reaching one thousand meters depths in proximity of the coast. Signs of submarine mass movement instability related to these canyons create a connection between shallow and deep water. The presence of these canyons in a tectonically active area generates a particular drained mechanism to the sediment in form of mass movement and slumping. Identification of potential areas where slope movements could be triggered requires data with high spatial resolution. Since this area is poorly explored, in the framework of an international project between Lebanese Navy, Lebanese National Center for Marine Sciences, University of Ferrara and Italian Hydrographic Institute, we analyse the morpho-bathymetric and sedimentological characters of the coastal and shelf sectors. Multibeam echosounder and sub-bottom profiler acoustic systems calibrated with ground truths (sediment grab and core samples) allow us to characterize the nature of seafloor and sub-seafloor with particular detail to the geotechnical properties of sediments and high resolution seismic stratigraphy of the shallow layers. The detection of particular undersea features provides detail maps which are in support to littoral morpho-dynamics, coastal transport and sediment budget. Multilayer hydro-oceanographic map, referring to the seafloor dynamics in connection with deep water environment and drainage system, in accordance to the International Hydrographic Standards and nautical supports, are produced. This high resolution multibeam bathymetry dataset, integrated

  1. Morphology of Neptune Node Sites, Barkley Canyon, Cascadia Margin

    Science.gov (United States)

    Lundsten, E. M.; Anderson, K.; Paull, C. K.; Caress, D. W.; Thomas, H. J.; Riedel, M.

    2014-12-01

    High-resolution multibeam bathymetry and chirp seismic reflection profiles collected with MBARI's mapping autonomous underwater vehicle reveal the fine-scale morphology and shallow seafloor structure of the flanks and floor of Barkley Canyon on the Cascadia continental margin off British Columbia. The surveys characterize the environment surrounding three nodes on the Neptune Canada cabled observatory located within the canyon. The canyon floor between 960 and 1020 m water depth lacks channeling and contains ≥ 24 m of acoustically uniform sediment fill, which is ponded between the canyon's steep sidewalls. The fill overlies a strong reflector that outlines an earlier, now buried, canyon floor channel system. Debris flow tongues contain meter scale blocks sticking-up through the fill. Apparently the present geomorphology surrounding the Canyon Axis node in 985 m is attributable to local debris flows, rather than organized down canyon processes. In the survey area the canyon sidewalls extend ~300 m up and in places the slope of the canyons sides exceed 40°. Both the Hydrate node in 870 m water depths and the Mid-Canyon node at 890 m are located on a headland that forms intermediate depth terraces on the canyon's western flank. While the seafloor immediately surrounding the Mid-canyon node is smooth, the Hydrate node is marked by 10 circular mounds up to 2 m high and 10 m in diameter, presumable associated with hydrate formation. Although wedges of sediment drape occur in places on the canyon sides, the chirp profiles show no detectible sediment drape at either node site and suggest these nodes are situated on older, presumably pre-Quaternary strata. The lack of reflectors in the chirp profiles indicates most of the canyon's sidewalls are largely sediment-bare. Lineations in the bathymetry mark the exposed edges of truncated beds. Rough, apparently fresh textures, within slide scarps show the importance of erosion on the development of the canyon flanks.

  2. Cold-Water Corals and Anthropogenic Impacts in La Fonera Submarine Canyon Head, Northwestern Mediterranean Sea.

    Directory of Open Access Journals (Sweden)

    Galderic Lastras

    Full Text Available We assess the occurrence and extent of cold-water coral (CWC species Madrepora oculata and Dendrophyllia cornigera, as well as gorgonian red coral Corallium rubrum, in La Fonera canyon head (Northwestern Mediterranean Sea, as well as human impacts taking place in their habitats. Occurrence is assessed based on Remotely Operated Vehicle (ROV video imaging. Terrain classification techniques are applied to high-resolution swath bathymetric data to obtain semi-automatic interpretative maps to identify the relationship between coral distribution patterns and canyon environments. A total of 21 ROV immersions were carried out in different canyon environments at depths ranging between 79 and 401 m. Large, healthy colonies of M. oculata occur on abrupt, protected, often overhanging, rocky sections of the canyon walls, especially in Illa Negra branch. D. cornigera is sparser and evenly distributed at depth, on relatively low sloping areas, in rocky but also partially sedimented areas. C. rubrum is most frequent between 100 and 160 m on highly sloping rocky areas. The probable extent of CWC habitats is quantified by applying a maximum entropy model to predict habitat suitability: 0.36 km2 yield M. oculata occurrence probabilities over 70%. Similar predictive models have been produced for D. cornigera and C. rubrum. All ROV transects document either the presence of litter on the seafloor or pervasive trawling marks. Nets and longlines are imaged entangled on coral colonies. Coral rubble is observed at the foot of impacted colonies. Some colonies are partially covered by sediment that could be the result of the resuspension generated by bottom trawling on neighbouring fishing grounds, which has been demonstrated to be responsible of daily increases in sediment fluxes within the canyon. The characteristics of the CWC community in La Fonera canyon are indicative that it withstands high environmental stress of both natural and human origin.

  3. A case report of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Anita Choudhary

    2017-09-01

    Full Text Available Huntington disease (HD is a progressive neurodegenerative disorder, characterized by autosomal dominant inheritance, movement disorder, dementia, and behavioural disturbances. It is caused by a mutation in IT15 gene on chromosome 4p16.3, which leads to unstable CAG trinucleotide repeat expansion. The onset of juvenile HD occurs before the 2nd decade of life and comprises approximately 10% of total HD patients. Juvenile HD differs in symptomatology and is usually transmitted from paternal side with genetic anticipation phenomenon. Magnetic resonance imaging (MRI of the brain shows specific changes of early affection of caudate nucleus and putamen. Multidisciplinary approach with symptomatic treatment of specific symptoms is the current available management. Gene editing and gene silencing treatment are under trial. Hereby, we introduce a case of an 8-year-old boy, who presented with typical symptoms of juvenile HD, positive family history with genetic anticipation phenomenon and characteristic MRI findings.

  4. Plants and phytochemicals for Huntington's disease.

    Science.gov (United States)

    Choudhary, Sunayna; Kumar, Puneet; Malik, Jai

    2013-07-01

    Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor dysfunction, including chorea and dystonia, emotional disturbances, memory, and weight loss. The medium spiny neurons of striatum and cortex are mainly effected in HD. Various hypotheses, including molecular genetics, oxidative stress, excitotoxicity, metabolic dysfunction, and mitochondrial impairment have been proposed to explain the pathogenesis of neuronal dysfunction and cell death. Despite no treatment is available to fully stop the progression of the disease, there are treatments available to help control the chorea. The present review deals with brief pathophysiology of the disease, plants and phytochemicals that have shown beneficial effects against HD like symptoms. The literature for the current review was collected using various databases such as Science direct, Pubmed, Scopus, Sci-finder, Google Scholar, and Cochrane database with a defined search strategy.

  5. The choreography of neuroinflammation in Huntington's disease.

    Science.gov (United States)

    Crotti, Andrea; Glass, Christopher K

    2015-06-01

    Currently, the concept of 'neuroinflammation' includes inflammation associated with neurodegenerative diseases, in which there is little or no infiltration of blood-derived immune cells into the brain. The roles of brain-resident and peripheral immune cells in these inflammatory settings are poorly understood, and it is unclear whether neuroinflammation results from immune reaction to neuronal dysfunction/degeneration, and/or represents cell-autonomous phenotypes of dysfunctional immune cells. Here, we review recent studies examining these questions in the context of Huntington's disease (HD), where mutant Huntingtin (HTT) is expressed in both neurons and glia. Insights into the cellular and molecular mechanisms underlying neuroinflammation in HD may provide a better understanding of inflammation in more complex neurodegenerative disorders, and of the contribution of the neuroinflammatory component to neurodegenerative disease pathogenesis.

  6. Huntington's Disease: Pathogenic Mechanisms and Therapeutic Targets.

    Science.gov (United States)

    Wright, Dean J; Renoir, Thibault; Gray, Laura J; Hannan, Anthony J

    2017-01-01

    Huntington's disease (HD) is a tandem repeat disorder involving neurodegeneration and a complex combination of symptoms. These include psychiatric symptoms, cognitive deficits culminating in dementia, and the movement disorder epitomised by motor signs such as chorea. HD is caused by a CAG repeat expansion encoding an extended tract of the amino acid glutamine in the huntingtin protein. This polyglutamine expansion appears to induce a 'change of function', possibly a 'gain of function', in the huntingtin protein, which leads to various molecular and cellular cascades of pathogenesis. In the current review, we will briefly describe these broader aspects of HD pathogenesis, but will then focus on specific aspects where there are substantial bodies of experimental evidence, including oxidative stress, mitochondrial dysfunction, glutamatergic dysfunction and neuroinflammation. Furthermore, we will review recent preclinical therapeutic approaches targeting some of these pathogenic pathways, their clinical implications and future directions.

  7. Huntington's Disease: Relationship Between Phenotype and Genotype.

    Science.gov (United States)

    Sun, Yi-Min; Zhang, Yan-Bin; Wu, Zhi-Ying

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease with the typical manifestations of involuntary movements, psychiatric and behavior disorders, and cognitive impairment. It is caused by the dynamic mutation in CAG triplet repeat number in exon 1 of huntingtin (HTT) gene. The symptoms of HD especially the age at onset are related to the genetic characteristics, both the CAG triplet repeat and the modified factors. Here, we reviewed the recent advancement on the genotype-phenotype relationship of HD, mainly focus on the characteristics of different expanded CAG repeat number, genetic modifiers, and CCG repeat number in the 3' end of CAG triplet repeat and their effects on the phenotype. We also reviewed the special forms of HD (juvenile HD, atypical onset HD, and homozygous HD) and their phenotype-genotype correlations. The review will aid clinicians to predict the onset age and disease course of HD, give the genetic counseling, and accelerate research into the HD mechanism.

  8. Huntington's Disease: Calcium Dyshomeostasis and Pathology Models.

    Science.gov (United States)

    Kolobkova, Y A; Vigont, V A; Shalygin, A V; Kaznacheyeva, E V

    2017-01-01

    Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and mental impairment. At the molecular level, HD is caused by a mutation in the first exon of the gene encoding the huntingtin protein. The mutation results in an expanded polyglutamine tract at the N-terminus of the huntingtin protein, causing the neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the main causes of the disease, which underlies the great interest in the problem among experts in molecular physiology. Recent studies have focused on the development of animal and insect HD models, as well as patient-specific induced pluripotent stem cells (HD-iPSCs), to simulate the disease's progression. Despite a sesquicentennial history of HD studies, the issues of diagnosis and manifestation of the disease have remained topical. The present review addresses these issues.

  9. Cerebrospinal Fluid Biomarkers for Huntington's Disease.

    Science.gov (United States)

    Byrne, Lauren M; Wild, Edward J

    2016-01-01

    Cerebrospinal fluid (CSF) is enriched in brain-derived components and represents an accessible and appealing means of interrogating the CNS milieu to study neurodegenerative diseases and identify biomarkers to facilitate the development of novel therapeutics. Many such CSF biomarkers have been proposed for Huntington's disease (HD) but none has been validated for clinical trial use. Across many studies proposing dozens of biomarker candidates, there is a notable lack of statistical power, consistency, rigor and validation. Here we review proposed CSF biomarkers including neurotransmitters, transglutaminase activity, kynurenine pathway metabolites, oxidative stress markers, inflammatory markers, neuroendocrine markers, protein markers of neuronal death, proteomic approaches and mutant huntingtin protein itself. We reflect on the need for large-scale, standardized CSF collections with detailed phenotypic data to validate and qualify much-needed CSF biomarkers for clinical trial use in HD.

  10. Contribution of Neuroepigenetics to Huntington's Disease.

    Science.gov (United States)

    Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

    2017-01-01

    Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.

  11. Neuronal Ca(2+) dyshomeostasis in Huntington disease.

    Science.gov (United States)

    Giacomello, Marta; Oliveros, Juan C; Naranjo, Jose R; Carafoli, Ernesto

    2013-01-01

    The expansion of the N-terminal poly-glutamine tract of the huntingtin (Htt) protein is responsible for Huntington disease (HD). A large number of studies have explored the neuronal phenotype of HD, but the molecular aethiology of the disease is still very poorly understood. This has hampered the development of an appropriate therapeutical strategy to at least alleviate its symptoms. In this short review, we have focused our attention on the alteration of a specific cellular mechanism common to all HD models, either genetic or induced by treatment with 3-NPA, i.e. the cellular dyshomeostasis of Ca(2+). We have highlighted the direct and indirect (i.e. transcriptionally mediated) effects of mutated Htt on the maintenance of the intracellular Ca(2+) balance, the correct modulation of which is fundamental to cell survival and the disturbance of which plays a key role in the death of the cell.

  12. Tidal Signatures of the Benthic Nepheloid Layer (BNL) in the Gaoping/Kaoping Submarine Canyon off Southwestern Taiwan

    Science.gov (United States)

    Liu, J. T.; Lee, I.; Wang, Y.

    2008-12-01

    nonlinear. The generation of nonlinearity could be through the flow-topography interaction and through the alternate entrainment and deposition of suspended sediment in the course of a semidiurnal tidal cycle. At this point, the relationship among barotropic tides, internal tides, and typhoon events and BNL is not clear. The role of the BNL in the sediment transport and sedimentation in submarine canyons worldwide is also not fully understood. Studies on these subjects in the KPSC are in progress.

  13. Fault tree analysis of the F&H Canyon Exhaust Systems at the Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Low, J.M.; Marshall, K.M.

    1993-10-01

    The Canyon Exhaust System (CES) for the F&H Canyon chemical Separations Facilities are considered safety class items (SCIs). SCIs are defined in DOE Order 6430.1A as systems, components, and structures, including portions of process systems, whose failure could adversely affect the environment or safety and health of the public. As such, any modification to SCIs must be carefully reviewed for impact to safety. During the last year, the Savannah River Technology Center of WSRC has been requested to perform two major evolutions on the Canyon Exhaust Systems. These evaluations include an Upgrade to Canyon Exhaust System (UCES) Project for both F&H Areas and a Backfit analysis for a standby diesel generator in F-Area. The purpose of the first evaluation was to evaluate the impact of cost reduction options on the UCES reliability. The purpose of the second analysis was to provide justification for not upgrading an existing standby diesel generator to meet current safety class standards.

  14. 78 FR 7775 - Boulder Canyon Project

    Science.gov (United States)

    2013-02-04

    .... \\1\\ 75 FR 57912 (September 23, 2010). \\2\\ 133 FERC ] 62,229. The proposed BCP electric service base... in power rate adjustments (10 CFR part 903) were published on September 18, 1985 (50 FR 87835... Area Power Administration Boulder Canyon Project AGENCY: Western Area Power Administration, DOE....

  15. ACUMEN 2012: Atlantic Canyons Undersea Mapping Expeditions

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Between February and August 2012, a team of NOAA and external partners will conduct a mapping ‘blitz’ focused on deepwater canyons off the northeastern...

  16. Submarine canyons off the Coromandel coast

    Digital Repository Service at National Institute of Oceanography (India)

    Varadachari, V.V.R.; Nair, R.R.; Murty, P.S.N.

    During the 26th Cruise of I.N.S. `KISTNA', a bathymetric survey was carried out in some detail off the Pondicherry coast. This survey has revealed the existence of three sets of distinctly separate canyons between Cuddalore and Palar River...

  17. Metabolic disruption identified in the Huntington's disease transgenic sheep model.

    Science.gov (United States)

    Handley, Renee R; Reid, Suzanne J; Patassini, Stefano; Rudiger, Skye R; Obolonkin, Vladimir; McLaughlan, Clive J; Jacobsen, Jessie C; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2016-02-11

    Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease.

  18. Anatomy of La Jolla submarine canyon system; offshore southern California

    Science.gov (United States)

    Paull, C.K.; Caress, D.W.; Lundsten, E.; Gwiazda, R.; Anderson, K.; McGann, M.; Conrad, J.; Edwards, B.; Sumner, E.J.

    2013-01-01

    An autonomous underwater vehicle (AUV) carrying a multibeam sonar and a chirp profiler was used to map sections of the seafloor within the La Jolla Canyon, offshore southern California, at sub-meter scales. Close-up observations and sampling were conducted during remotely operated vehicle (ROV) dives. Minisparker seismic-reflection profiles from a surface ship help to define the overall geometry of the La Jolla Canyon especially with respect to the pre-canyon host sediments. The floor of the axial channel is covered with unconsolidated sand similar to the sand on the shelf near the canyon head, lacks outcrops of the pre-canyon host strata, has an almost constant slope of 1.0° and is covered with trains of crescent shaped bedforms. The presence of modern plant material entombed within these sands confirms that the axial channel is presently active. The sand on the canyon floor liquefied during vibracore collection and flowed downslope, illustrating that the sediment filling the channel can easily fail even on this gentle slope. Data from the canyon walls help constrain the age of the canyon and extent of incision. Horizontal beds of moderately cohesive fine-grained sediments exposed on the steep canyon walls are consistently less than 1.232 million years old. The lateral continuity of seismic reflectors in minisparker profiles indicate that pre-canyon host strata extend uninterrupted from outside the canyon underneath some terraces within the canyon. Evidence of abandoned channels and point bar-like deposits are noticeably absent on the inside bend of channel meanders and in the subsurface of the terraces. While vibracores from the surface of terraces contain thin (< 10 cm) turbidites, they are inferred to be part of a veneer of recent sediment covering pre-canyon host sediments that underpin the terraces. The combined use of state of the art seafloor mapping and exploration tools provides a uniquely detailed view of the morphology within an active submarine canyon.

  19. Creationism in the Grand Canyon, Texas Textbooks

    Science.gov (United States)

    Folger, Peter

    2004-01-01

    AGU President Bob Dickinson, together with presidents of six other scientific societies, have written to Joseph Alston, Superintendent of Grand Canyon National Park, pointing out that a creationist book, The Grand Canyon: A Different View, is being sold in bookstores within the borders of the park as a scientific explanation about Grand Canyon geologic history. President Dickinson's 16 December letter urges that Alston clearly separate The Grand Canyon: A Different View from books and materials that discuss the legitimate scientific understanding of the origin of the Grand Canyon. The letter warns the Park Service against giving the impression that it approves of the anti-science movement known as young-Earth creationism, or that it endorses the advancement of religious tenets disguised as science. The text of the letter is on AGU's Web site http://www.agu.org/sci_soc/policy/sci_pol.html. Also, this fall, AGU sent an alert to Texas members about efforts by intelligent design creationists aimed at weakening the teaching of biological evolution in textbooks used in Texas schools. The alert pointed scientists to a letter, drafted by AGU, together with the American Institute of Physics, the American Physical Society, the Optical Society of America, and the American Astronomical Society, that urged the Texas State Board of Education to adopt textbooks that presented only accepted, peer-reviewed science and pedagogical expertise. Over 550 scientists in Texas added their names to the letter (http://www.agu.org/sci_soc/policy/texas_textbooks.pdf ), sent to the Board of Education on 1 November prior to their vote to adopt a slate of new science textbooks. The Board voted 11-5 in favor of keeping the textbooks free of changes advocated by groups supporting intelligent design creationism.

  20. Quantitative 7T phase imaging in premanifest Huntington disease.

    Science.gov (United States)

    Apple, A C; Possin, K L; Satris, G; Johnson, E; Lupo, J M; Jakary, A; Wong, K; Kelley, D A C; Kang, G A; Sha, S J; Kramer, J H; Geschwind, M D; Nelson, S J; Hess, C P

    2014-09-01

    In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease. © 2014 by American Journal of Neuroradiology.

  1. Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

    NARCIS (Netherlands)

    Cubo, E.; Gonzalez, M.; Puerto, I. del; Yebenes, J.G. de; Arconada, O.F.; Gabriel y Galan, J.M.; Kremer, H.P.H.; Warrenburg, B.P.C. van de

    2012-01-01

    BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disea

  2. 75 FR 33617 - Notice of Proposed Settlement Agreement and Opportunity for Public Comment: West Huntington Spill...

    Science.gov (United States)

    2010-06-14

    ... AGENCY Notice of Proposed Settlement Agreement and Opportunity for Public Comment: West Huntington Spill... United States Department of Justice on behalf of EPA, in connection with the West Huntington Spill Site, Huntington, West Virginia (``Site''). DATES: Written comments on the proposed settlement agreement must...

  3. Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

    NARCIS (Netherlands)

    Cubo, E.; Gonzalez, M.; Puerto, I. del; Yebenes, J.G. de; Arconada, O.F.; Gabriel y Galan, J.M.; Kremer, H.P.H.; Warrenburg, B.P.C. van de

    2012-01-01

    BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's

  4. Disease stage, but not sex, predicts depression and psychological distress in Huntington's disease

    DEFF Research Database (Denmark)

    Dale, Maria; Maltby, John; Shimozaki, Steve

    2016-01-01

    OBJECTIVE: Depression and anxiety significantly affect morbidity in Huntington's disease. Mice. models of Huntington's disease have identified sex differences in mood-like behaviours that vary across disease lifespan, but this interaction has not previously been explored in humans with Huntington...

  5. Westernmost Grand Canyon incision: Testing thermochronometric resolution

    Science.gov (United States)

    Fox, M.; Tripathy-Lang, A.; Shuster, D. L.; Winn, C.; Karlstrom, K.; Kelley, S.

    2017-09-01

    The timing of carving of Grand Canyon has been debated for over 100 years with competing endmember hypotheses advocating for either a 70 Ma (;old;) or history and corresponding estimates of landscape evolution have been in debate. In particular, 4He/3He thermochronometric data record the distribution of radiogenic 4He (from the 238U, 235U and 232Th decay series) within an individual apatite crystal and thus are highly sensitive to the thermal history corresponding to landscape evolution. However, there are several complicating factors that make interpreting such data challenging in geologic scenarios involving reheating. Here, we analyze new data that provide measures of the cooling of basement rocks at the base of westernmost Grand Canyon, and use these data as a testbed for exploring the resolving power and limitations of 4He/3He data in general. We explore a range of thermal histories and find that these data are most consistent with a ;young; Grand Canyon. A problem with the recovered thermal history, however, is that burial temperatures are under predicted based on sedimentological evidence. A solution to this problem is to increase the resistance of alpha recoil damage to annealing, thus modifying He diffusion kinetics, allowing for higher temperatures throughout the thermal history. This limitation in quantifying radiation damage (and hence crystal retentivity) introduces non-uniqueness to interpreting time-temperature paths in rocks that resided in the apatite helium partial retention zone for long durations. Another source of non-uniqueness, is due to unknown U and Th distributions within crystals. We show that for highly zoned with a decrease in effective U of 20 ppm over the outer 80% of the radius of the crystal, the 4He/3He data could be consistent with an ;old; canyon model. To reduce this non-uniqueness, we obtain U and Th zonation information for separate crystals from the same rock sample through LA-ICP-MS analysis. The observed U and Th

  6. 3D View of Grand Canyon, Arizona

    Science.gov (United States)

    2000-01-01

    The Grand Canyon is one of North America's most spectacular geologic features. Carved primarily by the Colorado River over the past six million years, the canyon sports vertical drops of 5,000 feet and spans a 445-kilometer-long stretch of Arizona desert. The strata along the steep walls of the canyon form a record of geologic time from the Paleozoic Era (250 million years ago) to the Precambrian (1.7 billion years ago).The above view was acquired by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument aboard the Terra spacecraft. Visible and near infrared data were combined to form an image that simulates the natural colors of water and vegetation. Rock colors, however, are not accurate. The image data were combined with elevation data to produce this perspective view, with no vertical exaggeration, looking from above the South Rim up Bright Angel Canyon towards the North Rim. The light lines on the plateau at lower right are the roads around the Canyon View Information Plaza. The Bright Angel Trail, which reaches the Colorado in 11.3 kilometers, can be seen dropping into the canyon over Plateau Point at bottom center. The blue and black areas on the North Rim indicate a forest fire that was smoldering as the data were acquired on May 12, 2000.Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of International Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. Dr. Anne Kahle at NASA's Jet Propulsion Laboratory, Pasadena, Calif., is the U.S. Science team leader; Moshe Pniel of JPL is the project manager. ASTER is the only high resolution imaging sensor on Terra. The primary goal of the ASTER mission is to obtain high-resolution image data in 14 channels over the entire land surface, as

  7. Huntington's disease: from molecular pathogenesis to clinical treatment.

    Science.gov (United States)

    Ross, Christopher A; Tabrizi, Sarah J

    2011-01-01

    Huntington's disease is a progressive, fatal, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, which encodes an abnormally long polyglutamine repeat in the huntingtin protein. Huntington's disease has served as a model for the study of other more common neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. These disorders all share features including: delayed onset; selective neuronal vulnerability, despite widespread expression of disease-related proteins during the whole lifetime; abnormal protein processing and aggregation; and cellular toxic effects involving both cell autonomous and cell-cell interaction mechanisms. Pathogenic pathways of Huntington's disease are beginning to be unravelled, offering targets for treatments. Additionally, predictive genetic testing and findings of neuroimaging studies show that, as in some other neurodegenerative disorders, neurodegeneration in affected individuals begins many years before onset of diagnosable signs and symptoms of Huntington's disease, and it is accompanied by subtle cognitive, motor, and psychiatric changes (so-called prodromal disease). Thus, Huntington's disease is also emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset.

  8. Investigational agents for the management of Huntington's disease.

    Science.gov (United States)

    Müller, Thomas

    2017-02-01

    An inherited, chronic progressive, neurodegenerative disorder is Huntington's disease, characterized by motor, cognitive, and psychiatric symptoms. Predictive genetic testing allows earlier diagnosis and identification of gene carriers for Huntington's disease. These individuals are ideal candidates for testing of therapeutic interventions for disease modification. Areas covered: According to queries in Pubmed, Embase and clinical register databases, research and clinical studies emerge on symptomatic and neuroprotective therapies in Huntington's disease. This review discusses novel agents for symptomatic therapy and disease modification. They are currently in phase I and II of drug development Expert opinion: There are promising, safe and well tolerated compounds for amelioration of motor and neuropsychiatric symptoms, but their efficacy still needs to be proven in clinical trials. Deterioration of mutant huntingtin expression, antiapoptotic or cell death inhibition as disease modifying concepts was efficacious in models of Huntington's disease. However, the risk for clinical trial failures is high not only due to ineffectiveness of the tested agent. Negative study outcomes may also result from design misconceptions, underestimation of the heterogeneity of Huntington's disease, too short study durations and too small study cohorts.

  9. Gravity instabilities in the Dohrn Canyon (Bay of Naples, Southern Tyrrhenian Sea): potential wave and run-up (tsunami) reconstruction from a fossil submarine landslide

    Science.gov (United States)

    di Fiore, Vincenzo; Aiello, Gemma; D'Argenio, Bruno

    2011-02-01

    We discuss a mathematical model for wave and run-up generated submarine landslides in the canyons of the Bay of Naples (Magnaghi-Dohrn canyon system). The morpho-bathymetry and submarine gravity instabilities of such incisions have been investigated through the interpretation of a high resolution DEM. The canyons are located in a sector of the bay where there is a variable interaction of volcanic activity (Phlegrean Fields and Ischia and Procida Islands) with sedimentary processes due to the Sarno-Sebeto rivers. At present the Naples canyon-system is inactive, as is shown by the Holocene sedimentary drapes deposited during the present sea-level highstand, but gravity instabilities occurred in the recent past at the canyons' heads. In particular the Dohrn Canyon is characterized by a double regressive head, while the Magnaghi Canyon shows a trilobate head, formed by the junction of three main tributary channels and coincident with the retreat of the shelf break around the 140 m isobath. The results of a simulation of failures in the above source areas show that the amplitude of wave run-up, expressed in terms of the sea floor depth percentage, may range up to 2.5 % of the water depth at the sea bottom.

  10. Topographic change detection at select archeological sites in Grand Canyon National Park, Arizona, 2007–2010

    Science.gov (United States)

    Collins, Brian D.; Corbett, Skye C.; Fairley, Helen C.; Minasian, Diane L.; Kayen, Robert; Dealy, Timothy P.; Bedford, David R.

    2012-01-01

    collected two new datasets in April and September 2010 and processed and improved upon existing methods to generate high-accuracy (3 to 5 cm vertical change threshold) topographic change-detection maps for 10 survey areas encompassing 9 archeological sites along the Colorado River corridor. We also used terrestrial lidar techniques to investigate several other metrics for studying archeological site stability, including monitoring cultural structures and artifacts and remotely measuring cryptobiotic soil crust areas. Our topographic change results indicate that 9 of 10 survey areas showed signs of either erosion, deposition, or both during the 2007–2010 time interval and that these changes can be linked to a variety of geomorphic processes, primarily overland flow gullying and aeolian sand transport. In several cases, large (>50 cm) vertical change occurred, and in one case, more than 100 m3 of sediment was eroded. Further, for all sites monitored throughout the river corridor during this time period, the overall signal was related to erosion rather than deposition. These results highlight the potential for rapid archeological site change in Grand Canyon. Whereas the topographic change results presented herein provide the highest level of change detection yet performed on entire archeological sites in Grand Canyon, additional work in combining these results with site-specific weather, hydrology, and geomorphology data is needed to provide a more thorough understanding of the causes of the documented topographic changes. Linking lidar-derived measurements of topographic changes with these other data sources should provide land managers with a scientific basis for making management decisions regarding archeological resources in Grand Canyon National Park and assist in answering open questions regarding the influence that sediment-depleted flows from Glen Canyon Dam have on archeological site stability.

  11. Surprise and Opportunity for Learning in Grand Canyon: the Glen Canyon Dam Adaptive Management Program

    Directory of Open Access Journals (Sweden)

    Theodore S. Melis

    2015-09-01

    Full Text Available With a focus on resources of the Colorado River ecosystem below Glen Canyon Dam, the Glen Canyon Dam Adaptive Management Program has included a variety of experimental policy tests, ranging from manipulation of water releases from the dam to removal of non-native fish within Grand Canyon National Park. None of these field-scale experiments has yet produced unambiguous results in terms of management prescriptions. But there has been adaptive learning, mostly from unanticipated or surprising resource responses relative to predictions from ecosystem modeling. Surprise learning opportunities may often be viewed with dismay by some stakeholders who might not be clear about the purpose of science and modeling in adaptive management. However, the experimental results from the Glen Canyon Dam program actually represent scientific successes in terms of revealing new opportunities for developing better river management policies. A new long-term experimental management planning process for Glen Canyon Dam operations, started in 2011 by the U.S. Department of the Interior, provides an opportunity to refocus management objectives, identify and evaluate key uncertainties about the influence of dam releases, and refine monitoring for learning over the next several decades. Adaptive learning since 1995 is critical input to this long-term planning effort. Embracing uncertainty and surprise outcomes revealed by monitoring and ecosystem modeling will likely continue the advancement of resource objectives below the dam, and may also promote efficient learning in other complex programs.

  12. Turbulent ventilation of a street canyon

    DEFF Research Database (Denmark)

    Nielsen, Morten

    2000-01-01

    A selection of turbulence data corresponding to 185 days of field measurements has een analysed. The non-ideal building geometry influenced the circulation patterns in the street canyon and the largest average vertical velocities were observed in the wake of an unbroken line of buildings. The sta......A selection of turbulence data corresponding to 185 days of field measurements has een analysed. The non-ideal building geometry influenced the circulation patterns in the street canyon and the largest average vertical velocities were observed in the wake of an unbroken line of buildings...... small, and this suggests that most of the velocity fluctuations were fairly local and not caused by unsteady street vortices. The observed velocities scaled with the ambient wind speed except under low-wind conditions....

  13. Single sperm analysis of the trinucleotide repeat in the Huntington`s disease gene

    Energy Technology Data Exchange (ETDEWEB)

    Leeflang, E.P.; Zhang, L.; Hubert, R. [Univ. of Southern California, Los Angeles, CA (United States)] [and others

    1994-09-01

    Huntington`s disease (HD) is one of several genetic diseases caused by trinucleotide repeat expansion. The CAG repeat is very unstable, with size changes occurring in more than 80% of transmissions. The degree of instability of this repeat in the male germline can be determined by analysis of individual sperm cells. An easy and sensitive PCR assay has been developed to amplify this trinucleotide repeat region from single sperm using two rounds of PCR. As many as 90% of the single sperm show amplification for the HD repeat. The PCR product can be easily detected on an ethidium bromide-stained agarose gel. Single sperm samples from an HD patient with 18 and 49 repeats were studied. We observed size variations for the expanded alleles while the size of the normal allele in sperm is very consistent. We did not detect any significant bias in the amplification of normal alleles over the larger HD alleles. Our preliminary study supports the observation made by PCR of total sperm that instability of the HD trinucleotide repeat occurs in the germline. HD preimplantation diagnosis on single embryo blastomeres may also possible.

  14. 22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium.

    Science.gov (United States)

    Baig, Sheharyar S; Strong, Mark; Rosser, Elisabeth; Taverner, Nicola V; Glew, Ruth; Miedzybrodzka, Zosia; Clarke, Angus; Craufurd, David; Quarrell, Oliver W

    2016-10-01

    Huntington's disease (HD) is a progressive neurodegenerative condition. At-risk individuals have accessed predictive testing via direct mutation testing since 1993. The UK Huntington's Prediction Consortium has collected anonymised data on UK predictive tests, annually, from 1993 to 2014: 9407 predictive tests were performed across 23 UK centres. Where gender was recorded, 4077 participants were male (44.3%) and 5122 were female (55.7%). The median age of participants was 37 years. The most common reason for predictive testing was to reduce uncertainty (70.5%). Of the 8441 predictive tests on individuals at 50% prior risk, 4629 (54.8%) were reported as mutation negative and 3790 (44.9%) were mutation positive, with 22 (0.3%) in the database being uninterpretable. Using a prevalence figure of 12.3 × 10(-5), the cumulative uptake of predictive testing in the 50% at-risk UK population from 1994 to 2014 was estimated at 17.4% (95% CI: 16.9-18.0%). We present the largest study conducted on predictive testing in HD. Our findings indicate that the vast majority of individuals at risk of HD (>80%) have not undergone predictive testing. Future therapies in HD will likely target presymptomatic individuals; therefore, identifying the at-risk population whose gene status is unknown is of significant public health value.

  15. A study on the trinucleotide repeat associated with Huntington`s disease in the Chinese

    Energy Technology Data Exchange (ETDEWEB)

    Bing-wen Soong; Jih-tsuu Wang [Neurological Institute, Taipei (Taiwan, Province of China)

    1994-09-01

    Analysis of the polymorphic (CAG)n repeat in the hungingtin gene in the chinese confirmed the presence of an expanded repeat on all Huntington`s disease chromosomes. Measurement of the specific CAG repeat sequence in 34 HD chromosomes from 15 unrelated families and 190 control chromosomes from the Chinese population showed a range from 9 to 29 repeats in normal subjects and 40 to 58 in affected subjects. The size distributions of normal and affected alleles did not overlap. A clear correlation bewteen early onset of symptoms and very high repeat number was seen, but the spread of the age-at-onset in the major repeat range producing characteristic HD it too wide to be of diagnostic value. There was also variability in the transmitted repeat size for both sexes in the HD size range. Maternal HD alleles showed a moderate instability with a preponderance of size decrease, while paternal HD alleles had a tendency to increase in repeat size on transmission, the degree of which appeared proportional to the initial size.

  16. The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population.

    Science.gov (United States)

    Baine, Fiona K; Krause, Amanda; Greenberg, L Jacquie

    2016-01-01

    Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa. © 2016 S. Karger AG, Basel.

  17. “SHANGRI-LA” IN NUJIANG CANYON

    Institute of Scientific and Technical Information of China (English)

    李晓勤

    2004-01-01

    A few hours' drive took me to a place called Bingzhongluo,the largest piece of flatland in the canyon,where the Nujiang River takes two abrupt turns, forming the first bend on the Nujiang River,which is a best known scenic spot in China. At the side of the river there is a tablet of pure white marble inscribed with words painted in bright red,reading:“Bingzhongluo,the Shangri-La.”

  18. Horseshoe Canyon and Mannville case studies

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, T. [Trident Exploration Corp., Calgary, AB (Canada)

    2005-07-01

    This presentation outlined the coalbed methane (CBM) activities underway at Trident Exploration Corp. with particular reference to the results achieved in the Horseshoe Canyon and Mannville formations. In order to be commercially successful, companies drilling for unconventional gas must spend millions of dollars testing and evaluating different drilling, completion and production methods. Early regional exploration programs are also important to gain an understanding of the economics of each particular play. The Horseshoe Canyon play extends for more than 250 miles and is 100 miles wide. Most of the wells drilled to date have been drilled by a few large operators, including Trident. Most of the Horseshoe Canyon is greatly underpressured and there may not be enough gas in place in some areas to justify drilling for the coals alone. The coal properties within the Horseshoe Canyon vary widely from well to well. The total coal thickness ranges from less than 5 to more than 30 metres. The number of seams per well varies from 8 to 25 and the average seam thickness is 1 metre. The well depths range from 150 metres in the east to more than 900 metres in the west. The Mannville is among the largest CBM resources in western Canada, with estimates of up to several hundred trillion cubic feet of recoverable reserves. Trident operates the largest and longest running Mannville pilot at Corbett, northwest of Edmonton. The pilot wells have shown the area has good quality coal, excellent gas content and good permeability. As of February 2005, there are 47 active producers, 2 disposal wells and 3 observation wells. Average production per well is 1.5 E{sup 3}m{sup 3} gas per day and 17 m{sup 3} water per day. Declining water production on individual wells along with limited gas production and high reservoir pressure suggests that the wells are progressively damaged. Initial experience with horizontal wells at Corbett has proved to be encouraging. figs.

  19. Exclusion testing in pregnancy for Huntington's disease.

    Science.gov (United States)

    Tyler, A; Quarrell, O W; Lazarou, L P; Meredith, A L; Harper, P S

    1990-01-01

    The results of DNA analysis are presented for a series of 90 couples, with one partner at 50% risk for Huntington's disease (HD), who were referred for exclusion testing in pregnancy over a three year period. Thirty-seven couples were studied in detail. The aims of the study were to evaluate attitudes towards prenatal testing, before pregnancy and afterwards, and the effectiveness of our counseling and methods of organising the service. Problems which could arise in relation to presymptomatic testing are documented. It is concluded that exclusion testing is a valuable form of prediction for some couples, particularly where family structure does not permit prediction for the person at risk. The need for intensive counselling was highlighted by the difficulties experienced by many couples in understanding how the test worked. Particular ethical and organisational problems may arise which require careful consideration beforehand and some recommendations are made. The proportion of couples who will continue to request exclusion testing as pre-symptomatic testing becomes more widely applicable remains unknown. PMID:2145437

  20. Cell-based technologies for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mônica Santoro Haddad

    Full Text Available ABSTRACT Huntington's disease (HD is a fatal genetic disorder, which causes the progressive breakdown of neurons in the human brain. HD deteriorates human physical and mental abilities over time and has no cure. Stem cell-based technologies are promising novel treatments, and in HD, they aim to replace lost neurons and/or to prevent neural cell death. Herein we discuss the use of human fetal tissue (hFT, neural stem cells (NSCs of hFT origin or embryonic stem cells (ESCs and induced pluripotent stem cells (IPSCs, in clinical and pre-clinical studies. The in vivo use of mesenchymal stem cells (MSCs, which are derived from non-neural tissues, will also be discussed. All these studies prove the potential of stem cells for transplantation therapy in HD, demonstrating cell grafting and the ability to differentiate into mature neurons, resulting in behavioral improvements. We claim that there are still many problems to overcome before these technologies become available for HD patient treatment, such as: a safety regarding the use of NSCs and pluripotent stem cells, which are potentially teratogenic; b safety regarding the transplantation procedure itself, which represents a risk and needs to be better studied; and finally c technical and ethical issues regarding cells of fetal and embryonic origin.

  1. Comprehension of prosody in Huntington's disease.

    Science.gov (United States)

    Speedie, L J; Brake, N; Folstein, S E; Bowers, D; Heilman, K M

    1990-07-01

    Patients with Huntington's Disease (HD) who were without dementia were compared to unilateral stroke patients and controls as previously reported in 1983, to discover if they had a prosodic defect. Subjects were presented tape-recorded speech filtered sentences and asked to indicate the tone of voice as happy, sad or angry (affective prosody), or as a question, command or statement (propositional prosody). HD patients were impaired in comprehension of both types of prosody compared to controls but were not different from stroke patients. A second study compared early HD patients with at-risk siblings and spouse controls on comprehension of affective and propositional prosody, discrimination of both types of prosody, rhythm discrimination and tonal memory (Seashore tests). HD patients were impaired in both comprehension and discrimination of all types of prosody. HD patients were less accurate than at-risk patients on the tonal memory task but not on the rhythm discrimination task. These findings suggest compromise in ability to understand the more subtle prosodic aspects of communication which may contribute to social impairment of HD patients very early in the course of the disease.

  2. Hypothalamic-endocrine aspects in Huntington's disease.

    Science.gov (United States)

    Petersén, Asa; Björkqvist, Maria

    2006-08-01

    Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic-pituitary-adrenal axis occurs as well as pancreatic beta-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions.

  3. DNA instability in replicating Huntington's disease lymphoblasts

    Directory of Open Access Journals (Sweden)

    Frati Luigi

    2009-02-01

    Full Text Available Abstract Background The expanded CAG repeat in the Huntington's disease (HD gene may display tissue-specific variability (e.g. triplet mosaicism in repeat length, the longest mutations involving mitotic (germ and glial cells and postmitotic (neurons cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths. Results Although most lymphoblastoid cell lines (88% showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting in cis to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations. Conclusion Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.

  4. Genetic diagnosis of Huntington's disease: cases report

    Institute of Scientific and Technical Information of China (English)

    Liao Ting-ting; Wu Wei; Wan Qi; Cui Yu-gui; Liu Jia-yin

    2011-01-01

    Objective:To assess the efficiency of the PCR combined DNA sequencing to ascertain CAG repeat size of Huntington's disease(HD)gene as for gene diagnosis of HD.Method:Three patients with HD were diagnosed genetically with the technology of polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis by assessing the CAG repeat size of HD gene.DNA sequencing then was used as verification test for HD gene.Results:Nine members of three nuclear families were included in this study,three patients were HD proband.In those families,CAG repeats of all spouse of propositus were in normal range.CAG repeats of all propositus and their descendants with the normal allele were in normal range,while CAG copy number of the other mobigenous allele was obviously abnormal.Conclusion:PCR combined DNA sequencing can be used to effectively ascertain CAG repeat of HD gene.CAG-repeat expansion mutations were accounted for 99% of HD cases,so HD can be accurately diagnosed by this method.

  5. Genetic Testing for Huntington's Disease in Parkinsonism.

    Science.gov (United States)

    Rahman, M S; Nagai, Y; Popiel, H A; Fujikake, N; Okamoto, Y; Ahmed, M U; Islam, M A; Islam, M T; Ahmed, S; Rahman, K M; Uddin, M J; Dey, S K; Ahmed, Q; Hossain, M A; Jahan, N; Toda, T

    2010-10-01

    The study was conducted to find out Huntington's disease (HD) by genetic analysis from those presenting with parkinsonism in the Neurology department of Mymensingh Medical College & Hospital. A sample of about 5ml blood was collected by veni puncture in EDTA tube with informed consent from 9 patients & 7 healthy individuals after approval of the institutional ethics committee for genetic study. The neurological disorder along with a complete history and physical findings were recorded in a prescribed questionnaire by the neurologists of Mymensingh Medical College & Hospital. Extraction of genomic DNA from the venous blood using FlexiGene DNA kit (Qiagen, Japan) was performed in Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh. The extracted DNA was stored and accumulated and then these DNA were sent to Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School, Suita, Osaka 565 0871, Japan for PCR and further analysis. PCR amplification of the CAG repeat in the 1T15 gene was performed with primers HD1 and HD3. HD PCR products revealed the DNA product of about 110bp (no. of CAG repeats=21) to 150bp (no. of CAG repeats=34) in both healthy individual and suspected PD patient DNA.

  6. Pridopidine for the treatment of Huntington's disease.

    Science.gov (United States)

    Shannon, Kathleen M

    2016-01-01

    Huntington's disease is a rare dominantly-inherited neurodegenerative disease with motor, cognitive and behavioral manifestations. It results from an expanded unstable trinucleotide repeat in the coding region of the huntingtin gene. Treatment is symptomatic, but a poor evidence baseguides selection of therapeutic agents. Non-choreic derangements in voluntary movement contribute to overall motor disability and are poorly addressed by current therapies. Pridopidine is a novel agent in the dopidine class believed to have 'state dependent' effects at dopamine receptors, thus show promise in the treatment of these disorders of voluntary movement. This review discusses the pharmacokinetics and pharmacodynamics of pridopidine and reviews clinical trials supporting development of the drug for HD. This information was culled from literature searches for dopidines, pridopidine, and HD experimental therapeutics in PubMed and at http://www.clinicaltrials.org . There is a compelling need to discover new treatments for motor disability in HD, particularly for non-choreic motor symptoms. While pridopidine failed to achieve its primary efficacy outcomes in 2 large trials, reproducible effects on secondary motor outcomes have fueled an ongoing trial studying higher doses and more focused clinical endpoints. This and phase III trials will define define the utility of pridopidine for HD.

  7. Lessons Learned from the Transgenic Huntington's Disease Rats

    Directory of Open Access Journals (Sweden)

    Rinske Vlamings

    2012-01-01

    Full Text Available Huntington's disease (HD is a fatal inherited disorder leading to selective neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment to slow down or to stop the disease. There is also no therapy to effectively reduce the symptoms. In the investigation of novel therapies, different animal models of Huntington's disease, varying from insects to nonhuman primates, have been created and used. Few years ago, the first transgenic rat model of HD, carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter, was introduced. We have been using this animal model in our research and review here our experience with the behavioural, neurophysiological, and histopathological phenotype of the transgenic Huntington's disease rats with relevant literature.

  8. Variation within the Huntington's disease gene influences normal brain structure.

    Directory of Open Access Journals (Sweden)

    Mark Mühlau

    Full Text Available Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.

  9. The marine soundscape of the Perth Canyon

    Science.gov (United States)

    Erbe, Christine; Verma, Arti; McCauley, Robert; Gavrilov, Alexander; Parnum, Iain

    2015-09-01

    The Perth Canyon is a submarine canyon off Rottnest Island in Western Australia. It is rich in biodiversity in general, and important as a feeding and resting ground for great whales on migration. Australia's Integrated Marine Observing System (IMOS) has moorings in the Perth Canyon monitoring its acoustical, physical and biological oceanography. Data from these moorings, as well as weather data from a near-by Bureau of Meteorology weather station on Rottnest Island and ship traffic data from the Australian Maritime Safety Authority were correlated to characterise and quantify the marine soundscape between 5 and 3000 Hz, consisting of its geophony, biophony and anthrophony. Overall, biological sources are a strong contributor to the soundscape at the IMOS site, with whales dominating seasonally at low (15-100 Hz) and mid frequencies (200-400 Hz), and fish or invertebrate choruses dominating at high frequencies (1800-2500 Hz) at night time throughout the year. Ships contribute significantly to the 8-100 Hz band at all times of the day, all year round, albeit for a few hours at a time only. Wind-dependent noise is significant at 200-3000 Hz; winter rains are audible underwater at 2000-3000 Hz. We discuss how passive acoustic data can be used as a proxy for ocean weather. Passive acoustics is an efficient way of monitoring animal visitation times and relative densities, and potential anthropogenic influences.

  10. Assessing GPS Constellation Resiliency in an Urban Canyon Environment

    Science.gov (United States)

    2015-03-26

    Assessing GPS Constellation Resiliency in an Urban Canyon Environment THESIS MARCH 2015 Aaron J. Burns, Second Lieutenant, USAF AFIT-ENS-MS-15-M-138...URBAN CANYON ENVIRONMENT THESIS Presented to the Faculty Department of Operational Sciences Graduate School of Engineering and Management Air Force...UNLIMITED. AFIT-ENS-MS-15-M-138 ASSESSING GPS CONSTELLATION RESILIENCY IN AN URBAN CANYON ENVIRONMENT Aaron J. Burns, B.S. Second Lieutenant, USAF Committee

  11. Brittle deformation and hoodoo development in Bryce Canyon National Park

    Science.gov (United States)

    Haddon, E. K.; Webb, C.; McNitt, J.; Pollock, G. L.; Davis, L.; MacLean, J. S.

    2015-12-01

    Bryce Canyon is a dramatic southeast-facing escarpment located in the transition zone between the Basin and Range Province and the Colorado Plateau. Stream erosion of the Paleocene-to-Eocene Claron Formation generates vast amphitheaters and alcoves replete with elaborate fins, windowed walls, and hoodoos from Fairyland to Bryce Point. Geomorphic models of hoodoo development describe the influence of differential weathering and ice wedging along systematic vertical fractures formed during uplift of the Colorado Plateau. Conjugate shear fractures in the footwall of the south-vergent Rubys Inn thrust fault may provide additional preexisting weaknesses intersecting the predominantly flat-lying strata. During a summer 2015 GeoCorpsTM America internship, we investigated the contribution of joint sets to focused erosion of exposed fins and hoodoo development in Bryce Canyon National Park. Our field mapping documents the nature and spatial distribution of known fractures as well as a previously undocumented third generation characterized by steeply-dipping conjugates and zones of distributed deformation. Evidence for normal reactivation of contractional structures in the Sevier River drainage (MacLean, 2014) suggests that distributed deformation evolved during Basin and Range extension, possibly associated with the nearby Paunsaugunt fault. Cross-cutting relations among fracture sets suggest modest uplift and vertical jointing prior to collapse of the Marysvale volcanic complex (~22-20 Ma) and more recent Basin and Range extension. Spatial trends in fracture density illustrate a systematic increase in vertical, shear fractures, and reactivated zones to the north, proximal to thrust faulting. The increase in fracture density leads to accelerated weathering and erosion, with a corresponding increase in windows, hoodoos, and gentle slopes. While erosional windows commonly develop along vertical fractures intersecting relatively weak lithologies, approximately 60% of the 130

  12. Capability to Recover Plutonium-238 in H-Canyon/HB-Line - 13248

    Energy Technology Data Exchange (ETDEWEB)

    Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R. [Savannah River Nuclear Solutions, LLC, Savannah River Site, Aiken, SC 29802 (United States)

    2013-07-01

    Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site had previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np- 237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-Canyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase- 3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ∼2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare equipment

  13. Tetrabenazine is neuroprotective in Huntington's disease mice

    Directory of Open Access Journals (Sweden)

    Tang Tie-Shan

    2010-04-01

    Full Text Available Abstract Background Huntington's disease (HD is a neurodegenerative disorder caused by a polyglutamine (polyQ expansion in Huntingtin protein (Htt. PolyQ expansion in Httexp causes selective degeneration of striatal medium spiny neurons (MSN in HD patients. A number of previous studies suggested that dopamine signaling plays an important role in HD pathogenesis. A specific inhibitor of vesicular monoamine transporter (VMAT2 tetrabenazine (TBZ has been recently approved by Food and Drug Administration for treatment of HD patients in the USA. TBZ acts by reducing dopaminergic input to the striatum. Results In previous studies we demonstrated that long-term feeding with TBZ (combined with L-Dopa alleviated the motor deficits and reduced the striatal neuronal loss in the yeast artificial chromosome transgenic mouse model of HD (YAC128 mice. To further investigate a potential beneficial effects of TBZ for HD treatment, we here repeated TBZ evaluation in YAC128 mice starting TBZ treatment at 2 months of age ("early" TBZ group and at 6 months of age ("late" TBZ group. In agreement with our previous studies, we found that both "early" and "late" TBZ treatments alleviated motor deficits and reduced striatal cell loss in YAC128 mice. In addition, we have been able to recapitulate and quantify depression-like symptoms in TBZ-treated mice, reminiscent of common side effects observed in HD patients taking TBZ. Conclusions Our results further support therapeutic value of TBZ for treatment of HD but also highlight the need to develop more specific dopamine antagonists which are less prone to side-effects.

  14. Everyday cognition in prodromal Huntington disease.

    Science.gov (United States)

    Williams, Janet K; Kim, Ji-In; Downing, Nancy; Farias, Sarah; Harrington, Deborah L; Long, Jeffrey D; Mills, James A; Paulsen, Jane S

    2015-03-01

    Assessment of daily functions affected by cognitive loss in prodromal Huntington's disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings. Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made. CFA revealed good fit of a 5-factor model having a global factor (total score), and subfactors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group. Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants' for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  15. Induced neural stem cells as a means of treatment in Huntington's disease.

    Science.gov (United States)

    Choi, Kyung-Ah; Hong, Sunghoi

    2017-08-09

    Huntington's disease (HD) is an inherited neurodegenerative disease characterized by chorea, dementia, and depression caused by progressive nerve cell degeneration, which is triggered by expanded CAG repeats in the huntingtin (Htt) gene. Currently, there is no cure for this disease, nor is there an effective medicine available to delay or improve the physical, mental, and behavioral severities caused by it. Areas covered: In this review, the authors describe the use of induced neural stem cells (iNSCs) by direct conversion technology, which offers great advantages as a therapeutic cell type to treat HD. Expert opinion: Cell conversion of somatic cells into a desired stem cell type is one of the most promising treatments for HD because it could be facilitated for the generation of patient-specific neural stem cells. The induced pluripotent stem cells (iPSCs) have a powerful potential for differentiation into neurons, but they may cause teratoma formation due to an undifferentiated pluripotent stem cell after transplantation Therefore, direct conversion of somatic cells into iNSCs is a promising alternative technology in regenerative medicine and the iNSCs may be provided as a therapeutic cell source for Huntington's disease.

  16. An improved assay for the determination of Huntington`s disease allele size

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, C.; Klinger, K.; Miller, G. [Intergrated Genetics, Framingham, MA (United States)

    1994-09-01

    The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra- or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.

  17. The Counselor and Genetic Disease: Huntington's Disease as a Model.

    Science.gov (United States)

    Wexler, Nancy S.

    This speech offers a brief description of Huntington's Disease (HD): its causes, symptoms, and incidence. It then concentrates on the psychological problems of persons one of whose parents had the disease, and the role of the counselor in helping these humans cope with their fears about contacting it themselves. A relatively detailed case study is…

  18. Age, CAG repeat length, and clinical progression in Huntington's disease.

    Science.gov (United States)

    Rosenblatt, Adam; Kumar, Brahma V; Mo, Alisa; Welsh, Claire S; Margolis, Russell L; Ross, Christopher A

    2012-02-01

    The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.

  19. Biological Markers of Cognition in Prodromal Huntington's Disease: A Review

    Science.gov (United States)

    Papp, Kathryn V.; Kaplan, Richard F.; Snyder, Peter J.

    2011-01-01

    Huntington's disease (HD), an autosomal-dominant genetic disorder, has historically been viewed as a degenerative movement disorder but it also includes psychiatric symptoms and progressive cognitive decline. There has been a lack of consensus in the literature about whether or not cognitive signs can be detected in carriers before clinical…

  20. Huntington II Simulation Program-POLUT. Teacher's Guide.

    Science.gov (United States)

    Braun, L.; And Others

    This teacher's guide is written to accompany the Huntington II Simulation Program - POLUT. POLUT is a program written in BASIC which provides simulation of the interaction between water and waste. It creates a context within which the user can control specific variables which effect the quality of a water resource. The teacher's guide provides…

  1. Exploring Genetic Factors Involved in Huntington Disease Age of Onset

    DEFF Research Database (Denmark)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel;

    2015-01-01

    Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of ...

  2. Clinical and genetic features of Huntington disease in Sri Lanka.

    Science.gov (United States)

    Sumathipala, Dulika S; Jayasekara, Rohan W; Dissanayake, Vajira H W

    2013-12-05

    Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka. Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics. Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.

  3. PSYCHIATRIC ASPECTS OF HUNTINGTON DISEASE – CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Mirela Batta

    2004-04-01

    Full Text Available Background. Huntington disease occurrs rarely, it can be encountered not only by neurologists and psychiatrists but also by other medical practitioners. Its characteristic features are involuntary movements, cognitive disorders and gradual development of dementia. Diagnosis is given on the basis of these clinical features, positive familial anamnesis, with the laboratory exclusion of other neuropsychiatric diseases and with the help of neuroimaging methods (in particular NMR. The disease can be only confirmed by means of genetic analysis.Patients and methods. In this article, four cases of patients with Huntington disease and diverse psychiatric disorders that were hospitalised at the psychiatric department of the Maribor General Hospital between October 2002 and March 2003 are described. All the patients fulfilled the valid criteria for the diagnosis of Huntington disease. However, they differed according to their accompanying psychiatric psychopathology, age and social problems.Conclusions. The purpose of this article is to draw attention to different psychiatric symptoms and clinical manifestations of Huntington disease that are often misleading in the diagnostic process. In addition, exigency of early diagnostics, guidelines for referrals to genetic testing and psychiatric monitoring of these patients are emphasised.

  4. Expression pattern of apoptosis-related markers in Huntington's disease

    NARCIS (Netherlands)

    Vis, José C; Schipper, Ellis; de Boer-van Huizen, Roelie T; Verbeek, Marcel M; de Waal, Rob M W; Wesseling, Pieter; ten Donkelaar, Hans J; Kremer, Berry

    2005-01-01

    Inappropriate apoptosis has been implicated in the mechanism of neuronal death in Huntington's disease (HD). In this study, we report the expression of apoptotic markers in HD caudate nucleus (grades 1-4) and compare this with controls without neurological disease. Terminal transferase-mediated biot

  5. 36 CFR 7.4 - Grand Canyon National Park.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Grand Canyon National Park. 7.4 Section 7.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.4 Grand Canyon National Park. (a)...

  6. Modeling the Effect of Wider Canyons on Urban Heating

    Directory of Open Access Journals (Sweden)

    Rizwan Ahmed Memon

    2011-04-01

    Full Text Available The k-? turbulence model is adopted in this study to simulate the impact of street canyon AR (Aspect Ratios on heating within street canyon. The two-dimensional model was validated for RANS (Reynolds Averaged Navier Stokes and energy transport equations. The validation process confirms that the results of the model for airtemperature and wind speed could be trusted. The application of the said model is carried out to ideal street canyons of ARs (ratio of building-height-to-street-width from 0.4 to 2 with the same boundary conditions. Notably, street canyon aspect ratio was calculated by varying the street width while keeping the building height constant. Results show that the weighted-average-air-temperature within AR 0.4 was around 0.8% (i.e. 2.4K higher than that within AR 2.0. Conversely, there was strong correlation (i.e., R2>0.9 between air temperature within the street canyon and street canyon AR. Results demonstrate stronger influence of vertical velocity on heating within street canyon. Evidently, increased vertical velocity decreased the temperatures. Conversely, temperatures were higher along the leeward side of the canyon in lower ARs.

  7. Wave run up in Zones of Underwater Canyons

    Directory of Open Access Journals (Sweden)

    Katline Koblev A. Julio

    2013-01-01

    Full Text Available The wave run up on coast and shore protection constructions in zones of underwater canyons is considered. The mathematical model of wave run up on the coast, considering distinctions in biases of underwater and surface parts of the coastal slope, allowing to receive setup parameters in zones of the underwater canyons, corresponding to data of supervision is offered.

  8. 78 FR 7810 - Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2013-02-04

    ... Bureau of Reclamation Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of Reclamation, Interior. ACTION: Notice of public meeting. SUMMARY: The Glen Canyon Dam Adaptive Management Work Group.... L. 102-575) of 1992. The AMP includes a Federal advisory committee, the AMWG, a technical work...

  9. 75 FR 34476 - Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2010-06-17

    ... Bureau of Reclamation Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of Reclamation... Interior (Secretary) is renewing the charter for the Glen Canyon Dam Adaptive Management Work Group. The purpose of the Adaptive Management Work Group is to advise and to provide recommendations to the...

  10. Adaptive Management of Glen Canyon Dam: Two Decades of Large Scale Experimental Treatments Intended to Benefit Resources of the Colorado River in Grand Canyon, USA

    Science.gov (United States)

    Melis, Theodore

    2010-05-01

    Glen Canyon Dam was closed in 1963, primarily to store water for the rapidly developing southwestern United States. The dam's hydropower plant, with a generating capacity of up to 1,300 megawatts of electrical energy, was initially operated without daily peaking constraints from 1966 to 1990, resulting in daily tides on the Colorado River through Grand Canyon National Park of up to 4 meters. The influences of Glen Canyon Dam's peaking operations on downstream river resources through Grand Canyon have been intensively studied for nearly four decades. Following experimental reoperation of the dam in summer 1990, and five years of studies associated with a major environmental impact statement, the Glen Canyon Dam Adaptive Management Program was created in 1997, to evaluate whether a new experimental flow regime, combined with other non-flow treatments, can mitigate the detrimental effects of the former hydropeaking flow regime. Experimental flow treatments associated with the program over the last two decades have included the adoption of hourly and daily operating rules that now govern and constrain hydropeaking, periodic release of experimental controlled floods to rebuild sandbar habitats along shorelines and occasional steady flow tests intended to benefit the river's endangered humpback chub; one of the endemic fish of the Colorado River basin that experienced a population decline following dam closure. Other non-flow experimental treatments being evaluated by the program include removal of nonnative fish species, such as rainbow trout and other exotic fish, as well as translocation of humpback chub into other habitats below the dam where they might successfully spawn. Since 1995, three controlled flood experiments have been released from the dam to determine whether the remaining sand supplies that enter the Colorado River below the dam (about 6 to 16 percent of the predam sand supply) can be managed to create and maintain sandbar habitats used by humpback chub

  11. Transfer processes in a simulated urban street canyon

    Science.gov (United States)

    Solazzo, E.; Britter, R. E.

    2007-07-01

    The transfer processes within and above a simulated urban street canyon were investigated in a generic manner. Computational fluid dynamics (CFD) was used to aid understanding and to produce some simple operational parameterisations. In this study we addressed specifically the commonly met situation where buoyancy effects arising from elevated surface temperatures are not important, i.e. when mechanical forces outweigh buoyancy forces. In a geophysical context this requires that some suitably defined Richardson number is small. From an engineering perspective this is interpreted as the important case when heat transfer within and above urban street canyons is by forced convection. Surprisingly, this particular scenario (for which the heat transfer coefficient between buildings and the flow is largest), has been less well studied than the situation where buoyancy effects are important. The CFD technique was compared against wind-tunnel experiments to provide model evaluation. The height-to-width ratio of the canyon was varied through the range 0.5 5 and the flow was normal to the canyon axis. By setting the canyon’s facets to have the same or different temperatures or to have a partial temperature distribution, simulations were carried out to investigate: (a) the influence of geometry on the flow and mixing within the canyon and (b) the exchange processes within the canyon and across the canyon top interface. Results showed that the vortex-type circulation and turbulence developed within the canyon produced a temperature distribution that was, essentially, spatially uniform (apart from a relatively thin near-wall thermal boundary layer) This allowed the temperatures within the street canyon to be specified by just one value T can , the canyon temperature. The variation of T can with wind speed, surface temperatures and geometry was extensively studied. Finally, the exchange velocity u E across the interface between the canyon and the flow above was calculated

  12. Employing Real Time PCR for the Diagnosis of Huntington Disease

    Directory of Open Access Journals (Sweden)

    Frouzandeh Mahjoubi

    2013-07-01

    Full Text Available Background: Huntington disease (HD is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia. The onset age of this disease is varied but usually is between the ages 40-50. Huntington's disease is caused by a triplet-repeat expansion in the IT15 gene (also known as huntingtin or HD which is located on chromosome 4p3.1. Since many clinical picture of HD are indistinguishable from other distinct genetic disorders molecular test such as PCR is the only way to confirm the disease. The aim of this study was to introduce a new and fast technique for the diagnosis of Huntington disease.Materials and Methods: Blood specimens were collected from individuals suspected for Huntington disease and also people with no symptoms and family history of this disease. DNAs were extracted according to standard protocol. Using conventional PCR, patient positive for Huntington disease were diagnosed. Then employing real time PCR on the basis of difference between melting temperature (Tm a new and fast diagnostic method was introduced.Results: Among 29 patients suspected to be HD only 8 HD patients were confirmed using PCR and real time PCR. The numbers of CAG repeat were between 42-50 and melting temperatures were between 89-92.Conclusion: The concept of using melting temperature in real time PCR protocol presented in here could be employed for the rapid diagnosis of the diseases caused by the increased in triple repeat sequences. It is fast, robust and has the potential use for the prenatal diagnosis.

  13. Major Superficial White Matter Abnormalities in Huntington's Disease

    Science.gov (United States)

    Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

    2016-01-01

    Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

  14. The Black Canyon of the Gunnison: Today and Yesterday

    Science.gov (United States)

    Hansen, Wallace R.

    1965-01-01

    Since the early visit of Captain John William Gunnison in the middle of the last century, the Black Canyon of the Gunnison has stirred mixed apprehension and wonder in the hearts of its viewers. It ranks high among the more awesome gorges of North America. Many great western canyons are as well remembered for their brightly colored walls as for their airy depths. Not so the Black Canyon. Though it is assuredly not black, the dark-gray tones of its walls and the hazy shadows of its gloomy depths join together to make its name well deserved. Its name conveys an impression, not a picture. After the first emotional impact of the canyon, the same questions come to the minds of most reflective viewers and in about the following order: How deep is the Black Canyon, how wide, how does it compare with other canyons, what are the rocks, how did it form, and how long did it take? Several western canyons exceed the Black Canyon in overall size. Some are longer; some are deeper; some are narrower; and a few have walls as steep. But no other canyon in North American combines the depth, narrowness, sheerness, and somber countenance of the Black Canyon. In many places the Black Canyon is as deep as it is wide. Between The Narrows and Chasm View in the Black Canyon of the Gunnison National Monument (fig. 15) it is much deeper than wide. Average depth in the monument is about 2,000 feet, ranging from a maximum of about 2,700 feet, north of Warner Point (which also is the greatest depth anywhere in the canyon), to a minimum of about 1,750 feet at The Narrows. The stretch of canyon between Pulpit Rock and Chasm View, including The Narrows, though the shallowest in the monument, is also the narrowest, has some of the steepest walls, and is, therefore, among the most impressive segments of the canyon (fig. 3). Profiles of several well-known western canyons are shown in figure 1. Deepest of these by far is Hells Canyon of the Snake, on the Idaho-Oregon border. Clearly, it dwarfs the

  15. Canyon conditions impact carbon flows in food webs of three sections of the Nazaré canyon

    NARCIS (Netherlands)

    Van Oevelen, D.; Soetaert, K.E.R.; Garcia, R.; De Stigter, H.; Cunha, M.R.; Pusceddu, A.; Danovaro, R.

    2011-01-01

    Submarine canyons transport large amounts of sediment and organic matter (OM) from the continental shelf to the abyssal plain. Three carbon-based food web models were constructed for the upper (300–750 m water depth), middle (2700–3500 m) and lower section (4000–5000 m) of the Nazaré canyon (eastern

  16. Hanging canyons of Haida Gwaii, British Columbia, Canada: Fault-control on submarine canyon geomorphology along active continental margins

    Science.gov (United States)

    Harris, Peter T.; Barrie, J. Vaughn; Conway, Kim W.; Greene, H. Gary

    2014-06-01

    Faulting commonly influences the geomorphology of submarine canyons that occur on active continental margins. Here, we examine the geomorphology of canyons located on the continental margin off Haida Gwaii, British Columbia, that are truncated on the mid-slope (1200-1400 m water depth) by the Queen Charlotte Fault Zone (QCFZ). The QCFZ is an oblique strike-slip fault zone that has rates of lateral motion of around 50-60 mm/yr and a small convergent component equal to about 3 mm/yr. Slow subduction along the Cascadia Subduction Zone has accreted a prism of marine sediment against the lower slope (1500-3500 m water depth), forming the Queen Charlotte Terrace, which blocks the mouths of submarine canyons formed on the upper slope (200-1400 m water depth). Consequently, canyons along this margin are short (4-8 km in length), closely spaced (around 800 m), and terminate uniformly along the 1400 m isobath, coinciding with the primary fault trend of the QCFZ. Vertical displacement along the fault has resulted in hanging canyons occurring locally. The Haida Gwaii canyons are compared and contrasted with the Sur Canyon system, located to the south of Monterey Bay, California, on a transform margin, which is not blocked by any accretionary prism, and where canyons thus extend to 4000 m depth, across the full breadth of the slope.

  17. Sediment transport to the deep canyons and open-slope of the western Gulf of Lions during the 2006 intense cascading and open-sea convection period

    Science.gov (United States)

    Palanques, A.; Puig, P.; Durrieu de Madron, X.; Sanchez-Vidal, A.; Pasqual, C.; Martín, J.; Calafat, A.; Heussner, S.; Canals, M.

    2012-11-01

    An array of mooring lines deployed between 300 and 1900 m depth along the Lacaze-Duthiers and Cap de Creus canyons and in the adjacent southern open slope was used to study the water and sediment transport on the western Gulf of Lions margin during the 2006 intense cascading period. Deep-reaching cascading pulses occurred in early January, in late January and from early March to mid-April. Dense water and sediment transport to the deep environments occurred not only through submarine canyons, but also along the southern open slope. During the deep cascading pulses, temporary upper and mid-canyon and open slope deposits were an important source of sediment to the deep margin. Significant sediment transport events at the canyon head only occurred in early January because of higher sediment availability on the shelf after the stratified and calm season, and in late February because of the interaction of dense shelf water cascading with a strong E-SE storm. During the January deep cascading pulses, increases in suspended sediment concentration within the canyon were greater and earlier at 1000 m depth than at 300 m depth, whereas during the March-April deep cascading pulses sediment concentration only increased below 300 m depth, indicating resuspension and redistribution of sediments previously deposited at upper and mid-canyon depths. Deeper than 1000 m depth, net fluxes show that most of the suspended sediment left the canyon and flowed along the southern open slope towards the Catalan margin, whereas a small part flowed down-canyon and was exported basinward. Additionally, on the mid- and lower-continental slope there was an increase in the near-bottom currents induced by deep open-sea convection processes and the propagation of eddies. This, combined with the arrival of deep cascading pulses, also generated moderate suspended sediment transport events in the deeper slope regions.

  18. Targeting the Cholinergic System to Develop a Novel Therapy for Huntington's Disease.

    Science.gov (United States)

    D'Souza, Gary X; Waldvogel, Henry J

    2016-12-15

    In this review, we outline the role of the cholinergic system in Huntington's disease, and briefly describe the dysfunction of cholinergic transmission, cholinergic neurons, cholinergic receptors and cholinergic survival factors observed in post-mortem human brains and animal models of Huntington's disease. We postulate how the dysfunctional cholinergic system can be targeted to develop novel therapies for Huntington's disease, and discuss the beneficial effects of cholinergic therapies in pre-clinical and clinical studies.

  19. Crime in Huntington's disease: a study of registered offences among patients, relatives, and controls

    OpenAIRE

    Jensen, P; Fenger, K; Bolwig, T; Sorensen, S. A.

    1998-01-01

    OBJECTIVES—Criminal behaviour has been described as a problem in Huntington's disease, but systematic studies including control groups have been missing. Based on information from Danish registries, rates and types of crime committed by patients with Huntington's disease, non-affected relatives, and controls were studied.
METHODS—99 males and 151 females with Huntington's disease were compared with 334 non-affected first degree relatives (134 men and 200 women) and to matche...

  20. 75 FR 76650 - Proposed Modification of Class E Airspace; Bryce Canyon, UT

    Science.gov (United States)

    2010-12-09

    ... Federal Aviation Administration 14 CFR Part 71 Proposed Modification of Class E Airspace; Bryce Canyon, UT...: This action proposes to modify Class E airspace at Bryce Canyon, UT to accommodate Area Navigation... airspace extending upward from 700 feet above the surface at Bryce Canyon Airport, Bryce Canyon,...

  1. Benthic foraminiferal thanatocoenoses from the Cap-Ferret Canyon area (NE Atlantic): A complex interplay between hydro-sedimentary and biological processes

    Science.gov (United States)

    Duros, P.; Jorissen, F. J.; Cesbron, F.; Zaragosi, S.; Schmidt, S.; Metzger, E.; Fontanier, C.

    2014-06-01

    Benthic foraminiferal thanatocoenoses from the Cap-Ferret Canyon area were studied in the >150-μm fraction of 4-5 cm deep sediment levels, at 13 stations. The shallowest station (151 m depth) is located at the shelf break, close to the canyon head. All other stations are located along two bathymetric transects: seven stations along the canyon axis between 300 and 3000 m depth, and five stations from 300 m to 2000 m depth along the southern flank of the canyon. The comparison between the live (Rose-Bengal-stained) and dead assemblages shows that biological (i.e. population dynamic) and taphonomic processes (i.e. test destruction, transport) generate important discrepancies between live and dead assemblages. An important question is, to what degree post-mortem transport and redeposition of foraminiferal tests contribute to the difference between living and dead assemblages? The composition of the thanatocoenoses (shells >150 μm from the inner continental shelf to the Cap-Ferret Canyon axis. However, transport of tests from outer shelf or upper canyon axis towards deeper sites occurs, as indicated by an increase of diversity indices of the dead fauna along the canyon axis. Moreover, some species (e.g., Cassidulina carinata) are observed in the living fauna restricted to the shallow sites, but occur in important amounts in the dead fauna at deeper stations, suggesting that these taxa have been transported from upper canyon stations toward deeper sites. Since Cap-Ferret Canyon is inactive in terms of massive sediment transport (i.e. gravity events), downslope transport of foraminiferal tests probably takes place in nepheloid layers. Downslope transports of foraminiferal tests may create important biases for the utilisation of paleoceanographic proxies using the assemblage characteristics and/or the geochemical composition of selected species. However, the study of dead assemblages along a canyon axis can give important clues about the sedimentary dynamics, especially

  2. Generations.

    Science.gov (United States)

    Chambers, David W

    2005-01-01

    Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession.

  3. Bottom-trawling along submarine canyons impacts deep sedimentary regimes

    Science.gov (United States)

    Paradis, Sarah; Puig, Pere; Masqué, Pere; Juan-Díaz, Xènia; Martín, Jacobo; Palanques, Albert

    2017-01-01

    Many studies highlight that fish trawling activities cause seafloor erosion, but the assessment of the remobilization of surface sediments and its relocation is still not well documented. These impacts were examined along the flanks and axes of three headless submarine canyons incised on the Barcelona continental margin, where trawling fleets have been operating for decades. Trawled grounds along canyon flanks presented eroded and highly reworked surface sediments resulting from the passage of heavy trawling gear. Sedimentation rates on the upper canyon axes tripled and quadrupled its natural (i.e. pre-industrialization) values after a substantial increase in total horsepower of the operating trawling fleets between 1960 s and 1970 s. These impacts affected the upper canyon reaches next to fishing grounds, where sediment resuspended by trawling can be transported towards the canyon axes. This study highlights that bottom trawling has the capacity to alter natural sedimentary environments by promoting sediment-starved canyon flanks, and by enhancing sedimentation rates along the contiguous axes, independently of canyons’ morphology. Considering the global mechanisation and offshore expansion of bottom trawling fisheries since the mid-20th century, these sedimentary alterations may occur in many trawled canyons worldwide, with further ecological impacts on the trophic status of these non-resilient benthic communities. PMID:28233856

  4. A Karst Connection model for Grand Canyon, Arizona, USA

    Science.gov (United States)

    Hill, C. A.; Eberz, N.; Buecher, R. H.

    2008-03-01

    A new model for the connection of the eastern and western Grand Canyon is proposed that involves westward flow of Redwall karst aquifer water under the Kaibab arch along the steepest hydraulic gradient to discharge at a structural low in a headward-eroding protowestern Grand Canyon. A karst-aquifer hydrological connection was first established between the eastern and western Grand Canyon, then collapse, incision, and headward erosion of the canyon followed this subterranean route. This proposed model is based on what is happening today on the northern Marble Platform where the Redwall-Muav aquifer is still intact. The three sinkhole/caves Ah Hol Sah, Indian Pit, and Black Abyss provide vertical flow routes down to the Redwall karst aquifer, joining water discharging from the Kaiparowits hydrologic basin to the Colorado River along the Fence Springs system. Projecting this process back in time and spatially southward, we propose that at around 6 Ma a sinkhole or sinkholes existed at the confluence of the Colorado River with the Little Colorado River. Little Colorado River water, then flowing northward to an interior lake basin ("Glen Lake") in southern Utah, became pirated down this sinkhole(s), thus causing a reversal of drainage (barbed tributaries) in Marble Canyon. Headward erosion then proceeded up Marble and Little Colorado Canyons from the collapsing sinkhole, with Marble Canyon incision breaching Glen Lake at around 5.5 Ma. This effected the "final connection" and total integration of the Colorado River from Colorado to the Gulf of California.

  5. CAPABILITY TO RECOVER PLUTONIUM-238 IN H-CANYON/HB-LINE

    Energy Technology Data Exchange (ETDEWEB)

    Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

    2013-01-09

    Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site had previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np-237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-anyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase-3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ~ 2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare equipment is

  6. Modelling photochemical pollutants in a deep urban street canyon: Application of a coupled two-box model approximation

    Science.gov (United States)

    Zhong, Jian; Cai, Xiao-Ming; Bloss, William James

    2016-10-01

    Air pollution associated with road transport is a major environmental issue in urban areas. Buildings in urban areas are the artificial obstacles to atmospheric flow and cause reduced ventilation for street canyons. For a deep street canyon, there is evidence of the formation of multiple segregated vortices, which generate flow regimes such that pollutants exhibit a significant contrast between these vortices. This results in poor air ventilation conditions at pedestrian level, thereby leading to elevated pollutant levels and potential breaches of air quality limits. The hypothesis of a well-mixed deep street canyon in the practical one-box model approach is shown to be inappropriate. This study implements a simplified simulation of the canyon volume: a coupled two-box model with a reduced chemical scheme to represent the key photochemical processes with timescales similar to and smaller than the turbulent mixing timescale. The two-box model captures the significant pollutant contrast between the lower and upper parts of a deep street canyon, particularly for NO2. Core important parameters (i.e. heterogeneity coefficient, exchange velocity and box height ratio) in the two-box model approach were investigated through sensitivity tests. The two-box model results identify the emission regimes and the meteorological conditions under which NO2 in the lower canyon (i.e. the region of interest for the assessment of human health effects) is in breach of air quality standards. Higher NO2 levels were observed for the cases with higher heterogeneity coefficients (the two boxes are more segregated), with lower exchange velocities (worse ventilation conditions), or with smaller box height ratios (reduced dilution possibly due to secondary smaller eddies in the lower canyon). The performance of a one-box model using the same chemical scheme is also evaluated against the two-box model. The one-box model was found to systematically underestimate NO2 levels compared with those in

  7. AUV Mapping and ROV Exploration of Los Frailes Submarine Canyon, Cabo Pulmo National Marine Park, Baja California Sur, Mexico

    Science.gov (United States)

    Troni, G.; Caress, D. W.; Graves, D.; Thomas, H. J.; Thompson, D.; Barry, J. P.; Aburto-Oropeza, O.; Johnson, A. F.; Lundsten, L.

    2015-12-01

    Los Frailes submarine canyon is located at the south boundary of the Cabo Pulmo National Marine Park on the southeast tip of the Baja California Peninsula. During the Monterey Bay Aquarium Research Institute (MBARI) 2015 Gulf of California expedition we used an autonomous underwater vehicle (AUV) to map this canyon from 50 m to 450 m depths, and then explored the canyon with a small remotely operated vehicle (ROV). This three day R/V Rachel Carson cruise was a collaboration with the Center for Marine Biodiversity and Conservation at Scripps Institution of Oceanography and the Centro para la Biodiversidad Marina y la Conservación in La Paz. The MBARI AUV D. Allan B. collected high resolution bathymetry, sidescan, and subbottom profiles of Los Frailes submarine canyon and part of the north Cabo Pulmo deep reef. In order to safely generate a 1-m lateral resolution multibeam bathymetry map in the nearshore high relief terrain, the mapping operations consisted of an initial short survey following the 100-m isobath followed by a series of short, incremental AUV missions located on the deep edge of the new AUV bathymetry. The MBARI Mini-ROV was used to explore the submarine canyon within the detailed map created by the MBARI AUV. The Mini-ROV is a 1.2-m-long, 350 kg, 1,500-m-depth-rated ROV designed and constructed by MBARI. It is controlled by six 600-watt thrusters and is equipped with a high-definition video camera and navigation sensors. This small ROV carries less accurate, lower cost navigation sensors than larger vehicles. We implemented new algorithms to localize combining Doppler velocity log sensor data and low-cost MEMS-based inertial sensor data with sporadic ultra-short baseline position measurements to provide a high accuracy position estimation. The navigation performance allowed us to colocate the ROV video imagery with the 1-m resolution bathymetric map of the submarine canyon. Upper Los Frailes Canyon is rugged and, aside from small sand pockets along

  8. Understanding how gravity flows shape deep-water channels. The Rhone delta canyon (Lake Geneva, Switzerland/France)

    Science.gov (United States)

    Corella, Juan Pablo; Loizeau, Jean Luc; Hilbe, Michael; le Dantec, Nicolas; Sastre, Vincent; Girardclos, Stéphanie

    2014-05-01

    Deep-water marine channels are highly dynamic environments due to the erosive power of sediment-laden currents that are continuously reshaping the morphology of these major sediment conduits. Proximal levees are prone to scarp failures generating gravity flows that can be transported thousands of kilometres from the original landslide. Nevertheless, the evolution of these underflows is still poorly understood because of the spatial scale of the processes and their difficult monitoring. For this reason, the smaller size, well-known boundary conditions and detailed bathymetric data makes Lake Geneva's sub-aquatic canyon in the Rhone delta an excellent analogue to understand these types of sedimentary processes that usually occur in deep-water channels in the marine realm. A multidisciplinary research strategy including innovative coring via MIR submersibles, in-situ geotechnical tests, geophysical and sedimentological analyses, as well as acquisition of different multibeam bathymetric data sets, were applied to understand the triggering processes, transport mechanisms and deposit features of gravity flows throughout the Rhone delta active canyon. The difference between two bathymetric surveys in 1986 and 2000 revealed an inversion in the topography of the distal active canyon, as a former distal canyon was transformed into a mound-like structure. A 12 m-thick layer was deposited in the canyon and modified the sediment transfer conduit. Sediment cores from this deposit were retrieved in-situ in 2002 and 2011 via the "F.-A. Forel" and Russian MIR submersibles, respectively. These cores contained a homogeneous, sandy material. Its sediment texture, grain-size, high density and shear strength, and low water content suggests that it corresponds to a debris-flow deposit that possibly took place after the initiation of a mass movement due to a scarp failure in proximal areas of the canyon. In addition, in-situ geotechnical tests on the modern canyon floor have shown a soft

  9. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.

    Science.gov (United States)

    2012-08-03

    Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. Here, The HD Consortium reports the generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls. Microarray profiling revealed CAG-repeat-expansion-associated gene expression patterns that distinguish patient lines from controls, and early onset versus late onset HD. Differentiated HD neural cells showed disease-associated changes in electrophysiology, metabolism, cell adhesion, and ultimately cell death for lines with both medium and longer CAG repeat expansions. The longer repeat lines were however the most vulnerable to cellular stressors and BDNF withdrawal, as assessed using a range of assays across consortium laboratories. The HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a human stem cell platform for screening new candidate therapeutics.

  10. Huntington disease in black Zimbabwean families living near the Mozambique border.

    Science.gov (United States)

    Scrimgeour, E M; Pfumojena, J W

    1992-12-01

    Huntington disease (HD) was identified in a black (Bantu) family living in the Manicaland region of Zimbabwe near the border with Mozambique. The pedigree included 11 affected individuals in 4 generations. There were 2 other probable HD patients from 2 unrelated black families in the same region. The prevalence rate of HD in this region of Zimbabwe was estimated to be 0.5-1 per 100,000. HD could have been introduced by Portuguese colonists from Mozambique, or by other European visitors, possibly before 1875. DNA studies may ultimately indicate if HD was introduced to this community, or if it arose by mutation. HD was previously reported in Zimbabwean blacks in 1978, when 4 cases of juvenile HD were described in a Bantu family with no apparent history of the disease.

  11. Annotated bibliography for the humpback chub (Gila cypha) with emphasis on the Grand Canyon population.

    Energy Technology Data Exchange (ETDEWEB)

    Goulet, C. T.; LaGory, K. E.; Environmental Science Division

    2009-10-05

    Glen Canyon Dam is a hydroelectric facility located on the Colorado River in Arizona that is operated by the U.S. Bureau of Reclamation (Reclamation) for multiple purposes including water storage, flood control, power generation, recreation, and enhancement of fish and wildlife. Glen Canyon Dam operations have been managed for the last several years to improve conditions for the humpback chub (Gila cypha) and other ecosystem components. An extensive amount of literature has been produced on the humpback chub. We developed this annotated bibliography to assist managers and researchers in the Grand Canyon as they perform assessments, refine management strategies, and develop new studies to examine the factors affecting humpback chub. The U.S. Geological Survey recently created a multispecies bibliography (including references on the humpback chub) entitled Bibliography of Native Colorado River Big Fishes (available at www.fort.usgs.gov/Products/data/COFishBib). That bibliography, while quite extensive and broader in scope than ours, is not annotated, and, therefore, does not provide any of the information in the original literature. In developing this annotated bibliography, we have attempted to assemble abstracts from relevant published literature. We present here abstracts taken unmodified from individual reports and articles except where noted. The bibliography spans references from 1976 to 2009 and is organized in five broad topical areas, including: (1) biology, (2) ecology, (3) impacts of dam operations, (4) other impacts, and (5) conservation and management, and includes twenty subcategories. Within each subcategory, we present abstracts alphabetically by author and chronologically by year. We present relevant articles not specific to either the humpback chub or Glen Canyon Dam, but cited in other included reports, under the Supporting Articles subcategory. We provide all citations in alphabetical order in Section 7.

  12. Haze in the Grand Canyon: An evaluation of the Winter Haze Intensive Tracer Experiment

    Energy Technology Data Exchange (ETDEWEB)

    1990-10-01

    The Grand Canyon is one of the most spectacular natural sights on earth. Approximately 4 million visitors travel to Grand Canyon National Park (GCNP) each year to enjoy its majestic geological formations and intensely colored views. However, visibility in GCNP can be impaired by small increases in concentrations of fine suspended particles that scatter and absorb light; the resulting visibility degradation is perceived as haze. Sulfate particles are a major factor in visibility impairment at Grand Canyon in summer and winter. Many wintertime hazes at GCNP are believed to result from the accumulation of emissions from local sources during conditions of air stagnation, which occur more frequently in winter than in summer. In January and February 1987, the National Park Service (NPS) carried out a large-scale experiment known as the Winter Haze Intensive Tracer Experiment (WHITEX) to investigate the causes of wintertime haze in the region of GCNP and Canyonlands National Park. The overall objective of WHITEX was to assess the feasibility of attributing visibility impairment in specific geographic regions to emissions from a single point source. The experiment called for the injection of a tracer, deuterated methane (CD{sub 4}), into one of the stacks of the Navajo Generating Station (NGS), a major coal-fired power plant located 25 km from the GCNP boundary and 110 km northeast of Grand Canyon Village. A network of field stations was established in the vicinity -- mostly to the northeast of GCNP and NGS -- to measure CD{sub 4} concentrations, atmospheric aerosol and optical properties, and other chemical and physical attributes. 19 refs., 3 figs.

  13. Family caregivers' views on coordination of care in Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C

    2015-01-01

    BACKGROUND: Collaboration between family caregivers and health professionals in specialised hospitals or community-based primary healthcare systems can be challenging. During the course of severe chronic disease, several health professionals might be involved at a given time, and the patient......'s illness may be unpredictable or not well understood by some of those involved in the treatment and care. AIM: The aim of this study was to explore the experiences and expectations of family caregivers for persons with Huntington's disease concerning collaboration with healthcare professionals. METHODS......: To shed light on collaboration from the perspectives of family caregivers, we conducted an explorative, qualitative interview study with 15 adult participants experienced from caring for family members in all stages of Huntington's disease. Data were analysed with systematic text condensation, a cross...

  14. Psychodynamic theory and counseling in predictive testing for Huntington's disease.

    Science.gov (United States)

    Tassicker, Roslyn J

    2005-04-01

    This paper revisits psychodynamic theory, which can be applied in predictive testing counseling for Huntington's Disease (HD). Psychodynamic theory has developed from the work of Freud and places importance on early parent-child experiences. The nature of these relationships, or attachments are reflected in adult expectations and relationships. Two significant concepts, identification and fear of abandonment, have been developed and expounded by the psychodynamic theorist, Melanie Klein. The processes of identification and fear of abandonment can become evident in predictive testing counseling and are colored by the client's experience of growing up with a parent affected by Huntington's Disease. In reflecting on family-of-origin experiences, clients can also express implied expectations of the future, and future relationships. Case examples are given to illustrate the dynamic processes of identification and fear of abandonment which may present in the clinical setting. Counselor recognition of these processes can illuminate and inform counseling practice.

  15. Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a Huntington disease mouse model.

    Science.gov (United States)

    Naseri, Nima N; Xu, Hui; Bonica, Joseph; Vonsattel, Jean Paul G; Cortes, Etty P; Park, Larry C; Arjomand, Jamshid; Gibson, Gary E

    2015-06-01

    Glucose metabolism is reduced in the brains of patients with Huntington disease (HD). The mechanisms underlying this deficit, its link to the pathology of the disease, and the vulnerability of the striatum in HD remain unknown. Abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase complex (PDHC) and the tricarboxylic acid (TCA) cycle, may contribute to these deficits. Here, activities for these enzymes and select protein levels were measured in human postmortem cortex and in striatum and cortex of an HD mouse model (Q175); mRNA levels encoding for these enzymes were also measured in the Q175 mouse cortex. The activities of PDHC and nearly all of the TCA cycle enzymes were dramatically lower (-50% to 90%) in humans than in mice. The activity of succinate dehydrogenase increased with HD in human (35%) and mouse (23%) cortex. No other changes were detected in the human HD cortex or mouse striatum. In Q175 cortex, there were increased activities of PDHC (+12%) and aconitase (+32%). Increased mRNA levels for succinyl thiokinase (+88%) and isocitrate dehydrogenase (+64%) suggested an upregulation of the TCA cycle. These patterns of change differ from those reported in other diseases, which may offer unique metabolic therapeutic opportunities for HD patients.

  16. Final Technical Report - Modernization of the Boulder Canyon Hydroelectric Project

    Energy Technology Data Exchange (ETDEWEB)

    Taddeucci, Joe [Dept. of Public Works, Boulder, CO (United States). Utilities Division

    2013-03-29

    The Boulder Canyon Hydroelectric Project (BCH) was purchased by the City of Boulder, CO (the city) in 2001. Project facilities were originally constructed in 1910 and upgraded in the 1930s and 1940s. By 2009, the two 10 MW turbine/generators had reached or were nearing the end of their useful lives. One generator had grounded out and was beyond repair, reducing plant capacity to 10 MW. The remaining 10 MW unit was expected to fail at any time. When the BCH power plant was originally constructed, a sizeable water supply was available for the sole purpose of hydroelectric power generation. Between 1950 and 2001, that water supply had gradually been converted to municipal water supply by the city. By 2001, the water available for hydroelectric power generation at BCH could not support even one 10 MW unit. Boulder lacked the financial resources to modernize the facilities, and Boulder anticipated that when the single, operational historical unit failed, the project would cease operation. In 2009, the City of Boulder applied for and received a U.S. Department of Energy (DOE) grant for $1.18 million toward a total estimated project cost of $5.155 million to modernize BCH. The federal funding allowed Boulder to move forward with plant modifications that would ensure BCH would continue operation. Federal funding was made available through the American Recovery and Reinvestment Act (ARRA) of 2009. Boulder determined that a single 5 MW turbine/generator would be the most appropriate capacity, given the reduced water supply to the plant. Average annual BCH generation with the old 10 MW unit had been about 8,500 MW-hr, whereas annual generation with a new, efficient turbine could average 11,000 to 12,000 MW-hr. The incremental change in annual generation represents a 30% increase in generation over pre-project conditions. The old turbine/generator was a single nozzle Pelton turbine with a 5-to-1 flow turndown and a maximum turbine/generator efficiency of 82%. The new unit is a

  17. Liquid-filled canyons on Titan

    Science.gov (United States)

    Poggiali, V.; Mastrogiuseppe, M.; Hayes, A. G.; Seu, R.; Birch, S. P. D.; Lorenz, R.; Grima, C.; Hofgartner, J. D.

    2016-08-01

    In May 2013 the Cassini RADAR altimeter observed channels in Vid Flumina, a drainage network connected to Titan's second largest hydrocarbon sea, Ligeia Mare. Analysis of these altimeter echoes shows that the channels are located in deep (up to 570 m), steep-sided, canyons and have strong specular surface reflections that indicate they are currently liquid filled. Elevations of the liquid in these channels are at the same level as Ligeia Mare to within a vertical precision of about 0.7 m, consistent with the interpretation of drowned river valleys. Specular reflections are also observed in lower order tributaries elevated above the level of Ligeia Mare, consistent with drainage feeding into the main channel system.

  18. New hexactinellid sponges from deep Mediterranean canyons.

    Science.gov (United States)

    Boury-Esnault, Nicole; Vacelet, Jean; Dubois, Maude; Goujard, Adrien; Fourt, Maïa; Pérez, Thierry; Chevaldonné, Pierre

    2017-02-21

    During the exploration of the NW Mediterranean deep-sea canyons (MedSeaCan and CorSeaCan cruises), several hexactinellid sponges were observed and collected by ROV and manned submersible. Two of them appeared to be new species of Farrea and Tretodictyum. The genus Farrea had so far been reported with doubt from the Mediterranean and was listed as "taxa inquirenda" for two undescribed species. We here provide a proper description for the specimens encountered and sampled. The genus Tretodictyum had been recorded several times in the Mediterranean and in the near Atlantic as T. tubulosum Schulze, 1866, again with doubt, since the type locality is the Japan Sea. We here confirm that the Mediterranean specimens are a distinct new species which we describe. We also provide18S rDNA sequences of the two new species and include them in a phylogenetic tree of related hexactinellids.

  19. Pluripotent hybrid stem cells from transgenic Huntington's disease monkey.

    Science.gov (United States)

    Laowtammathron, Chuti; Chan, Anthony W S

    2013-01-01

    Huntington's disease (HD) is a devastating disease that currently has no cure. Transgenic HD monkeys have developed key neuropathological and cognitive behavioral impairments similar to HD patients. Thus, pluripotent stem cells derived from transgenic HD monkeys could be a useful comparative model for clarifying HD pathogenesis and developing novel therapeutic approaches, which could be validated in HD monkeys. In order to create personal pluripotent stem cells from HD monkeys, here we present a tetraploid technique for deriving pluripotent hybrid HD monkey stem cells.

  20. Striatal degeneration impairs language learning: evidence from Huntington's disease.

    Science.gov (United States)

    De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

    2008-11-01

    Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly

  1. Long-term outcome of presymptomatic testing in Huntington disease

    OpenAIRE

    Gargiulo, Marcela; Lejeune, Séverine; Tanguy, Marie-Laure; Lahlou-Laforêt, Khadija; Faudet, Anne; Cohen, David; Feingold, Josué; Durr, Alexandra

    2008-01-01

    Our study on long-term outcome of presymptomatic testing for Huntington disease had two aims: the comparison of the psychological well-being and social adjustment of carriers and non-carriers of the mutation, and the identification of psychological determinants to improve care/support of testees. We performed a cross-sectional study of 351 persons who underwent presymptomatic testing. Those who had motor signs were excluded from the comparison of asymptomatic carrier and non-carriers. A struc...

  2. The structural involvement of the cingulate cortex in premanifest and early Huntington's disease.

    Science.gov (United States)

    Hobbs, Nicola Z; Pedrick, Amy V; Say, Miranda J; Frost, Chris; Dar Santos, Rachelle; Coleman, Allison; Sturrock, Aaron; Craufurd, David; Stout, Julie C; Leavitt, Blair R; Barnes, Josephine; Tabrizi, Sarah J; Scahill, Rachael I

    2011-08-01

    The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease.

  3. Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach.

    Science.gov (United States)

    Mariani, Louise-Laure; Tesson, Christelle; Charles, Perrine; Cazeneuve, Cécile; Hahn, Valérie; Youssov, Katia; Freeman, Leorah; Grabli, David; Roze, Emmanuel; Noël, Sandrine; Peuvion, Jean-Noel; Bachoud-Levi, Anne-Catherine; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra

    2016-09-01

    Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units. However, not all patients with an HD phenotype carry the pathological expansion in HTT, and the positive diagnosis rate is poor. To examine patients with HD phenotypes to determine the frequency of HD phenocopies with typical features of HD but without pathological CAG repeat expansions in HTT in an attempt to improve the positive diagnosis rate. Between January 1, 2004, and April 18, 2011, a total of 226 consecutive index patients with an HD phenotype were referred to specialized clinics of the French National Huntington Disease Reference Centre for Rare Diseases. They underwent detailed clinical examination and follow-up, as well as neuropsychological, biological, imaging, and genetic examinations. Nucleotide expansions in JPH3, ATN1, TBP, and C9ORF72 and mutations in PRNP, as well as acquired conditions commonly causing HD phenocopies, were first screened. The diagnostic rate of HD phenocopies and frequency of other etiologies using deep clinical phenotyping and next generation sequencing. Our goal was to improve the genetic diagnosis of HD phenocopies and to identify new HD related genes. One hundred ninety-eight patients carried a pathological CAG repeat expansion in HTT, whereas 28 patients (12 women and 16 men) did not. Huntington disease phenocopies accounted for 12.4%, and their mean (SD) age at onset was similar to those of the HD-HTT group (47.3 [12.7] years vs 50.3 [16.4] years, P = .29). We first identified 3 patients with abnormal CTG expansions in JPH3, a fourth patient with an antiphospholipid syndrome, and a fifth patient with B12 avitaminosis. A custom-made 63-gene panel was generated based on clinical evolution and exome sequencing. It contained genes responsible for HD phenocopies and other neurodegenerative conditions, as well as candidate genes from exome sequencing in 3 index cases with imaging features of brain

  4. Preimplantation genetic diagnosis for Huntington's disease with exclusion testing.

    Science.gov (United States)

    Sermon, Karen; De Rijcke, Martine; Lissens, Willy; De Vos, Anick; Platteau, Peter; Bonduelle, Maryse; Devroey, Paul; Van Steirteghem, André; Liebaers, Inge

    2002-10-01

    Huntington's disease is an autosomal dominant, late-onset disorder, for which the gene and the causative mutation have been known since 1993. Some at-risk patients choose for presymptomatic testing and can make reproductive choices accordingly. Others however, prefer not to know their carrier status, but may still wish to prevent the birth of a carrier child. For these patients, exclusion testing after prenatal sampling has been an option for many years. A disadvantage of this test is that unaffected pregnancies may be terminated if the parent at risk (50%) has not inherited the grandparental Huntington gene, leading to serious moral and ethical objections. As an alternative, preimplantation genetic diagnosis (PGD) on embryos obtained in vitro may be proposed, after which only embryos free of risk are replaced. Embryos can then be selected, either by the amplification of the CAG repeat in the embryos without communicating results to the patients (ie non-disclosure testing), which brings its own practical and moral problems, or exclusion testing. We describe here the first PGD cycles for exclusion testing for Huntington's disease in five couples. Three couples have had at least one PGD cycle so far. One pregnancy ensued and a healthy female baby was delivered.

  5. iPSC-based drug screening for Huntington's disease.

    Science.gov (United States)

    Zhang, Ningzhe; Bailus, Barbara J; Ring, Karen L; Ellerby, Lisa M

    2016-05-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. The disease generally manifests in middle age with both physical and mental symptoms. There are no effective treatments or cures and death usually occurs 10-20 years after initial symptoms. Since the original identification of the Huntington disease associated gene, in 1993, a variety of models have been created and used to advance our understanding of HD. The most recent advances have utilized stem cell models derived from HD-patient induced pluripotent stem cells (iPSCs) offering a variety of screening and model options that were not previously available. The discovery and advancement of technology to make human iPSCs has allowed for a more thorough characterization of human HD on a cellular and developmental level. The interaction between the genome editing and the stem cell fields promises to further expand the variety of HD cellular models available for researchers. In this review, we will discuss the history of Huntington's disease models, common screening assays, currently available models and future directions for modeling HD using iPSCs-derived from HD patients. This article is part of a Special Issue entitled SI: PSC and the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Informativeness of Early Huntington Disease Signs about Gene Status.

    Science.gov (United States)

    Oster, Emily; Eberly, Shirley W; Dorsey, E Ray; Kayson-Rubin, Elise; Oakes, David; Shoulson, Ira

    2015-01-01

    The cohort-level risk of Huntington disease (HD) is related to the age and symptom level of the cohort, but this relationship has not been made precise. To predict the evolving likelihood of carrying the Huntington disease (HD) gene for at-risk adults using age and sign level. Using data from adults with early signs and symptoms of HD linked to information on genetic status, we use Bayes' theorem to calculate the probability that an undiagnosed individual of a certain age and sign level has an expanded CAG repeat. Both age and sign levels have substantial influence on the likelihood of HD onset, and the probability of eventual diagnosis changes as those at risk age and exhibit (or fail to exhibit) symptoms. For example, our data suggest that in a cohort of individuals age 26 with a Unified Huntington's Disease Rating Scale (UHDRS) motor score of 7-10 70% of them will carry the HD mutation. For individuals age 56, the same motor score suggests only a 40% chance of carrying the mutation. Early motor signs of HD, overall and the chorea subscore, were highly predictive of disease onset at any age. However, body mass index (BMI) and cognitive performance scores were not as highly predictive. These results suggest that if researchers or clinicians are looking for early clues of HD, it may be more foretelling to look at motor rather than cognitive signs. Application of similar approaches could be used with other adult-onset genetic conditions.

  7. Contribution of imaging studies and neuro physiologic investigations to the diagnosis of Huntington`s chorea; L`imagerie medicale et les explorations neuro-physiologiques dans le diagnostic de la choree de Huntington

    Energy Technology Data Exchange (ETDEWEB)

    Paquet, J.M.; Turpin, J.CI. [Centre Hospitalier Universitaire, 51 - Reims (France)

    1997-05-01

    Although Huntington`s disease was described in 1872, its diagnosis continues to rest on clinical grounds. Recently developed techniques for imaging the brain (computed tomography and magnetic resonance imaging) or studying its function (single photon emission computed tomography and positron emission tomography) have demonstrated only non specific abnormalities at the early stages of the disease, thus failing to improve the pre-symptomatic diagnosis. Neuro-physiologic investigations (evoked potentials, electromyogram, electroencephalogram) have been similarly unrewarding. Investigations are useful only as an laid to the differential diagnosis. Molecular biology technology is the only available tool for identifying high-risk individuals and establishing a definitive diagnosis of Huntington`s disease. (authors). 10 refs.

  8. Habitat Mapping Cruise - Hudson Canyon (HB0904, EK60)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Objectives are to: 1) perform multibeam mapping of transitional and deepwater habitats in Hudson Canyon (off New Jersey) with the National Institute of Undersea...

  9. Faults--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the faults for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is included in...

  10. Faults--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the faults for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is included in...

  11. Folds--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the folds for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is included in...

  12. The Trail Inventory of Leslie Canyon NWR [Cycle 2

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this report is to create a baseline inventory of all non-motorized trails on Leslie Canyon National Wildlife Refuge. Trails in this inventory are...

  13. Paleoshorelines--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the paleoshorelines for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is...

  14. Investigations of Carbon Phases in Canyon Diablo Meteorite

    Science.gov (United States)

    Karczemska, A.; Jakubowski, T.; Ouzillou, M.; Batory, D.; Abramczyk, H.; Brozek-Pluska, B.; Kopec, M.; Kozanecki, M.; Wiosna-Salyga, G.

    2016-08-01

    X-ray diffraction, Raman mapping and micro-spectrofluorimetric studies have been used in investigations of carbon in Canyon Diablo meteorite. Results show the presence of defected diamond and not well recognized carbon phases (unclear Raman peaks).

  15. BackscatterC [7125]--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the acoustic-backscatter map of Monterey Canyon and Vicinity map area, California. Backscatter data are provided as separate...

  16. Paleoshorelines--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the paleoshorelines for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is...

  17. BackscatterB [EM300]--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the acoustic-backscatter map of Monterey Canyon and Vicinity map area, California. Backscatter data are provided as separate...

  18. Faults--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the faults for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is included...

  19. Folds--Monterey Canyon and Vicinity Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the folds for the geologic and geomorphic map of Monterey Canyon and Vicinity, California. The vector data file is included in...

  20. Ecological-geochemical assessment of soil of the Dniester canyon.

    Directory of Open Access Journals (Sweden)

    Zorin D.O.

    2008-05-01

    Full Text Available An method of calculation of background and anomalous heavy metals, petroleum products and pesticides in soil of the Dniester canyon area for the environmental assessment of the future national park.

  1. BackscatterC [7125]--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the acoustic-backscatter map of Monterey Canyon and Vicinity map area, California. Backscatter data are provided as separate...

  2. BackscatterB [EM300]--Monterey Canyon and Vicinity, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the acoustic-backscatter map of Monterey Canyon and Vicinity map area, California. Backscatter data are provided as separate...

  3. Safety Evaluation for Packaging (onsite) T Plant Canyon Items

    Energy Technology Data Exchange (ETDEWEB)

    OBRIEN, J.H.

    2000-07-14

    This safety evaluation for packaging (SEP) evaluates and documents the ability to safely ship mostly unique inventories of miscellaneous T Plant canyon waste items (T-P Items) encountered during the canyon deck clean off campaign. In addition, this SEP addresses contaminated items and material that may be shipped in a strong tight package (STP). The shipments meet the criteria for onsite shipments as specified by Fluor Hanford in HNF-PRO-154, Responsibilities and Procedures for all Hazardous Material Shipments.

  4. Diablo Canyon plant information management system and integrated communication system

    Energy Technology Data Exchange (ETDEWEB)

    Stanley, J.W.; Groff, C.

    1990-06-01

    The implementation of a comprehensive maintenance system called the plant information management system (PIMS) at the Diablo Canyon plant, together with its associated integrated communication system (ICS), is widely regarded as the most comprehensive undertaking of its kind in the nuclear industry. This paper provides an overview of the program at Diablo Canyon, an evaluation of system benefits, and highlights the future course of PIMS.

  5. Mexican Americans and the American Nation: A Response to Professor Huntington

    Science.gov (United States)

    Telles, Edward

    2006-01-01

    This essay is based on a talk I delivered at Texas A&M University on December 10, 2005, in response to an earlier lecture at the university by Professor Samuel P. Huntington. It relies on social science evidence to first address Huntington's contention that Mexicans are overwhelming American borders. It then turns to evidence that Mexican…

  6. PROBLEMS OF MODERNIZATION IN THE WORKS OF S. HUNTINGTON: THEORY AND PRACTICE

    Directory of Open Access Journals (Sweden)

    Britikova E. A.

    2016-06-01

    Full Text Available The article discusses the interpretation of the mechanisms of modernization of the American scientist - Samuel Huntington, which sees modernization as a complex process with a very uncertain result. As a representative of the multilinear approach, Samuel Huntington proves the uniqueness of the modernization paths of each individual national system

  7. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    Science.gov (United States)

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  8. Huntington disease and Huntington disease-like in a case series from Brazil.

    Science.gov (United States)

    Castilhos, R M; Souza, A F D; Furtado, G V; Gheno, T C; Silva, A L; Vargas, F R; Lima, M-A F D; Barsottini, O; Pedroso, J L; Godeiro, C; Salarini, D; Pereira, E T; Lin, K; Toralles, M-B; Saute, J A M; Rieder, C R; Quintas, M; Sequeiros, J; Alonso, I; Saraiva-Pereira, M L; Jardim, L B

    2014-10-01

    The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

  9. Measurement of caudate nucleus area - a more accurate measurement for Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Wardlaw, J.M.; Abernethy, L.J. (Royal Infirmary, London (United Kingdom). Dept. of Radiology); Sellar, R.J. (Western General Hospital, Edinburgh (United Kingdom). Dept. of Neuroradiology)

    1991-08-01

    Caudate nucleus atrophy occurs in Huntington's disease and methods of measuring this have been described using axial CT, but these are indirect and lack sensitivity. We measured caudate nucleus area (blind to the subjects' clinical state) in 30 subjects with or at risk of Huntington's disease, and in 100 normal age matched controls. Fifteen subjects with established symptomatic Huntington's disease, 3 with early symptoms, and 3 presymptomatic subjects (2 showing a high probability for the Huntington's disease gene on genetic testing, and one who has since developed symptoms) were correctly identified. Three normal (gene negative) family members were also correctly identified. Outcome is awaited in 6. CT caudate area measurement is simple and reproducible and we have found it to be a useful confirmatory test for Huntington's disease. (orig.).

  10. Effect of asymmetrical street canyons on pedestrian thermal comfort in warm-humid climate of Cuba

    Science.gov (United States)

    Rodríguez-Algeciras, José; Tablada, Abel; Matzarakis, Andreas

    2017-07-01

    Walkability and livability in cities can be enhanced by creating comfortable environments in the streets. The profile of an urban street canyon has a substantial impact on outdoor thermal conditions at pedestrian level. This paper deals with the effect of asymmetrical street canyon profiles, common in the historical centre of Camagüey, Cuba, on outdoor thermal comfort. Temporal-spatial analyses are conducted using the Heliodon2 and the RayMan model, which enable the generation of accurate predictions about solar radiation and thermal conditions of urban spaces, respectively. On these models, urban settings are represented by asymmetrical street canyons with five different height-to-width ratios and four street axis orientations (N-S, NE-SW, E-W, SE-NW). Results are evaluated for daytime hours across the street canyon, by means of the physiologically equivalent temperature (PET index) which allows the evaluation of the bioclimatic conditions of outdoor environments. Our findings revealed that high profiles (façades) located on the east-facing side of N-S streets, on the southeast-facing side of NE-SW streets, on the south-facing side of E-W street, and on the southwest-facing side of SE-NW streets, are recommended to reduce the total number of hours under thermal stress. E-W street canyons are the most thermally stressed ones, with extreme PET values around 36 °C. Deviating from this orientation ameliorates the heat stress with reductions of up to 4 h in summer. For all analysed E-W orientations, only about one fifth of the street can be comfortable, especially for high aspect ratios (H/W > 3). Optimal subzones in the street are next to the north side of the E-W street, northwest side of the NE-SW street, and southwest side of the SE-NW street. Besides, when the highest profile is located on the east side of N-S streets, then the subzone next to the east-facing façade is recommendable for pedestrians. The proposed urban guidelines enable urban planners to create

  11. Clinical and counselling implications of preimplantation genetic diagnosis for Huntington's disease in the UK.

    Science.gov (United States)

    Lashwood, A; Flinter, F

    2001-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disorder that usually occurs in adult life. Individuals at risk can have a gene test before the onset of symptoms, and prenatal diagnosis is available. Preimplantation genetic diagnosis (PGD) for Huntington's disease is now available for couples in whom one partner has the gene for Huntington's disease. A licence to practise PGD is required from the Human Fertilisation and Embryology Authority, and there are several complex issues relating to PGD for Huntington's disease that require consideration. The partner of the Huntington's disease gene carrier should have a presymptomatic test to ensure accuracy in a PGD cycle. There should be a delay between blood sampling and testing for Huntington's disease to allow time for reflection and withdrawal from testing. All PGD treatment has an associated risk of misdiagnosis. If confirmatory prenatal testing is not undertaken after a successful PGD cycle, no confirmation of diagnosis will be obtained at birth. Guidelines indicate that individuals who are at risk cannot be tested before 18 years. There is concern over the ability of a child or adolescent to make an informed choice about testing before this age. Confirmatory testing at birth after PGD would be in direct contravention of these guidelines. In the UK, the law requires consideration of the welfare of children born after assisted conception treatment. Presenting symptoms of Huntington's disease may affect the parenting abilities of an affected individual. There is a need for an assessment of a patient's current Huntington's disease status and their planned provision of care of children if Huntington's disease affects parenting. It has been necessary to create a detailed working protocol for the management of PGD for Huntington's disease to address these issues.

  12. Stochastic backscatter modelling for the prediction of pollutant removal from an urban street canyon: A large-eddy simulation

    Science.gov (United States)

    O'Neill, J. J.; Cai, X.-M.; Kinnersley, R.

    2016-10-01

    The large-eddy simulation (LES) approach has recently exhibited its appealing capability of capturing turbulent processes inside street canyons and the urban boundary layer aloft, and its potential for deriving the bulk parameters adopted in low-cost operational urban dispersion models. However, the thin roof-level shear layer may be under-resolved in most LES set-ups and thus sophisticated subgrid-scale (SGS) parameterisations may be required. In this paper, we consider the important case of pollutant removal from an urban street canyon of unit aspect ratio (i.e. building height equal to street width) with the external flow perpendicular to the street. We show that by employing a stochastic SGS model that explicitly accounts for backscatter (energy transfer from unresolved to resolved scales), the pollutant removal process is better simulated compared with the use of a simpler (fully dissipative) but widely-used SGS model. The backscatter induces additional mixing within the shear layer which acts to increase the rate of pollutant removal from the street canyon, giving better agreement with a recent wind-tunnel experiment. The exchange velocity, an important parameter in many operational models that determines the mass transfer between the urban canopy and the external flow, is predicted to be around 15% larger with the backscatter SGS model; consequently, the steady-state mean pollutant concentration within the street canyon is around 15% lower. A database of exchange velocities for various other urban configurations could be generated and used as improved input for operational street canyon models.

  13. Circulation in Vilkitsky Canyon in the eastern Arctic Ocean

    Science.gov (United States)

    Janout, Markus; Hölemann, Jens

    2016-04-01

    The eastern Arctic Ocean is characterized by steep continental slopes and vast shallow shelf seas that receive a large amount of riverine freshwater from some of the largest rivers on earth. The northwestern Laptev Sea is of particular interest, as it is a freshwater transport pathway for a swift surface-intensified current from the Kara Sea toward the Arctic Basin, as was recently highlighted by high-resolution model studies. The region features complex bathymetry including a narrow strait and a large submarine canyon, strong tides, polynyas and severe sea ice conditions throughout much of the year. A year-long mooring record as well as detailed hydrographic shipboard measurements resulted from summer expeditions to the area in 2013 and 2014, and now provide a detailed picture of the region's water properties and circulation. The hydrography is characterized by riverine Kara Sea freshwater near the surface in the southern part of the canyon, while warmer (~0°C) saline Atlantic-derived waters dominate throughout the canyon at depths >150m. Cold shelf-modified waters near the freezing point are found along the canyon edges. The mean flow at the 300 m-deep mooring location near the southern edge of the canyon is swift (30 cm/s) and oriented eastward near the surface as suggested by numerical models, while the deeper flow follows the canyon topography towards the north-east. Wind-driven deviations from the mean flow coincide with sudden changes in temperature and salinity. This study characterizes the general circulation in Vilkitsky Canyon and investigates its potential as a conduit for upwelling of Atlantic-derived waters from the Arctic Basin to the Laptev Sea shelf.

  14. Geology of the Hamm Canyon quadrangle, Colorado

    Science.gov (United States)

    Cater, Fred W.

    1953-01-01

    The Hamm Canyon quadrangle is on eof eighteen 7 1/2-minute quadrangles covering the principal carnotite-producing area of southwestern Colorado. The geology of these quadrangles was mapped by the U.S. Geological Survey for the Atomic Energy Commission as part of a comprehensive study of carnotite deposits. The rocks exposed in the eighteen quadrangles consist of crystalline rocks of pre-Cambrian age and sedimentary rocks that range in age from late Paleozoic to Quaternary. Over much of the area the sedimentary rocks are flat lying, but in places the rocks are disrupted by high-angle faults, and northwest-trending folds. Conspicuous among the folds are large anticlines having cores of intrusive salt and gypsum. Most of the carnotite deposits are confined to the Salt Wash sandstone member of the Jurassic Morrison formation. Within this sandstone, most of the deposits are spottily distributed through an arcuate zone known as the "Uravan Mineral Belt". Individual deposits range in size from irregular masses containing only a few tons of ore to large, tabular masses containing many thousands of tons. The ore consists largely of sandstone selectively impregnated and in part replaced by uranium and vanadium minerals. Most of the deposits appear to be related to certain sedimentary structures in sandstones of favorable composition.

  15. Current status of PET imaging in Huntington's disease.

    Science.gov (United States)

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

    2016-06-01

    To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading "Huntington Disease" combined with text and key words "Huntington Disease", "Neuroimaging" and "PET". Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([(18)F]FDG and [(15)O]H2O), presynaptic ([(18)F]fluorodopa, [(11)C]β-CIT and [(11)C]DTBZ) and postsynaptic ([(11)C]SCH22390, [(11)C]FLB457 and [(11)C]raclopride) dopaminergic function, phosphodiesterases ([(18)F]JNJ42259152, [(18)F]MNI-659 and [(11)C]IMA107), and adenosine ([(18)F]CPFPX), cannabinoid ([(18)F]MK-9470), opioid ([(11)C]diprenorphine) and GABA ([(11)C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment in HD.

  16. El trabajo interdisciplinar en la enfermedad de Huntington

    OpenAIRE

    Fernández Hawrylak, María; Grau Rubio, Claudia; Hernández Lozano, David; Fernández Sastre, Beatriz

    2014-01-01

    Se argumenta la importancia del trabajo en equipo en la atención de las personas afectadas por la Enfermedad de Huntington y de sus familias, y se describen las principales funciones de los distintos profesionales que han de cubrir sus necesidades en cada una de las etapas de la enfermedad en función de las alteraciones y secuelas. Siguiendo esta premisa, se presenta el trabajo de intervención basado en la complementariedad de distintos profesionales que atienden y cuidan a las personas afect...

  17. ENFERMEDAD DE HUNTINGTON: MODELOS EXPERIMENTALES Y PERSPECTIVAS TERAPÉUTICAS

    OpenAIRE

    TERESA SERRANO SÁNCHEZ; LISETTE BLANCO LEZCANO; ROCÍO GARCÍA MINET; ESTEBAN ALBERTI AMADOR; IVÁN DÍAZ ARMESTO; NANCY PAVÓN FUENTE; LOURDES LORIGADOS PEDRE; MARÍA ELENA GONZÁLEZ FRAGUELA; JORGE FELIPE MONTERO LEÓN; LISIS MARTÍNEZ MARTÍ; MARÍA DE LOS ANGELES ROBINSON AGRAMONTE; LILIANA FRANCIS TURNER

    2011-01-01

    La enfermedad de Huntington (EH) es un trastorno degenerativo de Weiss de origen hereditario. Hasta el momento no existe un tratamiento efectivo para la enfermedad que inexorablemente después de transcurridos 15 a 20 años, evoluciona hacia incapa- cidad total o muerte. En este trabajo se revisan las características clínicas y morfológicas de la EH y los modelos experimentales más utilizados para su estudio tomando como fuente, artículos indexados en la base de datos Medline publicados en los ...

  18. Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?

    Science.gov (United States)

    Hoffner, Guylaine; Djian, Philippe

    2015-12-01

    Huntington disease is a dominantly inherited disease of the central nervous system. The mutational expansion of polyglutamine beyond a critical length produces a toxic gain of function in huntingtin and results in neuronal death. In the course of the disease, expanded huntingtin is proteolyzed, becomes abnormally folded, and accumulates in oligomers, fibrils, and microscopic inclusions. The aggregated forms of the expanded protein are structurally diverse. Structural heterogeneity may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective. When defined, the toxic structures could then specifically be targeted by prophylactic or therapeutic drugs aimed at inhibiting polyglutamine aggregation.

  19. Reduced gluconeogenesis and lactate clearance in Huntington's disease

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Signe M B; Campos, André

    2010-01-01

    We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 ± 0.5 vs. 0.0 ± 0.2mM, P...... for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients....

  20. The Cambridge MRI database for animal models of Huntington disease.

    Science.gov (United States)

    Sawiak, Stephen J; Morton, A Jennifer

    2016-01-01

    We describe the Cambridge animal brain magnetic resonance imaging repository comprising 400 datasets to date from mouse models of Huntington disease. The data include raw images as well as segmented grey and white matter images with maps of cortical thickness. All images and phenotypic data for each subject are freely-available without restriction from (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site.

  1. Origin of Hot Creek Canyon, Long Valley caldera, California

    Energy Technology Data Exchange (ETDEWEB)

    Maloney, N.J. (California State Univ., Fullerton, CA (United States). Dept. of Geological Sciences)

    1993-04-01

    Hot Creek has eroded a canyon some thirty meters deep across the Hot Creek rhyolite flows located in the southeastern moat of Long Valley Caldera. Maloney (1987) showed that the canyon formed by headward erosion resulting from spring sapping along hydrothermally altered fractures in the rhyolite, and the capture of Mammoth Creek. This analysis ignored the continuing uplift of the central resurgent dome. Reid (1992) concluded that the downward erosion of the canyon must have kept pace with the uplift. Long Valley Lake occupied the caldera until 100,000 to 50,000 years before present. The elevation of the shoreline, determined by trigonometric leveling, is 2,166 m where the creek enters the canyon and 2,148 m on the downstream side of the rhyolite. The slope of the strand line is about equal to the stream gradient. The hill was lower and the stream gradient less at the time of stream capture. Rotational uplift increased the stream gradient which increased the rate of downward erosion and formed the V-shaped canyon

  2. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Science.gov (United States)

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  3. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    James R C Miller

    Full Text Available Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  4. Data from Oceanographer, Lydonia, and Gilbert Canyons acquired in 1965 (SCHWARTZ65 shapefile)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Submarine canyons occur at the edge of the continental shelf and cut across the slope and rise along the U.S. east coast. Three of these canyons (Oceanographer,...

  5. Software Configuration Management Plan for the B-Plant Canyon Ventilation Control System

    Energy Technology Data Exchange (ETDEWEB)

    MCDANIEL, K.S.

    1999-08-31

    Project W-059 installed a new B Plant Canyon Ventilation System. Monitoring and control of the system is implemented by the Canyon Ventilation Control System (CVCS). This Software Configuration Management Plan provides instructions for change control of the CVCS.

  6. Spatial Vegetation Data for Canyon De Chelly National Monument Vegetation Mapping Project

    Data.gov (United States)

    National Park Service, Department of the Interior — The Canyon de Chelly National Monument Vegetation Map Database was developed as a primary product in the Canyon de Chelly National Monument Vegetation...

  7. 2013 Pacific Gas and Electric Diablo Canyon Power Plant (DCPP): San Simeon, CA Central Coast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Diablo Canyon Power Plant (DCPP) LiDAR and Imagery datasets are comprised of three separate LiDAR surveys: Diablo Canyon (2010), Los Osos (2011), and San Simeon...

  8. Water classification of the Colorado River Corridor, Grand Canyon, Arizona, 2013—Data

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data area classified maps of water in the Colorado River at a discharge of approximately 227 meters squared/second in Grand Canyon from Glen Canyon Dam to...

  9. Riparian vegetation classification of the Colorado River Corridor, Grand Canyon, Arizona, 2013—Data

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data are classification maps of total riparian vegetation along the Colorado River in Grand Canyon from Glen Canyon Dam to Pearce Ferry in Arizona. The data...

  10. Data from Oceanographer, Lydonia, and Gilbert Canyons acquired in 1965 (SCHWARTZ65 shapefile)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Submarine canyons occur at the edge of the continental shelf and cut across the slope and rise along the U.S. east coast. Three of these canyons (Oceanographer,...

  11. 2011 Pacific Gas and Electric Diablo Canyon Power Plant (DCPP): Los Osos, CA Central Coast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Diablo Canyon Power Plant (DCPP) LiDAR and Imagery datasets are comprised of three separate LiDAR surveys: Diablo Canyon (2010), Los Osos (2011), and San Simeon...

  12. Samples from the Georges Bank Canyons acquired in 1936 (STETSON36 shapefile)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Submarine canyons cut into the edge of the continental shelf and the continental slope along much of the U.S. Atlantic coast. Three canyons along the southern edge...

  13. Impaired adult olfactory bulb neurogenesis in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Kohl Zacharias

    2010-09-01

    Full Text Available Abstract Background Huntington's disease (HD is an autosomal dominant neurodegenerative disorder linked to expanded CAG-triplet nucleotide repeats within the huntingtin gene. Intracellular huntingtin aggregates are present in neurons of distinct brain areas, among them regions of adult neurogenesis including the hippocampus and the subventricular zone/olfactory bulb system. Previously, reduced hippocampal neurogenesis has been detected in transgenic rodent models of HD. Therefore, we hypothesized that mutant huntingtin also affects newly generated neurons derived from the subventricular zone of adult R6/2 HD mice. Results We observed a redirection of immature neuroblasts towards the striatum, however failed to detect new mature neurons. We further analyzed adult neurogenesis in the granular cell layer and the glomerular layer of the olfactory bulb, the physiological target region of subventricular zone-derived neuroblasts. Using bromodeoxyuridine to label proliferating cells, we observed in both neurogenic regions of the olfactory bulb a reduction in newly generated neurons. Conclusion These findings suggest that the striatal environment, severely affected in R6/2 mice, is capable of attracting neuroblasts, however this region fails to provide sufficient signals for neuronal maturation. Moreover, in transgenic R6/2 animals, the hostile huntingtin-associated microenvironment in the olfactory bulb interferes with the survival and integration of new mature neurons. Taken together, endogenous cell repair strategies in HD may require additional factors for the differentiation and survival of newly generated neurons both in neurogenic and non-neurogenic regions.

  14. Final Technical Report - Modernization of the Boulder Canyon Hydroelectric Project

    Energy Technology Data Exchange (ETDEWEB)

    Taddeucci, Joe [Dept. of Public Works, Boulder, CO (United States). Utilities Division

    2013-03-29

    The Boulder Canyon Hydroelectric Project (BCH) was purchased by the City of Boulder, CO (the city) in 2001. Project facilities were originally constructed in 1910 and upgraded in the 1930s and 1940s. By 2009, the two 10 MW turbine/generators had reached or were nearing the end of their useful lives. One generator had grounded out and was beyond repair, reducing plant capacity to 10 MW. The remaining 10 MW unit was expected to fail at any time. When the BCH power plant was originally constructed, a sizeable water supply was available for the sole purpose of hydroelectric power generation. Between 1950 and 2001, that water supply had gradually been converted to municipal water supply by the city. By 2001, the water available for hydroelectric power generation at BCH could not support even one 10 MW unit. Boulder lacked the financial resources to modernize the facilities, and Boulder anticipated that when the single, operational historical unit failed, the project would cease operation. In 2009, the City of Boulder applied for and received a U.S. Department of Energy (DOE) grant for $1.18 million toward a total estimated project cost of $5.155 million to modernize BCH. The federal funding allowed Boulder to move forward with plant modifications that would ensure BCH would continue operation. Federal funding was made available through the American Recovery and Reinvestment Act (ARRA) of 2009. Boulder determined that a single 5 MW turbine/generator would be the most appropriate capacity, given the reduced water supply to the plant. Average annual BCH generation with the old 10 MW unit had been about 8,500 MW-hr, whereas annual generation with a new, efficient turbine could average 11,000 to 12,000 MW-hr. The incremental change in annual generation represents a 30% increase in generation over pre-project conditions. The old turbine/generator was a single nozzle Pelton turbine with a 5-to-1 flow turndown and a maximum turbine/generator efficiency of 82%. The new unit is a

  15. Variability in rainfall at monitoring stations and derivation of a long-term rainfall intensity record in the Grand Canyon Region, Arizona, USA

    Science.gov (United States)

    Caster, Joshua; Sankey, Joel B.

    2016-04-11

    can generate runoff which may erode alluvium. The characterization of past and present rainfall variability in this study will be useful for future studies that evaluate more spatially continuous datasets in order to better understand the rainfall dynamics within this, and potentially other, deep canyons.

  16. Directed urban canyons in megacities and its applications in meteorological modeling

    Science.gov (United States)

    Samsonov, Timofey; Konstantinov, Pavel; Varentsov, Mikhail

    2015-04-01

    Directed urban canyons study applies object-oriented analysis to extraction of urban canyons and introduces the concept of directed urban canyon which is then experimentally applied in urban meteorological modeling. Observation of current approach to description of urban canyon geometry is provided. Then a new theoretical approach to canyon delineation is presented that allows chaining the spaces between buildings into directed canyons that comprise three-level hierarchy. An original methodology based on triangular irregular network (TIN) is presented that allows extraction of regular and directed urban canyons from cartographic data, estimation of their geometric characteristics, including local and averaged height-width ratio, primary and secondary canyon directions. Obtained geometric properties of canyons are then applied in micro-scale temperature and wind modeling using URB-MOS model and estimation of possible wind accelerations along canyons. Extraction and analysis of directed canyons highly depends on the presence of linear street network. Thus, in the absence of this GIS layer, it should be reconstructed from another data sources. The future studies should give us an answer to the question, where the limits of directed canyons are and how they can be classified further in terms of the street longitudinal shape. For now all computations are performed in separate scripts and programs. We plan to develop comprehensive automation of described methods of urban canyon description in specialized software. The most perspective extension of proposed methodology seemes to be canyon -based analysis which is truely object-oriented. Various geometric properties of micro-, meso- and macro-scale canyons should be investigated and their applicability in urban climate modeling should be assesed. Object-oriented canyon analysis can also be applied in architectural studies, urban morphology, planning and various physical and social aspects that are concerned with human in

  17. Presymptomatic testing for Huntington's disease: a world wide survey. The World Federation of Neurology Research Group on Huntington's Disease.

    OpenAIRE

    1993-01-01

    World wide data on presymptomatic testing for Huntington's disease using closely linked DNA markers show that 1479 persons at risk received completed test results up to the end of 1991. Testing has been carried out in 19 countries, with at least 88 centres involved, and numbers have levelled off after a peak in 1990. Only 5% of those at risk have been tested in six countries with the longest established programmes. Continued monitoring of international data will be of value in assessing the s...

  18. Canyon conditions impact carbon flows in food webs of three sections of the Nazaré canyon

    Science.gov (United States)

    van Oevelen, Dick; Soetaert, Karline; Garcia, R.; de Stigter, Henko C.; Cunha, Marina R.; Pusceddu, Antonio; Danovaro, Roberto

    2011-12-01

    Submarine canyons transport large amounts of sediment and organic matter (OM) from the continental shelf to the abyssal plain. Three carbon-based food web models were constructed for the upper (300-750 m water depth), middle (2700-3500 m) and lower section (4000-5000 m) of the Nazaré canyon (eastern Atlantic Ocean) using linear inverse modeling to examine how the food web is influenced by the characteristics of the respective canyon section. The models were based on an empirical dataset consisting of biomass and carbon processing data, and general physiological data constraints from the literature. Environmental conditions, most notably organic matter (OM) input and hydrodynamic activity, differed between the canyon sections and strongly affected the benthic food web structure. Despite the large difference in depth, the OM inputs into the food webs of the upper and middle sections were of similar magnitude (7.98±0.84 and 9.30±0.71 mmol C m -2 d -1, respectively). OM input to the lower section was however almost 6-7 times lower (1.26±0.03 mmol C m -2 d -1). Carbon processing in the upper section was dominated by prokaryotes (70% of total respiration), though there was a significant meiofaunal (21%) and smaller macrofaunal (9%) contribution. The high total faunal contribution to carbon processing resembles that found in shallower continental shelves and upper slopes, although the meiofaunal contribution is surprisingly high and suggest that high current speeds and sediment resuspension in the upper canyon favor the role of the meiofauna. The high OM input and conditions in the accreting sediments of the middle canyon section were more beneficial for megafauna (holothurians), than for the other food web compartments. The high megafaunal biomass (516 mmol C m -2), their large contribution to respiration (56% of total respiration) and secondary production (0.08 mmol C m -2 d -1) shows that these accreting sediments in canyons are megafaunal hotspots in the deep

  19. Polymorphisms in the CAG repeat--a source of error in Huntington disease DNA testing.

    Science.gov (United States)

    Yu, S; Fimmel, A; Fung, D; Trent, R J

    2000-12-01

    Five of 400 patients (1.3%), referred for Huntington disease DNA testing, demonstrated a single allele on CAG alone, but two alleles when the CAG + CCG repeats were measured. The PCR assay failed to detect one allele in the CAG alone assay because of single-base silent polymorphisms in the penultimate or the last CAG repeat. The region around and within the CAG repeat sequence in the Huntington disease gene is a hot-spot for DNA polymorphisms, which can occur in up to 1% of subjects tested for Huntington disease. These polymorphisms may interfere with amplification by PCR, and so have the potential to produce a diagnostic error.

  20. Standardized methods for Grand Canyon fisheries research 2015

    Science.gov (United States)

    Persons, William R.; Ward, David L.; Avery, Luke A.

    2013-01-01

    This document presents protocols and guidelines to persons sampling fishes in the Grand Canyon, to help ensure consistency in fish handling, fish tagging, and data collection among different projects and organizations. Most such research and monitoring projects are conducted under the general umbrella of the Glen Canyon Dam Adaptive Management Program and include studies by the U.S. Geological Survey (USGS), U.S. Fish and Wildlife Service (FWS), National Park Service (NPS), the Arizona Game and Fish Department (AGFD), various universities, and private contractors. This document is intended to provide guidance to fieldworkers regarding protocols that may vary from year to year depending on specific projects and objectives. We also provide herein documentation of standard methods used in the Grand Canyon that can be cited in scientific publications, as well as a summary of changes in protocols since the document was first created in 2002.

  1. 75 FR 41232 - Deer Flat National Wildlife Refuge, Canyon, Owyhee, Payette, and Washington Counties, ID; Malheur...

    Science.gov (United States)

    2010-07-15

    ... Fish and Wildlife Service Deer Flat National Wildlife Refuge, Canyon, Owyhee, Payette, and Washington...). The Refuge has units located in Canyon, Owyhee, Payette, and Washington Counties, ID, and Malheur... the Snake River located in Canyon, Payette, Owyhee, and Washington Counties in ID; and Malheur...

  2. 76 FR 54487 - Charter Renewal, Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2011-09-01

    ... Bureau of Reclamation Charter Renewal, Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of... the Glen Canyon Dam Adaptive Management Work Group. The purpose of the Adaptive Management Work Group... of the Glen Canyon Dam Adaptive Management Work Group is in the public interest in connection...

  3. 78 FR 54482 - Charter Renewal, Glen Canyon Dam Adaptive Management Work Group

    Science.gov (United States)

    2013-09-04

    ... Bureau of Reclamation Charter Renewal, Glen Canyon Dam Adaptive Management Work Group AGENCY: Bureau of... the Glen Canyon Dam Adaptive Management Work Group. The purpose of the Adaptive Management Work Group... Canyon Dam Adaptive Management Work Group is in the public interest in connection with the performance...

  4. Measuring currents in submarine canyons: technological and scientific progress in the past 30 years

    Science.gov (United States)

    Xu, J. P.

    2011-01-01

    The development and application of acoustic and optical technologies and of accurate positioning systems in the past 30 years have opened new frontiers in the submarine canyon research communities. This paper reviews several key advancements in both technology and science in the field of currents in submarine canyons since the1979 publication of Currents in Submarine Canyons and Other Sea Valleys by Francis Shepard and colleagues. Precise placements of high-resolution, high-frequency instruments have not only allowed researchers to collect new data that are essential for advancing and generalizing theories governing the canyon currents, but have also revealed new natural phenomena that challenge the understandings of the theorists and experimenters in their predictions of submarine canyon flow fields. Baroclinic motions at tidal frequencies, found to be intensified both up canyon and toward the canyon floor, dominate the flow field and control the sediment transport processes in submarine canyons. Turbidity currents are found to frequently occur in active submarine canyons such as Monterey Canyon. These turbidity currents have maximum speeds of nearly 200 cm/s, much smaller than the speeds of turbidity currents in geological time, but still very destructive. In addition to traditional Eulerian measurements, Lagrangian flow data are essential in quantifying water and sediment transport in submarine canyons. A concerted experiment with multiple monitoring stations along the canyon axis and on nearby shelves is required to characterize the storm-trigger mechanism for turbidity currents.

  5. 75 FR 39147 - Establishment of Class E Airspace; Bryce Canyon, UT

    Science.gov (United States)

    2010-07-08

    ... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Bryce Canyon, UT AGENCY... E airspace at Bryce Canyon, UT, to accommodate aircraft using a new Area Navigation (RNAV) Global... Bryce Canyon, UT (74 FR 59492). The comments received prompted the FAA on April 26, 2010, to publish...

  6. 75 FR 21532 - Proposed Establishment of Class E Airspace; Bryce Canyon, UT

    Science.gov (United States)

    2010-04-26

    ..., UT AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Supplemental notice of proposed... surface airspace at Bryce Canyon Airport, Bryce Canyon, UT. In a NPRM published in the Federal Register... Airport, Bryce Canyon, UT (74 FR 59492). The comment period closed January 4, 2010. Two comments...

  7. 76 FR 14802 - Modification of Class E Airspace; Bryce Canyon, UT

    Science.gov (United States)

    2011-03-18

    ... Federal Aviation Administration 14 CFR Part 71 Modification of Class E Airspace; Bryce Canyon, UT AGENCY... airspace at Bryce Canyon, UT. Additional controlled airspace is necessary to accommodate aircraft using... a notice of proposed rulemaking to establish additional controlled airspace at Bryce Canyon, UT...

  8. Presymptomatic diagnosis in Huntington's disease: the Mexican experience.

    Science.gov (United States)

    Alonso, Maria Elisa; Ochoa, Adriana; Sosa, Ana Luisa; Rodríguez, Yaneth; Chávez, Mireya; Boll, Catherine; Yescas, Petra; Macías, Rosario; Rasmussen, Astrid

    2009-12-01

    Huntington's disease (HD) is an autosomal dominant progressive, disabling neurodegenerative disorder, for which there is no effective treatment. Predictive testing (PT) for this illness began in 1986 and by 1993 it became more precise after cloning of the gene and the discovery of a CAG repeat expansion as the underlying cause. The objective of this paper is to illustrate the implementation and results of a PT program in a group of at-risk Mexican individuals with 12 years of follow-up. Our PT program conforms to the guidelines proposed by the International Huntington Association and the HD Working group of the World Federation of Neurology. Seventy-five individuals requested the testing, four of them did not fulfill the inclusion criteria, and five abandoned the program voluntarily before receiving the test results. Therefore, 66 results were delivered to 41 noncarriers and 25 mutation carriers. We did not have any catastrophic event, but 4 individuals with normal results and 11 mutation carriers were depressed. Even if this is a small sample, it is the first report of PT in a Latin-American population in which we have been faced with the same problems referred to in larger series.

  9. Pluripotent Stem Cells Models for Huntington's Disease: Prospects and Challenges

    Institute of Scientific and Technical Information of China (English)

    Richard L. Carter; Anthony W.S. Chan

    2012-01-01

    Pluripotent cellular models have shown great promise in the study of a number of neurological disorders.Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types,providing a system for researchers to monitor disease progression during neurogenesis,along with serving as a platform for drug discovery.A number of stem cell derived models have been employed to establish in vitro research models of Huntington's disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies.Although some progress has been made,there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved,In this article we review current stem cell models that have been reported,as well as discuss the issues that impair these studies.We also highlight the prospective application of Huntington's disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.

  10. Progress in studies of gene therapy for Huntington's disease

    Directory of Open Access Journals (Sweden)

    JIN Fan-ying

    2012-06-01

    Full Text Available Huntington's disease (HD is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT -15 involving the expansion of a trinucleotide (CAG repeat encoding glutamine, which leads to abnormal conformation of huntingtin (Htt protein and finally emerge cytotoxic functions. Currently, HD remains a fatal untreatable disease. Gene therapy for HD discussed in this review is under preclinical studies. Silencing of mutant IT-15 via RNA interference (RNAi or antisense oligonucleotide (ASO has shown some effectiveness in mouse model studies. Increasing the clearance of mutant Htt protein could be achieved by viral-mediated delivery of anti-Htt intrabodies (iAbs or induction of autophagy, and beneficial results have been observed. Ectopic expression of neurotrophic factors, such as nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF, mediated either by viral vectors or transplantation of genetically modified cells, has also been proved to be effective. Other gene-modifying methods aiming at correction of transcriptional dysregulation by histone modification, activation of endogenous neural stem cells, and normalization of calcium signaling and mitochondrial function, are also under intensive research. Gene therapy for Huntington's disease is promising, yet a long way remains from preclinical studies to clinical trials.

  11. Clinical diagnosis and management in early Huntington's disease: a review

    Directory of Open Access Journals (Sweden)

    Schiefer J

    2015-03-01

    Full Text Available Johannes Schiefer,1,* Cornelius J Werner,1,* Kathrin Reetz1,2 1Euregional Huntington Center, 2Jülich Aachen Research Alliance (JARA – Translational Brain Medicine, Department of Neurology, RWTH Aachen University, Aachen, Germany *These authors contributed equally to this work Abstract: This review focuses on clinical diagnosis and both pharmacological and nonpharmacological therapeutic options in early stages of the autosomal dominant inherited neurodegenerative Huntington's disease (HD. The available literature has been reviewed for motor, cognitive, and psychiatric alterations, which are the three major symptom domains of this devastating progressive disease. From a clinical point of view, one has to be aware that the HD phenotype can vary highly across individuals and during the course of the disease. Also, symptoms in juvenile HD can differ substantially from those with adult-onset of HD. Although there is no cure of HD and management is limited, motor and psychiatric symptoms often respond to pharmacotherapy, and nonpharmacological approaches as well as supportive care are essential. International treatment recommendations based on study results, critical statements, and expert opinions have been included. This review is restricted to symptomatic and supportive approaches since all attempts to establish a cure for the disease or modifying therapies have failed so far. Keywords: Neurodegeneration, clinical picture, early symptoms, therapy, treatment

  12. Ethical considerations of genetic presymptomatic testing for Huntington's disease.

    Science.gov (United States)

    Coustasse, Alberto; Pekar, Alicia; Sikula, Andrew; Lurie, Sue

    2009-01-01

    The aim of this literature review was to determine if there is adequate ethical justification for presymptomatic genetic testing on potential Huntington's disease patients. Huntington's disease is a neurological genetic disorder characterized by midlife onset which consists of cognitive, physical, and emotional deterioration. Although genetic testing has traditionally been guided by the principle of autonomy, severe psychological consequences such as depression, anxiety, survival guilt, and suicide have complicated the ethical issue of providing a presymptomatic yet definitive diagnosis for an incurable disease. An analysis of available articles yielded inconclusive findings, namely due to insufficient evidence, self-selection bias of test participants, or lack of a longitudinal design. Additional results indicated psychological distress is not solely associated with test result, but rather with individual characteristics including, but not limited to, psychological history, test motivation, level of preparation, social support, and age. In the interest of upholding the principles of autonomy, beneficence, nonmaleficence, and justice, it is recommended that medical professionals follow strict protocol, provide extensive counseling, and employ vigilance when assessing at-risk individuals for HD presymptomatic test eligibility to ensure psychological well-being.

  13. Deep brain stimulation in Huntington's disease: assessment of potential targets.

    Science.gov (United States)

    Sharma, Mayur; Deogaonkar, Milind

    2015-05-01

    Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder that has very few effective therapeutic interventions. Since the disease has a defined neural circuitry abnormality, neuromodulation could be an option. Case reports, original research, and animal model studies were selected from the databases of Medline and PubMed. All related studies published up to July 2014 were included in this review. The following search terms were used: "Deep brain stimulation," "DBS," "thalamotomy," "pallidal stimulation," and "Huntington's Disease," "HD," "chorea," or "hyperkinetic movement disorders." This review examines potential nodes in the HD circuitry that could be modulated using deep brain stimulation (DBS) therapy. With rapid evolution of imaging and ability to reach difficult targets in the brain with refined DBS technology, some phenotypes of HD could potentially be treated with DBS in the near future. Further clinical studies are warranted to validate the efficacy of neuromodulation and to determine the most optimal target for HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Functional impairment of precerebral arteries in Huntington disease.

    Science.gov (United States)

    Kobal, Jan; Cankar, Ksenija; Pretnar, Janja; Zaletel, Marjan; Kobal, Lucijan; Teran, Natasa; Melik, Ziva

    2017-01-15

    Cardiovascular pathology of Huntington disease (HD) appears to be complex; while microvascular dysfunction seems to appear early, deaths from cardiomyopathy and stroke might occur in the late phase of HD. Our study evaluated global risk factors for coronary heart disease (CHD), structure and function of precerebral arteries in 41 HD subjects and 41 matched controls. HD subjects were divided into groups by the United Huntington disease rating scale (presymptomatic-PHD, early-EHD, midstage-MHD and late-LHD). CHD risk factors assessment and Doppler examination of precerebral arteries were performed, including measurements of the carotid artery intima-media thickness (IMT), and parameters indicating local carotid artery distensibility (stiffness index β, pulse wave velocity, pressure strain elasticity module and carotid artery compliance). In the HD and controls we identified a comparable number of non-obstructive plaques (50% lumen narrowing) were found. There was significantly increased IMT in MHD. In PHD and EHD the parameters of arterial stiffness were significantly higher and the carotid artery compliance was significantly lower. Our results reveal functional vascular pathology in PHD, EHD, and MHD. Precerebral arteries dysfunction in HD therefore appears to be mostly functional and in agreement with recently described autonomic nervous system changes in HD. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Clinical and genetic data of Huntington disease in Moroccan patients.

    Science.gov (United States)

    Bouhouche, Ahmed; Regragui, Wafaa; Lamghari, Hind; Khaldi, Khadija; Birouk, Nazha; Lytim, Safaa; Bellamine, Soufiane; Kriouile, Yamna; Bouslam, Naima; Haddou, El Hachmia Ait Ben; Faris, Mustapha Alaoui; Benomar, Ali; Yahyaoui, Mohamed

    2015-12-01

    Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10/100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin. Clinical and genetics data of 21 consecutive patients recruited from 2009 to 2014 from the outpatient clinic of six medical centers were analyzed. Statistical analysis was performed using descriptive statistics. Twenty one patients from 17 families were diagnosed positive for the IT15 gene CAG expansion. Clinical symptoms were predominantly motor (19/21). Twelve patients had psychiatric and behavioral disorders, and 11 patients had cognitive disorders essentially of memory impairment. Analysis of genetic results showed that 5 patients had reduced penetrant (RP) alleles and 16 had fully penetrant (FP) alleles. The mean CAG repeat length in patients with RP alleles was 38.4 ± 0.54, and 45.37 ± 8.30 in FP alleles. The age of onset and the size of the CAG repeat length showed significant inverse correlation (p <0.001, r = -0.754). Clinical and genetic data of Moroccan patients are similar to those of Caucasian populations previously reported in the literature.

  16. Review of the Diablo Canyon probabilistic risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bozoki, G.E.; Fitzpatrick, R.G.; Bohn, M.P. [Sandia National Lab., Albuquerque, NM (United States); Sabek, M.G. [Atomic Energy Authority, Nuclear Regulatory and Safety Center, Cairo (Egypt); Ravindra, M.K.; Johnson, J.J. [EQE Engineering, San Francisco, CA (United States)

    1994-08-01

    This report details the review of the Diablo Canyon Probabilistic Risk Assessment (DCPRA). The study was performed under contract from the Probabilistic Risk Analysis Branch, Office of Nuclear Reactor Research, USNRC by Brookhaven National Laboratory. The DCPRA is a full scope Level I effort and although the review touched on all aspects of the PRA, the internal events and seismic events received the vast majority of the review effort. The report includes a number of independent systems analyses sensitivity studies, importance analyses as well as conclusions on the adequacy of the DCPRA for use in the Diablo Canyon Long Term Seismic Program.

  17. Surprise and Opportunity for Learning in Grand Canyon: the Glen Canyon Dam Adaptive Management Program

    Science.gov (United States)

    Melis, T. S.; Walters, C. J.; Korman, J.

    2013-12-01

    With a focus on resources of the Colorado River ecosystem downstream of Glen Canyon Dam in Glen Canyon National Recreation Area (GCNRA) and Grand Canyon National Park (GCNP) of northern Arizona, the Glen Canyon Dam Adaptive Management Program has evaluated experimental flow and nonflow policy tests since 1990. Flow experiments have consisted of a variety of water releases from the dam within pre-existing annual downstream delivery agreements. The daily experimental dam operation, termed the Modified Low Fluctuating Flow (MLFF), implemented in 1996 to increase daily low flows and decrease daily peaks were intended to limit daily flow range to conserve tributary sand inputs and improve navigation among other objectives, including hydropower energy. Other flow tests have included controlled floods with some larger releases bypassing the dam's hydropower plant to rebuild and maintain eroded sandbars in GCNP. Experimental daily hydropeaking tests beyond MLFF have also been evaluated for managing the exotic recreational rainbow trout fishery in the dam's GCNRA tailwater. Experimental nonflow policies, such as physical removal of exotic fish below the tailwater, and experimental translocation of endangered native humpback chub from spawning habitats in the Little Colorado River (the largest natal origin site for chub in the basin) to other tributaries within GCNP have also been monitored. None of these large-scale field experiments has yet produced unambiguous results in terms of management prescriptions, owing to inadequate monitoring programs and confounding of treatment effects with effects of ongoing natural changes; most notably, a persistent warming of the river resulting from reduced storage in the dam's reservoir after 2003. But there have been several surprising results relative to predictions from models developed to identify monitoring needs and evaluate experimental design options at the start of the adaptive ecosystem assessment and management program in 1997

  18. Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.

    Science.gov (United States)

    Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntington's disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner.

  19. Submarine canyons as important habitat for cetaceans, with special reference to the Gully: A review

    Science.gov (United States)

    Moors-Murphy, Hilary B.

    2014-06-01

    There has been much research interest in the use of submarine canyons by cetaceans, particularly beaked whales (family Ziphiidae), which appear to be especially attracted to canyon habitats in some areas. However, not all submarine canyons are associated with large numbers of cetaceans and the mechanisms through which submarine canyons may attract cetaceans are not clearly understood. This paper reviews some of the cetacean associations with submarine canyons that have been anecdotally described or presented in scientific literature and discusses the physical, oceanographic and biological mechanisms that may lead to enhanced cetacean abundance around these canyons. Particular attention is paid to the Gully, a large submarine canyon and Marine Protected Area off eastern Canada for which there exists some of the strongest evidence available for submarine canyons as important cetacean habitat. Studies demonstrating increased cetacean abundance in the Gully and the processes that are likely to attract cetaceans to this relatively well-studied canyon are discussed. This review provides some limited evidence that cetaceans are more likely to associate with larger canyons; however, further studies are needed to fully understand the relationship between the physical characteristics of canyons and enhanced cetacean abundance. In general, toothed whales (especially beaked whales and sperm whales) appear to exhibit the strongest associations with submarine canyons, occurring in these features throughout the year and likely attracted by concentrating and aggregating processes. By contrast, baleen whales tend to occur in canyons seasonally and are most likely attracted to canyons by enrichment and concentrating processes. Existing evidence thus suggests that at least some submarine canyons are important foraging areas for cetaceans, and should be given special consideration for cetacean conservation and protection.

  20. Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles, Vermont

    Data.gov (United States)

    Vermont Center for Geographic Information — Digital Data from VG95-9A Thompson, PJ�and Thompson, TB, 1995, Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles,...

  1. Recent Trends in Detection of Huntingtin and Preclinical Models of Huntington's Disease.

    Science.gov (United States)

    Mantha, Neelima; Das, Nandita G; Das, Sudip K

    2014-01-01

    Huntington's disease is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain. Molecular biology techniques to detect and quantify huntingtin protein in biological samples involve fluorescence imaging, western blotting, and PCR. Modified cell lines are widely used as models for Huntington's disease for preclinical screening of drugs to study their ability to suppress the expression of huntingtin. Although worm and fly species have been experimented on as models for Huntington's disease, the most successful animal models have been reported to be primates. This review critically analyses the molecular biology techniques for detection and quantitation of huntingtin and evaluates the various animal species for use as models for Huntington's disease.

  2. The Current Status of Neural Grafting in the Treatment of Huntington's Disease. A Review

    National Research Council Canada - National Science Library

    Wijeyekoon, Ruwani; Barker, Roger A

    2011-01-01

    Huntington's disease (HD) is a devastating, fatal, autosomal dominant condition in which the abnormal gene codes for a mutant form of huntingtin that causes widespread neuronal dysfunction and death...

  3. Hypothalamic Alterations in Huntington's Disease Patients : Comparison with Genetic Rodent Models

    NARCIS (Netherlands)

    Van Wamelen, D.J.; Aziz, N A; Roos, R A C; Swaab, D F

    2014-01-01

    Unintended weight loss, sleep and circadian disturbances and autonomic dysfunction are prevalent features of Huntington's disease (HD), an autosomal dominantly inherited neurodegenerative disorder caused by an expanded CAG repeat sequence in the HTT gene. These features form a substantial contributi

  4. 77 FR 51064 - Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application...

    Science.gov (United States)

    2012-08-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Employment and Training Administration Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated May 21, 2012, the State...

  5. The role of tau in the pathological process and clinical expression of Huntington's disease

    DEFF Research Database (Denmark)

    Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan

    2015-01-01

    -mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report...... not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some...... instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington's disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau...

  6. Dynamics of the connectome in Huntington's disease : A longitudinal diffusion MRI study

    NARCIS (Netherlands)

    Odish, Omar F F; Caeyenberghs, Karen; Hosseini, Hadi; Van Den Bogaard, Simon J A; Roos, Raymund A C; Leemans, A

    2015-01-01

    Abstract Objectives To longitudinally investigate the connectome in different stages of Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI data. Experimental design We constructed weighted structural networks and calculated their topological properties. Twenty-two prem

  7. Evaluation of tetrathiomolybdate in the R6/2 model of Huntington disease.

    Science.gov (United States)

    Tallaksen-Greene, Sara J; Janiszewska, Anita; Benton, Kasha; Hou, Guoqing; Dick, Robert; Brewer, George J; Albin, Roger L

    2009-03-06

    Huntington disease is an uncommon autosomal dominant neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin protein. The proximate mechanisms responsible for neurodegeneration are unknown. Copper ions may play a role in Huntington disease by promoting oligomerization of expanded polyglutamine repeat protein fragments. Ammonium tetrathiomolybdate is a copper complexing agent with demonstrated tolerability and efficacy in another neurodegenerative disorder, Wilson disease. We evaluated ammonium tetrathiomolybdate in the R6/2 transgenic mouse model of Huntington disease. Ammonium tetrathiomolybdate treatment delayed the onset of motor dysfunction in R6/2 mice. There was a trend towards reduced striatal degeneration, suggesting a neuroprotective effect of ammonium tetrathiomolybdate in this model. Given its known tolerability in humans with neurodegeneration, ammonium tetrathiomolybdate could be considered as a candidate for clinical trials in Huntington disease.

  8. High-resolution topography and geomorphology of select archeological sites in Glen Canyon National Recreation Area, Arizona

    Science.gov (United States)

    Collins, Brian D.; Corbett, Skye C.; Sankey, Joel B.; Fairley, Helen C.

    2014-01-01

    better suited for reach- and regional-scale mapping. Our site-specific geomorphic analyses of the four archeological sites indicate that their current topographical conditions are a result of different and sometimes competing erosional agents, including bedrock- and terrace-based overland flow, fluvial-induced terrace bank collapse, and alluvial-fan-generated debris flows. Although the influences of anthropogenic-induced erosion from dam operations are not specifically analyzed in this report, we do identify geomorphic settings where dam operations are either more or less likely to affect archeological site stability. This information can be used to assist with future monitoring efforts of these sites and identification of similar conditions for other archeological sites along the Colorado River corridor in Glen Canyon.

  9. The role of tau in the pathological process and clinical expression of Huntington's disease.

    Science.gov (United States)

    Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan; Cisbani, Giulia; Drouin-Ouellet, Janelle; Spillantini, Maria G; Cicchetti, Francesca; Barker, Roger A

    2015-07-01

    Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington's disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington's disease. We explored this association in more detail at the neuropathological, genetic and clinical level. We first investigated tau pathology by looking for the presence of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and its oligomeric intermediates in post-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington's disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau entity) are present in the Huntington's disease brains. Finally we highlight the clinical significance of this pathology by demonstrating that the MAPT haplotypes affect the rate

  10. Increased brain tissue sodium concentration in Huntington's Disease - a sodium imaging study at 4 T.

    Science.gov (United States)

    Reetz, Kathrin; Romanzetti, Sandro; Dogan, Imis; Saß, Christian; Werner, Cornelius J; Schiefer, Johannes; Schulz, Jörg B; Shah, N Jon

    2012-10-15

    The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital

  11. [The life as a caregiver of a person affected by Chorea Huntington: multiple case study].

    Science.gov (United States)

    Winkler, Evi; Ausserhofer, Dietmar; Mantovan, Franco

    2012-10-01

    Chorea Huntington is an autosomal dominantly inherited, neurodegenerative brain disorder that leads to involuntary hyperkinesia, psychotic symptoms and dementia. The illness not only changes the life of the person itself but also the world of the caregivers. The challenges in the care of a person which is affected by Chorea Huntington have an effect on the daily living as an assemblage of natural and social conditions. a multiple case study was conducted. It included semi-structured interviews with three caregivers of people with Chorea Huntington in South Tyrol. The qualitative data was analyzed using the qualitative structured analysis of Mayring (2007). The objective of this study was to describe the phenomenon of change of life from family members that care people affected by Chorea Huntington in a specific cultural setting (South Tyrol, Italy). The caregivers reported that the diagnosis of Chorea Huntington leads to negative changes in "relationship and family". Particularly, frustration, aggression, impatience and apathy were perceived as stressful. At the same time they highlight the positive changes through home care. They report that the relationship became more intimate and integral and it was characterized by more cohesion. Family caregivers get valuable support from the home care service, however, they complain that there is no facility in South Tyrol, which is specialized to care people with Chorea Huntington. Therefore, the caregivers have to "give up a lot" and don't have any personal desires, dreams and expectations for the future. The caregivers have learned independently to deal with their changed life step by step, and to see also the positive effects of the caring role. The life of family caregivers of a person which is affected by Chorea Huntington is characterized by abandonment. A continuous and professional care would be important for the affected and his caregiver. A continuous and professional care is important for both, addressing the

  12. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.

    OpenAIRE

    Quinn, N.; Marsden, C. D.

    1984-01-01

    Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause...

  13. Submarine canyons as coral and sponge habitat on the eastern Bering Sea slope

    Directory of Open Access Journals (Sweden)

    Robert J. Miller

    2015-07-01

    Full Text Available Submarine canyons have been shown to positively influence pelagic and benthic biodiversity and ecosystem function. In the eastern Bering Sea, several immense canyons lie under the highly productive “green belt” along the continental slope. Two of these, Pribilof and Zhemchug canyons, are the focus of current conservation interest. We used a maximum entropy modeling approach to evaluate the importance of these two canyons, as well as canyons in general, as habitat for gorgonian (alcyonacean corals, pennatulacean corals, and sponges, in an area comprising most of the eastern Bering Sea slope and outer shelf. These invertebrates create physical structure that is a preferred habitat for many mobile species, including commercially important fish and invertebrates. We show that Pribilof canyon is a hotspot of structure-forming invertebrate habitat, containing over 50% of estimated high-quality gorgonian habitat and 45% of sponge habitat, despite making up only 1.7% of the total study area. The amount of quality habitat for gorgonians and sponges varied in other canyons, but canyons overall contained more high-quality habitat for structure-forming invertebrates compared to other slope areas. Bottom trawling effort was not well correlated with habitat quality for structure-forming invertebrates, and bottom-contact fishing effort in general, including longlining and trawling, was not particularly concentrated in the canyons examined. These results suggest that if conserving gorgonian coral habitat is a management goal, canyons, particularly Pribilof Canyon, may be a prime location to do this without excessive impact on fisheries.

  14. Grand Canyon Trekkers: School-Based Lunchtime Walking Program

    Science.gov (United States)

    Hawthorne, Alisa; Shaibi, Gabriel; Gance-Cleveland, Bonnie; McFall, Sarah

    2011-01-01

    The incidence of childhood overweight is especially troubling among low income Latino youth. Grand Canyon Trekkers (GCT) was implemented as a quasi-experimental study in 10 Title 1 elementary schools with a large Latino population to examine the effects of a 16-week structured walking program on components of health-related physical fitness: Body…

  15. College of the Canyons Nursing Alumni Surveys, Spring 2001. Report.

    Science.gov (United States)

    Meuschke, Daylene M; Dixon, P. Scott; Gribbons, Barry C.

    In the summer of 2001, College of the Canyons (California) conducted of study of registered nursing (RN) and licensed vocational nursing (LVN) alumni, as well as their employers, to assess satisfaction with the preparation and training they received through the College's nursing programs. Out of the 89 invited nursing alumni, 33 surveys were…

  16. 78 FR 60693 - Establishment of the Ballard Canyon Viticultural Area

    Science.gov (United States)

    2013-10-02

    ... duties in the administration and enforcement of this law. Part 4 of the TTB regulations (27 CFR part 4... adequate information as to the identity and quality of the product. The Alcohol and Tobacco Tax and Trade... professional'' who is familiar with wines produced in the Ballard Canyon area. None of the comments...

  17. Phytophthora ramorum causes cryptic bole cankers in Canyon line Oak

    Science.gov (United States)

    Unusual mortality of large canyon live oaks was observed in natural stands in San Mateo, California starting in 2007. A survey of affected stands showed that symptomatic trees were spatially associated with California bay, the primary source of Phytophthora ramorum spores in this forest type. Trunk ...

  18. Carbonaceous aerosol particles from common vegetation in the Grand Canyon

    Energy Technology Data Exchange (ETDEWEB)

    Hallock, K.A.; Mazurek, M.A. (Brookhaven National Lab., Upton, NY (United States)); Cass, G.R. (California Inst. of Tech., Pasadena, CA (United States). Dept. of Environmental Engineering Science)

    1992-05-01

    The problem of visibility reduction in the Grand Canyon due to fine organic aerosol particles in the atmosphere has become an area of increased environmental concern. Aerosol particles can be derived from many emission sources. In this report, we focus on identifying organic aerosols derived from common vegetation in the Grand Canyon. These aerosols are expected to be significant contributors to the total atmospheric organic aerosol content. Aerosol samples from living vegetation were collected by resuspension of surface wax and resin components liberated from the leaves of vegetation common to areas of the Grand Canyon. The samples were analyzed using high-resolution gas chromatography/mass spectrometry (GC/MS). Probable identification of compounds was made by comparison of sample spectra with National Institute of Standards and Technology (NIST) mass spectral references and positive identification of compounds was made when possible by comparison with authentic standards as well as NIST references. Using these references, we have been able to positively identify the presence of n-alkane and n-alkanoic acid homolog series in the surface waxes of the vegetation sampled. Several monoterpenes, sesquiterpenes, and diterpenes were identified also as possible biogenic aerosols which may contribute to the total organic aerosol abundance leading to visibility reduction in the Grand Canyon.

  19. Effects of electric vehicles on air quality in street canyons

    Directory of Open Access Journals (Sweden)

    Tilmann Schöllnhammer

    2014-09-01

    Full Text Available Road traffic is one of the main causes of poor air quality in European cities. Electric vehicles (EV are often presented as climate friendly and as a solution for air quality problems in cities. The aim of this study is to investigate how much of this claim is true and to find out the necessary shares of electric vehicles of different types needed to solve air quality problems in street canyons. For example, the German government has formulated the ambitious goal of increasing the amount of electric vehicles in Germany to 1 million in 2020 and 6 million in 2030. Will this improve the air quality significantly? The focus of the present study is the air quality in street canyons, with a focus on PM10 and NO2 concentrations. We concentrate our investigation on road traffic, taking the fleet composition into account. A sensitivity study with a dispersion model was carried out for two street canyons in North Rhine-Westphalia, typical for moderately polluted street canyons in European cities. It is shown that the reduction potential is larger for NO2 than for PM10. The necessary share of electric vehicles to comply with the limit values lies at about 40 % for NO2 and 100 % for PM10, respectively. Thus, the share of electric vehicles needed to comply with the limit values is far above the goal of the German government.

  20. Small Mammal Sampling in Mortandad and Los Alamos Canyons, 2005

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Kathy; Sherwood, Sherri; Robinson, Rhonda

    2006-08-15

    As part of an ongoing ecological field investigation at Los Alamos National Laboratory, a study was conducted that compared measured contaminant concentrations in sediment to population parameters for small mammals in the Mortandad Canyon watershed. Mortandad Canyon and its tributary canyons have received contaminants from multiple solid waste management units and areas of concern since establishment of the Laboratory in the 1940s. The study included three reaches within Effluent and Mortandad canyons (E-1W, M-2W, and M-3) that had a spread in the concentrations of metals and radionuclides and included locations where polychlorinated biphenyls and perchlorate had been detected. A reference location, reach LA-BKG in upper Los Alamos Canyon, was also included in the study for comparison purposes. A small mammal study was initiated to assess whether potential adverse effects were evident in Mortandad Canyon due to the presence of contaminants, designated as contaminants of potential ecological concern, in the terrestrial media. Study sites, including the reference site, were sampled in late July/early August. Species diversity and the mean daily capture rate were the highest for E-1W reach and the lowest for the reference site. Species composition among the three reaches in Mortandad was similar with very little overlap with the reference canyon. Differences in species composition and diversity were most likely due to differences in habitat. Sex ratios, body weights, and reproductive status of small mammals were also evaluated. However, small sample sizes of some species within some sites affected the analysis. Ratios of males to females by species of each site (n = 5) were tested using a Chi-square analysis. No differences were detected. Where there was sufficient sample size, body weights of adult small mammals were compared between sites. No differences in body weights were found. Reproductive status of species appears to be similar across sites. However, sample

  1. Phenology of the adult angel lichen moth (Cisthene angelus) in Grand Canyon, USA

    Science.gov (United States)

    Metcalfe, Anya; Kennedy, Theodore A.; Muehlbauer, Jeffrey D.

    2016-01-01

    We investigated the phenology of adult angel lichen moths (Cisthene angelus) along a 364-km long segment of the Colorado River in Grand Canyon, Arizona, USA, using a unique data set of 2,437 light-trap samples collected by citizen scientists. We found that adults of C. angelus were bivoltine from 2012 to 2014. We quantified plasticity in wing lengths and sex ratios among the two generations and across a 545-m elevation gradient. We found that abundance, but not wing length, increased at lower elevations and that the two generations differed in size and sex distributions. Our results shed light on the life history and morphology of a common, but poorly known, species of moth endemic to the southwestern United States and Mexico.

  2. Dynamics of the Bingham Canyon Mine landslides from seismic signal analysis

    Science.gov (United States)

    Hibert, Clément; Ekström, Göran; Stark, Colin P.

    2014-07-01

    Joint interpretation of long- and short-period seismic signals generated by landslides sheds light on the dynamics of slope failure, providing constraints on landslide initiation and termination and on the main phases of acceleration and deceleration. We carry out a combined analysis of the seismic signals generated by two massive landslides that struck the Bingham Canyon Mine pit on 10 April 2013. Inversion of the long-period waveforms yields time series for the bulk landslide forces and momenta, from which we deduce runout trajectories consistent with the deposit morphology. Comparing these time series with the short-period seismic data, we are able to infer when and where major changes take place in landslide momentum along the runout path. This combined analysis points to a progressive fracturing of the masses during acceleration indicates that deceleration starts the moment they reach the pit floor and suggests that the bulk movement is stopped by a topographic barrier.

  3. It wasn't Witchcraft--It was Huntington Disease!

    Science.gov (United States)

    Penaranda, Eribeth; Garcia, Angel; Montgomery, Lisa

    2011-01-01

    Huntington disease (HD) is an autosomal-dominant, incurable, progressive disorder that manifests with chorea and behavioral and cognitive impairment. The disease usually occurs during the fourth or fifth decade of life; however, it may present at any age. Clinical suspicion is confirmed by genetic testing. Death occurs, on average, 15 to 20 years after the onset of symptoms. Here we report about a Hispanic woman and her family who were affected by the disease; this case illustrates the role of cultural values and beliefs in the decision-making process, as well as the importance of the physician's cultural competency in fostering a trusting relationship that may lessen the burden of catastrophic diseases on individuals, families, and society at-large.

  4. Huntington's disease impairs recognition of angry and instrumental body language.

    Science.gov (United States)

    de Gelder, Beatrice; Van den Stock, Jan; Balaguer, Ruth de Diego; Bachoud-Lévi, Anne-Catherine

    2008-01-15

    Patients with Huntington's disease (HD) exhibit motor impairments as well as cognitive and emotional deficits. So far impairments in the ability to recognize emotional stimuli have mostly been investigated by using facial expressions and emotional voices. Other important emotional signals are provided by the whole body. To investigate the impact of motor deficits on body recognition and the relation between motor disorders and emotion perception deficits, we tested recognition of emotional body language (instrumental, angry, fearful and sad) in 19 HD patients and their matched controls with a nonverbal whole body expression matching task. Results indicate that HD patients are impaired in recognizing both instrumental and angry whole body postures. Furthermore, the body language perception deficits are correlated with measures of motor deficit. Taken together the results suggest a close relationship between emotion recognition (specifically anger) and motor abilities.

  5. Rapid eye movement sleep disturbances in Huntington disease

    DEFF Research Database (Denmark)

    Arnulf, I.; Nielsen, J.; Lohmann, E.

    2008-01-01

    with very mild HD and worsened with disease severity. In contrast to narcoleptic patients, HD patients had no cataplexy, hypnagogic hallucinations, or sleep paralysis. Four HD patients had abnormally low (sleep latencies, but none had multiple sleep-onset REM periods. Conclusions......Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages...... interview, nighttime video and sleep monitoring, and daytime multiple sleep latency tests. Their results were compared with those of patients with narcolepsy and control patients. Results: The HD patients had frequent insomnia, earlier sleep onset, lower sleep efficiency, increased stage I sleep, delayed...

  6. Nucleic Acid-Based Therapy Approaches for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Tatyana Vagner

    2012-01-01

    Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

  7. Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease.

    Science.gov (United States)

    Khakh, Baljit S; Beaumont, Vahri; Cachope, Roger; Munoz-Sanjuan, Ignacio; Goldman, Steven A; Grantyn, Rosemarie

    2017-07-01

    Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington's disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter clearance, as well as on the use of transplanted astrocytes to produce therapeutic benefit in mouse models of HD. Overall, the data suggest that astrocyte dysfunction is an important contributor to the onset and progression of some HD symptoms in mice. Additional exploration of astrocytes in HD mouse models and humans is needed and may provide new therapeutic opportunities to explore in conjunction with neuronal rescue and repair strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genetic counseling and testing for Huntington's disease: A historical review.

    Science.gov (United States)

    Nance, Martha A

    2017-01-01

    This manuscript describes the ways in which genetic counseling has evolved since John Pearson and Sheldon Reed first promoted "a genetic education" in the 1950s as a voluntary, non-directive clinical tool for permitting individual decision making. It reviews how the emergence of Huntington's disease (HD) registries and patient support organizations, genetic testing, and the discovery of a disease-causing CAG repeat expansion changed the contours of genetic counseling for families with HD. It also reviews the guidelines, outcomes, ethical and laboratory challenges, and uptake of predictive, prenatal, and preimplantation testing, and it casts a vision for how clinicians can better make use of genetic counseling to reach a broader pool of families that may be affected by HD and to ensure that genetic counseling is associated with the best levels of care. © 2016 Wiley Periodicals, Inc.

  9. Striatal Vulnerability in Huntington's Disease: Neuroprotection Versus Neurotoxicity.

    Science.gov (United States)

    Morigaki, Ryoma; Goto, Satoshi

    2017-06-07

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.

  10. Genetic Mouse Models of Huntington's Disease: Focus on Electrophysiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlos Cepeda

    2010-03-01

    Full Text Available The discovery of the HD (Huntington's disease gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell-cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.

  11. High resolution impedance manometric findings in dysphagia of Huntington's disease

    Institute of Scientific and Technical Information of China (English)

    Tae Hee Lee; Joon Seong Lee; Wan Jung Kim

    2012-01-01

    Conventional manometry presents significant challenges,espedally in assessment of pharyngeal swallowing,because of the asymmetry and deglutitive movements of oropharyngeal structures.It only provides information about intraluminal pressure and thus it is difficult to study functional details of esophageal motility disorders.New technology of solid high resolution impedance manometry (HRIM),with 32 pressure sensors and 6 impedance sensors,is likely to provide better assessment of pharyngeal swallowing as well as more information about esophageal motility disorders.However,the clinical usefulness of application of HRIM in patients with oropharyngeal dysphagia or esophageal dysphagia is not known.We experienced a case of Huntington's disease presenting with both oropharyngeal and esophageal dysphagia,in which HRIM revealed the mechanism of oropharyngeal dysphagia and provided comprehensive information about esophageal dysphagia.

  12. Observation of the Wigner-Huntington transition to metallic hydrogen

    Science.gov (United States)

    Dias, Ranga P.; Silvera, Isaac F.

    2017-02-01

    Producing metallic hydrogen has been a great challenge in condensed matter physics. Metallic hydrogen may be a room-temperature superconductor and metastable when the pressure is released and could have an important impact on energy and rocketry. We have studied solid molecular hydrogen under pressure at low temperatures. At a pressure of 495 gigapascals, hydrogen becomes metallic, with reflectivity as high as 0.91. We fit the reflectance using a Drude free-electron model to determine the plasma frequency of 32.5 ± 2.1 electron volts at a temperature of 5.5 kelvin, with a corresponding electron carrier density of 7.7 ± 1.1 × 1023 particles per cubic centimeter, which is consistent with theoretical estimates of the atomic density. The properties are those of an atomic metal. We have produced the Wigner-Huntington dissociative transition to atomic metallic hydrogen in the laboratory.

  13. Westphal variant Huntington disease and refractory catatonia: a case report.

    Science.gov (United States)

    Merida-Puga, Jorge; Ramirez-Bermudez, Jesus; Aguilar-Venegas, Luis Carlos; Fricchione, Gregory L; Espinola-Nadurille, Mariana

    2011-12-01

    A young woman with Westphal variant (juvenile) Huntington disease (HD) also developed catatonia. Catatonia is an underdiagnosed psychomotor syndrome often associated with neurological and psychiatric disorders, but it has rarely been documented in patients with HD. Catatonia usually responds to standard treatment with benzodiazepines and electroconvulsive therapy; however, this patient's catatonic syndrome did not improve until we augmented the standard treatment with amantadine and levodopa. The underlying pathophysiology and a neurochemical hypothesis of HD and catatonia can explain their comorbidity and the refractoriness of catatonia to treatment. Both conditions are linked to dysregulation of neurotransmitters in the striatocortical and corticocortical pathways. This understanding may serve as a guide for the use of nonstandard treatments. Our evidence also suggests that electroconvulsive therapy can be useful and safe in the treatment of HD.

  14. Autophagy in Huntington disease and huntingtin in autophagy.

    Science.gov (United States)

    Martin, Dale D O; Ladha, Safia; Ehrnhoefer, Dagmar E; Hayden, Michael R

    2015-01-01

    Autophagy is an important biological process that is essential for the removal of damaged organelles and toxic or aggregated proteins by delivering them to the lysosome for degradation. Consequently, autophagy has become a primary target for the treatment of neurodegenerative diseases that involve aggregating proteins. In Huntington disease (HD), an expansion of the polyglutamine (polyQ) tract in the N-terminus of the huntingtin (HTT) protein leads to protein aggregation. However, HD is unique among the neurodegenerative proteinopathies in that autophagy is not only dysfunctional but wild type (wt) HTT also appears to play several roles in regulating the dynamics of autophagy. Herein, we attempt to integrate the recently described novel roles of wtHTT and altered autophagy in HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Analysis of dust samples collected from spent nuclear fuel interim storage containers at Hope Creek, Delaware, and Diablo Canyon, California

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, Charles R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Enos, David George [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-07-01

    Potentially corrosive environments may form on the surface of spent nuclear fuel dry storage canisters by deliquescence of deposited dusts. To assess this, samples of dust were collected from in-service dry storage canisters at two near-marine sites, the Hope Creek and Diablo Canyon storage installations, and have been characterized with respect to mineralogy, chemistry, and texture. At both sites, terrestrially-derived silicate minerals, including quartz, feldspars, micas, and clays, comprise the largest fraction of the dust. Also significant at both sites were particles of iron and iron-chromium metal and oxides generated by the manufacturing process. Soluble salt phases were minor component of the Hope Creek dusts, and were compositionally similar to inland salt aerosols, rich in calcium, sulfate, and nitrate. At Diablo Canyon, however, sea-salt aerosols, occurring as aggregates of NaCl and Mg-sulfate, were a major component of the dust samples. The seasalt aerosols commonly occurred as hollow spheres, which may have formed by evaporation of suspended aerosol seawater droplets, possibly while rising through the heated annulus between the canister and the overpack. The differences in salt composition and abundance for the two sites are attributed to differences in proximity to the open ocean and wave action. The Diablo Canyon facility is on the shores of the Pacific Ocean, while the Hope Creek facility is on the shores of the Delaware River, several miles from the open ocean.

  16. 3-D basin-scale reconstruction of natural gas hydrate system of the Green Canyon, Gulf of Mexico

    Science.gov (United States)

    Burwicz, Ewa; Reichel, Thomas; Wallmann, Klaus; Rottke, Wolf; Haeckel, Matthias; Hensen, Christian

    2017-05-01

    Our study presents a basin-scale 3-D modeling solution, quantifying and exploring gas hydrate accumulations in the marine environment around the Green Canyon (GC955) area, Gulf of Mexico. It is the first modeling study that considers the full complexity of gas hydrate formation in a natural geological system. Overall, it comprises a comprehensive basin reconstruction, accounting for depositional and transient thermal history of the basin, source rock maturation, petroleum components generation, expulsion and migration, salt tectonics, and associated multistage fault development. The resulting 3-D gas hydrate distribution in the Green Canyon area is consistent with independent borehole observations. An important mechanism identified in this study and leading to high gas hydrate saturation (>80 vol %) at the base of the gas hydrate stability zone (GHSZ) is the recycling of gas hydrate and free gas enhanced by high Neogene sedimentation rates in the region. Our model predicts the rapid development of secondary intrasalt minibasins situated on top of the allochthonous salt deposits which leads to significant sediment subsidence and an ensuing dislocation of the lower GHSZ boundary. Consequently, large amounts of gas hydrates located in the deepest parts of the basin dissociate and the released free methane gas migrates upward to recharge the GHSZ. In total, we have predicted the gas hydrate budget for the Green Canyon area that amounts to ˜3256 Mt of gas hydrate, which is equivalent to ˜340 Mt of carbon (˜7 × 1011 m3 of CH4 at STP conditions), and consists mostly of biogenic hydrates.

  17. Analysis of dust samples collected from spent nuclear fuel interim storage containers at Hope Creek, Delaware, and Diablo Canyon, California.

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, Charles R.; Enos, David George

    2014-07-01

    Potentially corrosive environments may form on the surface of spent nuclear fuel dry storage canisters by deliquescence of deposited dusts. To assess this, samples of dust were collected from in-service dry storage canisters at two near-marine sites, the Hope Creek and Diablo Canyon storage installations, and have been characterized with respect to mineralogy, chemistry, and texture. At both sites, terrestrially-derived silicate minerals, including quartz, feldspars, micas, and clays, comprise the largest fraction of the dust. Also significant at both sites were particles of iron and iron-chromium metal and oxides generated by the manufacturing process. Soluble salt phases were minor component of the Hope Creek dusts, and were compositionally similar to inland salt aerosols, rich in calcium, sulfate, and nitrate. At Diablo Canyon, however, sea-salt aerosols, occurring as aggregates of NaCl and Mg-sulfate, were a major component of the dust samples. The seasalt aerosols commonly occurred as hollow spheres, which may have formed by evaporation of suspended aerosol seawater droplets, possibly while rising through the heated annulus between the canister and the overpack. The differences in salt composition and abundance for the two sites are attributed to differences in proximity to the open ocean and wave action. The Diablo Canyon facility is on the shores of the Pacific Ocean, while the Hope Creek facility is on the shores of the Delaware River, several miles from the open ocean.

  18. Diagnóstico molecular de la enfermedad de Huntington en Costa Rica Molecular diagnosis of Huntington´s disease in Costa Rica

    OpenAIRE

    Melissa Vásquez-Cerdas; Fernando Morales-Montero; Húbert Fernández-Morales; Gerardo el Valle-Carazo; Jaime Fornaguera-Trías; Patricia Cuenca-Berger

    2008-01-01

    Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2008 Justificación y objetivo. Este estudio representa un esfuerzo para establecer por primera vez en Costa Rica el diagnóstico molecular de la enfermedad de Huntington; esto favorecerá un mejor manejo clínico de los pacientes y podrá ser traducido en un incremento de la calidad de vida de las familias. Se pretende determinar el número de repeticiones CAG en personas con la enfermedad de Huntington y f...

  19. Discrepancies in reporting the CAG repeat lengths for Huntington's disease.

    Science.gov (United States)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty; Dumoulin, Christine; Ramos-Arroyo, Maria; Biunno, Ida; Bauer, Peter; Kline, Margaret; Landwehrmeyer, G Bernhard

    2012-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

  20. Orphan drugs in development for Huntington's disease: challenges and progress

    Directory of Open Access Journals (Sweden)

    Burgunder JM

    2015-02-01

    advanced strategies to develop novel treatments in Huntington's disease are examined. Keywords: Huntington's disease, symptomatic treatment, disease-modifying therapy

  1. Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

    Science.gov (United States)

    Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

    2012-04-01

    Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

  2. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  3. Proteomic and oxidative stress analysis in human brain samples of Huntington disease.

    Science.gov (United States)

    Sorolla, Ma Alba; Reverter-Branchat, Gemma; Tamarit, Jordi; Ferrer, Isidre; Ros, Joaquim; Cabiscol, Elisa

    2008-09-01

    Huntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG repeats in exon 1 of the huntingtin gene, affecting initially the striatum and progressively the cortex. This work reports a proteomic analysis of human brain postmortem samples obtained from striatum and cortex of patients with HD compared to samples of age- and sex-matched controls. Antioxidant defense proteins that were strongly induced in striatum, but also detectable in cortex, were identified as peroxiredoxins 1, 2, and 6, as well as glutathione peroxidases 1 and 6. The activities of other antioxidant enzymes such as mitochondrial superoxide dismutase and catalase were also increased in HD. Aconitase, a protein involved in energy metabolism, showed decreased activities in striatum of HD patients. Protein carbonyls, used as markers of oxidative stress, were increased in HD, and glial fibrillary acidic protein, aconitase, gamma-enolase, and creatine kinase B were identified as the main targets. Taken together, these results indicate that oxidative stress and damage to specific macromolecules would participate in the disease progression. Also, these data support the rationale for therapeutic strategies that either potentiate antioxidant defenses or avoid oxidative stress generation to delay disease progression.

  4. Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice.

    Science.gov (United States)

    Møllersen, Linda; Rowe, Alexander D; Larsen, Elisabeth; Rognes, Torbjørn; Klungland, Arne

    2010-12-09

    Huntington's disease (HD) is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability is observed in the brain, correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat instability are poorly understood, but locally formed secondary DNA structures generated during replication and/or repair are believed to underlie triplet repeat expansion. Recent studies in HD mice have demonstrated that mismatch repair (MMR) and base excision repair (BER) proteins are expansion inducing components in brain tissues. This study was designed to simultaneously investigate the rates and modes of expansion in different tissues of HD R6/1 mice in order to further understand the expansion mechanisms in vivo. We demonstrate continuous small expansions in most somatic tissues (exemplified by tail), which bear the signature of many short, probably single-repeat expansions and contractions occurring over time. In contrast, striatum and cortex display a dramatic--and apparently irreversible--periodic expansion. Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues.

  5. Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice.

    Directory of Open Access Journals (Sweden)

    Linda Møllersen

    Full Text Available Huntington's disease (HD is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability is observed in the brain, correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat instability are poorly understood, but locally formed secondary DNA structures generated during replication and/or repair are believed to underlie triplet repeat expansion. Recent studies in HD mice have demonstrated that mismatch repair (MMR and base excision repair (BER proteins are expansion inducing components in brain tissues. This study was designed to simultaneously investigate the rates and modes of expansion in different tissues of HD R6/1 mice in order to further understand the expansion mechanisms in vivo. We demonstrate continuous small expansions in most somatic tissues (exemplified by tail, which bear the signature of many short, probably single-repeat expansions and contractions occurring over time. In contrast, striatum and cortex display a dramatic--and apparently irreversible--periodic expansion. Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues.

  6. Protective Effect of Antioxidants on Neuronal Dysfunction and Plasticity in Huntington's Disease

    Science.gov (United States)

    Velusamy, Thirunavukkarasu; Panneerselvam, Archana S.; Purushottam, Meera; Anusuyadevi, Muthuswamy; Pal, Pramod Kumar; Jain, Sanjeev; Essa, Musthafa Mohamed

    2017-01-01

    Huntington's disease (HD) is characterised by movement disorders, cognitive impairments, and psychiatric problems. The abnormal generation of reactive oxygen species and the resulting oxidative stress-induced mitochondrial damage in neurons upon CAG mutations in the HTT gene have been hypothesized as the contributing factors of neurodegeneration in HD. The potential use of antioxidants against free radical toxicity has been an emerging field in the management of ageing and many neurodegenerative disorders. Neural stem cells derived adult neurogenesis represents the regenerative capacity of the adult brain. The process of adult neurogenesis has been implicated in the cognitive functions of the brain and is highly modulated positively by different factors including antioxidants. The supportive role of antioxidants to reduce the severity of HD via promoting the functional neurogenesis and neuroprotection in the pathological adult brain has great promise. This review comprehends the recent studies describing the therapeutic roles of antioxidants in HD and other neurologic disorders and highlights the scope of using antioxidants to promote adult neurogenesis in HD. It also advocates a new line of research to delineate the mechanisms by which antioxidants promote adult neurogenesis in HD. PMID:28168008

  7. Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

    Science.gov (United States)

    Mo, Christina; Hannan, Anthony J; Renoir, Thibault

    2015-05-01

    Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity.

  8. Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections.

    Science.gov (United States)

    de Die-Smulders, C E M; de Wert, G M W R; Liebaers, I; Tibben, A; Evers-Kiebooms, G

    2013-01-01

    BACKGROUND Huntington's disease (HD) is an autosomal dominant neurodegenerative late onset disorder. This review of reproductive options aims to increase reproductive confidence and to prevent suffering in relation to family planning around HD and possibly other late onset neurodegenerative disorders. METHODS Selected relevant literature and own views and experiences as clinical geneticists, psychologists and ethicists have been used. RESULTS Possible options, with emphasis on prenatal diagnosis (PD) and preimplantation genetic diagnosis (PGD) to prevent the transmission of HD to the next generation, are described and discussed. They are formally presented in a decision tree, taking into account the presence or absence of a fully penetrant allele (FPA), a reduced penetrant allele (RPA) or an intermediate allele (IA). A table compares invasive and non-invasive PD and PGD. From a psychological perspective, the complex process of counselling and decision-making regarding reproductive options is discussed. Special attention is paid to the decision to avoid the transmission of the mutation and to the confrontation and coping of a mutation-free child growing up with a parent developing disease symptoms. From an ethical point of view, reflections on both PD and PGD are brought forward taking into account the difference between FPA, RPA and IA, direct testing or exclusion testing and taking into account the welfare of the child in the context of medically assisted reproduction. CONCLUSION Recommendations and suggestions for good clinical practice in the reproductive care for HD families are formulated.

  9. Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches.

    Science.gov (United States)

    Sampaio, Cristina; Borowsky, Beth; Reilmann, Ralf

    2014-09-15

    Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field.

  10. Influence of Species Differences on the Neuropathology of Transgenic Huntington's Disease Animal Models

    Institute of Scientific and Technical Information of China (English)

    Xiao-Jiang Li; Shihua Li

    2012-01-01

    Transgenic animal models have revealed much about the pathogenesis of age-dependent neurodegenerative diseases and proved to be a useful tool for uncovering therapeutic targets.Huntington's disease is a well-characterized neurodegenerative disorder that is caused by expansion of a CAG repeat,which results in expansion of a polyglutamine tract in the N-terminal region of huntingtin (HTT).Similar CAG/glutamine expansions are also found to cause eight other neurodegenerative diseases that affect distinct brain regions in an agedependent manner.Identification of this CAG/glutamine expansion has led to the generation of a variety of transgenic animal models.Of these different animal models,transgenic mice have been investigated extensively,and they show similar neuropathology and phenotypes as seen in their respective diseases.The common pathological hallmark of age-dependent neurodegeneration is the formation of aggregates or inclusions consisting of misfolded proteins in the affected brain regions; however,overt or striking neurodegeneration and apoptosis have not been reported in most transgenic mouse models for age-dependent diseases,including HD.By comparing the neuropathology of transgenic HD mouse,pig,and monkey models,we found that mutant HTT is more toxic to larger animals than mice,and larger animals also show neuropathology that has not been uncovered by transgenic mouse models.This review will discuss the importancc of transgenic large animal models for analyzing the pathogenesis of neurodegenerative diseases and developing effective treatments.

  11. Protective Effect of Antioxidants on Neuronal Dysfunction and Plasticity in Huntington's Disease.

    Science.gov (United States)

    Velusamy, Thirunavukkarasu; Panneerselvam, Archana S; Purushottam, Meera; Anusuyadevi, Muthuswamy; Pal, Pramod Kumar; Jain, Sanjeev; Essa, Musthafa Mohamed; Guillemin, Gilles J; Kandasamy, Mahesh

    2017-01-01

    Huntington's disease (HD) is characterised by movement disorders, cognitive impairments, and psychiatric problems. The abnormal generation of reactive oxygen species and the resulting oxidative stress-induced mitochondrial damage in neurons upon CAG mutations in the HTT gene have been hypothesized as the contributing factors of neurodegeneration in HD. The potential use of antioxidants against free radical toxicity has been an emerging field in the management of ageing and many neurodegenerative disorders. Neural stem cells derived adult neurogenesis represents the regenerative capacity of the adult brain. The process of adult neurogenesis has been implicated in the cognitive functions of the brain and is highly modulated positively by different factors including antioxidants. The supportive role of antioxidants to reduce the severity of HD via promoting the functional neurogenesis and neuroprotection in the pathological adult brain has great promise. This review comprehends the recent studies describing the therapeutic roles of antioxidants in HD and other neurologic disorders and highlights the scope of using antioxidants to promote adult neurogenesis in HD. It also advocates a new line of research to delineate the mechanisms by which antioxidants promote adult neurogenesis in HD.

  12. Phylogenetic and chronological analysis of proteins causing Alzheimer's, Parkinson's and Huntington's diseases

    Directory of Open Access Journals (Sweden)

    Bilal Hussain

    2012-09-01

    Full Text Available It is evident that Neurodegenerative diseases (Alzheimer's, Parkinson's and Huntington's have many similarities at cellular and molecular level as they carry parallel mechanisms including protein aggregation and inclusion body formation caused by protein mis-folding. The main objective of this study was to have detailed insight on variation and resemblance among these proteins. One hundred and four protein sequences, both directly and indirectly involved in disease mechanism to perform phylogenetic analysis revealing insight on evolutionary relationship among these proteins, were selected. The percentage of replicate trees, in which the associated taxa clustered together in the bootstrap test, was 1000 replicates. Various statistical tests were performed for the confirmation of results e.g., Tajma's Neutrality Test showed D gt 6, nucleotide diversity π gt 0.6 and ps value as greater than 1. Phylogenetic analysis showed that the protein sequences of neurodegenerative diseases had high sequence similarity and identity to each other as depicted by the evolutionary tree. It showed the similar mechanism of evolving from each other and had similar mechanism of generating mis-folding leading towards symptoms of disease.

  13. Hope in Huntington's disease A survey in counseling patients with Huntington's disease,as well as the caregivers

    Institute of Scientific and Technical Information of China (English)

    Jerzy T Marcinkowski; Daniel Zielonka

    2009-01-01

    BACKGROUND: It is difficult to attract interest in non-compulsory, preventive, medical care, and persons diagnosed with certain diseases often ignore the existence of these diseases. However, Huntington's disease (HD) is an exception. OBJECTIVE: To qualitatively analyze factors motivating HD patients to participate in a study, namely the European Huntington's Disease Network (EHDN) REGISTRY. DESIGN, TIME AND SETTING: An observational survey was conducted in the EHDN Study Site in Pozna(n), Poland between 2007 and 2008.PARTICIPANTS: The study involved 22 persons affected with HD and 3 pre-symptomatic individuals, totaling 9 males and 16 females. The 24 participants in this study had 24 different caregivers. A total of 25 symptomatic or pre-symptomatic subjects participated in the initial REGISTRY visit, as well as 6 in the second, and 1 in the third. All subjects did not know each other prior to the visit. METHODS: A mutation in the IT15 gene was confirmed in each patient or pre-symptomatic mutation carrier. An in-depth interview produced detailed information on the HD patients, as well as the caregivers, for the REGISTRY study. MAIN OUTCOME MEASURES: A qualitative analysis of the factors motivating HD patients and the pre-symptomatic mutation carriers to participate in the REGISTRY longitudinal, observational, research project was performed. RESULTS: The primary motivating factor for involvement of HD patients and the caregivers in the REGISTRY study was the hope that an effective HD therapy would soon be discovered. In HD patients and the pre-symptomatic group, the response to participate in the REGISTRY project reached 100%, despite the fact that they knew the project was only an observational study. CONCLUSION: Patient hope is thought to be a factor for engaging in preventive, therapeutic activities. However, this is rarely mentioned in medical papers and clinical textbooks, and is usually overlooked in medical teaching. Clearly, efforts should be made to

  14. Environmental analysis of Lower Pueblo/Lower Los Alamos Canyon, Los Alamos, New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Ferenbaugh, R.W.; Buhl, T.E.; Stoker, A.K.; Becker, N.M.; Rodgers, J.C.; Hansen, W.R.

    1994-12-01

    The radiological survey of the former radioactive waste treatment plant site (TA-45), Acid Canyon, Pueblo Canyon, and Los Alamos Canyon found residual contamination at the site itself and in the channel and banks of Acid, Pueblo, and lower Los Alamos Canyons all the way to the Rio Grande. The largest reservoir of residual radioactivity is in lower Pueblo Canyon, which is on DOE property. However, residual radioactivity does not exceed proposed cleanup criteria in either lower Pueblo or lower Los Alamos Canyons. The three alternatives proposed are (1) to take no action, (2) to construct a sediment trap in lower Pueblo Canyon to prevent further transport of residual radioactivity onto San Ildefonso Indian Pueblo land, and (3) to clean the residual radioactivity from the canyon system. Alternative 2, to cleanup the canyon system, is rejected as a viable alternative. Thousands of truckloads of sediment would have to be removed and disposed of, and this effort is unwarranted by the low levels of contamination present. Residual radioactivity levels, under either present conditions or projected future conditions, will not result in significant radiation doses to persons exposed. Modeling efforts show that future transport activity will not result in any residual radioactivity concentrations higher than those already existing. Thus, although construction of a sediment trap in lower Pueblo Canyon is a viable alternative, this effort also is unwarranted, and the no-action alternative is the preferred alternative.

  15. Canyon formation constraints on the discharge of catastrophic outburst floods of Earth and Mars

    Science.gov (United States)

    Lapotre, Mathieu G. A.; Lamb, Michael P.; Williams, Rebecca M. E.

    2016-07-01

    Catastrophic outburst floods carved amphitheater-headed canyons on Earth and Mars, and the steep headwalls of these canyons suggest that some formed by upstream headwall propagation through waterfall erosion processes. Because topography evolves in concert with water flow during canyon erosion, we suggest that bedrock canyon morphology preserves hydraulic information about canyon-forming floods. In particular, we propose that for a canyon to form with a roughly uniform width by upstream headwall retreat, erosion must occur around the canyon head, but not along the sidewalls, such that canyon width is related to flood discharge. We develop a new theory for bedrock canyon formation by megafloods based on flow convergence of large outburst floods toward a horseshoe-shaped waterfall. The model is developed for waterfall erosion by rock toppling, a candidate erosion mechanism in well fractured rock, like columnar basalt. We apply the model to 14 terrestrial (Channeled Scablands, Washington; Snake River Plain, Idaho; and Ásbyrgi canyon, Iceland) and nine Martian (near Ares Vallis and Echus Chasma) bedrock canyons and show that predicted flood discharges are nearly 3 orders of magnitude less than previously estimated, and predicted flood durations are longer than previously estimated, from less than a day to a few months. Results also show a positive correlation between flood discharge per unit width and canyon width, which supports our hypothesis that canyon width is set in part by flood discharge. Despite lower discharges than previously estimated, the flood volumes remain large enough for individual outburst floods to have perturbed the global hydrology of Mars.

  16. Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations.

    Science.gov (United States)

    Mestre, Tiago A; van Duijn, Erik; Davis, Aileen M; Bachoud-Lévi, Anne-Catherine; Busse, Monica; Anderson, Karen E; Ferreira, Joaquim J; Mahlknecht, Philipp; Tumas, Vitor; Sampaio, Cristina; Goetz, Chris G; Cubo, Esther; Stebbins, Glenn T; Martinez-Martin, Pablo

    2016-10-01

    Behavioral symptoms are an important feature of Huntington's disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington's disease to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington's disease. For the purpose of this review, 7 behavioral domains were deemed significant in Huntington's disease: irritability, anxiety, depression, apathy, obsessive-compulsive behaviors, psychosis, and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as "recommended" exclusively for screening purposes: the Irritability Scale for irritability, the Beck Depression Inventory-II, and the Hospital Anxiety and Depression Scale for depression. There were no "recommended" scales for other purposes such as diagnosis, severity, or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington's disease are the co-occurrence of multiple behavioral symptoms, the particular features of a behavioral symptom in Huntington's disease, and the need to address stage- and disease-specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington's disease to address gaps in scale validation for specific behavioral domains and purpose of use. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  17. Submarine canyon development in the Izu-Bonin forearc: A SeaMARC II and seismic survey of Aoga Shima Canyon

    Science.gov (United States)

    Klaus, Adam; Taylor, Brian

    1991-05-01

    SeaMARC II sidescan (imagery and bathymetry) and seismic data reveal the morphology, sedimentary processes, and structural controls on submarine canyon development in the central Izu-Bonin forearc, south of Japan. Canyons extend up to 150 km across the forearc from the trench-slope break to the active volcanic arc. The canyons are most deeply incised (1200 1700 m) into the gentle gradients (1 2°) upslope on the outer arc high (OAH) and lose bathymetric expression on the steep (6 18°) inner trench-slope. The drainage patterns indicate that canyons are formed by both headward erosion and downcutting. Headward erosion proceeds on two scales. Initially, pervasive small-scale mass wasting creates curvilinear channels and pinnate drainage patterns. Large-scale slumping, evidenced by abundant crescent-shaped scarps along the walls and tributaries of Aoga Shima Canyon, occurs only after a channel is present, and provides a mechanism for canyon branching. The largest slump has removed >16 km3 of sediment from an ˜85 km2 area of seafloor bounded by scarps more than 200 m high and may be in the initial stages of forming a new canyon branch. The northern branch of Aoga Shima Canyon has eroded upslope to the flanks of the arc volcanoes allowing direct tapping of this volcaniclastic sediment source. Headward erosion of the southern branch is not as advanced but the canyon may capture sediments supplied by unconfined (non-channelized) mass flows. Oligocene forearc sedimentary processes were dominated by unconfined mass flows that created sub-parallel and continuous sedimentary sequences. Pervasive channel cut-and-fill is limited to the Neogene forearc sedimentary sequences which are characterized by migrating and unconformable seismic sequences. Extensive canyon formation permitting sediment bypassing of the forearc by canyon-confined mass flows began in the early Miocene after the basin was filled to the spill points of the OAH. Structural lows in the OAH determined the

  18. A study of the CCG polymorphism in the IT15 cDNA in the Scottish Huntington`s disease and normal populations

    Energy Technology Data Exchange (ETDEWEB)

    Barron, L.H.; Rae, A.; Brock, D.J.H. [Univ. of Edinburgh (United Kingdom)] [and others

    1994-09-01

    The CCG rich sequence immediately 3{prime} to the CAG repeat that is expanded in Huntington`s disease (HD) has recently been shown to be polymorphic with at least 5 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 200 Scottish HD families and have found very strong evidence for almost complete disequilibrium in this population. For all the families phase was unambiguously determined and 196 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observation is significantly different to the normal population distribution where 31% of people have an allele of 185 bp. This overrepresentation of the 176 bp allele is also seen in the normal population on chromosomes with greater than 26 CAG repeats. The DNA sequence across the CAG and CCG repeats has been obtained for the four HD patients that do not have a 176 bp CCG repeat size and will be presented. We present strong evidence of genetic heterogeneity in the Scottish HD population making it very unlikely that there is a founder effect in the Scottish HD population. These data suggest that we may have identified a region of the IT15 gene that is critical in the mechanism of Huntington`s disease CAG expansion.

  19. Numerical Study of Urban Canyon Microclimate Related to Geometrical Parameters

    Directory of Open Access Journals (Sweden)

    Andrea de Lieto Vollaro

    2014-11-01

    Full Text Available In this study a microclimate analysis on a particular urban configuration: the—street canyon—has been carried out. The analysis, conducted by performing numerical simulations using the finite volumes commercial code ANSYS-Fluent, shows the flow field in an urban environment, taking into account three different aspect ratios (H/W. This analysis can be helpful in the study on urban microclimate and on the heat exchanges with the buildings. Fluid-dynamic fields on vertical planes within the canyon, have been evaluated. The results show the importance of the geometrical configuration, in relation to the ratio between the height (H of the buildings and the width (W of the road. This is a very important subject from the point of view of “Smart Cities”, considering the urban canyon as a subsystem of a larger one (the city, which is affected by climate changes.

  20. Long-term monitoring of sandbars on the Colorado River in Grand Canyon using remote sensing

    Science.gov (United States)

    Ross, Robert P.; Grams, Paul E.

    2015-01-01

    Closure of Glen Canyon Dam in 1963 dramatically changed discharge and sediment supply to the downstream Colorado River in Marble and Grand Canyons. Magnitudes of seasonal flow variation have been suppressed, while daily fluctuations have increased because of hydropower generation. Lake Powell, the upstream reservoir, traps all sediment, leaving the Paria and Little Colorado Rivers as the main suppliers of fine sediment to the system below Glen Canyon Dam. The reduction in sediment supply, along with changes in discharge, have resulted in finesediment deficit (Topping et al., 2000), leading to a decrease in the size and number of alluvial sandbars (Schmidt and Graf, 1990; Schmidt et al., 2004). However, the understanding of these important spatial and temporal changes in sandbars located along the banks of the river have been limited to infrequent measurements mostly made by direct visitation and topographic surveying (Hazel et al., 2010). Aerial photographs are the only data available from which it is possible to evaluate changes in alluvial deposits at a large number of sites and compare recent conditions with those that existed prior to the initiation of ground-based monitoring in the early 1990s. Previous studies have evaluated the effects of Glen Canyon Dam on sandbars by analysis of comprehensive maps of surficial geology that are based on seven sets of aerial imagery taken between 1935 and 1996 for selected reaches in the first 120 km downstream from Lees Ferry, Arizona (Figure 1). These studies showed that the area of exposed sand in eddy-deposition zones was less in the post-dam period than in the pre-dam period (Leschin and Schmidt, 1995; Schmidt et al., 1999b; Sondossi, 2001, Sondossi and Schmidt, 2001, Schmidt et al., 2004). In this study, we extend these analyses to encompass a 74-year period by including maps of sand deposits visible in aerial imagery taken in 2002, 2005, and 2009 for the same reaches that were mapped in the earlier studies. Results

  1. Numerical and Experimental Studies on Flow and Pollutant Dispersion in Urban Street Canyons

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this study numerical simulations and water tank experiments were used to investigate the flow and pollutant dispersion in an urban street canyon. Two types of canyon geometry were tested. The studies indicate that in a step-up notch canyon (higher buildings on the downstream side of the canyon), the height and shape of the upstream lower buildings plays an important role in flow pattern and pollutant dispersion,while in a step-down notch canyon (lower buildings on the downstream side), the downstream lower buildings have little influence. The studies also show that the substitution of tall towers for parallelepiped buildings on one side of the canyon may enhance the street ventilation and decrease the pollutant concentration emitted by motor vehicles.

  2. Apatite 4He/3He and (U-Th)/He evidence for an ancient Grand Canyon.

    Science.gov (United States)

    Flowers, R M; Farley, K A

    2012-12-21

    The Grand Canyon is one of the most dramatic features on Earth, yet when and why it was carved have been controversial topics for more than 150 years. Here, we present apatite (4)He/(3)He thermochronometry data from the Grand Canyon basement that tightly constrain the near-surface cooling history associated with canyon incision. (4)He/(3)He spectra for eastern Grand Canyon apatites of differing He date, radiation damage, and U-Th zonation yield a self-consistent cooling history that substantially validates the He diffusion kinetic model applied here. Similar data for the western Grand Canyon provide evidence that it was excavated to within a few hundred meters of modern depths by ~70 million years ago (Ma), in contrast to the conventional model in which the entire canyon was carved since 5 to 6 Ma.

  3. A review of proposed Glen Canyon Dam interim operating criteria

    Energy Technology Data Exchange (ETDEWEB)

    LaGory, K.; Hlohowskyj, I.; Tomasko, D.; Hayse, J.; Durham, L.

    1992-04-01

    Three sets of interim operating criteria for Glen Canyon Dam on the Colorado River have been proposed for the period of November 1991, to the completion of the record of decision for the Glen Canyon Dam environmental impact statement (about 1993). These criteria set specific limits on dam releases, including maximum and minimum flows, up-ramp and down-ramp rates, and maximum daily fluctuation. Under the proposed interim criteria, all of these parameters would be reduced relative to historical operating criteria to protect downstream natural resources, including sediment deposits, threatened and endangered fishes, trout, the aquatic food base, and riparian plant communities. The scientific bases of the three sets of proposed operating criteria are evaluated in the present report:(1) criteria proposed by the Research/Scientific Group, associated with the Glen Canyon Environmental Studies (GCES); (2) criteria proposed state and federal officials charged with managing downstream resources; and (3) test criteria imposed from July 1991, to November 1991. Data from Phase 1 of the GCES and other sources established that the targeted natural resources are affected by dam operations, but the specific interim criteria chosen were not supported by any existing studies. It is unlikely that irreversible changes to any of the resources would occur over the interim period if historical operating criteria remained in place. It is likely that adoption of any of the sets of proposed interim operating criteria would reduce the levels of sediment transport and erosion below Glen Canyon Dam; however, these interim criteria could result in some adverse effects, including the accumulation of debris at tributary mouths, a shift of new high-water-zone vegetation into more flood-prone areas, and further declines in vegetation in the old high water zone.

  4. Los Alamos Canyon Ice Rink Parking Flood Plain Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Hathcock, Charles Dean [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Keller, David Charles [Los Alamos National Lab. (LANL), Los Alamos, NM (United States

    2015-02-10

    The project location is in Los Alamos Canyon east of the ice rink facility at the intersection of West and Omega roads (Figure 1). Forty eight parking spaces will be constructed on the north and south side of Omega Road, and a lighted walking path will be constructed to the ice rink. Some trees will be removed during this action. A guardrail of approximately 400 feet will be constructed along the north side of West Road to prevent unsafe parking in that area.

  5. Outbreak of leptospirosis among canyoning participants, Martinique, 2011.

    OpenAIRE

    Hochedez, Patrick; Escher, M.; Decoussy, H.; Pasgrimaud, L.; R. Martinez; Rosine, J.; Théodose, R.; Bourhy,Pascale; Picardeau, Mathieu; Olive, C.; Ledrans, M.; Cabie, André

    2013-01-01

    International audience; Two gendarmes who participated in canyoning activities on 27 June 2011 on the Caribbean island of Martinique were diagnosed with leptospirosis using quantitative real-time polymerase chain reaction (qPCR), 9 and 12 days after the event. Among the 45 participants who were contacted, 41 returned a completed questionnaire, of whom eight met the outbreak case definition. The eight cases sought medical attention and were given antibiotics within the first week after fever o...

  6. On subsurface cooling associated with the Biobio River Canyon (Chile)

    Science.gov (United States)

    Sobarzo, Marcus; Saldías, Gonzalo S.; Tapia, Fabian J.; Bravo, Luis; Moffat, Carlos; Largier, John L.

    2016-07-01

    Submarine canyons cutting across the continental shelf can modulate the cross-shelf circulation being effective pathways to bring water from the deep ocean onto the shelf. Here, we use 69 days of moored array observations of temperature and ocean currents collected during the spring of 2013 and winter-spring 2014, as well as shipboard hydrographic surveys and sea-level observations to characterize cold, oxygen poor, and nutrient-rich upwelling events along the Biobio Submarine Canyon (BbC). The BbC is located within the Gulf of Arauco at 36° 50'S in the Central Chilean Coast. The majority of subtidal temperature at 150 m depth is explained by subtidal variability in alongshore currents on the canyon with a lag of less than a day (r2 = 0.65). Using the vertical displacement of the 10° and 10.5°C isotherms, we identified nine upwelling events, lasting between 20 h to 4.5 days, that resulted in vertical isothermal displacements ranging from 29 to 137 m. The upwelled water likely originated below 200 m. Majority of the cooling events were related with strong northward (opposite Kelvin wave propagation) flow and low pressure at the coast. Most of these low pressure events occur during relatively weak local wind forcing conditions, and were instead related with Coastal Trapped Waves (CTWs) propagating southwards from lower latitudes. These cold, high-nutrient, low-oxygen waters may be further upwelled and advected into the Gulf of Arauco by wind forcing. Thus, canyon upwelling may be a key driver of biological productivity and oxygen conditions in this Gulf.

  7. 76 FR 60492 - Adequacy Status of the Ohio Portion of the Huntington/Ashland Submitted Annual Fine Particulate...

    Science.gov (United States)

    2011-09-29

    ..., starting at 69 FR 40038, and we used the information in these resources in making our adequacy... AGENCY Adequacy Status of the Ohio Portion of the Huntington/Ashland Submitted Annual Fine Particulate... Ohio portion of the Huntington/Ashland WV-KY-OH area. Ohio submitted the insignificance findings...

  8. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation.

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P; Luthi-Carter, Ruth; Lowdell, Mark W; Björkqvist, Maria; Ostroff, Gary R; Aronin, Neil; Tabrizi, Sarah J

    2014-03-01

    Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.

  9. Striatal and white matter predictors of estimated diagnosis for Huntington disease

    Science.gov (United States)

    Paulsen, Jane S.; Nopoulos, Peggy C.; Aylward, Elizabeth; Ross, Christopher A.; Johnson, Hans; Magnotta, Vincent A.; Juhl, Andrew; Pierson, Ronald K.; Mills, James; Langbehn, Douglas; Nance, Martha

    2010-01-01

    Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at one of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity. PMID:20385209

  10. Huntington disease skeletal muscle is hyperexcitable owing to chloride and potassium channel dysfunction.

    Science.gov (United States)

    Waters, Christopher W; Varuzhanyan, Grigor; Talmadge, Robert J; Voss, Andrew A

    2013-05-28

    Huntington disease is a progressive and fatal genetic disorder with debilitating motor and cognitive defects. Chorea, rigidity, dystonia, and muscle weakness are characteristic motor defects of the disease that are commonly attributed to central neurodegeneration. However, no previous study has examined the membrane properties that control contraction in Huntington disease muscle. We show primary defects in ex vivo adult skeletal muscle from the R6/2 transgenic mouse model of Huntington disease. Action potentials in diseased fibers are more easily triggered and prolonged than in fibers from WT littermates. Furthermore, some action potentials in the diseased fibers self-trigger. These defects occur because of decreases in the resting chloride and potassium conductances. Consistent with this, the expression of the muscle chloride channel, ClC-1, in Huntington disease muscle was compromised by improper splicing and a corresponding reduction in total Clcn1 (gene for ClC-1) mRNA. Additionally, the total Kcnj2 (gene for the Kir2.1 potassium channel) mRNA was reduced in disease muscle. The resulting muscle hyperexcitability causes involuntary and prolonged contractions that may contribute to the chorea, rigidity, and dystonia that characterize Huntington disease.

  11. Striatal and white matter predictors of estimated diagnosis for Huntington disease.

    Science.gov (United States)

    Paulsen, Jane S; Nopoulos, Peggy C; Aylward, Elizabeth; Ross, Christopher A; Johnson, Hans; Magnotta, Vincent A; Juhl, Andrew; Pierson, Ronald K; Mills, James; Langbehn, Douglas; Nance, Martha

    2010-05-31

    Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.

  12. Electrical resistance sensors record spring flow timing, Grand Canyon, Arizona

    Science.gov (United States)

    Adams, E.A.; Monroe, S.A.; Springer, A.E.; Blasch, K.W.; Bills, D.J.

    2006-01-01

    Springs along the south rim of the Grand Canyon, Arizona, are important ecological and cultural resources in Grand Canyon National Park and are discharge points for regional and local aquifers of the Coconino Plateau. This study evaluated the applicability of electrical resistance (ER) sensors for measuring diffuse, low-stage (flow in the steep, rocky spring-fed tributaries of the south rim. ER sensors were used to conduct a baseline survey of spring flow timing at eight sites in three spring-fed tributaries in Grand Canyon. Sensors were attached to a nearly vertical rock wall at a spring outlet and were installed in alluvial and bedrock channels. Spring flow timing data inferred by the ER sensors were consistent with observations during site visits, with flow events recorded with collocated streamflow gauging stations and with local precipitation gauges. ER sensors were able to distinguish the presence of flow along nearly vertical rock surfaces with flow depths between 0.3 and 1.0 cm. Laboratory experiments confirmed the ability of the sensors to monitor the timing of diffuse flow on impervious surfaces. A comparison of flow patterns along the stream reaches and at springs identified the timing and location of perennial and intermittent flow, and periods of increased evapotranspiration.

  13. Factors associated with Mediterranean diet adherence in Huntington's disease.

    Science.gov (United States)

    Rivadeneyra, Jéssica; Cubo, Esther; Gil, Cecilia; Calvo, Sara; Mariscal, Natividad; Martínez, Asunción

    2016-04-01

    Little is known about the importance of the Mediterranean Diet (MeDi) and dietary intake as environmental neuroprotective factors in Huntington's disease (HD); so, we evaluated and analyzed the prevalence and factors associated with MeDi adherence, and dietary intake in HD. Spanish participants of the European Huntington Disease Network (EHDN) Registry study diagnosed with HD or premanifest HD gene carriers were included from June 2012 to August 2013. Self-reported dietary intake was collected by 3-day dietary record, MeDi adherence was assessed by 0-9 range (proposed by Trichopoulou et al.) and, other contributing factors related to nutrition were collected by telephone. Demographics and clinical variables were obtained from the EHDN Registry study database. Association of HD with MeDi adherence and nutritional characteristics were performed using logistic regression models. Ninety eight participants were included in the study, median age of 48 years (38-60 range), and median total functional capacity (TFC) 9 (5-13 range). HD severity was similar between participants with low vs moderate/high MeDi; however, quality of life (P = 0.009) was significantly higher among participants with moderate/high MeDi adherence. In terms of nutrients, higher MUFA/SFA intake was moderately correlated with better TFC and Unified HD Rating Scale (UHDRS) cognitive. Better TFC was associated with having a caregiver (OR = 11.86, P adherence to MeDi, was associated with older participants (OR = 1.19, P = 0.031), lower comorbidity (OR = 0.18, P = 0.018), lower UHDRS motor (OR = 0.90, P = 0.041), and lower risk for abdominal obesity (OR = 0.02, P = 0.011). In HD the moderate MeDi adherence is associated with better quality of life, lower comorbidity, lower motor impairment and lower risk for abdominal obesity compared to those participants with low MeDi adherence. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All

  14. Establishing a pre-mining geochemical baseline at a uranium mine near Grand Canyon National Park, USA

    Science.gov (United States)

    Naftz, David L.; Walton-Day, Katherine

    2016-01-01

    During 2012, approximately 404,000 ha of Federal Land in northern Arizona was withdrawn from consideration of mineral extraction for a 20-year period to protect the Grand Canyon watershed from potentially adverse effects of U mineral exploration and development. The development, operation, and reclamation of the Canyon Mine during the withdrawal period provide an excellent field site to understand and document off-site migration of radionuclides within the withdrawal area. As part of the Department of Interior's (DOI's) study plan for the exclusion area, the objective of our study is to utilize pre-defined decision units (DUs) in areas within and surrounding the Canyon Mine to demonstrate how newly established incremental sampling methodologies (ISM) combined with multivariate statistical methods can be used to document a repeatable and statistically defensible measure of pre-mining baseline conditions in surface soils and stream sediment samples prior to ore extraction. During the survey in June 2013, the highest pre-mining 95% upper confidence level (UCL) concentrations with respect to As, Mo, U, and V were found in the triplicate samples collected from surface soils in the mine site DU designated as M1. Gamma activities were slightly elevated in soils within the M1 DU (up to 28 μR/h); however, off-site gamma activities in soil and stream-sediment samples were lower (< 6 to 12 μR/h). Hierarchical cluster analysis (HCA) was applied to 33 chemical constituents contained in the multivariate data generated from the analysis of triplicate samples collected in the soil and stream sediment DUs within and surrounding Canyon Mine. Most of the triplicate samples from individual DUs were grouped in the same dendrogram cluster when using a similarity value (SV) of 0.70 (unitless). Different group membership of triplicate samples from two of the four haul road DUs was likely the result of heterogeneity induced by non-native soil material introduced from the gravel road base

  15. Partly standing internal tides in a dendritic submarine canyon observed by an ocean glider

    Science.gov (United States)

    Hall, Rob A.; Aslam, Tahmeena; Huvenne, Veerle A. I.

    2017-08-01

    An autonomous ocean glider is used to make the first direct measurements of internal tides within Whittard Canyon, a large, dendritic submarine canyon system that incises the Celtic Sea continental slope and a site of high benthic biodiversity. This is the first time a glider has been used for targeted observations of internal tides in a submarine canyon. Vertical isopycnal displacement observations at different stations fit a one-dimensional model of partly standing semidiurnal internal tides - comprised of a major, incident wave propagating up the canyon limbs and a minor wave reflected back down-canyon by steep, supercritical bathymetry near the canyon heads. The up-canyon internal tide energy flux in the primary study limb decreases from 9.2 to 2.0 kW m-1 over 28 km (a dissipation rate of 1 - 2.5 ×10-7 Wkg-1), comparable to elevated energy fluxes and internal tide driven mixing measured in other canyon systems. Within Whittard Canyon, enhanced mixing is inferred from collapsed temperature-salinity curves and weakened dissolved oxygen concentration gradients near the canyon heads. It has previously been hypothesised that internal tides impact benthic fauna through elevated near-bottom current velocities and particle resuspension. In support of this, we infer order 20 cm s-1 near-bottom current velocities in the canyon and observe high concentrations of suspended particulate matter. The glider observations are also used to estimate a 1 °C temperature range and 12 μmol kg-1 dissolved oxygen concentration range, experienced twice a day by organisms on the canyon walls, due to the presence of internal tides. This study highlights how a well-designed glider mission, incorporating a series of tide-resolving stations at key locations, can be used to understand internal tide dynamics in a region of complex topography, a sampling strategy that is applicable to continental shelves and slopes worldwide.

  16. Three-Dimensional Scale-Model Tank Experiment of the Hudson Canyon Region

    Science.gov (United States)

    2014-09-30

    Three-Dimensional Scale-Model Tank Experiment of the Hudson Canyon Region Jason D. Sagers Applied Research Laboratories at The University of...planning for future experiments in ocean environments with slopes and canyons . APPROACH The development of fully 3D numerical acoustic propagation models...Experiment of the Hudson Canyon Region 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER

  17. Late Holocene earthquake history of the Brigham City segment of the Wasatch fault zone at the Hansen Canyon, Kotter Canyon, and Pearsons Canyon trench sites, Box Elder County, Utah

    Science.gov (United States)

    DuRoss, Christopher B.; Personius, Stephen F.; Crone, Anthony J.; McDonald, Greg N.; Briggs, Richard W.

    2012-01-01

    Of the five central segments of the Wasatch fault zone (WFZ) having evidence of recurrent Holocene surface-faulting earthquakes, the Brigham City segment (BCS) has the longest elapsed time since its most recent surface-faulting event (~2.1 kyr) compared to its mean recurrence time between events (~1.3 kyr). Thus, the BCS has the highest time-dependent earthquake probability of the central WFZ. We excavated trenches at three sites––the Kotter Canyon and Hansen Canyon sites on the north-central BCS and Pearsons Canyon site on the southern BCS––to determine whether a surface-faulting earthquake younger than 2.1 ka occurred on the BCS. Paleoseismic data for Hansen Canyon and Kotter Canyon confirm that the youngest earthquake on the north-central BCS occurred before 2 ka, consistent with previous north-central BCS investigations at Bowden Canyon and Box Elder Canyon. At Hansen Canyon, the most recent earthquake is constrained to 2.1–4.2 ka and had 0.6–2.5 m of vertical displacement. At Kotter Canyon, we found evidence for two events at 2.5 ± 0.3 ka and 3.5 ± 0.3 ka, with an average displacement per event of 1.9–2.3 m. Paleoseismic data from Pearsons Canyon, on the previously unstudied southern BCS, indicate that a post-2 ka earthquake ruptured this part of the segment. The Pearsons Canyon earthquake occurred at 1.2 ± 0.04 ka and had 0.1–0.8 m of vertical displacement, consistent with our observation of continuous, youthful scarps on the southern 9 km of the BCS having 1–2 m of late Holocene(?) surface offset. The 1.2-ka earthquake on the southern BCS likely represents rupture across the Weber–Brigham City segment boundary from the penultimate Weber-segment earthquake at about 1.1 ka. The Pearsons Canyon data result in a revised length of the BCS that has not ruptured since 2 ka (with time-dependent probability implications), and provide compelling evidence of at least one segment-boundary failure and multi-segment rupture on the central WFZ. Our

  18. Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

    Science.gov (United States)

    Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

    Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients.

  19. ENFERMEDAD DE HUNTINGTON: MODELOS EXPERIMENTALES Y PERSPECTIVAS TERAPÉUTICAS Huntington'disease: Experimentals Models and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    TERESA SERRANO SÁNCHEZ

    Full Text Available La enfermedad de Huntington (EH es un trastorno degenerativo de Weiss de origen hereditario. Hasta el momento no existe un tratamiento efectivo para la enfermedad que inexorablemente después de transcurridos 15 a 20 años, evoluciona hacia incapacidad total o muerte. En este trabajo se revisan las características clínicas y morfológicas de la EH y los modelos experimentales más utilizados para su estudio tomando como fuente, artículos indexados en la base de datos Medline publicados en los últimos 20 años. Se valoran las ventajas y desventajas de estos modelos y su perspectiva para el desarrollo de ensayos clínicos. El consenso de lo reportado plantea que de los modelos tóxicos, los inducidos por neurotoxinas tales como ácido quinolínico parecen ser los más adecuados para reproducir las características neuropatológicas, y por otro lado los modelos genéticos contribuyen con más evidencias al conocimiento del origen etiológico de la enfermedad. Numerosos tratamientos han sido aplicados en el manejo de las manifestaciones clínicas que aparecen en EH, sin poder detener o disminuir las afectaciones que derivan de la pérdida neuronal. La sintomatología clínica ha sido posible reproducirla, al menos en parte, en animales de experimentación lo que ha permitido realizar ensayos terapéuticos. Desde el punto de vista de tratamiento, lo que más promisorio parece ser, la terapia celular con células provenientes de diferentes fuentes y dentro de ellas las no neurales, que implican menor censura ética y mayor factibilidad de obtención para la aplicación en los enfermos. Por otro lado el desarrollo de la tecnología del ARN de interferencia, emerge como una herramienta terapéutica potencial para el tratamiento de EH, así como para responder interrogantes básicas relacionadas con el desarrollo de la enfermedad.Huntington'disease (HD is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment

  20. UV Radiation in an Urban Canyon in Southeast Queensland

    Science.gov (United States)

    McKinley, A. R.; Moore, M. R.; Kimlin, M. G.

    2006-12-01

    Ultraviolet radiation (UV) has the possibility to both harm and to benefit human beings when unprotected exposure occurs. After receiving small amounts of UV our bodies begin to synthesise vitamin D, which is essential for maintaining healthy bones, however excessive UV exposure can result in a variety of damaging outcomes ranging from sunburn to skin cancer and cataracts. For this reason it is very important to understand the different environments in which people encounter UV so as to better prepare the public to make smart and healthy sun exposure decisions. Each day more and more people are moving into large cities around the world and spending their time inside the urban canyon, however UV measurements are generally taken at scientific stations in open areas or on top of tall buildings, meaning that at times the environmental characteristics measured may not accurately represent those found at street-level in these highly urbanized areas. Urban canyons are home to both very tall buildings and tropospheric air pollution, each of which reduces the amount of UV reaching street-level. This study measured the varying difference between UV measurements taken at street-level and at a standard UV monitoring site on top of a building outside of the urban canyon. Investigation was conducted in the central business district (CBD) of Brisbane, Australia, which models the CBDs of large cities around the world in that it boasts a great number of tall buildings, including many skyscrapers. Data was collected under clear sky conditions at five different street-level sites in the CBD (on either side of two streets running perpendicular to one another (four sites) and in a public square) and then compared to that obtained on the same day at the Queensland University of Technology's Australian Sun and Health Research Laboratory (ASHRL), which is located 2.5 kilometres outside Brisbane's CBD. Minimum erythemal dose (MED) data was collected at each location and it was found that

  1. Sand Wave Migrations Within Monterey Submarine Canyon, California

    Science.gov (United States)

    Xu, J.; Wong, F. L.

    2006-12-01

    Repeated high-resolution multi-beam surveys revealed the existence of a sand wave field along the axis of the Monterey submarine canyon between 20 and 300 m water depth. These sand waves range in wave length from 20 to 70 m and 2 to 5 m in height. Comparison of sequential multi-beam grid data (months apart) indicates that the sand waves apparently migrate upcanyon at some places while the same data clearly show that the sand waves migrate downcanyon at other locations. One hypothesis is that strong internal tidal flows, whose upcanyon component is intensified by the narrow canyon, are responsible for forming the sand wave field and for migrating the sand waves upcanyon. Another hypothesis is that the sand wave field is formed by creeping (analogous to the movement within glaciers), and in general they move in the downcanyon direction. A field experiment was conducted in 2005-06 to measure the driving forces (in hypothesis #1) that form and move the sand waves, and to collect the internal sedimentological structure within the sand waves that could reveal information on hypothesis #2. A mooring designed to measure near-floor velocity profiles, temperature, salinity, and sediment concentration in the water column was deployed for one year (June 2005 -July 2006) at 250 m water depth, slightly downcanyon of the sand wave field. In addition, a mapping survey was conducted in February, 2006 for collecting multi-beam and chirp profiles in the canyon head area of the sand wave field. Preliminary examination of the ADCP (downward looking) showed some very interesting features - the near- floor current dramatically changes with the spring-neap cycle of the surface tide. The time variation of the along-canyon current during neap tides - a sudden jump of upcanyon velocity before gradually tapering down, is typical of internal tides (internal bores). The time variation during spring tides when along canyon velocities reverse directions from upcanyon to downcanyon and gradually

  2. [IT15 gene analysis in two pedigrees of Huntington's disease].

    Science.gov (United States)

    Zhang, Bao-Rong; Song, Fei; Yin, Xin-Zhen; Xia, Kun; Tian, Jun; Huang, Jian-Zheng; Xia, Jia-Hui

    2006-11-01

    To investigate the relationship between the clinical features and (CAG)n trinucleotide repeats in two pedigrees of Chinese Huntington's disease (HD). Clinical and neuroimaging features, the age of disease onset and pattern of transmission of the patients were studied in the two pedigrees of HD. Genomic DNA of 42 family members was used for amplification of the (CAG)n repeats of IT15 gene by PCR. The numbers of (CAG)n were determined by electrophoresis through a 6% polyacrylamide gel and direct sequence analysis. Results showed that patients in pedigree 1 were absent of the typical triad of HD symptoms or caudate atrophy. A total of 9 (5 patients and 4 asymptomatic) out of 18 family members had 40-50 (CAG)n repeats in the IT15 gene. In pedigree 2, all the patients were characterized by a triad of symptoms, including motor disturbance, cognitive impairment and psychiatric features. Three patients and two asymptomatic relatives had more than 50 (CAG)n repeats in the IT15 gene. In conclusion, the clinical symptoms are partly determined by (CAG)n repeats in the IT15 gene. The age of onset was correlated with (CAG)n repeats over 50, and the phenomenon called "anticipation" was found to have played a role.

  3. Familial aggregation of schizophrenia-like symptoms in Huntington's disease.

    Science.gov (United States)

    Tsuang, D; DiGiacomo, L; Lipe, H; Bird, T D

    1998-07-10

    An increased incidence of schizophrenia-like symptoms in Huntington's disease (HD) has been well-documented in the past. The reasons for this association, however, have never been explained. At the University of Washington Medical Genetics Clinic, we had the opportunity to evaluate a unique juvenile-onset HD proband who had schizophrenia-like symptoms. This patient was referred to our clinic because of new onset of somatic delusions and command auditory hallucinations early in the course of her illness. Since we had already evaluated other affected individuals in her family, we selected another family with a nonpsychotic juvenile-onset proband for comparison. Using these two families in a small case-control study, we investigated the following hypotheses which could explain the association between schizophrenia-like symptoms and HD: first, schizophrenia-like symptoms may be related to the number of CAG repeats in the HD gene; second, schizophrenia-like symptoms may segregate in certain HD families, for unknown reasons; and third, there may coincidentally be an unrelated gene for schizophrenia in certain HD families. Comparisons of clinical characteristics and the HD genotype showed that family history of schizophrenia-like symptoms segregated with the HD gene; however, age of onset of HD, size of CAG repeat, and sex of the transmitting parent were not associated with psychotic symptoms. Further genetic and neurobiological studies are necessary to investigate the potential mechanism underlying this association.

  4. The Role of Dopamine and Glutamate Modulation in Huntington Disease

    Science.gov (United States)

    Mittal, Sumeer K.; Eddy, Clare

    2013-01-01

    Background: Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes within the striatum are likely to lead to alterations in dopamine and glutamate activity in frontostriatal circuitry, resulting in characteristic motor, behavioural and cognitive symptoms. Methods: We conducted a systematic literature search in order to identify and review randomised, double-blinded, placebo-controlled trials of anti-dopaminergic and anti-glutamatergic therapy in HD. Results: Ten studies satisfied our selection criteria. These studies investigated a range of agents which act to antagonise dopamine (tetrabenazine, typical and atypical antipsychotics) or glutamate (amantadine, riluzole) transmission. Discussion: Although most agents showed efficacy in terms of amelioration of chorea, the available evidence did not allow us to identify a universally effective treatment. One difficulty associated with analysing the available evidence was a high prevalence of side effects, which prevented the full therapeutic potential of the medications from being adequately investigated. A further limitation is that many studies evaluated treatment effectiveness only in relation to patients' motor symptoms, even though behavioural and cognitive changes may negatively impact patients' quality of life. There is a clear need for further higher-level evidence addressing the effects of dopaminergic and glutamatergic agents on global functioning in HD. PMID:22713410

  5. [Huntington disease: presymptomatic testing, prenatal diagnosis, preimplantation genetic diagnosis experience].

    Science.gov (United States)

    Durr, A; Viville, S

    2007-10-01

    Presymptomatic testing for Huntington disease has been available for 15 years. The possibility of determining the genetic status of an at-risk person for the disorder which runs in his or her family raises questions because of the absence of preventive treatments. In addition, being carrier does not allow to determine when the disease starts and how it will evolve, impairing the possibilities of planning the future. A pluridisciplinary approach to predictive testing with care before, during and after the test taking into account the medical, social and psychological aspects of the disease is good practice. At the present time, only a minority of at-risk individuals request presymptomatic testing and almost 50% do not pursue until the results. The consequences of the test may be harmful, more frequently after an unfavorable than after a favorable result. Motivations and the outcome in terms of request for prenatal testing after a carrier result are known today and the number or prenatal testing remains very limited. Preimplantation genetic testing is an alternative for couples who knows or do not their own genetic status. We report our experience in two French centres: Paris for presymptomatic and prenatal testing and Strasbourg for preimplantation diagnosis.

  6. Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Analyne M Schroeder

    Full Text Available While Huntington's disease (HD is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD.

  7. Tractography of the corpus callosum in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Owen Phillips

    Full Text Available White matter abnormalities have been shown in presymptomatic and symptomatic Huntington's disease (HD subjects using Magnetic Resonance Imaging (MRI and Diffusion Tensor Imaging (DTI methods. The largest white matter tract, the corpus callosum (CC, has been shown to be particularly vulnerable; however, little work has been done to investigate the regional specificity of tract abnormalities in the CC. Thus, this study examined the major callosal tracts by applying DTI-based tractography. Using TrackVis, a previously defined region of interest tractography method parcellating CC into seven major tracts based on target region was applied to 30 direction DTI data collected from 100 subjects: presymptomatic HD (Pre-HD subjects (n=25, HD patients (n=25 and healthy control subjects (n=50. Tractography results showed decreased fractional anisotropy (FA and increased radial diffusivity (RD across broad regions of the CC in Pre-HD subjects. Similar though more severe deficits were seen in HD patients. In Pre-HD and HD, callosal FA and RD were correlated with Disease Burden/CAG repeat length as well as motor (UHDRSI and cognitive (URDRS2 assessments. These results add evidence that CC pathways are compromised prior to disease onset with possible demyelination occurring early in the disease and suggest that CAG repeat length is a contributing factor to connectivity deficits. Furthermore, disruption of these callosal pathways potentially contributes to the disturbances of motor and cognitive processing that characterize HD.

  8. The story of George Huntington and his disease

    Directory of Open Access Journals (Sweden)

    Kalyan B Bhattacharyya

    2016-01-01

    Full Text Available George Huntington described some families with choreiform movements in 1872 in the United States of America and since then many such families have been described in other parts of the world and works on the genetics of the disease have brought new vistas in the understanding of the disease. In 1958, Americo Negrette, a young Venezuelan physician observed similar subjects in the vicinity of Lake Maracaibo which was presented by his co-worker, Ramon Avilla Giron at New York in 1972 when United States of America had been commemorating the centenary year of Huntington′s disease. Nancy Wexler, a psychoanalyst, whose mother had been suffering from the disease attended the meeting and organized a research team to Venezuela and they systematically studied more than 18,000 individuals in order to work out a common pedigree. They identified the genetic locus of the disease in the short arm of chromosome 4 and observed that it was a trinucleotide repeat disorder.

  9. Therapeutic Effect of Berberine on Huntington's Disease Transgenic Mouse Model.

    Directory of Open Access Journals (Sweden)

    Wenxiao Jiang

    Full Text Available Huntington disease (HD represents a family of neurodegenerative diseases that are caused by misfolded proteins. The misfolded proteins accumulate in the affected brain regions in an age-dependent manner to cause late-onset neurodegeneration. Transgenic mouse models expressing the HD protein, huntingtin, have been widely used to identify therapeutics that may retard disease progression. Here we report that Berberine (BBR, an organic small molecule isolated from plants, has protective effects on transgenic HD (N171-82Q mice. We found that BBR can reduce the accumulation of mutant huntingtin in cultured cells. More importantly, when given orally, BBR could effectively alleviate motor dysfunction and prolong the survival of transgenic N171-82Q HD mice. We found that BBR could promote the degradation of mutant huntingtin by enhancing autophagic function. Since BBR is an orally-taken drug that has been safely used to treat a number of diseases, our findings suggest that BBR can be tested on different HD animal models and HD patients to further evaluate its therapeutic effects.

  10. Triplet repeat primed PCR simplifies testing for Huntington disease.

    Science.gov (United States)

    Jama, Mohamed; Millson, Alison; Miller, Christine E; Lyon, Elaine

    2013-03-01

    Diagnostic and predictive testing for Huntington disease (HD) requires an accurate determination of the number of CAG repeats in the Huntingtin (HHT) gene. Currently, when a sample appears to be homozygous for a normal allele, additional testing is required to confirm amplification from both alleles. If the sample still appears homozygous, Southern blot analysis is performed to rule out an undetected expanded HTT allele. Southern blot analysis is expensive, time-consuming, and labor intensive and requires high concentrations of DNA. We have developed a chimeric PCR process to help streamline workflow; true homozygous alleles are easily distinguished by this simplified method, and only very large expanded alleles still require Southern blot analysis. Two hundred forty-six HD samples, previously run with a different fragment analysis method, were analyzed with our new method. All samples were correctly genotyped, resulting in 100% concordance between the methods. The chimeric PCR assay was able to identify expanded alleles up to >150 CAG repeats. This method offers a simple strategy to differentiate normal from expanded CAG alleles, thereby reducing the number of samples reflexed to Southern blot analysis. It also provides assurance that expanded alleles are not routinely missed because of allele dropout.

  11. Advances in the pharmacological management of Huntington's disease.

    Science.gov (United States)

    Frank, Samuel; Jankovic, Joseph

    2010-03-26

    There is inevitable physical, cognitive and behavioural decline in Huntington's disease (HD), a dominantly inherited progressive neurological disorder. The hallmark of the disease is chorea, an involuntary brief movement that tends to flow between body regions. HD is diagnosed clinically with genetic confirmation. Predictive testing is available; however, it should be undertaken with caution in patients at risk for the disease but without clinical disease expression. Ongoing observational trials have identified not only early subtle motor signs, but also striatal volume, verbal memory and olfaction as possible early manifestations of clinical disease. Multiple areas of the brain degenerate, with dopamine, glutamate and GABA being the predominant neurotransmitters affected in HD. Although many pharmacotherapies have been evaluated targeting these neurotransmitters, few well conducted trials for symptomatic or neuroprotective interventions have yielded positive results. Tetrabenazine is one of the better studied and more effective agents for reducing chorea, although with a risk of potentially serious adverse effects. Newer antipsychotic agents such as olanzapine and aripiprazole may have adequate efficacy with a more favourable adverse-effect profile than older antipsychotics for treating chorea and psychosis. In this review, the pathogenesis, epidemiology and diagnosis of HD are discussed as background for understanding potential pharmacological treatment options. Potential strategies to delay the progression of HD that have been studied and are planned for the future are summarized. Although there is no current method to change the course of this devastating disease, education and symptomatic therapies are effective tools available to clinicians and the families affected by HD.

  12. Genetic Testing for Huntington's Disease: How Is the Decision Taken?

    Science.gov (United States)

    Etchegary, Holly

    2006-01-01

    Research on genetic decision-making normally constructs the decision as an opportunity for choice. However, minimal research investigates how these decisions are taken and whether those who live with genetic risk perceive the test as an opportunity for choice. Employing semistructured interviews with at-risk persons, this study explored decisions about genetic testing for Huntington's disease (HD)--a fatal genetic disorder. A primary aim was to understand how test decisions were perceived. Qualitative data analysis revealed four decision pathways: (1) no decision to be made, (2) constrained decisions, (3) reevaluating the decision, and (4) indicators of HD. Contrary to the rational, "information-processor" approach to decision making, some test decisions were immediate and automatic. These stories challenged the conventional construction of a genetic-test decision as an opportunity for choice. Participant narratives suggested that this construction may be inadequate, at least for some people who live with genetic risk. Test decisions were sometimes constrained by perceived responsibility to other family members, notably offspring. For others at risk, the test decision was a dynamic process of critical thought and evaluation. Finally, behaviors that could be symptoms of HD were the catalyst for testing.

  13. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia.

    Science.gov (United States)

    Dong, Y; Sun, Y-M; Liu, Z-J; Ni, W; Shi, S-S; Wu, Z-Y

    2013-04-01

    Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 ± 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes.

  14. Huntington's disease in Greece: the experience of 14 years.

    Science.gov (United States)

    Panas, M; Karadima, G; Vassos, E; Kalfakis, N; Kladi, A; Christodoulou, K; Vassilopoulos, D

    2011-12-01

    A large scale genetic and epidemiological study of Huntington's disease (HD) was carried out in Greece from January 1995 to December 2008. Diagnostic testing was carried out in 461 symptomatic individuals, while 256 were tested for presymptomatic purposes. The diagnosis of HD with a CAG expansion ≥ 36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 2.5 to 5.4:100,000, while the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) sent for confirmation. The false-positive cases 15.6% were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was 8.6%. A prenatal test was requested in six pregnancies. The findings of our study do not differ significantly from those of similar studies from other European countries despite the relative genetic isolation of Greece. Of interest is the identification of clusters of HD in Greece. The presence or absence of a family history of HD should be interpreted cautiously, during the diagnostic process.

  15. Impaired PGC-1alpha function in muscle in Huntington's disease.

    Science.gov (United States)

    Chaturvedi, Rajnish K; Adhihetty, Peter; Shukla, Shubha; Hennessy, Thomas; Calingasan, Noel; Yang, Lichuan; Starkov, Anatoly; Kiaei, Mahmoud; Cannella, Milena; Sassone, Jenny; Ciammola, Andrea; Squitieri, Fernando; Beal, M Flint

    2009-08-15

    We investigated the role of PPAR gamma coactivator 1alpha (PGC-1alpha) in muscle dysfunction in Huntington's disease (HD). We observed reduced PGC-1alpha and target genes expression in muscle of HD transgenic mice. We produced chronic energy deprivation in HD mice by administering the catabolic stressor beta-guanidinopropionic acid (GPA), a creatine analogue that reduces ATP levels, activates AMP-activated protein kinase (AMPK), which in turn activates PGC-1alpha. Treatment with GPA resulted in increased expression of AMPK, PGC-1alpha target genes, genes for oxidative phosphorylation, electron transport chain and mitochondrial biogenesis, increased oxidative muscle fibers, numbers of mitochondria and motor performance in wild-type, but not in HD mice. In muscle biopsies from HD patients, there was decreased PGC-1alpha, PGC-1beta and oxidative fibers. Oxygen consumption, PGC-1alpha, NRF1 and response to GPA were significantly reduced in myoblasts from HD patients. Knockdown of mutant huntingtin resulted in increased PGC-1alpha expression in HD myoblast. Lastly, adenoviral-mediated delivery of PGC-1alpha resulted increased expression of PGC-1alpha and markers for oxidative muscle fibers and reversal of blunted response for GPA in HD mice. These findings show that impaired function of PGC-1alpha plays a critical role in muscle dysfunction in HD, and that treatment with agents to enhance PGC-1alpha function could exert therapeutic benefits. Furthermore, muscle may provide a readily accessible tissue in which to monitor therapeutic interventions.

  16. Transcriptional dysregulation in Huntington's disease: The role of histone deacetylases.

    Science.gov (United States)

    Sharma, Sorabh; Taliyan, Rajeev

    2015-10-01

    Huntington's disease (HD) is a progressive neurological disorder for which there are no disease-modifying treatments. Although, the exact underlying mechanism(s) leading to the neural cell death in HD still remains elusive, the transcriptional dysregulation is a major molecular feature. Recently, the transcriptional activation and repression regulated by chromatin acetylation has been found to be impaired in HD pathology. The acetylation and deacetylation of histone proteins is carried out by opposing actions of histone acetyl-transferases and histone deacetylases (HDACs), respectively. Studies carried out in cell culture, yeast, Drosophila and rodent model(s) have indicated that HDAC inhibitors (HDACIs) might provide useful class of therapeutic agents for HD. Clinical trials have also reported the beneficial effects of HDACIs in patients suffering from HD. Therefore, the development of HDACIs as therapeutics for HD has been vigorously pursued. In this review, we highlight and summarize the putative role of HDACs in HD like pathology and further discuss the potential of HDACIs as new therapeutic avenues for the treatment of HD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Synaptopathic mechanisms of neurodegeneration and dementia: Insights from Huntington's disease.

    Science.gov (United States)

    Tyebji, Shiraz; Hannan, Anthony J

    2017-06-01

    Dementia encapsulates a set of symptoms that include loss of mental abilities such as memory, problem solving or language, and reduces a person's ability to perform daily activities. Alzheimer's disease is the most common form of dementia, however dementia can also occur in other neurological disorders such as Huntington's disease (HD). Many studies have demonstrated that loss of neuronal cell function manifests pre-symptomatically and thus is a relevant therapeutic target to alleviate symptoms. Synaptopathy, the physiological dysfunction of synapses, is now being approached as the target for many neurological and psychiatric disorders, including HD. HD is an autosomal dominant and progressive degenerative disorder, with clinical manifestations that encompass movement, cognition, mood and behaviour. HD is one of the most common tandem repeat disorders and is caused by a trinucleotide (CAG) repeat expansion, encoding an extended polyglutamine tract in the huntingtin protein. Animal models as well as human studies have provided detailed, although not exhaustive, evidence of synaptic dysfunction in HD. In this review, we discuss the neuropathology of HD and how the changes in synaptic signalling in the diseased brain lead to its symptoms, which include dementia. Here, we review and discuss the mechanisms by which the 'molecular orchestras' and their 'synaptic symphonies' are disrupted in neurodegeneration and dementia, focusing on HD as a model disease. We also explore the therapeutic strategies currently in pre-clinical and clinical testing that are targeted towards improving synaptic function in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Microglial Activation in the Pathogenesis of Huntington's Disease.

    Science.gov (United States)

    Yang, Hui-Ming; Yang, Su; Huang, Shan-Shan; Tang, Bei-Sha; Guo, Ji-Feng

    2017-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of HTT gene that encodes huntingtin protein. Although HD is characterized by a predominant loss of neurons in the striatum and cortex, previous studies point to a critical role of aberrant accumulation of mutant huntingtin in microglia that contributes to the progressive neurodegeneration in HD, through both cell-autonomous and non-cell-autonomous mechanisms. Microglia are resident immune cells in the central nervous system (CNS), which function to surveil the microenvironment at a quiescent state. In response to various pro-inflammatory stimuli, microglia become activated and undergo two separate phases (M1 and M2 phenotype), which release pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), anti-inflammatory cytokines, and growth factors (TGF-β, CD206, and Arg1), respectively. Immunoregulation by microglial activation could be either neurotoxic or neuroprotective. In this review, we summarized current understanding about microglial activation in the pathogenesis and progression of HD, with a primary focus of M1 and M2 phenotype of activated microglia and their corresponding signaling pathways.

  19. Antidepressants for neuroprotection in Huntington's disease: A review.

    Science.gov (United States)

    Jamwal, Sumit; Kumar, Puneet

    2015-12-15

    Huntington Disease (HD), which is characterized by abnormal dance-like movements, is a neurodegenerative disorder caused by a genetic mutation that results in an expanded polyglutamine stretch in the NH2 terminus of huntingtin protein (HTT). The principal neuropathological hallmarks of disease include loss of striatal and cortical projection neurons. HTT is ubiquitously expressed and is implicated in several cellular functions including neurogenesis, cell trafficking and brain-derived neurotrophic factor (BDNF) production. Major depression is the most common symptom among pre-symptomatic HD carriers and numerous pieces of preclinical evidence have suggested the use of antidepressants in HD not only elevates mood but also slows down the disease progression by activating different neuroprotective mechanism like BDNF/TrkB pathway, MAPK/ERK signalling, neurogenesis and Wnt signalling. HTT plays major role in neurogenesis, a physiological phenomenon that is implicated in some of the behavioral effects of antidepressants. Currently, there is no clinically available treatment that can halt or slow down the progression of HD except tetrabenazine (the only FDA approved drug); however, this drug also induces depression and sedation in patients. In this review, a brief discussion has been made about the mutant HTT that induced various cellular and molecular mechanisms underlying behavioral disorders in HD. Further, an attempt has been made to understand the various cellular mechanisms involved in mediating the neuroprotective effects of antidepressants in HD. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Non-Verbal and Verbal Fluency in Prodromal Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Tarja-Brita Robins Wahlin

    2015-12-01

    Full Text Available Background: This study examines non-verbal (design and verbal (phonemic and semantic fluency in prodromal Huntington's disease (HD. An accumulating body of research indicates subtle deficits in cognitive functioning among prodromal mutation carriers for HD. Methods: Performance was compared between 32 mutation carriers and 38 non-carriers in order to examine the magnitude of impairment across fluency tasks. The predicted years to onset (PYTO in mutation carriers was calculated by a regression equation and used to divide the group according to whether onset was predicted as less than 12.75 years (HD+CLOSE; n = 16 or greater than 12.75 years (HD+DISTANT; n = 16. Results: The results indicate that both non-verbal and verbal fluency is sensitive to subtle impairment in prodromal HD. HD+CLOSE group produced fewer items in all assessed fluency tasks compared to non-carriers. HD+DISTANT produced fewer drawings than non-carriers in the non-verbal task. PYTO correlated significantly with all measures of non-verbal and verbal fluency. Conclusion: The pattern of results indicates that subtle cognitive deficits exist in prodromal HD, and that less structured tasks with high executive demands are the most sensitive in detecting divergence from the normal range of functioning. These selective impairments can be attributed to the early involvement of frontostriatal circuitry and frontal lobes.

  1. Huntington disease: natural history, biomarkers and prospects for therapeutics.

    Science.gov (United States)

    Ross, Christopher A; Aylward, Elizabeth H; Wild, Edward J; Langbehn, Douglas R; Long, Jeffrey D; Warner, John H; Scahill, Rachael I; Leavitt, Blair R; Stout, Julie C; Paulsen, Jane S; Reilmann, Ralf; Unschuld, Paul G; Wexler, Alice; Margolis, Russell L; Tabrizi, Sarah J

    2014-04-01

    Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.

  2. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    Science.gov (United States)

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.

  3. Wigner and Huntington: the long quest for metallic hydrogen

    Science.gov (United States)

    Nellis, W. J.

    2013-06-01

    In 1935, Wigner and Huntington (WH) predicted that at a density D Met=0.62 mole H/cm3, 'very low temperatures', and a pressure greater than 25 GPa, body-centered cubic H2 would undergo an isostructural phase transition directly to H with an associated insulator-metal transition (IMT). WH also predicted an H2 structure type that might occur if the simple H2/H dissociative IMT does not exist: 'It is possible … that a layer-like lattice … is obtainable under high pressure'. In 1991, Ashcroft predicted that the 'geometric and dynamic nature of the (H-H) pairing', possibly in a layered graphite-like structure, would substantially impede achieving metallic H2. In 1996, metallic fluid H was made under dynamic compression at 0.64 mole H/cm3, 140 GPa and T/T F≪1, where T F is Fermi temperature. In 2012, a layer-like lattice, called Phase IV, was discovered above ∼220 GPa static pressure. Phase IV is insulating and possibly semi-metallic up to ∼360 GPa, above which it has been predicted to become metallic. This paper is a historical perspective - a comparison of WH's predictions with recent dynamic, static and theoretical high pressure results. WH did extremely well.

  4. Making a measurable difference in advanced Huntington disease care.

    Science.gov (United States)

    Moskowitz, Carol Brown; Rao, Ashwini K

    2017-01-01

    Neurologists' role in the care of people with advanced Huntington disease (HD) (total functional capacity <7), often limited by a lack of clinical research to support good practice, includes the following: (1) provide comprehensive health records to an interdisciplinary care staff before admission to a more intense care setting (home health services, day program, assisted living, group home, long-term skilled nursing facility, palliative care); (2) consult with and refer to rehabilitation (occupational therapy, physical therapy, speech and language pathology), behavioral and psychiatric professionals for problem-solving strategies, which must be reviewed with direct care staff before implementation; (3) encourage and support qualitative and quantitative interdisciplinary research studies, and randomized controlled studies of nonpharmacologic interventions; and (4) assist in the development of meaningful measures to further document what works to provide a good quality of life for the patient and family and a comfortable thoughtful approach to a good death. Collaborative models of care depend on: (1) clear communication; (2) ongoing education and support programs; with (3) pharmacologic and rehabilitation interventions, always in the context of respect for the person with HD, a preservation of the individuals' dignity, autonomy, and individual preferences. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Cognitive and behavioral changes in Huntington disease before diagnosis.

    Science.gov (United States)

    Paulsen, Jane S; Miller, Amanda C; Hayes, Terry; Shaw, Emily

    2017-01-01

    Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Founder mutation for Huntington disease in Caucasus Jews.

    Science.gov (United States)

    Melamed, O; Behar, D M; Bram, C; Magal, N; Pras, E; Reznik-Wolf, H; Borochowitz, Z U; Davidov, B; Mor-Cohen, R; Baris, H N

    2015-02-01

    Huntington disease (HD), an autosomal dominant disorder involving HTT, is characterized by chorea, psychiatric illness and cognitive decline. Diagnosis and age of onset depend on the degree of expansion of the trinucleotide CAG repeat within the gene. The prevalence of HD is known for Europeans but has not been studied in the Israeli population. Between 2006 and 2011 we diagnosed in our adult genetics clinic ten HD probands, nine of whom were Caucasus Jews (CJ) (Azerbaijani), and one Ashkenazi Jewish. We performed haplotype analysis to look for evidence of a founder mutation, and found that of the nine CJ, eight shared the same haplotype that was compatible with the A1 haplogroup. We calculated the coalescence age of the mutation to be between 80 and 150 years. Ninety percent of our HD patients are CJ, as are 27% of the HD patients in Israel, although the CJ comprise only 1.4% of the Israeli population. Our findings suggest a higher prevalence of HD among CJ compared to the general Israeli population and are consistent with a recent founder mutation. We recommend a higher degree of suspicion for HD in CJ with subtle clinical findings. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Cognitive and Brain Reserve in Prodromal Huntington Disease

    Science.gov (United States)

    Bonner-Jackson, Aaron; Long, Jeffrey D.; Westervelt, Holly; Tremont, Geoffrey; Aylward, Elizabeth; Paulsen, Jane S.

    2013-01-01

    Background Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Methods Participants were genetically-confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on 4 cognitive measures and 3 brain volumes over approximately 6 years. Results Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Conclusions Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals. PMID:23702309

  8. Rate of change in early Huntington's disease: a clinicometric analysis.

    Science.gov (United States)

    Meyer, Christina; Landwehrmeyer, Bernhard; Schwenke, Carsten; Doble, Adam; Orth, Michael; Ludolph, Albert C

    2012-01-01

    Sensitive outcome measures for patients with Huntington's disease (HD) are required for future clinical trials. Longitudinal data were collected from a 3-year study of 379 patients suffering from early HD who were not treated by antipsychotics. Progression of UHDRS item scores was evaluated by linear regression and slope, whereas correlation coefficient, standard error, and P values were estimated on the basis of the data of eight evaluations from screening to study end (36 months). For the functional assessment dimension, the proportion of "no" responses at baseline and at study end was determined. Linear progression was observed for the motor score and for all three functional measures (i.e., functional assessment score, independence assessment score, and total functional capacity score). In contrast, there was little evidence for progression of the behavioral assessment score over the study period, whereas the cognitive assessment score was intermediate. Twenty-two motor-score items showed linear progression, with a slope of >0.003. These included all chorea items, finger tapping and pronation/supination (left and right), gait, tongue protrusion, and tandem walking. Different symptom domains and individual items evolved at different rates in this group of patients suffering from early HD. It may be possible to select sensitive items to create a simplified version of the UHDRS, which would be more efficient and more sensitive for the assessment of disease progression in clinical trials and natural history studies.

  9. Did the “Woman in the Attic” in Jane Eyre Have Huntington Disease?

    Science.gov (United States)

    Coon, Elizabeth A.; Hassan, Anhar

    2015-01-01

    Background References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. Aim Our aim was to compare Charlotte Brontë’s depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington’s original essay “On chorea” with the hypothesis that Mason was displaying features of Huntington disease. Results Charlotte Brontë’s 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington’s tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. Conclusion Brontë’s character had features of Huntington disease as originally described by Huntington. Brontë’s keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era. PMID:26273542

  10. Results on single cell PCR for Huntington's gene and WAVE product analysis for preimplantation genetic diagnosis.

    Science.gov (United States)

    Drury, K C; Liu, M C; Lilleberg, S; Kipersztok, S; Williams, R S

    2001-10-22

    Triple repeat base pair amplification is the basis for a number of prevalent genetic diseases such as Huntington's, Fragile X, Myotonic Dystrophy and others. We have chosen to investigate the use of PCR to amplify a portion of the Huntington's gene in single cells in order to develop a clinical test system for preimplantation genetic diagnosis (PGD). Amplification of CAG triple repeat sequences poses difficulties due to resistance of GC melting for amplification. Special PCR modifications are necessary to carry out the amplification of GC rich areas found in most triple base pair expansions. We have used a modified polymerase chain reaction (PCR) protocol to amplify the expanded repeat sequence of the Huntington's gene with satisfactory efficiency. Detection of the amplified expanded CAG repeats is shown to be possible using both agarose gel electrophoresis and high definition denaturing high pressure liquid (DHPLC) chromatography. The incidence of allele dropout (ADO) is documented.

  11. Operant-based instrumental learning for analysis of genetically modified models of Huntington's disease.

    Science.gov (United States)

    Trueman, R C; Dunnett, S B; Brooks, S P

    2012-06-01

    Huntington's disease is the result of an expanded CAG repeat in the gene that codes for the protein huntingtin and results in a progressive sequelae of motor, cognitive and psychiatric symptoms. The development of genetically modified rodent models of Huntington's disease has led to the need for sensitive behavioural phenotyping. Operant tests for rodents have been developed that can determine the functional deficits in these genetically modified models, from motor, cognitive and emotional domains. The current review discusses tests that employ operant equipment, an automated and highly flexible method for testing rodents. Different operant paradigms are examined in relation to their relevance to Huntington's disease symptomology, as well as summarising research to date on genetic models with these tests.

  12. Acetylcholinesterase inhibitors in cognitive impairment in Huntington's disease: A brief review.

    Science.gov (United States)

    Vattakatuchery, Joe John; Kurien, Renjith

    2013-09-22

    Huntington's disease (HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cognitive dysfunction includes executive dysfunction, psychomotor symptoms, visuospatial deficits, perceptual deficits, memory loss and difficulty learning new skills. Acetylcholinesterase inhibitors have shown good effect in the treatment of other types of dementia and it is postulated that it might delay cognitive decline in HD. We reviewed the evidence for Acetylcholinesterase inhibitors in the treatment of cognitive decline and dementia associated with Huntington's disease. We identified 6 articles that investigated the role of Acetylcholinesterase inhibitors for treatment of cognitive deficits in Huntington's disease. Following the review, the authors concluded that there is limited evidence for the use of Acetylcholinesterase inhibitors for cognitive impairment in HD.

  13. An update on Huntington's disease: from the gene to the clinic.

    Science.gov (United States)

    Kim, Samuel D; Fung, Victor S C

    2014-08-01

    This review highlights the recent advances in Huntington's disease, with a particular focus on development of disease biomarkers for use in therapeutic trials in the premotor phase of the disease, as well as the growing literature regarding pathophysiological mechanisms and their relevance to potential therapeutic targets. There have been continued advances in the development of disease biomarkers, and promising neuroprotection trials are beginning to emerge in the premotor stage of Huntington's disease. Deeper understanding of the pathophysiological mechanisms is being translated into potential therapeutic strategies. The premotor stage of Huntington's disease provides an ideal time to trial disease-modifying therapy, but reliable biomarkers are required for monitoring disease progression, and this remains an area of intense research. Our understanding of the underlying pathophysiological mechanisms continues to expand, and a number of promising therapeutic strategies are emerging, including strategies to silence mutant huntingtin expression.

  14. [Fatty acid patterns and glucose tolerance in Huntington's chorea (author's transl)].

    Science.gov (United States)

    Schubotz, R; Hausmann, L; Kaffarnik, H; Zehner, J; Oepen, H

    1976-07-02

    Fatty acid patterns of plasma lipids and glucose-tolerance in Huntington's chorea. 25 patients with Huntington's chorea of various manifestation (9 predisposed symptomefree, 5 with light and 11 with severe manifestation) had studies of carbohydrate and lipid metabolism. These studies measured glucose-tolerance tests, insulin-, HGH-secretion, serum lipids and plasma fatty acid conposition of the cholesterylesters, triglycerides and phospholipids. The reactive insulin- but not HGH-levels were significantly raised, 32 % of the patients with Huntington's chorea had abnormal glucose-tolerance tests, compared with 3.2 % in a control group. Duration of symptoms correlated with higher cholesterol levels. Minor deviations were found in the fatty acid patterns in various lipid clases.

  15. Ecology and Taxonomy of Water Canyon, Canadian County, Oklahoma, Master's Thesis, University of Oklahoma 1961 [Revised 2013

    Directory of Open Access Journals (Sweden)

    Constance E. Taylor

    2014-03-01

    Full Text Available Numerous canyons have been cut into the Rush Springs Sandstone of Permian age in West Central Oklahoma and subsequently refilled. Some of these canyons have been partly exposed by erosion of the sediment fill. Fossils collected indicate the canyon fill is sub-Pleistocene to geologically recent. The microclimate of these canyons is more mesic compared to the dryer prairie uplands. Sugar maple (Acer saccharum persists there, far west of its other locations in very eastern Oklahoma. Beginning in 1932 several of these sediment-filled canyons began a process of rapid erosion, exposing the rock walls of the canyons. This study is a comparison of Water Canyon and two of its branches: Water Branch Canyon, a stable canyon wooded with mature vegetation including sugar maple and Activity Branch Canyon, a newly excavated canyon branch that began eroding after excessive rainfall in 1932. This study was completed in 1960. Six transects are used to show the distribution of the 233 plant species found in the Water Canyon complex. Herbaceous species generally were unique to each canyon type.

  16. Fractal properties of fractured sandstones of the Guartela Canyon, Parana Basin - Brazil; Propriedades fractais de arenitos fraturados do Canyon Guartela, Formacao Furnas, Bacia do Parana

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Jeferson de; Figueira, Isabela Francoso Rebutini; Santos, Thais Borba [Universidade Federal do Rio Grande do Norte (PPGG/DG/UFRN), Natal (Brazil). Dept. de Geologia. Programa de Pos-Graducao em Geologia; Rostirolla, Sidnei Pires [Universidade Federal do Rio Grande do Norte (DG/UFRN), Natal (Brazil). Dept. de Geologia; Pierin, Andre Ramiro; Spisila, Andre Luis [Universidade Federal do Rio Grande do Norte (DG/UFRN), Natal (Brazil). Dept. de Geologia. Programa de Iniciacao Cientifica

    2008-03-15

    The statistical and geometrical properties of fracture systems were obtained by analyzing remote sense images and outcrop data, in the Region of Guartela Canyon, in the central-eastern of Parana State. The probability distributions of fractures, with their parameters and attributes, were obtained through extensive statistical exploration of data. These parameters were used as input data for generating 3-D stochastic fractures models through the 'discrete fracture network - DFN' method. The modeling is performed by using the code FRED. To study the persistence of statistical parameters in multiple scales were used remote sensing images (SRTM, Landsat TM7 and aerial photos), covering a scale range from outcrops (few meters) to basin scales (hundreds of kilometers). The results indicated the presence of power-law (fractal) statistics for the spatial and size distributions. Fractals distributions were found for all sets studied, in some cases with different fractal exponents. The implications of fractal behavior for the generation of discrete fracture network, and consequently for the hydraulic properties, are briefly discussed. (author)

  17. Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease.

    Science.gov (United States)

    Nana, Alissa L; Kim, Eric H; Thu, Doris C V; Oorschot, Dorothy E; Tippett, Lynette J; Hogg, Virginia M; Synek, Beth J; Roxburgh, Richard; Waldvogel, Henry J; Faull, Richard L M

    2014-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.

  18. Characterisation of aggression in Huntington's disease: rates, types and antecedents in an inpatient rehabilitation setting.

    Science.gov (United States)

    Brown, Anahita; Sewell, Katherine; Fisher, Caroline A

    2016-10-12

    To systematically review aggression in an inpatient Huntington's cohort examining rates, types and antecedents. Although the prevalence of aggression in Huntington's disease is high, research into this problematic behaviour has been limited. Few studies have investigated the nature of aggressive behaviour in Huntington's disease or antecedents that contribute to its occurrence. A systematic, double-coded, electronic medical file audit. The electronic hospital medical records of 10 people with Huntington's disease admitted to a brain disorders unit were audited for a 90-day period using the Overt Aggression Scale-Modified for Neurorehabilitation framework, yielding 900 days of clinical data. Nine of 10 clients exhibited aggression during the audit period. Both verbal (37·1%) aggression and physical aggression were common (33·8%), along with episodes of mixed verbal and physical aggression (15·2%), while aggression to objects/furniture was less prevalent (5·5%). The most common antecedent was physical guidance with personal care, far exceeding any other documented antecedents, and acting as the most common trigger for four of the nine clients who exhibited aggression. For the remaining five clients, there was intraindividual heterogeneity in susceptibility to specific antecedents. In Huntington's sufferers at mid- to late stages following disease onset, particular care should be made with personal care assistance due to the propensity for these procedures to elicit an episode of aggression. However, given the degree of intraindividual heterogeneity in susceptibility to specific antecedents observed in the present study, individualised behaviour support plans and sensory modulation interventions may be the most useful in identifying triggers and managing aggressive episodes. Rates of aggression in Huntington's disease inpatients can be high. Knowledge of potential triggers, such as personal care, is important for nursing and care staff, so that attempts can be

  19. A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Eirini Kalliolia

    Full Text Available Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.We studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington's disease subjects. We also quantified fasting levels of vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid stimulating hormone, free triiodothyronine, free total thyroxine, prolactin, adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone releasing hormone, insulin-like growth factor-1 and insulin-like factor binding protein-3 were quantified at 06:00 (fasting, 15:00 and 23:00. A battery of clinical tests, including neurological rating and function scales were performed.24-hour concentrations of adrenocorticotropic hormone, cortisol, luteinizing hormone and follicle-stimulating hormone did not differ significantly between the Huntington's disease group and controls. Daytime growth hormone secretion was similar in control and Huntington's disease subjects. Stage II/III Huntington's disease subjects had lower concentration of post-sleep growth hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which did not reach significance. In Huntington's disease subjects, baseline levels of hypothalamo-pituitary axis hormones measured did not significantly differ from those of healthy controls.The relatively small subject group means that the study may not detect subtle perturbations in hormone concentrations. A targeted study of the somatotropic axis in larger cohorts may be warranted. However, the lack of significant results despite many

  20. Measured and modelled concentrations and vertical profiles of airborne particulate matter within the boundary layer of a street canyon.

    Science.gov (United States)

    Colls, J J; Micallef, A

    1999-09-01

    Concentrations and vertical profiles of various fractions of airborne particulate matter (suspended particulate matter (SPM), PM10 and PM2.5) have been measured over the first three metres from ground in a street canyon. Measurements were carried out using automated near real-time apparatus called the Kinetic Sequential Sampling (KSS) system. KSS system is essentially an electronically-controlled lift carrying a real-time particle monitor for sampling air sequentially, at different heights within the breathing zone, which includes all heights within the surface layer of a street canyon at which people may breathe. Data is automatically logged at the different receptor levels, for the determination of the average vertical concentration profile of airborne particulate matter. For measuring the airborne particle concentration, a Grimm Dust Monitor 1.104/5 was used. The recorded data also allows for time series analysis of airborne particulate matter concentration at different heights. Time series data and hourly-average vertical concentration profiles in the boundary layer of the confines of a street are thought to be mainly determined by traffic emissions and traffic associated processes. Hence the measured data were compared with results of a street canyon emission-dispersion model in time and space. This Street Level Air Quality (SLAQ) model employs the plume-box technique and includes modules for simulating vehicle-generated effects such as thermally- and mechanically-generated turbulence and resuspension of road dust. Environmental processes, such as turbulence resulting from surface sensible heat and the formation of sulphate aerosol from sulphur dioxide exhaust emissions, are taken into account. The paper presents an outline description of the measuring technique and model used, and a comparison of the measured and modelled data.

  1. Measured and modelled concentrations and vertical profiles of airborne particulate matter within the boundary layer of a street canyon

    Energy Technology Data Exchange (ETDEWEB)

    Colls, J.J.; Micallef, A. [Division of Environmental Science, School of Biological Sciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD (United Kingdom)

    1999-09-01

    Concentrations and vertical profiles of various fractions of airborne particulate matter (suspended particulate matter (SPM), PM{sub 10} and PM{sub 2.5}) have been measured over the first three metres from ground in a street canyon. Measurements were carried out using automated near real-time apparatus called the Kinetic Sequential Sampling (KSS) system. KSS system is essentially an electronically-controlled lift carrying a real-time particle monitor for sampling air sequentially, at different heights within the breathing zone, which includes all heights within the surface layer of a street canyon at which people may breathe. Data is automatically logged at the different receptor levels, for the determination of the average vertical concentration profile of airborne particulate matter. For measuring the airborne particle concentration, a Grimm Dust Monitor 1.104/5 was used. The recorded data also allows for time series analysis of airborne particulate matter concentration at different heights. Time series data and hourly-average vertical concentration profiles in the boundary layer of the confines of a street are thought to be mainly determined by traffic emissions and traffic associated processes. Hence the measured data were compared with results of a street canyon emission-dispersion model in time and space. This Street Level Air Quality (SLAQ) model employs the plume-box technique and includes modules for simulating vehicle-generated effects such as thermally- and mechanically-generated turbulence and resuspension of road dust. Environmental processes, such as turbulence resulting from surface sensible heat and the formation of sulphate aerosol from sulphur dioxide exhaust emissions, are taken into account. The paper presents an outline description of the measuring technique and model used, and a comparison of the measured and modelled data.

  2. Analysis of maximum allowable fragment heights during dissolution of high flux isotope reactor fuel in an h-canyon dissolver

    Energy Technology Data Exchange (ETDEWEB)

    Daniel, G. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Rudisill, T. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-07-17

    As part of the Spent Nuclear Fuel (SNF) processing campaign, H-Canyon is planning to begin dissolving High Flux Isotope Reactor (HFIR) fuel in late FY17 or early FY18. Each HFIR fuel core contains inner and outer fuel elements which were fabricated from uranium oxide (U3O8) dispersed in a continuous Al phase using traditional powder metallurgy techniques. Fuels fabricated in this manner, like other SNF’s processed in H-Canyon, dissolve by the same general mechanisms with similar gas generation rates and the production of H2. The HFIR fuel cores will be dissolved using a flowsheet developed by the Savannah River National Laboratory (SRNL) in either the 6.4D or 6.1D dissolver using a unique insert. Multiple cores will be charged to the same dissolver solution maximizing the concentration of dissolved Al. The recovered U will be down-blended into low-enriched U for subsequent use as commercial reactor fuel. During the development of the HFIR fuel dissolution flowsheet, the cycle time for the initial core was estimated at 28 to 40 h. Once the cycle is complete, H-Canyon personnel will open the dissolver and probe the HFIR insert wells to determine the height of any fuel fragments which did not dissolve. Before the next core can be charged to the dissolver, an analysis of the potential for H2 gas generation must show that the combined surface area of the fuel fragments and the subsequent core will not generate H2 concentrations in the dissolver offgas which exceeds 60% of the lower flammability limit (LFL) of H2 at 200 °C. The objective of this study is to identify the maximum fuel fragment height as a function of the Al concentration in the dissolving solution which will provide criteria for charging successive HFIR cores to an H-Canyon dissolver.

  3. NMDA receptor gene variations as modifiers in Huntington disease: a replication study

    OpenAIRE

    2011-01-01

    Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the ...

  4. Guidelines for presymptomatic testing for Huntington's disease: past, present and future in France.

    Science.gov (United States)

    Clément, S; Gargiulo, M; Feingold, J; Durr, A

    2015-01-01

    Huntington's disease was the first adult onset neurological disease for which presymptomatic genetic testing became possible. It served as a model for the approach which constituted a radical change in medical practice and provided an important framework for multi-step, multidisciplinary, counselling for at risk persons. We will review the historical context of guidelines and good clinical practices, the experiences of our team which covers more than 20 years of presymptomatic testing for Huntington's disease in France, and explore the impact of the new French legislation for the future of presymptomatic testing of diseases for which neither preventive measures nor curative treatments are yet available.

  5. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B;

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  6. Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

    Science.gov (United States)

    Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

    1980-12-01

    Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

  7. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.

    Science.gov (United States)

    Quinn, N; Marsden, C D

    1984-08-01

    Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause tardive dyskinesia. Among currently available treatments, it may therefore be considered a drug of choice for treatment of tardive dyskinesia.

  8. The influence of the San Gregorio fault on the morphology of Monterey Canyon

    Science.gov (United States)

    McHugh, C.M.G.; Ryan, William B. F.; Eittreim, S.; Donald, Reed

    1998-01-01

    A side-scan sonar survey was conducted of Monterey Canyon and the San Gregorio fault zone, off shore of Monterey Bay. The acoustic character and morphology of the sonar images, enhanced by SeaBeam bathymetry, show the path of the San Gregorio fault zone across the shelf, upper slope, and Monterey Canyon. High backscatter linear features a few kilometers long and 100 to 200 m wide delineate the sea-floor expression of the fault zone on the shelf. Previous studies have shown that brachiopod pavements and carbonate crusts are the source of the lineations backscatter. In Monterey Canyon, the fault zone occurs where the path of the canyon makes a sharp bend from WNW to SSW (1800 m). Here, the fault is marked by NW-SE-trending, high reflectivity lineations that cross the canyon floor between 1850 m and 1900 m. The lineations can be traced to ridges on the northwestern canyon wall where they have ~ 15 m of relief. Above the low-relief ridges, bowl-shaped features have been excavated on the canyon wall contributing to the widening of the canyon. We suggest that shear along the San Gregorio fault has led to the formation of the low-relief ridges near the canyon wall and that carbonate crusts, as along the shelf, may be the source of the high backscatter features on the canyon floor. The path of the fault zone across the upper slope is marked by elongated tributary canyons with high backscatter floors and 'U'-shaped cross-sectional profiles. Linear features and stepped scarps suggestive of recent crustal movement and mass-wasting, occur on the walls and floors of these canyons. Three magnitude-4 earthquakes have occurred within the last 30 years in the vicinity of the canyons that may have contributed to the observed features. As shown by others, motion along the fault zone has juxtaposed diverse lithologies that outcrop on the canyon walls. Gully morphology and the canyon's drainage patterns have been influenced by the substrate into which the gullies have formed.

  9. Unusually high food availability in Kaikoura Canyon linked to distinct deep-sea nematode community

    Science.gov (United States)

    Leduc, D.; Rowden, A. A.; Nodder, S. D.; Berkenbusch, K.; Probert, P. K.; Hadfield, M. G.

    2014-06-01

    Kaikoura Canyon, on the eastern New Zealand continental margin, is the most productive, non-chemosynthetic deep-sea habitat described to date, with megafaunal biomass 100-fold higher than those of other deep-sea habitats. The present study, which focused on free-living nematodes, provides the first comparison of faunal community structure and diversity between Kaikoura Canyon and nearby open slope habitats. Results show substantially higher food availability in the canyon relative to open slope sediments, which probably reflects greater levels of primary productivity above the canyon, coupled with downwelling and/or topographically-induced channelling, which serves to concentrate surface-derived organic matter along the canyon axis. This high food availability appears to be responsible for the elevated nematode biomass in Kaikoura Canyon, with values exceeding all published nematode biomass data from canyons elsewhere. There was also markedly lower local species diversity of nematodes inside the canyon relative to the open slope habitat, as well as a distinct community structure. The canyon community was dominated by species, such as Sabateria pulchra, which were absent from the open slope and are typically associated with highly eutrophic and/or disturbed environments. The presence of these taxa, as well as the low observed diversity, is likely to reflect the high food availability, and potentially the high levels of physically and biologically induced disturbance within the canyon. Kaikoura Canyon is a relatively small habitat characterised by different environmental conditions that makes a disproportionate contribution to deep-sea diversity in the region, despite its low species richness.

  10. Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington's disease gene carriers.

    Science.gov (United States)

    Wilson, Heather; Niccolini, Flavia; Haider, Salman; Marques, Tiago Reis; Pagano, Gennaro; Coello, Christopher; Natesan, Sridhar; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Tabrizi, Sarah J; Politis, Marios

    2016-09-15

    Huntington's disease (HD) is a monogenic neurodegenerative disorder with an underlying pathology involving the toxic effect of mutant huntingtin protein primarily in striatal and cortical neurons. Phosphodiesterase 10A (PDE10A) regulates intracellular signalling cascades, thus having a key role in promoting neuronal survival. Using positron emission tomography (PET) with [(11)C]IMA107, we investigated the in vivo extra-striatal expression of PDE10A in 12 early premanifest HD gene carriers. Image processing and kinetic modelling was performed using MIAKAT™. Parametric images of [(11)C]IMA107 non-displaceable binding potential (BPND) were generated from the dynamic [(11)C]IMA107 scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding. We set a threshold criterion for meaningful quantification of [(11)C]IMA107 BPND at 0.30 in healthy control data; regions meeting this criterion were designated as regions of interest (ROIs). MRI-based volumetric analysis showed no atrophy in ROIs. We found significant differences in mean ROIs [(11)C]IMA107 BPND between HD gene carriers and healthy controls. HD gene carriers had significant loss of PDE10A within the insular cortex and occipital fusiform gyrus compared to healthy controls. Insula and occipital fusiform gyrus are important brain areas for the regulation of cognitive and limbic function that is impaired in HD. Our findings suggest that dysregulation of PDE10A-mediated intracellular signalling could be an early phenomenon in the course of HD with relevance also for extra-striatal brain areas.

  11. Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain.

    Science.gov (United States)

    Shelbourne, Peggy F; Keller-McGandy, Christine; Bi, Wenya Linda; Yoon, Song-Ro; Dubeau, Louis; Veitch, Nicola J; Vonsattel, Jean Paul; Wexler, Nancy S; Arnheim, Norman; Augood, Sarah J

    2007-05-15

    Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Here, we provide evidence supporting the hypothesis that somatic increases of mutation length play a role in the progressive nature and cell-selective aspects of HD pathogenesis. Results from micro-dissected tissue and individual laser-dissected cells obtained from human HD cases and knock-in HD mice indicate that the CAG repeat is unstable in all cell types tested although neurons tend to have longer mutation length gains than glia. Mutation length gains occur early in the disease process and continue to accumulate as the disease progresses. In keeping with observed patterns of cell loss, neuronal mutation length gains tend to be more prominent in the striatum than in the cortex of low-grade human HD cases, less so in more advanced cases. Interestingly, neuronal sub-populations of HD mice appear to have different propensities for mutation length gains; in particular, smaller mutation length gains occur in nitric oxide synthase-positive striatal interneurons (a relatively spared cell type in HD) compared with the pan-striatal neuronal population. More generally, the data demonstrate that neuronal changes in HD repeat length can be at least as great, if not greater, than those observed in the germline. The fact that significant CAG repeat length gains occur in non-replicating cells also argues that processes such as inappropriate mismatch repair rather than DNA replication are involved in generating mutation instability in HD brain tissue.

  12. Alterations in Striatal Synaptic Transmission are Consistent across Genetic Mouse Models of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Damian M Cummings

    2010-05-01

    Full Text Available Since the identification of the gene responsible for HD (Huntington's disease, many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI*** (knock-in mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition.

  13. A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity.

    Science.gov (United States)

    Bañez-Coronel, Mónica; Porta, Silvia; Kagerbauer, Birgit; Mateu-Huertas, Elisabet; Pantano, Lorena; Ferrer, Isidre; Guzmán, Manuel; Estivill, Xavier; Martí, Eulàlia

    2012-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches.

  14. Perceptions of discrimination among persons who have undergone predictive testing for Huntington's disease.

    Science.gov (United States)

    Penziner, Elizabeth; Williams, Janet K; Erwin, Cheryl; Bombard, Yvonne; Wallis, Anne; Beglinger, Leigh J; Hayden, Michael R; Paulsen, Jane S

    2008-04-05

    Potential discrimination from genetic testing may undermine technological advances for health care. Researching long-term consequences of testing for genetic conditions that may lead to discrimination is a public health priority. The consequences of genetic discrimination generate social, health, and economic burdens for society by diminishing opportunities for at-risk individuals in a range of contexts. The current study objective was to investigate perceptions of genetic stigmatization and discrimination among persons who completed predictive testing for Huntington's disease (HD). Using semi-structured interviews and computerized qualitative analysis, the perceptions of 15 presymptomatic persons with a positive gene test predicting HD were examined with regard to differential treatment following testing. The sample comprised 11 women and 4 men, mostly married (73%), aged between 22 and 62 years, with an average education of 14.6 years (SD +/- 2.57) and residing in urban, rural and suburban settings of eight U.S. States. Participants reported perceptions of consequences following disclosure of genetic test results in three areas: employment, insurance, and social relationships. Although most employed participants (90%) revealed their test results to their employers, nearly all reported they would not disclose this information to future employers. Most (87%) participants disclosed test results to their physician, but a similar majority (83%) did not tell their genetic status to insurers. Most participants (87%) disclosed test results to family and peers; patterns of disclosure varied widely. Discrimination concerns remain high in this sample and point to the need for more information to determine the extent and scope of the problem.

  15. Alterations in striatal synaptic transmission are consistent across genetic mouse models of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Damian M Cummings

    2010-06-01

    Full Text Available Since the identification of the gene responsible for HD (Huntington's disease, many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI (knock-in mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition.

  16. Downward and suspended sediment fluxes in the Palamós submarine canyon (North-Western Mediterranean)

    Science.gov (United States)

    Palanques, A.; Martín, J.; Puig, P.; Guillén, J.

    2003-04-01

    The Palamós canyon is deeply incised in the Northern Catatonia continental shelf (North-western Mediterranean) which favour an active shelf-slope sediment transfer. To study particle dynamics in this canyon, seven moorings arrays equipped with current meters, turbidimeters and sediment traps were deployed near the bottom along the main canyon axis (400, 1200 and 1700 m depth), on both canyon walls (1200 m depth) and on the adjacent slope (1200 m depth). One set of these instruments was also deployed at intermediate waters (400 m water depth) in the canyon axis. At surface and mid-depths, suspended sediment fluxes were oriented along the mean flow direction (NE-SW), whereas near-bottom sediment fluxes were more constrained by the local bathymetry. The higher near-bottom downward and suspended particle fluxes were not recorded in the canyon head but in the mid-canyon axis, suggesting additional sediment supplies through or over the canyon walls and/or sediment resuspension in the mid canyon region. Several events of sharp sediment flux increases took place in the mid-canyon axis site during the water stratification season. These events could be related to the action of internal waves and even to fishing activities. In the canyon walls, downward and suspended particle fluxes were higher in the southern wall, where currents were lower than in the northern wall, evidencing an asymmetrical pattern. In the adjacent slope sediment fluxes were significantly lower than in the canyon. An important increase of downward particle fluxes in the canyon axis and both walls occurred by mid-November when a severe storm took place. The pattern of the sediment fluxes in the Palamós Canyon has some differences in relation to those observed in other Mediterranean submarine canyons and has downward particle fluxes from 2 to10 times higher than other studied canyons of this region.

  17. Expanded CAG repeats in the murine Huntington's disease gene increases neuronal differentiation of embryonic and neural stem cells.

    Science.gov (United States)

    Lorincz, Matthew T; Zawistowski, Virginia A

    2009-01-01

    Huntington's disease is an uncommon autosomal dominant neurodegenerative disorder caused by expanded polyglutamine repeats. Increased neurogenesis was demonstrated recently in Huntington's disease post-mortem samples. In this manuscript, neuronally differentiated embryonic stem cells with expanded CAG repeats in the murine Huntington's disease homologue and neural progenitors isolated from the subventricular zone of an accurate mouse Huntington's disease were examined for increased neurogenesis. Embryonic stem cells with expanded CAG repeats in the murine Huntington's disease homologue were demonstrated to undergo facilitated differentiation first into neural progenitors, then into more mature neurons. Neural progenitor cells isolated from the subventricular zone of a Huntington's disease knock-in animal displayed increased production of neural progenitors and increased neurogenesis. These findings suggested that neuronally differentiating embryonic stem cells with expanded CAG repeats is a reasonable system to identify factors responsible for increased neurogenesis in Huntington's disease. Expression profiling analysis comparing neuronally differentiating embryonic stem cells with expanded CAG repeats to neuronally differentiating embryonic stem cells without expanded CAG repeats identified transcripts involved in development and transcriptional regulation as factors possibly mediating increased neurogenesis in response to expanded CAG repeats.

  18. Captured in Stone: Women in the Rock Art of Canyon de Chelly.

    Science.gov (United States)

    Travis, Tara

    1997-01-01

    Describes the pictographs (painted images on stone) and petroglyphs (pecked images on stone) found in the Canyon de Chelly National Monument in Arizona. Canyon de Chelly includes one of the largest concentrations of American Indian rock art in the southwest. Discusses the depiction of women in these images. (MJP)

  19. 33 CFR 165.1155 - Security Zone; Diablo Canyon Nuclear Power Plant, Avila Beach, California.

    Science.gov (United States)

    2010-07-01

    ... Nuclear Power Plant, Avila Beach, California. 165.1155 Section 165.1155 Navigation and Navigable Waters... Coast Guard District § 165.1155 Security Zone; Diablo Canyon Nuclear Power Plant, Avila Beach... surface to bottom, within a 2,000 yard radius of Diablo Canyon Nuclear Power Plant centered at position...

  20. Biological Resources Survey of Mountain Springs Canyon on the Naval Weapons Center.

    Science.gov (United States)

    1983-03-01

    Coleo - gyne association (Beatley, 1976) further up the canyon where the aspect of the north- facing slope changes from northwest to north near Mountain...argusensis) was collected in the upper half of the canyon. Although common in Coleo - j ne habitat, it is considered sensitive by BLM (1980) due to its endemic