Soldier’s Load and the Multifunctional Utility/Logistics and Equipment-Transport

DTIC Science & Technology

2010-06-11

Utility/Logistics Equipment-Countermine and an armed reconnaissance variant called the Armed Robotic Vehicle-Assault (Light). All three Lockheed...mission and requires various levels of human- robot interaction (National Institute of Standards and Technology 2004, 14). Teleoperation. A mode of...use of robots as an act of cowardice, especially in cultures which hold in high esteem the nobility of sacrificing oneself for a higher purpose (Singer

AmeriFlux US-A32 ARM-SGP Medford hay pasture

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

Kueppers, Lara; Torn, Margaret; Biraud, Sebastien

This is the AmeriFlux version of the carbon flux data for the site US-A32 ARM-SGP Medford hay pasture. Site Description - This site is located at the ARM SGP Extended Facility E32, 8 km West of Medford, OK

AmeriFlux US-A74 ARM SGP milo field

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

Kueppers, Lara; Torn, Margaret; Biraud, Sebastien

This is the AmeriFlux version of the carbon flux data for the site US-A74 ARM SGP milo field. Site Description - This site is located near the ARM SGP Central Facility at the intersection of Oklahoma highways 11 and 74, 16.5 km East of Medford, OK

HbA2 levels in β-thalassaemia carriers with the Filipino β0-deletion: are the levels higher than what is found with non-deletional forms of β0-thalassaemia?

PubMed

George, E; Teh, Lai Kuan; Tan, Jama; Lai, Mei I; Wong, Lily

2013-01-01

Classical carriers of β-thalassaemia are identified by a raised HbA2 level. Earlier studies indicated that the Filipino β-deletion has high raised HbA2 levels. The introduction of automated high performance liquid chromatography (HPLC) for thalassaemia screening is an important advance in technology for haematology laboratories. The BioRad Variant II Hb analyser is a common instrument used to quantify HbA2 levels in thalassaemia screening. This study aimed to determine HbA2 levels in carriers of Filipino β-mutation using the BioRad Variant II Hb analyser. The Filipino β-deletion was identified using gap-polymerase chain reaction (PCR) in the parents of transfusion dependent β-thalassaemia patients who were homozygous for the Filipino β-deletion in the indigenous population of Sabah, Malaysia. Hb subtypes were quantified on the BioRad Variant II Hb analyser. Concurrent α-thalassaemia was identified by multiplex gap-PCR for deletions and amplification refractory mutation system (ARMS)-PCR for non-deletional mutations. The mean HbA2 level for Filipino β-thalassaemia trait was 5.9 ± 0.47 and with coinheritance of α-thalassaemia was 6.3 ± 0.44 (-α heterozygous) and 6.7 ± 0.36 (-α homozygous). The HbA2 levels were all >4% in keeping with the findings of classical β-thalassaemia trait and significantly higher than levels seen in non-deletional forms of β-thalassaemia. The HbA2 level measured on the BioRad Variant II Hb analyser was lower than the level in the first description of the Filipino β-thalassaemia. β-thalassaemia trait with coinheritance of α-thalassaemia (-α) is associated with significantly higher HbA2 level.

Molecular identification of Gd A- and Gd B- G6PD deficient variants by ARMS-PCR in a Tunisian population.

PubMed

Haloui, Sabrine; Laouini, Naouel; Sahli, Chaima Abdelhafidh; Daboubi, Rim; Becher, Mariem; Jouini, Latifa; Kazdaghli, Kalthoum; Tinsa, Faten; Cherif, Semia; Khemiri, Monia; Fredj, Sondess Hadj; Othmani, Rim; Ouali, Faida; Siala, Hajer; Toumi, Nour El Houda; Barsaoui, Sihem; Bibi, Amina; Messaoud, Taieb

2016-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy. More than 200 mutations in the G6PD gene have been described. In Tunisia, the A-African and the B-Mediterranean mutations predominate the mutational spectrum. The purpose of this study was to apply the amplification refractory mutation system (ARMS-PCR) to the identification of Gd A+, Gd A- and Gd B- variants in a cohort of deficient individuals and to establish a phenotype/genotype association. 90 subjects were screened for enzymatic deficiency by spectrophotometric assay. The molecular analyses were performed in a group of 50 unrelated patients. Of the 54 altered chromosomes examined, 60% had the Gd A- mutation, 18% showed the Gd B- mutation and in 20% of cases, no mutations have been identified. The ARMS-PCR showed complete concordance with the endonuclease cleavage reference method and agreed perfectly with previous Tunisian studies where Gd A- and Gd B- were the most encountered. Also, similarities in spectrum mutations with North African and Mediterranean countries suggest gene migration from Africa to Europe through Spain. In conclusion, ARMS has been introduced in this study for common G6PD alleles identification in Tunisia. It gives some advantages compared to the traditional endonuclease digestion method since it is more convenient and timesaving and also offers the possibility to be applied in mass screening surveys.

ARMS2 variants may predict the 3-year outcome of photodynamic therapy for wet age-related macular degeneration

PubMed Central

Nakai, Shunichiro; Matsumiya, Wataru; Miki, Akiko; Nakamura, Makoto

2017-01-01

Purpose To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 3-year outcomes of photodynamic therapy (PDT) in wet age-related macular degeneration (wet AMD). Methods The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene of 65 patients with wet AMD who underwent PDT was genotyped using the TaqMan assay. The clinical characteristics and the outcomes of PDT were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 36 months after the first PDT. Results A significant difference was found among the genotypes in the age and the baseline lesion size. The patients with the GG genotype showed a significant improvement in vision, and the patients with the TT genotype showed a significant worsening of vision at all time points measured after the initial PDT. In the multivariate regression analysis, the number of the G allele at rs10490924 was associated with a significantly greater improvement in the baseline best-corrected visual acuity (BCVA) at 36 months after the first PDT. Conclusions ARMS2 variants are likely associated with the 3-year outcomes of PDT in patients with wet AMD. PMID:28761324

Association of Single-Nucleotide Polymorphisms in Age-Related Macular Degeneration With Pseudodrusen: Secondary Analysis of Data From the Comparison of AMD Treatments Trials.

PubMed

Lin, Lisa Y; Zhou, Qiang; Hagstrom, Stephanie; Maguire, Maureen G; Daniel, Ebenezer; Grunwald, Juan E; Martin, Daniel F; Ying, Gui-Shuang

2018-06-01

Previous studies investigating the association of single-nucleotide polymorphisms (SNPs) that confer increased risk of age-related macular degeneration (AMD) with pseudodrusen have yielded conflicting results and have not evaluated other AMD SNPs or pseudodrusen subtypes. To determine the association of SNPs in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), HtrA serine peptidase 1 (HTRA1), complement C2 (C2), complement C3 (C3), lipase C (LIPC), and complement factor B (CFB) genes with the presence of pseudodrusen and pseudodrusen subtypes (ie, dot, reticular, and confluent). In this post hoc analysis of cross-sectional data from US participants in the Comparison of AMD Treatments Trials, genotyping was performed in 835 participants with TaqMan assays for the SNPs rs1061170 (Y402H variant in CFH), rs800292 (I62V variant in CFH), rs10490924 (A69S variant in ARMS2), rs11200638 (HTRA1), rs547154 (C2), rs2230199 (R102G variant in C3), rs10468017 (LIPC), and rs4151667 (L9H variant in CFB). Presence and subtype of baseline pseudodrusen in either eye determined using color fundus photography, red-free images, and fluorescein angiograms. Among 835 participants enrolled for genotyping, 755 (90.4%) were evaluated for pseudodrusen. Of these, 471 (62.4%) were female and 750 (99.3%) were white, and the mean (SD) age was 78.3 (7.5) years. A total of 213 of 755 participants (28.2%) had pseudodrusen (107 [14.2%] had dot pseudodrusen, 180 [23.8%] had reticular pseudodrusen, and 102 [13.5%] had confluent pseudodrusen). After adjusting for age, sex, and smoking status, the ARMS2 risk allele T was associated with higher risk of pseudodrusen (odds ratio [OR], 1.93; 95% CI, 1.19-3.12) for TT vs GG (P = .04). A similar association was found for HTRA1 (OR, 2.04; 95% CI, 1.26-3.31) for AA vs GG (P = .03). The CFH Y402H risk allele C was associated with lower risk of pseudodrusen (OR, 0.61; 95% CI, 0.38-0.97) for CC vs TT but was not statistically significant after correcting for multiple comparison (P = .20). CFH Y402H, ARMS2, HTRA1, and C3 were significantly associated with reticular pseudodrusen. Among patients with neovascular AMD, the AMD risk alleles ARMS2 and HTRA1 were associated with an increased risk of pseudodrusen and the risk allele CFH Y402H was associated with lower risk of pseudodrusen, supporting findings from previous studies. Understanding the role of these SNPs in the development of pseudodrusen might improve our understanding of the pathogenesis of AMD and help develop future therapies.

76 FR 43662 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

... and control systems with modern technology. The new guidance and control system uses a mixture of... Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i... million TOTAL $86 million * as defined in Section 47(6) of the Arms Export Control Act. (iii) Description...

Fenestration of axillary vein by a variant axillary artery.

PubMed

Hadimani, S; Desai, S D; Bagoji, I B; Patil, B S

2013-01-01

Variations of venous pattern in the arm are common. In this case report, we present a variation of axillary artery and vein. During routine educational dissections of axillary region, it was observed that a fenestrated axillary vein was perforated by a variant axillary artery in right arm of an old male cadaver. The axillary artery which was fenestrated through axillary vein had only two branches arising from its second part and no branches from its remaining distal parts. The branches are thoraco-acromial (usual) and another large collateral (unusual) branch. This collateral branch is the origin of several important arteries as the subscapular, circumflex scapular, posterior circumflex humeral and lateral thoracic arteries. We propose to name this artery as collateral axillary arterial trunk. The course of this collateral axillary arterial trunk and its branches and also clinical significance of this variation are discussed in the paper.

49 CFR 572.131 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Assembly 880105-300 Lower Torso Assembly 880105-450 Complete Leg Assembly—left 880105-560-1 Complete Leg Assembly—right 880105-560-2 Complete Arm Assembly—left 880105-728-1 Complete Arm Assembly—right 880105-728...

49 CFR 572.131 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Assembly 880105-300 Lower Torso Assembly 880105-450 Complete Leg Assembly—left 880105-560-1 Complete Leg Assembly—right 880105-560-2 Complete Arm Assembly—left 880105-728-1 Complete Arm Assembly—right 880105-728...

The aerodynamics of flight in an insect flight-mill

PubMed Central

Barkan, Shay; Soroker, Victoria

2017-01-01

Predicting the dispersal of pest insects is important for pest management schemes. Flight-mills provide a simple way to evaluate the flight potential of insects, but there are several complications in relating tethered-flight to natural flight. We used high-speed video to evaluate the effect of flight-mill design on flight of the red palm weevil (Rynchophorous ferruginneus) in four variants of a flight-mill. Two variants had the rotating radial arm pivoted on the main shaft of the rotation axis, allowing freedom to elevate the arm as the insect applied lift force. Two other variants had the pivot point fixed, restricting the radial arm to horizontal motion. Beetles were tethered with their lateral axis horizontal or rotated by 40°, as in a banked turn. Flight-mill type did not affect flight speed or wing-beat frequency, but did affect flapping kinematics. The wingtip internal to the circular trajectory was always moved faster relative to air, suggesting that the beetles were attempting to steer in the opposite direction to the curved trajectory forced by the flight-mill. However, banked beetles had lower flapping asymmetry, generated higher lift forces and lost more of their body mass per time and distance flown during prolonged flight compared to beetles flying level. The results indicate, that flapping asymmetry and low lift can be rectified by tethering the beetle in a banked orientation, but the flight still does not correspond directly to free-flight. This should be recognized and taken into account when designing flight-mills and interoperating their data. PMID:29091924

The aerodynamics of flight in an insect flight-mill.

PubMed

Ribak, Gal; Barkan, Shay; Soroker, Victoria

2017-01-01

Predicting the dispersal of pest insects is important for pest management schemes. Flight-mills provide a simple way to evaluate the flight potential of insects, but there are several complications in relating tethered-flight to natural flight. We used high-speed video to evaluate the effect of flight-mill design on flight of the red palm weevil (Rynchophorous ferruginneus) in four variants of a flight-mill. Two variants had the rotating radial arm pivoted on the main shaft of the rotation axis, allowing freedom to elevate the arm as the insect applied lift force. Two other variants had the pivot point fixed, restricting the radial arm to horizontal motion. Beetles were tethered with their lateral axis horizontal or rotated by 40°, as in a banked turn. Flight-mill type did not affect flight speed or wing-beat frequency, but did affect flapping kinematics. The wingtip internal to the circular trajectory was always moved faster relative to air, suggesting that the beetles were attempting to steer in the opposite direction to the curved trajectory forced by the flight-mill. However, banked beetles had lower flapping asymmetry, generated higher lift forces and lost more of their body mass per time and distance flown during prolonged flight compared to beetles flying level. The results indicate, that flapping asymmetry and low lift can be rectified by tethering the beetle in a banked orientation, but the flight still does not correspond directly to free-flight. This should be recognized and taken into account when designing flight-mills and interoperating their data.

A new model for gravitational potential perturbations in disks of spiral galaxies. An application to our Galaxy

NASA Astrophysics Data System (ADS)

Junqueira, T. C.; Lépine, J. R. D.; Braga, C. A. S.; Barros, D. A.

2013-02-01

Aims: We propose a new, more realistic description of the perturbed gravitational potential of spiral galaxies, with spiral arms having Gaussian-shaped groove profiles. The aim is to reach a self-consistent description of the spiral structure, that is, one in which an initial potential perturbation generates, by means of the stellar orbits, spiral arms with a profile similar to that of the imposed perturbation. Self-consistency is a condition for having long-lived structures. Methods: Using the new perturbed potential, we investigate the stable stellar orbits in galactic disks for galaxies with no bar or with only a weak bar. The model is applied to our Galaxy by making use of the axisymmetric component of the potential computed from the Galactic rotation curve, in addition to other input parameters similar to those of our Galaxy. The influence of the bulge mass on the stellar orbits in the inner regions of a disk is also investigated. Results: The new description offers the advantage of easy control of the parameters of the Gaussian profile of its potential. We compute the density contrast between arm and inter-arm regions. We find a range of values for the perturbation amplitude from 400 to 800 km2 s-2 kpc-1, which implies an approximate maximum ratio of the tangential force to the axisymmetric force between 3% and 6%. Good self-consistency of arm shapes is obtained between the Inner Lindblad resonance (ILR) and the 4:1 resonance. Near the 4:1 resonance the response density starts to deviate from the imposed logarithmic spiral form. This creates bifurcations that appear as short arms. Therefore the deviation from a perfect logarithmic spiral in galaxies can be understood as a natural effect of the 4:1 resonance. Beyond the 4:1 resonance we find closed orbits that have similarities with the arms observed in our Galaxy. In regions near the center, elongated stellar orbits appear naturally, in the presence of a massive bulge, without imposing any bar-shaped potential, but only extending the spiral perturbation a little inward of the ILR. This suggests that a bar is formed with a half-size ~3 kpc by a mechanism similar to that of the spiral arms. Conclusions: The potential energy perturbation that we adopted represents an important step in the direction of self-consistency, compared to previous sine function descriptions of the potential. In addition, our model produces a realistic description of the spiral structure, which is able to explain several details that were not yet understood.

User interface development and metadata considerations for the Atmospheric Radiation Measurement (ARM) archive

NASA Technical Reports Server (NTRS)

Singley, P. T.; Bell, J. D.; Daugherty, P. F.; Hubbs, C. A.; Tuggle, J. G.

1993-01-01

This paper will discuss user interface development and the structure and use of metadata for the Atmospheric Radiation Measurement (ARM) Archive. The ARM Archive, located at Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee, is the data repository for the U.S. Department of Energy's (DOE's) ARM Project. After a short description of the ARM Project and the ARM Archive's role, we will consider the philosophy and goals, constraints, and prototype implementation of the user interface for the archive. We will also describe the metadata that are stored at the archive and support the user interface.

System For Research On Multiple-Arm Robots

NASA Technical Reports Server (NTRS)

Backes, Paul G.; Hayati, Samad; Tso, Kam S.; Hayward, Vincent

1991-01-01

Kali system of computer programs and equipment provides environment for research on distributed programming and distributed control of coordinated-multiple-arm robots. Suitable for telerobotics research involving sensing and execution of low level tasks. Software and configuration of hardware designed flexible so system modified easily to test various concepts in control and programming of robots, including multiple-arm control, redundant-arm control, shared control, traded control, force control, force/position hybrid control, design and integration of sensors, teleoperation, task-space description and control, methods of adaptive control, control of flexible arms, and human factors.

Non-RF Chain of Custody Item Monitor (CoCIM) User Manual.

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

Brotz, Jay Kristoffer; Wade, James Rokwel; Schwartz, Steven Robert

This User Manual contains a description of the wired and infrared (IR) variants of the Chain of Custody Item Monitor (CoCIM), the Coordinator for reading stored messages, and the inspector Message Viewer user interface (UI) software, as well as instructions for use. This manual does not include descriptions or use instructions for the radio frequency (RF) variant of the CoCIM. The intended audience is planners and participants in treaty verification exercises where chain of custody (CoC) elements are required.

Pigmentary Markers in Danes – Associations with Quantitative Skin Colour, Nevi Count, Familial Atypical Multiple-Mole, and Melanoma Syndrome

PubMed Central

Johansen, Peter; Andersen, Jeppe Dyrberg; Madsen, Linnea Nørgård; Ullum, Henrik; Glud, Martin; Børsting, Claus; Gniadecki, Robert; Morling, Niels

2016-01-01

To investigate whether pigmentation genes involved in the melanogenic pathway (melanogenesis) contributed to melanoma predisposition, we compared pigmentary genetics with quantitative skin pigmentation measurements, the number of atypical nevi, the total nevus count, and the familial atypical multiple mole and melanoma (FAMMM) syndrome. We typed 32 pigmentary SNP markers and sequenced MC1R in 246 healthy individuals and 116 individuals attending periodic control for malignant melanoma development, 50 of which were diagnosed with FAMMM. It was observed that individuals with any two grouped MC1R variants (missense, NM_002386:c. 456C > A (p.TYR152*), or NM_002386:c.83_84insA (p.Asn29Glnfs*14) had significantly (p<0.001) lighter skin pigmentation of the upper-inner arm than those with none or one MC1R variant. We did not observe any significant association of the MC1R variants with constitutive pigmentation measured on the buttock area. We hypothesize that the effect of MC1R variants on arm pigmentation is primarily reflecting the inability to tan when subjected to UVR. A gender specific effect on skin pigmentation was also observed, and it was found that the skin pigmentation of females on average were darker than that of males (p<0.01). We conclude that MC1R variants are associated with quantitative skin colour in a lightly pigmented Danish population. We did not observe any association between any pigmentary marker and the FAMMM syndrome. We suggest that the genetics of FAMMM is not related to the genetics of the pigmentary pathway. PMID:26938746

[Towards the problem of necessity to reduce the medical evacuation stages in conditions of local wars and armed conflicts].

PubMed

Gaĭdar, B V; Ivantsov, V A; Sidel'nikov, V O; Rusev, I T; Madaĭ, D Iu; Kokoev, V G; Zinov'ev, E V; Mutalibov, M M

2004-06-01

The article is devoted to the review of modern opinions concerning the experience of military operation medical support in conditions of local wars and military conflicts. On the base of analysis of medical assistance rendered to the wounded and casualties in Republic of Chechnya the advantages and defects of different approaches are discussed. The experience in rendering assistance to the casualties in the Armed Forces of NATO countries during the local wars for the last decades is discussed. It is shown that the optimal variant of organization of treatment-and-evacuation measures during the local armed conflicts and wars is the two-stage scheme of evacuation: the first medical aid--the qualified (specialized) medical aid.

A real-time robot arm collision avoidance system

NASA Technical Reports Server (NTRS)

Shaffer, Clifford A.; Herb, Gregory M.

1992-01-01

A data structure and update algorithm are presented for a prototype real-time collision avoidance safety system simulating a multirobot workspace. The data structure is a variant of the octree, which serves as a spatial index. An octree recursively decomposes 3D space into eight equal cubic octants until each octant meets some decomposition criteria. The N-objects octree, which indexes a collection of 3D primitive solids is used. These primitives make up the two (seven-degrees-of-freedom) robot arms and workspace modeled by the system. As robot arms move, the octree is updated to reflect their changed positions. During most update cycles, any given primitive does not change which octree nodes it is in. Thus, modification to the octree is rarely required. Cycle time for interpreting current arm joint angles, updating the octree to reflect new positions, and detecting/reporting imminent collisions averages 30 ms on an Intel 80386 processor running at 20 MHz.

49 CFR 572.71 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... D SA 106C 041 Arm Assembly (right) SA 106C 001, sheet 14 A SA 106C 042 Arm Assembly (left) SA 106C... Assembly (left) SA 106C 001, sheet 17 A (c) Adjacent segments are joined in a manner such that except for...

49 CFR 572.71 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... D SA 106C 041 Arm Assembly (right) SA 106C 001, sheet 14 A SA 106C 042 Arm Assembly (left) SA 106C... Assembly (left) SA 106C 001, sheet 17 A (c) Adjacent segments are joined in a manner such that except for...

Association of Efavirenz Hypersusceptibility with Virologic Response in ACTG 368, a Randomized Trial of Abacavir (ABC) in Combination with Efavirenz (EFV) and Indinavir (IDV) in HIV-infected Subjects with Prior Nucleoside Analog Experience

PubMed Central

Demeter, Lisa M.; DeGruttola, Victor; Lustgarten, Stephanie; Bettendorf, Daniel; Fischl, Margaret; Eshleman, Susan; Spreen, William; Nguyen, Bach-Yen; Koval, Christine E.; Eron, Joseph J.; Hammer, Scott; Squires, Kathleen

2010-01-01

Purpose To evaluate the association of efavirenz hypersusceptibility (EFV-HS) with clinical outcome in a double-blind, placebo-controlled, randomized trial of EFV plus indinavir (EFV+IDV) vs. EFV+IDV plus abacavir (ABC) in 283 nucleoside-experienced HIV-infected patients. Methods and Results Rates of virologic failure were similar in the 2 arms at week 16 (p=0.509). Treatment discontinuations were more common in the ABC arm (p=0.001). Using logistic regression, there was no association between virologic failure and either baseline ABC resistance or regimen sensitivity score. Using 3 different genotypic scoring systems, EFV-HS was significantly associated with reduced virologic failure at week 16, independent of treatment assignment. In some patients on the nucleoside-sparing arm, the nucleoside-resistant mutant L74V was selected for in combination with the uncommonly occurring EFV-resistant mutant K103N+L100I; L74V was not detected as a minority variant, using clonal sequence analysis, when the nucleoside-sparing regimen was initiated. Conclusions Premature treatment discontinuations in the ABC arm and the presence of EFV-hypersusceptible HIV variants in this patient population likely made it difficult to detect a benefit of adding ABC to EFV+IDV. In addition, L74V, when combined with K103N+L100I, may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance. PMID:18215978

Polymorphisms in folate-metabolizing enzymes and response to 5-fluorouracil among patients with stage II or III rectal cancer (INT-0144; SWOG 9304).

PubMed

Ulrich, Cornelia M; Rankin, Cathryn; Toriola, Adetunji T; Makar, Karen W; Altug-Teber, Özge; Benedetti, Jacqueline K; Holmes, Rebecca S; Smalley, Stephen R; Blanke, Charles D; Lenz, Heinz-Josef

2014-11-01

Recurrence and toxicity occur commonly among patients with rectal cancer who are treated with 5-fluorouracil (5-FU). The authors hypothesized that genetic variation in folate-metabolizing genes could play a role in interindividual variability. The objective of the current study was to evaluate the associations between genetic variants in folate-metabolizing genes and clinical outcomes among patients with rectal cancer treated with 5-FU. The authors investigated 8 functionally significant polymorphisms in 6 genes (methylenetetrahydrofolate reductase [MTHFR] [C677T, A1298C], SLC19A1 [G80A], SHMT1 [C1420T], dihydrofolate reductase [DHFR] [Del19bp], TS 1494del,and TSER) involved in folate metabolism in 745 patients with TNM stage II or III rectal cancer enrolled in a phase 3 adjuvant clinical trial of 3 regimens of 5-FU and radiotherapy (INT-0144 and SWOG 9304). There were no statistically significant associations noted between polymorphisms in any of the genes and overall survival, disease-free survival (DFS), and toxicity in the overall analyses. Nevertheless, there was a trend toward worse DFS among patients with the variant allele of MTHFR C677T compared with wild-type, particularly in treatment arm 2, in which patients with the MTHFR C677T TT genotype had worse overall survival (hazards ratio, 1.76; 95% confidence interval, 1.06-2.93 [P = .03]) and DFS (hazards ratio, 1.84; 95% confidence interval, 1.12-3.03 [P = .02]) compared with those with homozygous wild-type. In addition, there was a trend toward reduced hematological toxicity among patients with variants of SLC19A1 G80A in treatment arm 1 (P for trend, .06) and reduced esophagitis/stomatitis noted among patients with variants of TSER in treatment arm 3 (P for trend, .06). Genetic variability in folate-metabolizing enzymes was found to be associated only to a limited degree with clinical outcomes among patients with rectal cancer treated with 5-FU. © 2014 American Cancer Society.

A State-Of-The-Art Survey on Automatic Indexing.

ERIC Educational Resources Information Center

Liebesny, Felix

This survey covers the literature relating to automatic indexing techniques, services, and applications published during 1969-1973. Works are summarized and described in the areas of: (1) general papers on automatic indexing; (2) KWIC indexes; (3) KWIC variants listed alphabetically by acronym with descriptions; (4) other KWIC variants arranged by…

Automated Quantification of Arbitrary Arm-Segment Structure in Spiral Galaxies

NASA Astrophysics Data System (ADS)

Davis, Darren Robert

This thesis describes a system that, given approximately-centered images of spiral galaxies, produces quantitative descriptions of spiral galaxy structure without the need for per-image human input. This structure information consists of a list of spiral arm segments, each associated with a fitted logarithmic spiral arc and a pixel region. This list-of-arcs representation allows description of arbitrary spiral galaxy structure: the arms do not need to be symmetric, may have forks or bends, and, more generally, may be arranged in any manner with a consistent spiral-pattern center (non-merging galaxies have a sufficiently well-defined center). Such flexibility is important in order to accommodate the myriad structure variations observed in spiral galaxies. From the arcs produced from our method it is possible to calculate measures of spiral galaxy structure such as winding direction, winding tightness, arm counts, asymmetry, or other values of interest (including user-defined measures). In addition to providing information about the spiral arm "skeleton" of each galaxy, our method can enable analyses of brightness within individual spiral arms, since we provide the pixel regions associated with each spiral arm segment. For winding direction, arm tightness, and arm count, comparable information is available (to various extents) from previous efforts; to the extent that such information is available, we find strong correspondence with our output. We also characterize the changes to (and invariances in) our output as a function of modifications to important algorithm parameters. By enabling generation of extensive data about spiral galaxy structure from large-scale sky surveys, our method will enable new discoveries and tests regarding the nature of galaxies and the universe, and will facilitate subsequent work to automatically fit detailed brightness models of spiral galaxies.

The Impact of Financial Sophistication on Adjustable Rate Mortgage Ownership

ERIC Educational Resources Information Center

Smith, Hyrum; Finke, Michael S.; Huston, Sandra J.

2011-01-01

The influence of a financial sophistication scale on adjustable-rate mortgage (ARM) borrowing is explored. Descriptive statistics and regression analysis using recent data from the Survey of Consumer Finances reveal that ARM borrowing is driven by both the least and most financially sophisticated households but for different reasons. Less…

33 CFR 167.1703 - In Prince William Sound: Valdez Arm Traffic Separation Scheme.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Arm Traffic Separation Scheme. 167.1703 Section 167.1703 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY OFFSHORE TRAFFIC SEPARATION SCHEMES Description of Traffic Separation Schemes and Precautionary Areas Pacific West Coast § 167.1703 In Prince...

33 CFR 167.1703 - In Prince William Sound: Valdez Arm Traffic Separation Scheme.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Arm Traffic Separation Scheme. 167.1703 Section 167.1703 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY OFFSHORE TRAFFIC SEPARATION SCHEMES Description of Traffic Separation Schemes and Precautionary Areas Pacific West Coast § 167.1703 In Prince...

33 CFR 167.1703 - In Prince William Sound: Valdez Arm Traffic Separation Scheme.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Arm Traffic Separation Scheme. 167.1703 Section 167.1703 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY OFFSHORE TRAFFIC SEPARATION SCHEMES Description of Traffic Separation Schemes and Precautionary Areas Pacific West Coast § 167.1703 In Prince...

33 CFR 167.1703 - In Prince William Sound: Valdez Arm Traffic Separation Scheme.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Arm Traffic Separation Scheme. 167.1703 Section 167.1703 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY OFFSHORE TRAFFIC SEPARATION SCHEMES Description of Traffic Separation Schemes and Precautionary Areas Pacific West Coast § 167.1703 In Prince...

33 CFR 167.1703 - In Prince William Sound: Valdez Arm Traffic Separation Scheme.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Arm Traffic Separation Scheme. 167.1703 Section 167.1703 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY OFFSHORE TRAFFIC SEPARATION SCHEMES Description of Traffic Separation Schemes and Precautionary Areas Pacific West Coast § 167.1703 In Prince...

Sometimes two arms are enough--an unusual life-stage in brittle stars (Echinodermata: Ophiuroidea).

PubMed

Stöhr, Sabine; Alme, Øydis

2015-08-03

Off West Africa (Angola-Morocco), benthos samples were collected in the years 2005-2012. These contained 124 specimens of brittle stars with two long arms and three extremely short or absent arms and an elongated, narrow disc. These unusual brittle stars, as well as 33 specimens with five fully developed arms, were identified as Amphiura ungulata. The specimens with unequal arms were juvenile stages, whereas adults had five equal arms. The large number of specimens with unequal arms suggests that this condition is not the result of damage and regeneration, but a normal growth pattern in this species. This study documents the morphology by SEM, amends the species description, and discusses possible explanations for the evolution of this condition. Although brittle star species with unequal arm growth have been reported, this is an extreme case that was unknown before this study.

A prospective study of common variants in the RAR-related orphan receptor alpha (RORalpha) gene and risk of neovascular age-related macular degeneration

PubMed Central

Schaumberg, Debra A.; Chasman, Daniel; Morrison, Margaux A.; Adams, Scott M.; Guo, Qun; Hunter, David J.; Hankinson, Susan E.; DeAngelis, Margaret M.

2010-01-01

Objectives The RAR-related orphan receptor alpha (RORalpha) gene is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and two clinic-based cross sectional studies. We aimed to determine if common variants in RORalpha predict future risk of neovascular AMD. Methods We measured genotypes for 18 variants in intron 1 of the RORalpha gene among 164 cases who developed neovascular AMD and 485 age- and sex-matched controls in a prospective nested case-control study within the Nurses’ Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios (IRR) and 95% confidence intervals (CI) for neovascular AMD for each variant, and examined interactions with other AMD-associated variants and modifiable risk factors. Results We identified a single SNP (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with one and two copies of the “G” allele were 1.73 (CI= 1.32–2.27) and 2.99 (CI=1.74–5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the “G” allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascular AMD (CI=10.1–164; P for interaction=0.017). Cigarette smokers who carried two copies of the “G” allele had a 9.89-fold risk of neovascular AMD, but the interaction was not significant (P=0.08). We identified a significant AMD-associated haplotype block containing SNPs rs730754, rs8034864, and rs12900948, with P-values for ACA=1.16 × 10−9, ACG=5.85 × 10−12, and GAA=0.0001 when compared to all other haplotypes. Conclusion Common variants and haplotypes within the RORalpha gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should help efforts at risk prediction. PMID:21060049

White matter pathology in ALS and lower motor neuron ALS variants: a diffusion tensor imaging study using tract-based spatial statistics.

PubMed

Prudlo, Johannes; Bißbort, Charlotte; Glass, Aenne; Grossmann, Annette; Hauenstein, Karlheinz; Benecke, Reiner; Teipel, Stefan J

2012-09-01

The aim of this work was to investigate white-matter microstructural changes within and outside the corticospinal tract in classical amyotrophic lateral sclerosis (ALS) and in lower motor neuron (LMN) ALS variants by means of diffusion tensor imaging (DTI). We investigated 22 ALS patients and 21 age-matched controls utilizing a whole-brain approach with a 1.5-T scanner for DTI. The patient group was comprised of 15 classical ALS- and seven LMN ALS-variant patients (progressive muscular atrophy, flail arm and flail leg syndrome). Disease severity was measured by the revised version of the functional rating scale. White matter fractional anisotropy (FA) was assessed using tract-based spatial statistics (TBSS) and a region of interest (ROI) approach. We found significant FA reductions in motor and extra-motor cerebral fiber tracts in classical ALS and in the LMN ALS-variant patients compared to controls. The voxel-based TBSS results were confirmed by the ROI findings. The white matter damage correlated with the disease severity in the patient group and was found in a similar distribution, but to a lesser extent, among the LMN ALS-variant subgroup. ALS and LMN ALS variants are multisystem degenerations. DTI shows the potential to determine an earlier diagnosis, particularly in LMN ALS variants. The statistically identical findings of white matter lesions in classical ALS and LMN variants as ascertained by DTI further underline that these variants should be regarded as part of the ALS spectrum.

77 FR 70151 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

... defined in Section 47(6) of the Arms Export Control Act. (iii) Description and Quantity or Quantities of.... The sensitivity is primarily in the software programs that instruct the system how to operate in the... Only Memory (ROM) maps, which do not provide the software program itself. The overall hardware is...

78 FR 22850 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-17

... million * As defined in Section 47(6) of the Arms Export Control Act. (iii) Description and Quantity or... software continues to be modified via a pre-planned product improvement (P3I) program in order to improve its counter- countermeasure capabilities. No software source code or algorithms will be released. The...

Evolving artificial metalloenzymes via random mutagenesis

NASA Astrophysics Data System (ADS)

Yang, Hao; Swartz, Alan M.; Park, Hyun June; Srivastava, Poonam; Ellis-Guardiola, Ken; Upp, David M.; Lee, Gihoon; Belsare, Ketaki; Gu, Yifan; Zhang, Chen; Moellering, Raymond E.; Lewis, Jared C.

2018-03-01

Random mutagenesis has the potential to optimize the efficiency and selectivity of protein catalysts without requiring detailed knowledge of protein structure; however, introducing synthetic metal cofactors complicates the expression and screening of enzyme libraries, and activity arising from free cofactor must be eliminated. Here we report an efficient platform to create and screen libraries of artificial metalloenzymes (ArMs) via random mutagenesis, which we use to evolve highly selective dirhodium cyclopropanases. Error-prone PCR and combinatorial codon mutagenesis enabled multiplexed analysis of random mutations, including at sites distal to the putative ArM active site that are difficult to identify using targeted mutagenesis approaches. Variants that exhibited significantly improved selectivity for each of the cyclopropane product enantiomers were identified, and higher activity than previously reported ArM cyclopropanases obtained via targeted mutagenesis was also observed. This improved selectivity carried over to other dirhodium-catalysed transformations, including N-H, S-H and Si-H insertion, demonstrating that ArMs evolved for one reaction can serve as starting points to evolve catalysts for others.

Cutaneous lupus erythematosus in dogs: a comprehensive review.

PubMed

Olivry, Thierry; Linder, Keith E; Banovic, Frane

2018-04-18

Since the first description of discoid lupus erythematosus (LE) in two dogs in 1979, the spectrum of canine cutaneous lupus erythematosus (CLE) variants has expanded markedly.In this review, we first propose an adaptation of the Gilliam-Sontheimer classification of CLE for dogs. We then review the signalment, clinical signs, laboratory and histopathology and treatment outcome of the currently recognized variants of canine CLE, which are vesicular CLE, exfoliative CLE, mucocutaneous LE and facial or generalized discoid LE. We end with a short description of the rare cutaneous manifestations of systemic LE in dogs.Canine CLE variants are heterogeneous, some of them mirror their human counterparts while others appear-thus far-unique to the dog. As most CLE subtypes seem to have a good prognosis after diagnosis, veterinarians are encouraged to become familiar with the spectrum of often-characteristic and unique clinical signs that would permit an early diagnosis and the rapid implementation of an effective treatment.

SpArcFiRe: Scalable automated detection of spiral galaxy arm segments

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

Davis, Darren R.; Hayes, Wayne B., E-mail: drdavis@uci.edu, E-mail: whayes@uci.edu

Given an approximately centered image of a spiral galaxy, we describe an entirely automated method that finds, centers, and sizes the galaxy (possibly masking nearby stars and other objects if necessary in order to isolate the galaxy itself) and then automatically extracts structural information about the spiral arms. For each arm segment found, we list the pixels in that segment, allowing image analysis on a per-arm-segment basis. We also perform a least-squares fit of a logarithmic spiral arc to the pixels in that segment, giving per-arc parameters, such as the pitch angle, arm segment length, location, etc. The algorithm takesmore » about one minute per galaxies, and can easily be scaled using parallelism. We have run it on all ∼644,000 Sloan objects that are larger than 40 pixels across and classified as 'galaxies'. We find a very good correlation between our quantitative description of a spiral structure and the qualitative description provided by Galaxy Zoo humans. Our objective, quantitative measures of structure demonstrate the difficulty in defining exactly what constitutes a spiral 'arm', leading us to prefer the term 'arm segment'. We find that pitch angle often varies significantly segment-to-segment in a single spiral galaxy, making it difficult to define the pitch angle for a single galaxy. We demonstrate how our new database of arm segments can be queried to find galaxies satisfying specific quantitative visual criteria. For example, even though our code does not explicitly find rings, a good surrogate is to look for galaxies having one long, low-pitch-angle arm—which is how our code views ring galaxies. SpArcFiRe is available at http://sparcfire.ics.uci.edu.« less

Inferring processes of cultural transmission: the critical role of rare variants in distinguishing neutrality from novelty biases.

PubMed

O'Dwyer, James P; Kandler, Anne

2017-12-05

Neutral evolution assumes that there are no selective forces distinguishing different variants in a population. Despite this striking assumption, many recent studies have sought to assess whether neutrality can provide a good description of different episodes of cultural change. One approach has been to test whether neutral predictions are consistent with observed progeny distributions, recording the number of variants that have produced a given number of new instances within a specified time interval: a classic example is the distribution of baby names. Using an overlapping generations model, we show that these distributions consist of two phases: a power-law phase with a constant exponent of [Formula: see text], followed by an exponential cut-off for variants with very large numbers of progeny. Maximum-likelihood estimations of the model parameters provide a direct way to establish whether observed empirical patterns are consistent with neutral evolution. We apply our approach to a complete dataset of baby names from Australia. Crucially, we show that analyses based on only the most popular variants, as is often the case in studies of cultural evolution, can provide misleading evidence for underlying transmission hypotheses. While neutrality provides a plausible description of progeny distributions of abundant variants, rare variants deviate from neutrality. Further, we develop a simulation framework that allows the detection of alternative cultural transmission processes. We show that anti-novelty bias is able to replicate the complete progeny distribution of the Australian dataset.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

Modulation of GLP-1 Levels by a Genetic Variant That Regulates the Cardiovascular Effects of Intensive Glycemic Control in ACCORD.

PubMed

Shah, Hetal S; Morieri, Mario Luca; Marcovina, Santica M; Sigal, Ronald J; Gerstein, Hertzel C; Wagner, Michael J; Motsinger-Reif, Alison A; Buse, John B; Kraft, Peter; Mychaleckyj, Josyf C; Doria, Alessandro

2018-02-01

A genome-wide association study in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial identified two markers (rs57922 and rs9299870) that were significantly associated with cardiovascular mortality during intensive glycemic control and could potentially be used, when combined into a genetic risk score (GRS), to identify patients with diabetes likely to derive benefit from intensive control rather than harm. The aim of this study was to gain insights into the pathways involved in the modulatory effect of these variants. Fasting levels of 65 biomarkers were measured at baseline and at 12 months of follow-up in the ACCORD-Memory in Diabetes (ACCORD-MIND) MRI substudy ( n = 562). Using linear regression models, we tested the association of the GRS with baseline and 12-month biomarker levels, and with their difference (Δ), among white subjects, with genotype data ( n = 351) stratified by intervention arm. A significant association was observed between GRS and ΔGLP-1 (glucagon-like peptide 1, active) in the intensive arm ( P = 3 × 10 -4 ). This effect was driven by rs57922 ( P = 5 × 10 -4 ). C/C homozygotes, who had been found to derive cardiovascular benefits from intensive treatment, showed a 22% increase in GLP-1 levels during follow-up. By contrast, T/T homozygotes, who had been found to experience increased cardiac mortality with intensive treatment, showed a 28% reduction in GLP-1 levels. No association between ΔGLP-1 and GRS or rs57922 was observed in the standard treatment arm. Differences in GLP-1 axis activation may mediate the modulatory effect of variant rs57922 on the cardiovascular response to intensive glycemic control. These findings highlight the importance of GLP-1 as a cardioprotective factor. © 2017 by the American Diabetes Association.

COMOC: Three dimensional boundary region variant, programmer's manual

NASA Technical Reports Server (NTRS)

Orzechowski, J. A.; Baker, A. J.

1974-01-01

The three-dimensional boundary region variant of the COMOC computer program system solves the partial differential equation system governing certain three-dimensional flows of a viscous, heat conducting, multiple-species, compressible fluid including combustion. The solution is established in physical variables, using a finite element algorithm for the boundary value portion of the problem description in combination with an explicit marching technique for the initial value character. The computational lattice may be arbitrarily nonregular, and boundary condition constraints are readily applied. The theoretical foundation of the algorithm, a detailed description on the construction and operation of the program, and instructions on utilization of the many features of the code are presented.

Motion control of 7-DOF arms - The configuration control approach

NASA Technical Reports Server (NTRS)

Seraji, Homayoun; Long, Mark K.; Lee, Thomas S.

1993-01-01

Graphics simulation and real-time implementation of configuration control schemes for a redundant 7-DOF Robotics Research arm are described. The arm kinematics and motion control schemes are described briefly. This is followed by a description of a graphics simulation environment for 7-DOF arm control on the Silicon Graphics IRIS Workstation. Computer simulation results are presented to demonstrate elbow control, collision avoidance, and optimal joint movement as redundancy resolution goals. The laboratory setup for experimental validation of motion control of the 7-DOF Robotics Research arm is then described. The configuration control approach is implemented on a Motorola-68020/VME-bus-based real-time controller, with elbow positioning for redundancy resolution. Experimental results demonstrate the efficacy of configuration control for real-time control.

Molecular Diagnosis of Cystic Fibrosis.

PubMed

Deignan, Joshua L; Grody, Wayne W

2016-01-01

This unit describes a recommended approach to identifying causal genetic variants in an individual suspected of having cystic fibrosis. An introduction to the genetics and clinical presentation of cystic fibrosis is initially presented, followed by a description of the two main strategies used in the molecular diagnosis of cystic fibrosis: (1) an initial targeted variant panel used to detect only the most common cystic fibrosis-causing variants in the CFTR gene, and (2) sequencing of the entire coding region of the CFTR gene to detect additional rare causal CFTR variants. Finally, the unit concludes with a discussion regarding the analytic and clinical validity of these approaches. Copyright © 2016 John Wiley & Sons, Inc.

CSI related dynamics and control issues in space robotics

NASA Technical Reports Server (NTRS)

Schmitz, Eric; Ramey, Madison

1993-01-01

The research addressed includes: (1) CSI issues in space robotics; (2) control of elastic payloads, which includes 1-DOF example, and 3-DOF harmonic drive arm with elastic beam; and (3) control of large space arms with elastic links, which includes testbed description, modeling, and experimental implementation of colocated PD and end-point tip position controllers.

75 FR 54599 - Takes of Marine Mammals Incidental to Specified Activities; Construction of the Knik Arm Crossing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... phocoena). KABATA has not requested authorization for incidental take by injury (Level A harassment), serious injury or mortality. Specified Activities KABATA is proposing to construct a new bridge spanning... sides of the Arm that will run adjacent to the water's edge to varying degrees. A full description of...

Myogenin, AP2β, NOS-1, and HMGA2 are surrogate markers of fusion status in rhabdomyosarcoma: a report from the soft tissue sarcoma committee of the children's oncology group.

PubMed

Rudzinski, Erin R; Anderson, James R; Lyden, Elizabeth R; Bridge, Julia A; Barr, Frederic G; Gastier-Foster, Julie M; Bachmeyer, Karen; Skapek, Stephen X; Hawkins, Douglas S; Teot, Lisa A; Parham, David M

2014-05-01

Pediatric rhabdomyosarcoma (RMS) is traditionally classified on the basis of the histologic appearance into alveolar (ARMS) and embryonal (ERMS) subtypes. The majority of ARMS contain a PAX3-FOXO1 or PAX7-FOXO1 gene fusion, but about 20% do not. Intergroup Rhabdomyosarcoma Study stage-matched and group-matched ARMS typically behaves more aggressively than ERMS, but recent studies have shown that it is, in fact, the fusion status that drives the outcome for RMS. Gene expression microarray data indicate that several genes discriminate between fusion-positive and fusion-negative RMS with high specificity. Using tissue microarrays containing a series of both ARMS and ERMS, we identified a panel of 4 immunohistochemical markers-myogenin, AP2β, NOS-1, and HMGA2-which can be used as surrogate markers of fusion status in RMS. These antibodies provide an alternative to molecular methods for identification of fusion-positive RMS, particularly in cases in which there is scant or poor-quality material. In addition, these antibodies may be useful in fusion-negative ARMS as an indicator that a variant gene fusion may be present.

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients.

PubMed

Bardak, H; Gunay, M; Ercalik, Y; Bardak, Y; Ozbas, H; Bagci, O

2017-01-23

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

49 CFR 172.202 - Description of hazardous material on shipping papers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HAZARDOUS MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE... description must be indicated (by mass or volume, or by activity for Class 7 materials) and must include an... mass. For an explosive that is an article, such as Cartridges, small arms, the net explosive mass may...

Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research.

PubMed

Manolio, Teri A; Fowler, Douglas M; Starita, Lea M; Haendel, Melissa A; MacArthur, Daniel G; Biesecker, Leslie G; Worthey, Elizabeth; Chisholm, Rex L; Green, Eric D; Jacob, Howard J; McLeod, Howard L; Roden, Dan; Rodriguez, Laura Lyman; Williams, Marc S; Cooper, Gregory M; Cox, Nancy J; Herman, Gail E; Kingsmore, Stephen; Lo, Cecilia; Lutz, Cathleen; MacRae, Calum A; Nussbaum, Robert L; Ordovas, Jose M; Ramos, Erin M; Robinson, Peter N; Rubinstein, Wendy S; Seidman, Christine; Stranger, Barbara E; Wang, Haoyi; Westerfield, Monte; Bult, Carol

2017-03-23

Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations, we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing. Published by Elsevier Inc.

Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research

PubMed Central

Manolio, Teri A.; Fowler, Douglas M.; Starita, Lea M.; Haendel, Melissa A.; MacArthur, Daniel G.; Biesecker, Leslie G.; Worthey, Elizabeth; Chisholm, Rex L.; Green, Eric D.; Jacob, Howard J.; McLeod, Howard L.; Roden, Dan; Rodriguez, Laura Lyman; Williams, Marc S.; Cooper, Gregory M.; Cox, Nancy J.; Herman, Gail E.; Kingsmore, Stephen; Lo, Cecilia; Lutz, Cathleen; MacRae, Calum A.; Nussbaum, Robert L.; Ordovas, Jose M.; Ramos, Erin M.; Robinson, Peter N.; Rubinstein, Wendy S.; Seidman, Christine; Stranger, Barbara E.; Wang, Haoyi; Westerfield, Monte; Bult, Carol

2017-01-01

Summary Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing. PMID:28340351

Selective Activation of Shoulder, Trunk, and Arm Muscles: A Comparative Analysis of Different Push-Up Variants.

PubMed

Marcolin, Giuseppe; Petrone, Nicola; Moro, Tatiana; Battaglia, Giuseppe; Bianco, Antonino; Paoli, Antonio

2015-11-01

The push-up is a widely used exercise for upper limb strengthening that can be performed with many variants. A comprehensive analysis of muscle activation during the ascendant phase (AP) and descendant phase (DP) in different variants could be useful for trainers and rehabilitators. To obtain information on the effect of different push-up variants on the electromyography (EMG) of a large sample of upper limb muscles and to investigate the role of the trunk and abdomen muscles during the AP and DP. Cross-sectional study. University laboratory. Eight healthy, young volunteers without a history of upper extremity or spine injury. Participants performed a set of 10 repetitions for each push-up variant: standard, wide, narrow, forward (FP), and backward (BP). Surface EMG of 12 selected muscles and kinematics data were synchronously recorded to describe the AP and DP. Mean EMG activity of the following muscles was analyzed: serratus anterior, deltoideus anterior, erector spinae, latissimus dorsi, rectus abdominis, triceps brachii caput longus, triceps brachii caput lateralis, obliquus externus abdominis, pectoralis major sternal head, pectoralis major clavicular head, trapezius transversalis, and biceps brachii. The triceps brachii and pectoralis major exhibited greater activation during the narrow-base variant. The highest activation of abdomen and back muscles was recorded for the FP and BP variants. The DP demonstrated the least electrical activity across all muscles, with less marked differences for the abdominal and erector spinae muscles because of their role as stabilizers. Based on these findings, we suggest the narrow-base variant to emphasize triceps and pectoralis activity and the BP variant for total upper body strength conditioning. The FP and BP variants should be implemented carefully in participants with low back pain because of the greater activation of abdominal and back muscles.

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

PubMed Central

2013-01-01

Background As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. Methods We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Results Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. Conclusions SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics. PMID:23819695

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

PubMed

Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

2013-07-03

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

Thermal Nondestructive Evaluation Report: Inspection of the Refurbished Manipulator Arm System in the Manipulator Development Facility at Johnson Space Center 10-12 January 2001

NASA Technical Reports Server (NTRS)

Cramer, K. Elliott

2002-01-01

On 4 December 2002, a failure of the Refurbished Manipulator Arm System (RMAS) occurred in the Manipulator Development Facility (MDF) at Johnson Space Center. When the Test Director commanded a should pitch maneuver to lift the arm from its payload bay pedestal, the yaw controls failed. This, coupled with a gravitational forces (due to the angle of the shoulder joint with respect to vertical), resulted in uncontrolled arm motion. The shoulder yaw joint moved approximately 20 degrees, causing the extended arm to strike and severely damage the port side MDF catwalk handrails. The arm motion stopped after impact with the handrails. On 10-12 January 2001, inspections were performed on the port face of the lower and upper arms of the RMAS using a infrared thermography developed at Langley Research Center. This paper presents the results of those nondestructive inspections and provides a complete description of the anomalies found and their locations.

Impact Disdrometers Instrument Handbook

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

Bartholomew, Mary Jane

2016-03-01

To improve the quantitative description of precipitation processes in climate models, the U.S. Department of Energy’s Atmospheric Radiation Measurement (ARM) Climate Research Facility has been collecting observations of the drop size spectra of rain events since early in 2006. Impact disdrometers were the initial choice due to their reliability, ease of maintenance, and relatively low cost. Each of the two units deployed was accompanied by a nearby tipping bucket. In 2010, the tipping buckets were replaced by weighing buckets rain gauges. Five video disdrometers were subsequently purchased and are described in ARM’s VDIS Handbook.1 As of April 2011, three ofmore » the weighing bucket instruments were deployed, one was to travel with the second ARM Mobile Facility, and the fifth was a spare. Two of the video disdrometers were deployed, a third was to be deployed later in the spring of 2011, one was to travel with the second ARM Mobile Facility, and the last was a spare. Detailed descriptions of impact disdrometers and their datastreams are provided in this document.« less

The Changing American Child: The Perspective of Educators.

ERIC Educational Resources Information Center

Zimiles, Herbert

A study was based on retrospective descriptions obtained from interviews with a large number of teachers who have taught for over 20 years. Three areas of change in students were consistently noted in the descriptions: children today know more, are freer, and grow up more rapidly. More autonomous, and armed with greater knowledge, children emerge…

Dose Range Evaluation of Mycograb C28Y Variant, a Human Recombinant Antibody Fragment to Heat Shock Protein 90, in Combination with Amphotericin B-Desoxycholate for Treatment of Murine Systemic Candidiasis ▿

PubMed Central

Louie, Arnold; Stein, Daniel S.; Zack, Julia Z.; Liu, Weiguo; Conde, Haley; Fregeau, Christine; VanScoy, Brian D.; Drusano, George L.

2011-01-01

Systemic candidiasis causes significant mortality in patients despite amphotericin B (AMB) therapy. Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, is closely related to Mycograb, which showed a survival advantage in combination with AMB in a phase III human trial. The Mycograb C28Y variant could potentially increase the antifungal effect of AMB. In our study, the interaction between AMB-desoxycholate (DAMB) and the Mycograb C28Y variant was characterized in vitro by using a checkerboard method. Quantitative cultures of kidneys, livers, and spleens of neutropenic mice with systemic Candida albicans infections were used to assess the in vivo interaction between 1.4 mg/kg of body weight/day of DAMB and 0.15, 1.5, and 15 mg/kg/day of the Mycograb C28Y variant after 1, 3, and 5 days of therapy. DAMB and Mycograb C28Y variant monotherapies, vehicle, and a no-treatment arm served as controls. Also, single- and multidose pharmacokinetics for the Mycograb C28Y variant were determined. Indifference or synergy between DAMB and the Mycograb C28Y variant was seen in two trials by the checkerboard method. The pharmacokinetics of the Mycograb C28Y variant was best described by a 2-compartment model with a median serum t1/2α of ∼0.198 h and a t1/2β of ∼1.77 h. In mice, DAMB together with the Mycograb C28Y variant was no more effective than AMB alone (P > 0.05 by analysis of variance). The Mycograb C28Y variant alone had no antifungal activity. We therefore conclude that the Mycograb C28Y variant in combination with DAMB offered no benefit over DAMB monotherapy in a neutropenic murine model of systemic candidiasis. PMID:21502626

The Myth of Air Control: Reassessing the History

DTIC Science & Technology

2000-01-01

Française au Maroc (1911–1939),” Revue Historique des Armées, no. 4 (1978): 107–20, especially 113. 47. Millet, 54. 48. Laine, 112–18. 49. Capt...W. Breyton, “L’Aviation Sanitaire au Maroc en 1933,” Revue de L’Armée de L’Air, no. 56 (March 1934): 243–64. See the descriptions of aircraft on 246

49 CFR 572.15 - General description.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Assembly SA 103C 030 Torso Assembly SA 103C 041 Upper Arm Assembly Left SA 103C 042 Upper Arm Assembly Right SA 103C 051 Forearm Hand Assembly Left SA 103C 052 Forearm Hand Assembly Right SA 103C 061Upper Leg Assembly Left SA 103C 062 Upper Leg Assembly Right SA 103C 071 Lower Leg Assembly Left SA 103C 072...

49 CFR 572.15 - General description.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Assembly SA 103C 030 Torso Assembly SA 103C 041 Upper Arm Assembly Left SA 103C 042 Upper Arm Assembly Right SA 103C 051 Forearm Hand Assembly Left SA 103C 052 Forearm Hand Assembly Right SA 103C 061Upper Leg Assembly Left SA 103C 062 Upper Leg Assembly Right SA 103C 071 Lower Leg Assembly Left SA 103C 072...

49 CFR 572.15 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Assembly SA 103C 030 Torso Assembly SA 103C 041 Upper Arm Assembly Left SA 103C 042 Upper Arm Assembly Right SA 103C 051 Forearm Hand Assembly Left SA 103C 052 Forearm Hand Assembly Right SA 103C 061Upper Leg Assembly Left SA 103C 062 Upper Leg Assembly Right SA 103C 071 Lower Leg Assembly Left SA 103C 072...

49 CFR 572.15 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Assembly SA 103C 030 Torso Assembly SA 103C 041 Upper Arm Assembly Left SA 103C 042 Upper Arm Assembly Right SA 103C 051 Forearm Hand Assembly Left SA 103C 052 Forearm Hand Assembly Right SA 103C 061Upper Leg Assembly Left SA 103C 062 Upper Leg Assembly Right SA 103C 071 Lower Leg Assembly Left SA 103C 072...

Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

PubMed

Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia

2015-08-01

Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.

AmeriFlux US-ARb ARM Southern Great Plains burn site- Lamont

DOE Data Explorer

Torn, Margaret [Lawrence Berkeley National Laboratory

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-ARb ARM Southern Great Plains burn site- Lamont. Site Description - The ARM SGP Burn site is located in the native tallgrass prairies of the USDA Grazinglands Research Laboratory near El Reno, OK. One of two adjacent 35 ha plots, the US-ARb plot was burned on 2005/03/08. The second plot, US-ARc, was left unburned as the control for experimental purposes. Aside from 2005, the region evaded burning activities for at least 15 years. Current disturbances consist of only light grazing activities.

TU-G-BRB-01: Continuous Path Optimization for Non-Coplanar Variant SAD IMRT Delivery Using C-Arm Machines.

PubMed

Ruan, D; Dong, P; Low, D; Sheng, K

2012-06-01

To develop and investigate a continuous path optimization methodology to traverse prescribed non-coplanar IMRT beams with variant SADs, by orchestrating the couch and gantry movement with zero-collision, minimal patient motion consequence and machine travel time. We convert the given collision zone definition and the prescribed beam location/angles to a tumor-centric coordinate, and represent the traversing path as a continuous open curve. We proceed to optimize a composite objective function consisting of (1) a strong attraction energy to ensure all prescribed beams are en-route, (2) a penalty for patient-motion inducing couch motion, and (3) a penalty for travel-time inducing overall path-length. Feasibility manifold is defined as complement to collision zone and the optimization is performed with a level set representation evolved with variational flows. The proposed method has been implemented and tested on clinically derived data. In the absence of any existing solutions for the same problem, we validate by: (1) visual inspecting the generated path rendered in the 3D tumor-centric coordinates, and (2) comparing with a traveling-salesman (TSP) solution obtained from relaxing the variant SADs and continuous collision-avoidance requirement. The proposed method has generated delivery paths that are smooth and intuitively appealing. Under relaxed settings, our results outperform the generic TSP solutions and agree with specially tuned versions. We have proposed a novel systematic approach that automatically determines the continuous path to cover non-coplanar, varying SAD IMRT beams. The proposed approach accommodates patient-specific collision zone definition and ensures its avoidance continuously. The differential penalty to couch and gantry motions allows customizable tradeoff between patient geometry stability and delivery efficiency. This development paves the path to achieve safe, accurate and efficient non-coplanar IMRT delivery with the advanced robotic controls in new-generation C-arm systems, enabling practical harvesting of the dose benefit offered by non-coplanar, variant SAD IMRT treatment. © 2012 American Association of Physicists in Medicine.

A real-time robot arm collision detection system

NASA Technical Reports Server (NTRS)

Shaffer, Clifford A.; Herb, Gregory M.

1990-01-01

A data structure and update algorithm are presented for a prototype real time collision detection safety system for a multi-robot environment. The data structure is a variant of the octree, which serves as a spatial index. An octree recursively decomposes 3-D space into eight equal cubic octants until each octant meets some decomposition criteria. The octree stores cylspheres (cylinders with spheres on each end) and rectangular solids as primitives (other primitives can easily be added as required). These primitives make up the two seven degrees-of-freedom robot arms and environment modeled by the system. Octree nodes containing more than a predetermined number N of primitives are decomposed. This rule keeps the octree small, as the entire environment for the application can be modeled using a few dozen primitives. As robot arms move, the octree is updated to reflect their changed positions. During most update cycles, any given primitive does not change which octree nodes it is in. Thus, modification to the octree is rarely required. Incidents in which one robot arm comes too close to another arm or an object are reported. Cycle time for interpreting current joint angles, updating the octree, and detecting/reporting imminent collisions averages 30 milliseconds on an Intel 80386 processor running at 20 MHz.

Characterization and functional analyses of a novel chicken CD8a variant X1 (CD8a1)

USDA-ARS?s Scientific Manuscript database

We provide the first description of cloning, as well as structural and functional analysis of a novel variant in the chicken CD8alpha family, termed the CD8-alpha X1 (CD8alpha1) gene. Multiple alignment of CD8alpha1 with known CD8alpha and beta sequences of other species revealed relatively low con...

Leadership Theory and Practice: Where East Meets West

DTIC Science & Technology

1989-06-01

leadership concepts can be assimilated to good advantage by the Chinese. and what additional research ei’forts for the armed forces of the Republic... research ef- forts for the armed forces of the Republic of China should be undertaken. The this7s "su ,, L.,uitJ _ description of the eCHO sampiing...29 A. THE ECHO SAMPLING TECHNIQUE ....................... 29 B. THE MCBER SAMPLING METHOD .. ....................... 33 IV. CRITICAL

Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration

PubMed Central

Klein, Michael L.; Ferris, Frederick L.; Francis, Peter J.; Lindblad, Anne S.; Chew, Emily Y.; Hamon, Sara C.; Ott, Jurg

2009-01-01

Purpose To determine if genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Design Prospective analysis of participants in a randomized controlled clinical trial. Participants 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS). Methods Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed. Main Outcome Measures Genotype frequencies and change in cumulative area of GA. Results The mean growth rate of geographic atrophy for the 114 eyes was 1.79 mm2/year (range= 0.17–4.76 mm2/year). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3genes. For the single nucleotide polymorphism (SNP) rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared to the homozygous non-risk genotype (unadjusted p-value = 0.002; Bonferroni corrected p-value = 0.014) and for allelic association(Bonferroni corrected p-value = 0.011). Analyses of other measures of geographic atrophy progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype. Conclusion GA growth rates calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, and TLR3 genes. There was a nominally statistically significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations would be needed to establish the existence of an association. PMID:20381870

Modal analysis and control of flexible manipulator arms. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Neto, O. M.

1974-01-01

The possibility of modeling and controlling flexible manipulator arms was examined. A modal approach was used for obtaining the mathematical model and control techniques. The arm model was represented mathematically by a state space description defined in terms of joint angles and mode amplitudes obtained from truncation on the distributed systems, and included the motion of a two link two joint arm. Three basic techniques were used for controlling the system: pole allocation with gains obtained from the rigid system with interjoint feedbacks, Simon-Mitter algorithm for pole allocation, and sensitivity analysis with respect to parameter variations. An improvement in arm bandwidth was obtained. Optimization of some geometric parameters was undertaken to maximize bandwidth for various payload sizes and programmed tasks. The controlled system is examined under constant gains and using the nonlinear model for simulations following a time varying state trajectory.

Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy.

PubMed

de Haas, Sanne; Delmar, Paul; Bansal, Aruna T; Moisse, Matthieu; Miles, David W; Leighl, Natasha; Escudier, Bernard; Van Cutsem, Eric; Carmeliet, Peter; Scherer, Stefan J; Pallaud, Celine; Lambrechts, Diether

2014-10-01

Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified. We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome. The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene. This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy.

A single promoter inversion switches Photorhabdus between pathogenic and mutualistic states.

PubMed

Somvanshi, Vishal S; Sloup, Rudolph E; Crawford, Jason M; Martin, Alexander R; Heidt, Anthony J; Kim, Kwi-suk; Clardy, Jon; Ciche, Todd A

2012-07-06

Microbial populations stochastically generate variants with strikingly different properties, such as virulence or avirulence and antibiotic tolerance or sensitivity. Photorhabdus luminescens bacteria have a variable life history in which they alternate between pathogens to a wide variety of insects and mutualists to their specific host nematodes. Here, we show that the P. luminescens pathogenic variant (P form) switches to a smaller-cell variant (M form) to initiate mutualism in host nematode intestines. A stochastic promoter inversion causes the switch between the two distinct forms. M-form cells are much smaller (one-seventh the volume), slower growing, and less bioluminescent than P-form cells; they are also avirulent and produce fewer secondary metabolites. Observations of form switching by individual cells in nematodes revealed that the M form persisted in maternal nematode intestines, were the first cells to colonize infective juvenile (IJ) offspring, and then switched to P form in the IJ intestine, which armed these nematodes for the next cycle of insect infection.

Selective Activation of Shoulder, Trunk, and Arm Muscles: A Comparative Analysis of Different Push-Up Variants

PubMed Central

Marcolin, Giuseppe; Petrone, Nicola; Moro, Tatiana; Battaglia, Giuseppe; Bianco, Antonino; Paoli, Antonio

2015-01-01

Context The push-up is a widely used exercise for upper limb strengthening that can be performed with many variants. A comprehensive analysis of muscle activation during the ascendant phase (AP) and descendant phase (DP) in different variants could be useful for trainers and rehabilitators. Objective To obtain information on the effect of different push-up variants on the electromyography (EMG) of a large sample of upper limb muscles and to investigate the role of the trunk and abdomen muscles during the AP and DP. Design Cross-sectional study. Setting University laboratory. Patients or Other Participants Eight healthy, young volunteers without a history of upper extremity or spine injury. Intervention(s) Participants performed a set of 10 repetitions for each push-up variant: standard, wide, narrow, forward (FP), and backward (BP). Surface EMG of 12 selected muscles and kinematics data were synchronously recorded to describe the AP and DP. Main Outcome Measure(s) Mean EMG activity of the following muscles was analyzed: serratus anterior, deltoideus anterior, erector spinae, latissimus dorsi, rectus abdominis, triceps brachii caput longus, triceps brachii caput lateralis, obliquus externus abdominis, pectoralis major sternal head, pectoralis major clavicular head, trapezius transversalis, and biceps brachii. Results The triceps brachii and pectoralis major exhibited greater activation during the narrow-base variant. The highest activation of abdomen and back muscles was recorded for the FP and BP variants. The DP demonstrated the least electrical activity across all muscles, with less marked differences for the abdominal and erector spinae muscles because of their role as stabilizers. Conclusions Based on these findings, we suggest the narrow-base variant to emphasize triceps and pectoralis activity and the BP variant for total upper body strength conditioning. The FP and BP variants should be implemented carefully in participants with low back pain because of the greater activation of abdominal and back muscles. PMID:26488636

A Military Guide to Terrorism in the Twenty-First Century

DTIC Science & Technology

2004-10-12

defending against catastrophic terrorism, and emergency preparedness and response.17 A survey of these mission sets aligns easily with functions of...and descriptions present a survey of conventional small arms often used by terrorists. Intelligence summaries provide the basis for this sampling...of hand or shoulder fired weapons. E: Improvised Explosive Devices. Illustrations, photographs, and descriptions present a survey of explosive

Isolated lower brachial plexus (Klumpke) palsy with compound arm presentation: case report.

PubMed

Buchanan, Edward P; Richardson, Randal; Tse, Raymond

2013-08-01

Klumpke palsy has yet to be clearly documented in the newborn, because previous reports lack any description of the obstetrical history, clinical progression, or outcome. Based on a high incidence of breach presentation in the few clinical series that report Klumpke palsy, hyperabduction with arm overhead during delivery has been the presumed mechanism. We report a child with isolated lower brachial plexus palsy and Horner syndrome who presented at birth with a vertex compound arm presentation. Recognition of this condition and details of the clinical progression and outcome are important, because guidelines for management are currently not available. Copyright © 2013. Published by Elsevier Inc.

Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis.

PubMed

Kraus, William E; Muoio, Deborah M; Stevens, Robert; Craig, Damian; Bain, James R; Grass, Elizabeth; Haynes, Carol; Kwee, Lydia; Qin, Xuejun; Slentz, Dorothy H; Krupp, Deidre; Muehlbauer, Michael; Hauser, Elizabeth R; Gregory, Simon G; Newgard, Christopher B; Shah, Svati H

2015-11-01

Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA), long-chain dicarboxylacylcarnitine (LCDA) and medium chain acylcarnitine (MCA) metabolites are heritable and predict cardiovascular disease (CVD) events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490), we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER) stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1) These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6-2.3x10-10). Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2). Expression quantitative trait loci (eQTL) pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS) arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk.

Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis

PubMed Central

Kraus, William E.; Muoio, Deborah M.; Stevens, Robert; Craig, Damian; Bain, James R.; Grass, Elizabeth; Haynes, Carol; Kwee, Lydia; Qin, Xuejun; Slentz, Dorothy H.; Krupp, Deidre; Muehlbauer, Michael; Hauser, Elizabeth R.; Gregory, Simon G.; Newgard, Christopher B.; Shah, Svati H.

2015-01-01

Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA), long-chain dicarboxylacylcarnitine (LCDA) and medium chain acylcarnitine (MCA) metabolites are heritable and predict cardiovascular disease (CVD) events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490), we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER) stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1) These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6–2.3x10-10). Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2). Expression quantitative trait loci (eQTL) pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS) arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk. PMID:26540294

Selenium- or vitamin E-related gene variants, interaction with supplementation, and risk of high-grade prostate cancer in SELECT

PubMed Central

Chan, June M.; Darke, Amy K.; Penney, Kathryn L.; Tangen, Catherine M.; Goodman, Phyllis J.; Lee, Gwo-Shu Mary; Sun, Tong; Peisch, Sam; Tinianow, Alex M.; Rae, James M.; Klein, Eric A.; Thompson, Ian M.

2016-01-01

Background Epidemiological studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. Methods We undertook a case-cohort study of SELECT participants randomized to placebo, selenium or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N=278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. Results We noted statistically significant (p<0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2 and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA. In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. Conclusion Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man’s response to vitamin E or selenium supplementation with regards to these risks. Impact The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. PMID:27197287

Molecular outcomes, clinical consequences, and genetic diagnosis of Oculocutaneous Albinism in Pakistani population.

PubMed

Shahzad, Mohsin; Yousaf, Sairah; Waryah, Yar M; Gul, Hadia; Kausar, Tasleem; Tariq, Nabeela; Mahmood, Umair; Ali, Muhammad; Khan, Muzammil A; Waryah, Ali M; Shaikh, Rehan S; Riazuddin, Saima; Ahmed, Zubair M

2017-03-07

Nonsyndromic oculocutaneous Albinism (nsOCA) is clinically characterized by the loss of pigmentation in the skin, hair, and iris. OCA is amongst the most common causes of vision impairment in children. To date, pathogenic variants in six genes have been identified in individuals with nsOCA. Here, we determined the identities, frequencies, and clinical consequences of OCA alleles in 94 previously unreported Pakistani families. Combination of Sanger and Exome sequencing revealed 38 alleles, including 22 novel variants, segregating with nsOCA phenotype in 80 families. Variants of TYR and OCA2 genes were the most common cause of nsOCA, occurring in 43 and 30 families, respectively. Twenty-two novel variants include nine missense, four splice site, two non-sense, one insertion and six gross deletions. In vitro studies revealed retention of OCA proteins harboring novel missense alleles in the endoplasmic reticulum (ER) of transfected cells. Exon-trapping assays with constructs containing splice site alleles revealed errors in splicing. As eight alleles account for approximately 56% (95% CI: 46.52-65.24%) of nsOCA cases, primarily enrolled from Punjab province of Pakistan, hierarchical strategies for variant detection would be feasible and cost-efficient genetic tests for OCA in families with similar origin. Thus, we developed Tetra-primer ARMS assays for rapid, reliable, reproducible and economical screening of most of these common alleles.

Arm swing magnitude and asymmetry during gait in the early stages of Parkinson's disease.

PubMed

Lewek, Michael D; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

2010-02-01

The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in "off" state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p = 0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p = 0.907) or less (p = 0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9 + or - 7.9%) compared to the control group (asymmetry angle: 5.1 + or - 4.0%; p = 0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. Copyright 2009 Elsevier B.V. All rights reserved.

Arm Swing Magnitude and Asymmetry During Gait in the Early Stages of Parkinson's Disease

PubMed Central

Lewek, Michael D.; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

2009-01-01

The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in “off” state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p=0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p=0.907) or less (p=0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9±7.9%) compared to the control group (asymmetry angle: 5.1±4.0%; p=0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. PMID:19945285

CFH haplotypes and ARMS2, C2, C3, and CFB alleles show association with susceptibility to age-related macular degeneration in Mexicans

PubMed Central

Zenteno, Juan Carlos; Fernández-López, Juan Carlos; Rodríguez-Corona, Ulises; Falfán-Valencia, Ramcés; Sebastian, Leticia; Morales, Fabiola; Ochoa-Contreras, Daniel; Carnevale, Alessandra; Silva-Zolezzi, Irma

2014-01-01

Purpose To evaluate the contribution of genetic variants of complement factor H (CFH), complement component 2 and 3 (C2 and C3), complement factor B (CFB), and age-related maculopathy susceptibility 2 (ARMS2) to age-related macular degeneration (AMD) risk in the Mexican Mestizo population. Methods Analysis included 282 unrelated Mexican patients with advanced AMD, 205 healthy controls, and 280 population controls. Stereoscopic fundus images were graded on the Clinical Age-Related Maculopathy System (CARMS). We designed a resequencing strategy using primers with M13 adaptor for the 23 exons of the CFH gene in a subgroup of 96 individuals clinically evaluated: 48 AMD cases and 48 age- and sex-matched healthy controls. Single nucleotide polymorphisms (SNPs) in C3 (Arg80Gly and Pro292Leu), C2 (rs547154), CFB (Leu9His), and ARMS2 (Ala69Ser) were genotyped in all patients, healthy and population controls using TaqMan assay. Results All evaluated individuals were Mexican Mestizos, and their genetic ancestry was validated using 224 ancestry informative markers and calculating Fst values. The CFH resequencing revealed 19 SNPs and a common variant in the intron 2 splice acceptor site; three CFH haplotypes inferred from individual genotypes, showed significant differences between cases and controls. The risk alleles in C3 (rs1047286, odds ratio [OR]=2.48, 95% confidence interval [CI]=1.64–3.75, p=1.59E-05; rs2230199, OR=2.15, 95% CI=1.48–3.13, p=6.28E-05) and in ARMS2 (rs10490924, OR=3.09, 95% CI=2.48–3.86, p=5.42E-23) were strongly associated with risk of AMD. The protective effect of alleles in C2 (rs547154) and CFB (rs4151667) showed a trend but was not significantly associated after correction for multiple testing. Conclusions Our results show that ARMS2 and C3 are major contributors to advanced AMD in Mexican patients, while the contributions of CFH, C2, and CFB are minor to those of other populations, reveling significant ethnic differences in minor allele frequencies. We provide evidence that two specific common haplotypes in the CFH gene predispose individuals to AMD, while another may confer reduced risk of disease in this admixed population. PMID:24453474

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders

PubMed Central

Karbassi, Izabela; Maston, Glenn A.; Love, Angela; DiVincenzo, Christina; Braastad, Corey D.; Elzinga, Christopher D.; Bright, Alison R.; Previte, Domenic; Zhang, Ke; Rowland, Charles M.; McCarthy, Michele; Lapierre, Jennifer L.; Dubois, Felicita; Medeiros, Katelyn A.; Batish, Sat Dev; Jones, Jeffrey; Liaquat, Khalida; Hoffman, Carol A.; Jaremko, Malgorzata; Wang, Zhenyuan; Sun, Weimin; Buller‐Burckle, Arlene; Strom, Charles M.; Keiles, Steven B.

2015-01-01

ABSTRACT We developed a rules‐based scoring system to classify DNA variants into five categories including pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign, and benign. Over 16,500 pathogenicity assessments on 11,894 variants from 338 genes were analyzed for pathogenicity based on prediction tools, population frequency, co‐occurrence, segregation, and functional studies collected from internal and external sources. Scores were calculated by trained scientists using a quantitative framework that assigned differential weighting to these five types of data. We performed descriptive and comparative statistics on the dataset and tested interobserver concordance among the trained scientists. Private variants defined as variants found within single families (n = 5,182), were either VUS (80.5%; n = 4,169) or likely pathogenic (19.5%; n = 1,013). The remaining variants (n = 6,712) were VUS (38.4%; n = 2,577) or likely benign/benign (34.7%; n = 2,327) or likely pathogenic/pathogenic (26.9%, n = 1,808). Exact agreement between the trained scientists on the final variant score was 98.5% [95% confidence interval (CI) (98.0, 98.9)] with an interobserver consistency of 97% [95% CI (91.5, 99.4)]. Variant scores were stable and showed increasing odds of being in agreement with new data when re‐evaluated periodically. This carefully curated, standardized variant pathogenicity scoring system provides reliable pathogenicity scores for DNA variants encountered in a clinical laboratory setting. PMID:26467025

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

PubMed

Karbassi, Izabela; Maston, Glenn A; Love, Angela; DiVincenzo, Christina; Braastad, Corey D; Elzinga, Christopher D; Bright, Alison R; Previte, Domenic; Zhang, Ke; Rowland, Charles M; McCarthy, Michele; Lapierre, Jennifer L; Dubois, Felicita; Medeiros, Katelyn A; Batish, Sat Dev; Jones, Jeffrey; Liaquat, Khalida; Hoffman, Carol A; Jaremko, Malgorzata; Wang, Zhenyuan; Sun, Weimin; Buller-Burckle, Arlene; Strom, Charles M; Keiles, Steven B; Higgins, Joseph J

2016-01-01

We developed a rules-based scoring system to classify DNA variants into five categories including pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign, and benign. Over 16,500 pathogenicity assessments on 11,894 variants from 338 genes were analyzed for pathogenicity based on prediction tools, population frequency, co-occurrence, segregation, and functional studies collected from internal and external sources. Scores were calculated by trained scientists using a quantitative framework that assigned differential weighting to these five types of data. We performed descriptive and comparative statistics on the dataset and tested interobserver concordance among the trained scientists. Private variants defined as variants found within single families (n = 5,182), were either VUS (80.5%; n = 4,169) or likely pathogenic (19.5%; n = 1,013). The remaining variants (n = 6,712) were VUS (38.4%; n = 2,577) or likely benign/benign (34.7%; n = 2,327) or likely pathogenic/pathogenic (26.9%, n = 1,808). Exact agreement between the trained scientists on the final variant score was 98.5% [95% confidence interval (CI) (98.0, 98.9)] with an interobserver consistency of 97% [95% CI (91.5, 99.4)]. Variant scores were stable and showed increasing odds of being in agreement with new data when re-evaluated periodically. This carefully curated, standardized variant pathogenicity scoring system provides reliable pathogenicity scores for DNA variants encountered in a clinical laboratory setting. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

Chromosome 2 short arm translocations revealed by M-FISH analysis of neuroblastoma cell lines.

PubMed

Van Roy, N; Van Limbergen, H; Vandesompele, J; Van Gele, M; Poppe, B; Laureys, G; De Paepe, A; Speleman, F

2000-12-01

M-FISH analysis was performed on 18 neuroblastoma cell lines, which were previously studied with cytogenetic, standard FISH and CGH data. One of the most striking findings of this study was the detection of chromosome 2 short arm rearrangements in 61% of the investigated cell lines. These rearrangements resulted from translocations with various partner chromosomes. All translocations, except one were unbalanced, leading to the consistent gain of chromosome segment 2pter-p22. A cryptic balanced translocation t(2;4) was observed with a breakpoint located in the vicinity of MYCN in cell line NBL-S. Combination of M-FISH results together with cytogenetic, standard FISH and CGH data yielded the most comprehensive description of chromosome 2 short arm rearrangements, leading to a consistent gain of chromosome 2 short arm material. Copyright 2000 Wiley-Liss, Inc.

AmeriFlux US-AR2 ARM USDA UNL OSU Woodward Switchgrass 2

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

Billesbach, Dave; Bradford, James

This is the AmeriFlux version of the carbon flux data for the site US-AR2 ARM USDA UNL OSU Woodward Switchgrass 2. Site Description - The ARM USDA UNL OSU Woodward Switchgrass 2 tower is located on public land owned by the USDA-ARS Southern Plains Range Research Station in Woodward, Oklahoma. The site is on a former wheat field that is in the process of changing to switchgrass. A companion site (ARM USDA UNL OSU Woodward Switchgrass 1) is on a former native prairie. Previous wheat was planted in Fall 2008. In Spring 2009, herbicide was applied to kill the wheatmore » prior to switchgrass planting. Later in the year, the site was sprayed with post-emergence herbicide. In 2010, fertilization occurred before herbicide was sprayed for broadleaf control.« less

Accessory branch of median nerve supplying the brachialis muscle: a case report and clinical significance.

PubMed

Paraskevas, George; Anastasopoulos, Nikolaos; Nitsa, Zoi; Kitsoulis, Panagiotis; Spyridakis, Ioannis

2014-12-01

A very rare case of an accessory branch of the median nerve taking its origin in the region of the right arm was observed to supply the infero-medial portion of the brachialis muscle in a male cadaver. Simultaneously, the ipsilateral musculocutaneous nerve was innervating the muscles of the anterior compartment of the arm. Such an aberrant muscular branch of the median nerve for the brachialis muscle is very rarely reported in the literature. Lesion of the median nerve proximal to the branch's origin site could induce weak flexion of the elbow, whereas injury of the musculocutaneous nerve could lead to misinterpretation of symptoms. We discuss the patterns of brachialis muscle innervation as well as the clinical applications of such a variant.

Amyotrophic Lateral Sclerosis Regional Variants (Brachial Amyotrophic Diplegia, Leg Amyotrophic Diplegia, and Isolated Bulbar Amyotrophic Lateral Sclerosis).

PubMed

Jawdat, Omar; Statland, Jeffrey M; Barohn, Richard J; Katz, Jonathan S; Dimachkie, Mazen M

2015-11-01

Amyotrophic lateral sclerosis (ALS), a rapidly progressive, invariably fatal disease, involves mixed upper and lower motor neurons in different spinal cord regions. Patients with bulbar onset progress more rapidly than patients with limb onset or with a lower motor neuron presentation. Recent descriptions of regional variants suggest some patients have ALS isolated to a single spinal region for many years, including brachial amyotrophic diplegia, leg amyotrophic diplegia, and isolated bulbar palsy. Clearer definitions of regional variants will have implications for prognosis, understanding the pathophysiology of ALS, identifying genetic factors related to slower disease progression, and future planning of clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Uniform National Discharge Standards (UNDS) for Vessels of the Armed Forces

EPA Pesticide Factsheets

The Uniform National Discharge Standards homepage links to a description of the EPA's rulemaking process and provides information to the public on outreach efforts and answers some frequently asked questions.

Reporting of interventions and "standard of care" control arms in pediatric clinical trials: a quantitative analysis.

PubMed

Yu, Ashley M; Balasubramanaiam, Bannuya; Offringa, Martin; Kelly, Lauren E

2018-06-13

In pediatric medicine, the usual treatment received by children ("standard of care") varies across centers. Evaluations of new treatments often compare to the existing "standard of care" to determine if a treatment is more effective, has a better safety profile, or costs less. The objective of our study was to evaluate intervention and "standard of care" control arms reported in published pediatric clinical trials. Pediatric clinical trials, published in 2014, reporting the use of a "standard of care" control arm were included. Duplicate assessment of reporting completeness was done using the 12-item TIDieR (Template for Intervention Description and Replication) checklist for both the "standard of care" control arms and intervention arms within the same published study. Following screening, 214 pediatric trials in diverse therapeutic areas were included. Several different terms were used to describe "standard of care." There was a significant difference between the mean reported TIDieR checklist items of "standard of care" control arms (5.81 (SD 2.13) and intervention arms (8.45 (SD 1.39, p < 0.0001). Reporting of intervention and "standard of care" control arms in pediatric clinical trials should be improved as current "standard of care" reporting deficiencies limit reproducibility of research and may ultimately contribute to research waste.

Computer coordination of limb motion for locomotion of a multiple-armed robot for space assembly

NASA Technical Reports Server (NTRS)

Klein, C. A.; Patterson, M. R.

1982-01-01

Consideration is given to a possible robotic system for the construction of large space structures, which may be described as a multiple general purpose arm manipulator vehicle that can walk over the structure under construction to a given site for further work. A description is presented of the locomotion of such a vehicle, modeling its arms in terms of a currently available industrial manipulator. It is noted that for whatever maximum speed of operation is chosen, rapid changes in robot velocity create situations in which already-selected handholds are no longer practical. A step is added to the 'free gait' walking algorithm in order to solve this problem.

The chemical component dictionary: complete descriptions of constituent molecules in experimentally determined 3D macromolecules in the Protein Data Bank

PubMed Central

Westbrook, John D.; Shao, Chenghua; Feng, Zukang; Zhuravleva, Marina; Velankar, Sameer; Young, Jasmine

2015-01-01

Summary: The Chemical Component Dictionary (CCD) is a chemical reference data resource that describes all residue and small molecule components found in Protein Data Bank (PDB) entries. The CCD contains detailed chemical descriptions for standard and modified amino acids/nucleotides, small molecule ligands and solvent molecules. Each chemical definition includes descriptions of chemical properties such as stereochemical assignments, chemical descriptors, systematic chemical names and idealized coordinates. The content, preparation, validation and distribution of this CCD chemical reference dataset are described. Availability and implementation: The CCD is updated regularly in conjunction with the scheduled weekly release of new PDB structure data. The CCD and amino acid variant reference datasets are hosted in the public PDB ftp repository at ftp://ftp.wwpdb.org/pub/pdb/data/monomers/components.cif.gz, ftp://ftp.wwpdb.org/pub/pdb/data/monomers/aa-variants-v1.cif.gz, and its mirror sites, and can be accessed from http://wwpdb.org. Contact: jwest@rcsb.rutgers.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25540181

Reevaluation of the superior radial collateral artery in the human upper arm.

PubMed

Ichimura, Koichiro; Kinose, Shota; Kawasaki, Yuto; Kato, Kota; Sakai, Tatsuo

2018-01-01

The superior radial collateral artery (SRCA) was described in well-established anatomy textbooks published in the 1800s. According to those textbooks, the SRCA originates from the brachial artery, passes transversely between the coracobrachialis and the humerus, and distributes to the most distal portion of the deltoid. The SRCA is not listed in the international standard on anatomical terminology, Terminologia Anatomica, or in modern anatomy textbooks. In the present study, we reevaluated the anatomical features of the SRCA by cadaveric dissection. We found that two kinds of SRCAs were consistently present in the upper arm. One was similar to the previous descriptions of the SRCA in terms of origin and course, but the distribution was somewhat different. The other was similar to the previous descriptions in terms of the distribution, although it differed in origin and course. The discrepancy between the description of the SRCA in classical textbooks and the actual morphologies of the SRCA presumably prompted previous anatomists to question the existence of the SRCA, resulting in its absence from anatomical textbooks after a particular time point.

[Measuring the blood pressure in both arms is of little use; longitudinal study into blood pressure differences between both arms and its reproducibility in patients with diabetes mellitus type 2].

PubMed

Kleefstra, N; Houweling, S T; Meyboom-de Jong, B; Bilo, H J G

2007-07-07

To determine the prevalence of inter-arm blood pressure differences > 10 mmHg in patients with diabetes mellitus type 2 (DM2) and to determine whether these differences are consistent over time. Descriptive. In an evaluation study of 169 DM2 patients from 5 general practices in 2003 and 2004, different methods of oscillatory measurement were used to investigate inter-arm blood pressure differences > 10 mmHg systolic or diastolic. These methods were: one measurement in each arm non-simultaneously (method A), one measurement simultaneously (B) and the mean of two simultaneous measurements (C). With method A an inter-arm blood pressure difference was found in 33% of patients. This percentage diminished to 9 with method C. In 44% (n = 7) of the patients in whom method C detected a relevant blood pressure difference, this difference was not found with method A. In 79% of patients the inter-arm blood pressure difference was not reproduced after one year. In daily practice, one non-simultaneous blood pressure measurement in each arm (method A) was of little value for identification of patients with inter-arm blood pressure differences. The reproducibility was poor one year later. Bilateral blood pressure measurement is therefore of little value.

Infections in Combat Casualties During Operations Iraqi and Enduring Freedom

DTIC Science & Technology

2009-04-01

bacteria other 39 112.1 Vulva/vaginal candidiasis 1 381.4 Nonsuppurative otitis media 1 451.82 Superficial phlebitis arm 2 451.83 Deep phlebitis arm 1...Coding by Pathogen Pathogen Code Code Description Number Fungus 112.1 Vulva/vaginal candidiasis 1 112.3 Candidiasis of skin/nails 1 112.5 Disseminated... candidiasis 3 112.89 Candidiasis site not available 6 112.9 Candidiasis site unspecified 13 117.3 Aspergillus 5 117.9 Mycoses 14 Gram-negative 003.8

Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori

NASA Astrophysics Data System (ADS)

Wang, Liang-Wei; Liu, Yu-Nan; Lyu, Ping-Chiang; Jackson, Sophie E.; Hsu, Shang-Te Danny

2015-09-01

Understanding the mechanism by which a polypeptide chain thread itself spontaneously to attain a knotted conformation has been a major challenge in the field of protein folding. HP0242 is a homodimeric protein from Helicobacter pylori with intertwined helices to form a unique pseudo-knotted folding topology. A tandem HP0242 repeat has been constructed to become the first engineered trefoil-knotted protein. Its small size renders it a model system for computational analyses to examine its folding and knotting pathways. Here we report a multi-parametric study on the folding stability and kinetics of a library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat, using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium chemical denaturation of HP0242 variants shows the presence of highly populated dimeric and structurally heterogeneous folding intermediates. Such equilibrium folding intermediates retain significant amount of helical structures except those at the N- and C-terminal regions in the native structure. Stopped-flow fluorescence measurements of HP0242 variants show that spontaneous refolding into knotted structures can be achieved within seconds, which is several orders of magnitude faster than previously observed for other knotted proteins. Nevertheless, the complex chevron plots indicate that HP0242 variants are prone to misfold into kinetic traps, leading to severely rolled-over refolding arms. The experimental observations are in general agreement with the previously reported molecular dynamics simulations. Based on our results, kinetic folding pathways are proposed to qualitatively describe the complex folding processes of HP0242 variants.

Octopus arm movements under constrained conditions: adaptation, modification and plasticity of motor primitives.

PubMed

Richter, Jonas N; Hochner, Binyamin; Kuba, Michael J

2015-04-01

The motor control of the eight highly flexible arms of the common octopus (Octopus vulgaris) has been the focus of several recent studies. Our study is the first to manage to introduce a physical constraint to an octopus arm and investigate the adaptability of stereotypical bend propagation in reaching movements and the pseudo-limb articulation during fetching. Subjects (N=6) were placed inside a transparent Perspex box with a hole at the center that allowed the insertion of a single arm. Animals had to reach out through the hole toward a target, to retrieve a food reward and fetch it. All subjects successfully adjusted their movements to the constraint without an adaptation phase. During reaching tasks, the animals showed two movement strategies: stereotypical bend propagation reachings, which were established at the hole of the Perspex box and variant waving-like movements that showed no bend propagations. During fetching movements, no complete pseudo-joint fetching was observed outside the box and subjects pulled their arms through the hole in a pull-in like movement. Our findings show that there is some flexibility in the octopus motor system to adapt to a novel situation. However, at present, it seems that these changes are more an effect of random choices between different alternative motor programs, without showing clear learning effects in the choice between the alternatives. Interestingly, animals were able to adapt the fetching movements to the physical constraint, or as an alternative explanation, they could switch the motor primitive fetching to a different motor primitive 'arm pulling'. © 2015. Published by The Company of Biologists Ltd.

An anatomic description of intrinsic brachial muscles in the crab-eating fox (Cerdocyon thous, Linnaeus 1776) and report of a variant arterial distribution.

PubMed

Vélez, J; Ramírez, J; Aristizábal, O

2018-04-01

The crab-eating fox (Cerdocyon thous) is a wild canid distributed throughout South America. It is one of the wild canids reported being hit by vehicles and injured in snares, thus inducing trauma or injury to the musculoskeletal system, possibly occurring in the brachial region. The main objective of this research was to provide an anatomic description of the crab-eating fox's intrinsic brachial muscles including shape, origin, insertion, innervation and arterial blood supply, compared with that of the domestic dog. We dissected from superficial to deep two thoracic limbs of seven dead specimens donated to the University of Caldas by CORPOCALDAS. These muscles presented anatomic characteristics similar to those reported in the domestic dog (Canis lupus familiaris) but with a variant in arterial blood supply, allowing us to suggest that surgical procedures that need the knowledge of intrinsic brachial muscles in the crab-eating fox may be homologous to the domestic dog. However, one should consider its variant arterial distribution by part of the collateral radial artery and deep brachial artery to prevent incorrect incisions that may damage these arteries. © 2017 Blackwell Verlag GmbH.

The cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations.

PubMed

Huang, Linda; Fernandes, Helen; Zia, Hamid; Tavassoli, Peyman; Rennert, Hanna; Pisapia, David; Imielinski, Marcin; Sboner, Andrea; Rubin, Mark A; Kluk, Michael; Elemento, Olivier

2017-05-01

This paper describes the Precision Medicine Knowledge Base (PMKB; https://pmkb.weill.cornell.edu ), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations. PMKB was built using the Ruby on Rails Web application framework. Leveraging existing standards such as the Human Genome Variation Society variant description format, we implemented a data model that links variants to tumor-specific and tissue-specific interpretations. Key features of PMKB include support for all major variant types, standardized authentication, distinct user roles including high-level approvers, and detailed activity history. A REpresentational State Transfer (REST) application-programming interface (API) was implemented to query the PMKB programmatically. At the time of writing, PMKB contains 457 variant descriptions with 281 clinical-grade interpretations. The EGFR, BRAF, KRAS, and KIT genes are associated with the largest numbers of interpretable variants. PMKB's interpretations have been used in over 1500 AmpliSeq tests and 750 whole-exome sequencing tests. The interpretations are accessed either directly via the Web interface or programmatically via the existing API. An accurate and up-to-date knowledge base of genomic alterations of clinical significance is critical to the success of precision medicine programs. The open-access, programmatically accessible PMKB represents an important attempt at creating such a resource in the field of oncology. The PMKB was designed to help collect and maintain clinical-grade mutation interpretations and facilitate reporting for clinical cancer genomic testing. The PMKB was also designed to enable the creation of clinical cancer genomics automated reporting pipelines via an API. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.

The cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations

PubMed Central

Huang, Linda; Fernandes, Helen; Zia, Hamid; Tavassoli, Peyman; Rennert, Hanna; Pisapia, David; Imielinski, Marcin; Sboner, Andrea; Rubin, Mark A; Kluk, Michael

2017-01-01

Objective: This paper describes the Precision Medicine Knowledge Base (PMKB; https://pmkb.weill.cornell.edu), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations. Materials and Methods: PMKB was built using the Ruby on Rails Web application framework. Leveraging existing standards such as the Human Genome Variation Society variant description format, we implemented a data model that links variants to tumor-specific and tissue-specific interpretations. Key features of PMKB include support for all major variant types, standardized authentication, distinct user roles including high-level approvers, and detailed activity history. A REpresentational State Transfer (REST) application-programming interface (API) was implemented to query the PMKB programmatically. Results: At the time of writing, PMKB contains 457 variant descriptions with 281 clinical-grade interpretations. The EGFR, BRAF, KRAS, and KIT genes are associated with the largest numbers of interpretable variants. PMKB’s interpretations have been used in over 1500 AmpliSeq tests and 750 whole-exome sequencing tests. The interpretations are accessed either directly via the Web interface or programmatically via the existing API. Discussion: An accurate and up-to-date knowledge base of genomic alterations of clinical significance is critical to the success of precision medicine programs. The open-access, programmatically accessible PMKB represents an important attempt at creating such a resource in the field of oncology. Conclusion: The PMKB was designed to help collect and maintain clinical-grade mutation interpretations and facilitate reporting for clinical cancer genomic testing. The PMKB was also designed to enable the creation of clinical cancer genomics automated reporting pipelines via an API. PMID:27789569

ANRIL Genetic Variants in Iranian Breast Cancer Patients

PubMed Central

Khorshidi, Hamid Reza; Taheri, Mohammad; Noroozi, Rezvan; Sarrafzadeh, Shaghayegh; Sayad, Arezou; Ghafouri-Fard, Soudeh

2017-01-01

Objective The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 locus) as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients. Materials and Methods In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms (SNPs) in 122 breast can- cer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). Results The TT genotype at rs1333045 was significantly over-represented among pa- tients (P=0.038) but did not remain significant after multiple-testing correction. In addi- tion, among all observed haplotypes (with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278), four haplotypes were shown to be associated with breast cancer risk. However, after multiple testing corrections, TCGA was the only haplotype which remained significant. Conclusion These results suggest that breast cancer risk is significantly associated with ANRIL variants. Future work analyzing the expression of different associated ANRIL haplotypes would further shed light on the role of ANRIL in this disease. PMID:28580310

SLC30A8 nonsynonymous variant is associated with recovery following exercise and skeletal muscle size and strength.

PubMed

Sprouse, Courtney; Gordish-Dressman, Heather; Orkunoglu-Suer, E Funda; Lipof, Jason S; Moeckel-Cole, Stephanie; Patel, Ronak R; Adham, Kasra; Larkin, Justin S; Hubal, Monica J; Kearns, Amy K; Clarkson, Priscilla M; Thompson, Paul D; Angelopoulos, Theodore J; Gordon, Paul M; Moyna, Niall M; Pescatello, Linda S; Visich, Paul S; Zoeller, Robert F; Hoffman, Eric P; Tosi, Laura L; Devaney, Joseph M

2014-01-01

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training.

Association between MTHFR variant and diabetic neuropathy.

PubMed

Kakavand Hamidi, Armita; Radfar, Mania; Amoli, Mahsa M

2018-02-01

Methylene-tetrahydrofolate reductase (MTHFR) gene variant may play an important role in the pathophysiology of diabetes and its complications due to its influence on plasma homocysteine levels and also its effect on scavenging peroxynitrite radicals. Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to investigate the relationship between diabetic neuropathy and MTHFR gene C677T and 1298A ⁄C polymorphisms. Patients with type 2 diabetes N=248 were enrolled in the study, consisting of patients with neuropathy (N=141) and patients without neuropathy (N=107). MTHFR C677T polymorphism was analyzed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) of genomic DNA for genotyping of samples. 1298A/C polymorphism was evaluated using ARMS-PCR. There was a significant difference in MTHFR polymorphism between the groups with and without neuropathy. Our results suggest that MTHFR 677 variant confer risk for diabetic neuropathy among Iranian patients with type 2 diabetes. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials

PubMed Central

Papandonatos, George D.; Pan, Qing; Pajewski, Nicholas M.; Delahanty, Linda M.; Peter, Inga; Erar, Bahar; Ahmad, Shafqat; Harden, Maegan; Chen, Ling; Fontanillas, Pierre; Wagenknecht, Lynne E.; Kahn, Steven E.; Wing, Rena R.; Jablonski, Kathleen A.; Huggins, Gordon S.; Knowler, William C.; Florez, Jose C.

2015-01-01

Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2–4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism×treatment interaction (P = 4.3 × 10−3). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 10−4). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle. PMID:26253612

CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training.

PubMed

Harmon, Brennan T; Orkunoglu-Suer, E Funda; Adham, Kasra; Larkin, Justin S; Gordish-Dressman, Heather; Clarkson, Priscilla M; Thompson, Paul D; Angelopoulos, Theodore J; Gordon, Paul M; Moyna, Niall M; Pescatello, Linda S; Visich, Paul S; Zoeller, Robert F; Hubal, Monica J; Tosi, Laura L; Hoffman, Eric P; Devaney, Joseph M

2010-12-01

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.

Principles and Recommendations for Standardizing the Use of the Next-Generation Sequencing Variant File in Clinical Settings.

PubMed

Lubin, Ira M; Aziz, Nazneen; Babb, Lawrence J; Ballinger, Dennis; Bisht, Himani; Church, Deanna M; Cordes, Shaun; Eilbeck, Karen; Hyland, Fiona; Kalman, Lisa; Landrum, Melissa; Lockhart, Edward R; Maglott, Donna; Marth, Gabor; Pfeifer, John D; Rehm, Heidi L; Roy, Somak; Tezak, Zivana; Truty, Rebecca; Ullman-Cullere, Mollie; Voelkerding, Karl V; Worthey, Elizabeth A; Zaranek, Alexander W; Zook, Justin M

2017-05-01

A national workgroup convened by the Centers for Disease Control and Prevention identified principles and made recommendations for standardizing the description of sequence data contained within the variant file generated during the course of clinical next-generation sequence analysis for diagnosing human heritable conditions. The specifications for variant files were initially developed to be flexible with regard to content representation to support a variety of research applications. This flexibility permits variation with regard to how sequence findings are described and this depends, in part, on the conventions used. For clinical laboratory testing, this poses a problem because these differences can compromise the capability to compare sequence findings among laboratories to confirm results and to query databases to identify clinically relevant variants. To provide for a more consistent representation of sequence findings described within variant files, the workgroup made several recommendations that considered alignment to a common reference sequence, variant caller settings, use of genomic coordinates, and gene and variant naming conventions. These recommendations were considered with regard to the existing variant file specifications presently used in the clinical setting. Adoption of these recommendations is anticipated to reduce the potential for ambiguity in describing sequence findings and facilitate the sharing of genomic data among clinical laboratories and other entities. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

CRISPR-directed mitotic recombination enables genetic mapping without crosses.

PubMed

Sadhu, Meru J; Bloom, Joshua S; Day, Laura; Kruglyak, Leonid

2016-05-27

Linkage and association studies have mapped thousands of genomic regions that contribute to phenotypic variation, but narrowing these regions to the underlying causal genes and variants has proven much more challenging. Resolution of genetic mapping is limited by the recombination rate. We developed a method that uses CRISPR (clustered, regularly interspaced, short palindromic repeats) to build mapping panels with targeted recombination events. We tested the method by generating a panel with recombination events spaced along a yeast chromosome arm, mapping trait variation, and then targeting a high density of recombination events to the region of interest. Using this approach, we fine-mapped manganese sensitivity to a single polymorphism in the transporter Pmr1. Targeting recombination events to regions of interest allows us to rapidly and systematically identify causal variants underlying trait differences. Copyright © 2016, American Association for the Advancement of Science.

AmeriFlux US-ARc ARM Southern Great Plains control site- Lamont

DOE Data Explorer

Torn, Margaret [Lawrence Berkeley National Laboratory

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-ARc ARM Southern Great Plains control site- Lamont. Site Description - The ARM SGP Control site is located in the native tallgrass prairies of the USDA Grazinglands Research Laboratory near El Reno, OK. One of two adjacent 35 ha plots with identical towers, measurements at the US-ARc unburned plot are used as the experimental control. The second plot, US-Arb, was burned on 2005/03/08. Measurement comparisons between the control and burn plot are used to address questions regarding the effects of burning activities on carbon fluxes. The region evaded burning activities for at least 15 years. Current disturbances consist of only light grazing activities.

Atmospheric Radiation Measurement (ARM) Climate Research Facility Management Plan

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

Mather, James

2016-04-01

Mission and Vision Statements for the U.S. Department of Energy (DOE)’s Atmospheric Radiation Measurement (ARM) Climate Research Facility Mission The ARM Climate Research Facility, a DOE scientific user facility, provides the climate research community with strategically located in situ and remote-sensing observatories designed to improve the understanding and representation, in climate and earth system models, of clouds and aerosols as well as their interactions and coupling with the Earth’s surface. Vision To provide a detailed and accurate description of the Earth atmosphere in diverse climate regimes to resolve the uncertainties in climate and Earth system models toward the development ofmore » sustainable solutions for the nation's energy and environmental challenges.« less

3-D scapular kinematics during arm elevation: effect of motion velocity.

PubMed

Fayad, F; Hoffmann, G; Hanneton, S; Yazbeck, C; Lefevre-Colau, M M; Poiraudeau, S; Revel, M; Roby-Brami, A

2006-11-01

No three-dimensional (3-D) data exist on the influence of motion velocity on scapular kinematics. The effect of arm elevation velocity has been studied only in a two-dimensional setting. Thirty healthy subjects performed dominant (right) arm elevation in two planes, sagittal and frontal, and at slow and fast self-selected arm speed. Scapular orientation and humeral elevation were measured at 30 Hz recording frequency with use of a 6-degree-of-freedom electromagnetic system (Polhemus Fastraka). Motion was computed according to the International Society of Biomechanics standards. Scapular orientation was also determined with the arm held in different static positions. We obtained a full 3-D kinematic description of scapula achieving a reliable, complex 3-D motion during humeral elevation and lowering. The maximal sagittal arm elevation showed a characteristic "M"-shape pattern of protraction/retraction curve. Scapular rotations did not differ significantly between slow and fast movements. Moreover, protraction/retraction and tilt angular values did not differ significantly between static and dynamic tasks. However, scapular lateral rotation values differed between static and dynamic measurements during sagittal and frontal arm elevation. Lateral scapular rotation appears to be less in static than in dynamic measurement, particularly in the sagittal plane. Interpolation of statically recorded positions of the bones cannot reflect the kinematics of the scapula.

HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server.

PubMed

Hardison, Ross C; Chui, David H K; Giardine, Belinda; Riemer, Cathy; Patrinos, George P; Anagnou, Nicholas; Miller, Webb; Wajcman, Henri

2002-03-01

We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying "all beta-globin variants associated with instability and found in Scottish populations." This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci. Copyright 2002 Wiley-Liss, Inc.

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.

PubMed

Black, Holly A; Leighton, Danielle J; Cleary, Elaine M; Rose, Elaine; Stephenson, Laura; Colville, Shuna; Ross, David; Warner, Jon; Porteous, Mary; Gorrie, George H; Swingler, Robert; Goldstein, David; Harms, Matthew B; Connick, Peter; Pal, Suvankar; Aitman, Timothy J; Chandran, Siddharthan

2017-03-01

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Relationship of Throwing Arm Mechanics and Elbow Varus Torque: Within-Subject Variation for Professional Baseball Pitchers Across 82,000 Throws.

PubMed

Camp, Christopher L; Tubbs, Travis G; Fleisig, Glenn S; Dines, Joshua S; Dines, David M; Altchek, David W; Dowling, Brittany

2017-11-01

Likely due to the high level of strain exerted across the elbow during the throwing motion, elbow injuries are on the rise in baseball. To identify at-risk athletes and guide postinjury return-to-throw programs, a better understanding of the variables that influence elbow varus torque is desired. To describe the within-subject relationship between elbow varus torque and arm slot and arm rotation in professional baseball pitchers. Descriptive laboratory study. A total of 81 professional pitchers performed 82,000 throws while wearing a motusBASEBALL sensor and sleeve. These throws represented a combination of throw types, such as warm-up/catch, structured long-toss, bullpen throwing from a mound, and live game activity. Variables recorded for each throw included arm slot (angle of the forearm relative to the ground at ball release), arm speed (maximal rotational velocity of the forearm), arm rotation (maximal external rotation of the throwing arm relative to the ground), and elbow varus torque. Linear mixed-effects models and likelihood ratio tests were used to estimate the relationship between elbow varus torque and arm slot, arm speed, and arm rotation within individual pitchers. All 3 metrics-arm slot (χ 2 = 428, P < .001), arm speed (χ 2 = 57,683, P < .001), and arm rotation (χ 2 = 1392, P < .001)-were found to have a significant relationship with elbow varus torque. Within individual athletes, a 1-N.m increase in elbow varus torque was associated with a 13° decrease in arm slot, a 116 deg/s increase in arm speed, and an 8° increase in arm rotation. Elbow varus torque increased significantly as pitchers increased their arm rotation during the arm cocking phase, increased the rotational velocity of their arm during the arm acceleration phase of throwing, and decreased arm slot at ball release. Thus, shoulder flexibility, arm speed, and elbow varus torque (and likely injury risk) are interrelated and should be considered collectively when treating pitchers. It is well established that elbow varus torque is related to ulnar collateral ligament injuries in overhead throwers. This study describes the relationship of arm slot, arm speed, and arm rotation to elbow varus torque in an attempt to identify modifiable risk factors for injury.

DNA variant databases improve test accuracy and phenotype prediction in Alport syndrome.

PubMed

Savige, Judy; Ars, Elisabet; Cotton, Richard G H; Crockett, David; Dagher, Hayat; Deltas, Constantinos; Ding, Jie; Flinter, Frances; Pont-Kingdon, Genevieve; Smaoui, Nizar; Torra, Roser; Storey, Helen

2014-06-01

X-linked Alport syndrome is a form of progressive renal failure caused by pathogenic variants in the COL4A5 gene. More than 700 variants have been described and a further 400 are estimated to be known to individual laboratories but are unpublished. The major genetic testing laboratories for X-linked Alport syndrome worldwide have established a Web-based database for published and unpublished COL4A5 variants ( https://grenada.lumc.nl/LOVD2/COL4A/home.php?select_db=COL4A5 ). This conforms with the recommendations of the Human Variome Project: it uses the Leiden Open Variation Database (LOVD) format, describes variants according to the human reference sequence with standardized nomenclature, indicates likely pathogenicity and associated clinical features, and credits the submitting laboratory. The database includes non-pathogenic and recurrent variants, and is linked to another COL4A5 mutation database and relevant bioinformatics sites. Access is free. Increasing the number of COL4A5 variants in the public domain helps patients, diagnostic laboratories, clinicians, and researchers. The database improves the accuracy and efficiency of genetic testing because its variants are already categorized for pathogenicity. The description of further COL4A5 variants and clinical associations will improve our ability to predict phenotype and our understanding of collagen IV biochemistry. The database for X-linked Alport syndrome represents a model for databases in other inherited renal diseases.

A novel Tetra-primer ARMS-PCR based assay for genotyping SNP rs12303764(G/T) of human Unc-51 like kinase 1 gene.

PubMed

Randhawa, Rohit; Duseja, Ajay; Changotra, Harish

2017-02-01

Various case-control studies have shown association of single nucleotide polymorphism rs12303764(G/T) in ULK1 with crohn's disease. The techniques used in these studies were time consuming, complicated and require sophisticated/expensive instruments. Therefore, in order to overcome these problems, we have developed a new, rapid and cost effective Tetra-primer ARMS-PCR assay to genotype single nucleotide polymorphism rs12303764(G/T) of ULK1 gene. We manually designed allele specific primers. DNA fragment amplified using outer primers was sequenced to obtain samples with known genotypes (GG, GT and TT) for further use in the development of T-ARMS-PCR assay. Amplification conditions were optimized for parameters; annealing temperature, Taq DNA polymerase and primers. The developed T-ARMS-PCR assay was applied to genotype one hundred samples from healthy individuals. Genotyping results of 10 DNA samples from healthy individuals for rs12303764(G/T) by T-ARMS-PCR assay and sequencing were concordant. The newly developed assay was further applied to genotype samples from 100 healthy individuals of North Indian origin. Genotype frequencies were 9, 34 and 57 % for GG, GT and TT, respectively. Allele frequencies were 0.26 and 0.74 for G and T, respectively. The allele frequencies were in Hardy-Weinberg's equilibrium (p = 0.2443). T-ARMS-PCR assay developed in our laboratory for genotyping rs12303764 (G/T) of ULK1 gene is time saving and cost-effective as compared to the available methods. Furthermore, this is the first study reporting allelic and genotype frequencies of ULK1 rs12303764 (G/T) variants in North Indian population.

Arm pain in youth baseball players: a survey of healthy players.

PubMed

Makhni, Eric C; Morrow, Zachary S; Luchetti, Timothy J; Mishra-Kalyani, Pallavi S; Gualtieri, Anthony P; Lee, Randall W; Ahmad, Christopher S

2015-01-01

Overuse injury in youth baseball players is increasing in prevalence, and these injuries have been correlated to pitching mechanics and pitch counts/types. Prior studies regarding arm pain in these athletes have focused simply on presence or absence of pain during the season rather than on detailed factors related to arm pain with respect to frequency, severity, and associated performance and psychosocial effect. The goal of this study was to investigate frequency, quality, and effect of arm pain in healthy youth baseball players. The hypothesis was that arm pain will affect a majority of healthy baseball players and will be associated with adverse psychosocial effects. Descriptive epidemiological study. A novel survey focusing on arm pain in youth baseball players was developed for the purpose of this study. Survey questions were formulated by a consortium of trainers, clinicians, and coaches. Surveys were administered to healthy youth baseball players throughout the states of New Jersey and New York. A total of 203 healthy players completed the survey; 23% of players (n=47) reported a prior overuse injury. Only 26% and 20% of players reported that their arm never hurt when throwing or the day after throwing, respectively; 30% of players reported that arm pain at least sometimes caused them to have less fun playing; and 46% of players reported at least once being encouraged to keep playing despite having arm pain. Pitchers were more likely to report arm pain while throwing and the day after throwing and to indicate that arm pain held them back from being a better player (all P<.05). Those with prior overuse injury were more likely to have arm pain while throwing, to have arm fatigue during a game or practice, and to be encouraged to keep playing despite having pain (all P<.05). A majority of healthy (actively competing) youth baseball players report at least some baseline arm pain and fatigue, and many players suffer adverse psychosocial effects from this pain. © 2014 The Author(s).

The chemical component dictionary: complete descriptions of constituent molecules in experimentally determined 3D macromolecules in the Protein Data Bank.

PubMed

Westbrook, John D; Shao, Chenghua; Feng, Zukang; Zhuravleva, Marina; Velankar, Sameer; Young, Jasmine

2015-04-15

The Chemical Component Dictionary (CCD) is a chemical reference data resource that describes all residue and small molecule components found in Protein Data Bank (PDB) entries. The CCD contains detailed chemical descriptions for standard and modified amino acids/nucleotides, small molecule ligands and solvent molecules. Each chemical definition includes descriptions of chemical properties such as stereochemical assignments, chemical descriptors, systematic chemical names and idealized coordinates. The content, preparation, validation and distribution of this CCD chemical reference dataset are described. The CCD is updated regularly in conjunction with the scheduled weekly release of new PDB structure data. The CCD and amino acid variant reference datasets are hosted in the public PDB ftp repository at ftp://ftp.wwpdb.org/pub/pdb/data/monomers/components.cif.gz, ftp://ftp.wwpdb.org/pub/pdb/data/monomers/aa-variants-v1.cif.gz, and its mirror sites, and can be accessed from http://wwpdb.org. jwest@rcsb.rutgers.edu. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tests with an integrated helmet system for the TIGER helicopter

NASA Astrophysics Data System (ADS)

Boehm, Hans-Dieter V.; Evers, Carl; Stenner, K.-H.

1998-08-01

The TIGER helicopter is under development by the MODs of France and Germany for their armies. The initial German requirement was for anti-tank missions only. This task has been extended to support missions which resulted in an upgrade to the German 'UH-TIGER' variant. German MOD is planning to procure 212 UH-TIGER helicopters armed with TRIGAT-, HOT anti-tank missiles, STINGER air-to-air missiles, 68 mm rockets and a gun pod with a 12.7 mm gun.

Solitary morphea profunda following trauma sustained in an automobile accident.

PubMed

Touloei, Khasha; Wiener, Adam; Glick, Bradley P

2015-01-01

Solitary morphea profunda (SMP) is a variant of localized scleroderma (LS). We report the case of a 50-year-old white woman with a history of trauma sustained in an automobile accident who presented with SMP on the right upper arm. We also provide a review of the classification, epidemiology, etiology, diagnostic studies, pathogenesis, physical findings, histopathology, treatment, and prognosis of SMP, along with other important details pertaining to the disease. We also provide a brief overview of LS and morphea profunda (MP).

CLOSE AIR SUPPORT (CAS) FOR COUNTERINSURGENCY (COIN) AND THE UPWARD TRAJECTORY OF UNMANNED AIRCRAFT SYSTEMS (UAS): NAVIGATING THE UNDISCOVERED DOMAIN

DTIC Science & Technology

2015-10-01

collateral damage. Further mitigating collateral damage, “…the SDB Focused Lethality Munition (FLM) variant incorporates a carbon fiber composite ...Effectiveness Modern attack helicopters execute the CAS mission with various standoff weapons. RW assets are slow moving and susceptible to MANPADS and...small arms fire, and attack helicopters used for CAS are primarily in a medium or low threat environment where enemy air defenses are weak or not

Clinical implications of SCN1A missense and truncation variants in a large Japanese cohort with Dravet syndrome.

PubMed

Ishii, Atsushi; Watkins, Joseph C; Chen, Debbie; Hirose, Shinichi; Hammer, Michael F

2017-02-01

Two major classes of SCN1A variants are associated with Dravet syndrome (DS): those that result in haploinsufficiency (truncating) and those that result in an amino acid substitution (missense). The aim of this retrospective study was to describe the first large cohort of Japanese patients with SCN1A mutation-positive DS (n = 285), and investigate the relationship between variant (type and position) and clinical expression and response to treatment. We sequenced all exons and intron-exon boundaries of SCN1A in our cohort, investigated differences in the distribution of truncating and missense variants, tested for associations between variant type and phenotype, and compared these patterns with those of cohorts with milder epilepsy and healthy individuals. Unlike truncation variants, missense variants are found at higher density in the S4 voltage sensor and pore loops and at lower density in the domain I-II and II-III linkers and the first three segments of domain II. Relative to healthy individuals, there is an increased frequency of truncating (but not missense) variants in the noncoding C-terminus. The rate of cognitive decline is more rapid for patients with truncation variants regardless of age at seizure onset, whereas age at onset is a predictor of the rate of cognitive decline for patients with missense variants. We found significant differences in the distribution of truncating and missense variants across the SCN1A sequence among healthy individuals, patients with DS, and those with milder forms of SCN1A-variant positive epilepsy. Testing for associations with phenotype revealed that variant type can be predictive of rate of cognitive decline. Analysis of descriptive medication data suggests that in addition to conventional drug therapy in DS, bromide, clonazepam and topiramate may reduce seizure frequency. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Representation and visualization of variability in a 3D anatomical atlas using the kidney as an example

NASA Astrophysics Data System (ADS)

Hacker, Silke; Handels, Heinz

2006-03-01

Computer-based 3D atlases allow an interactive exploration of the human body. However, in most cases such 3D atlases are derived from one single individual, and therefore do not regard the variability of anatomical structures concerning their shape and size. Since the geometric variability across humans plays an important role in many medical applications, our goal is to develop a framework of an anatomical atlas for representation and visualization of the variability of selected anatomical structures. The basis of the project presented is the VOXEL-MAN atlas of inner organs that was created from the Visible Human data set. For modeling anatomical shapes and their variability we utilize "m-reps" which allow a compact representation of anatomical objects on the basis of their skeletons. As an example we used a statistical model of the kidney that is based on 48 different variants. With the integration of a shape description into the VOXEL-MAN atlas it is now possible to query and visualize different shape variations of an organ, e.g. by specifying a person's age or gender. In addition to the representation of individual shape variants, the average shape of a population can be displayed. Besides a surface representation, a volume-based representation of the kidney's shape variants is also possible. It results from the deformation of the reference kidney of the volume-based model using the m-rep shape description. In this way a realistic visualization of the shape variants becomes possible, as well as the visualization of the organ's internal structures.

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature.

PubMed

Alharthi, Abdulla A; El-Hallous, Ehab I; Talaat, Iman M; Alghamdi, Hamed A; Almalki, Matar I; Gaber, Ahmed

2017-10-01

Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene ( SHOX ) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX . In Saudi Arabia ISS patients, rather than SHOX , it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

How different terminology for ductal carcinoma in situ impacts women's concern and treatment preferences: a randomised comparison within a national community survey

PubMed Central

McCaffery, Kirsten; Nickel, Brooke; Moynihan, Ray; Hersch, Jolyn; Teixeira-Pinto, Armando; Irwig, Les; Barratt, Alexandra

2015-01-01

Objective There have been calls to remove ‘carcinoma’ from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as ‘abnormal cells’ versus ‘pre-invasive breast cancer cells’ on women's concern and treatment preferences. Setting and participants Community sample of Australian women (n=269) who spoke English as their main language at home. Design Randomised comparison within a community survey. Women considered a hypothetical scenario involving a diagnosis of DCIS described as either ‘abnormal cells’ (arm A) or ‘pre-invasive breast cancer cells’ (arm B). Within each arm, the initial description was followed by the alternative term and outcomes reassessed. Results Women in both arms indicated high concern, but still indicated strong initial preferences for watchful waiting (64%). There were no differences in initial concern or preferences by trial arm. However, more women in arm A (‘abnormal cells’ first term) indicated they would feel more concerned if given the alternative term (‘pre-invasive breast cancer cells’) compared to women in arm B who received the terms in the opposite order (67% arm A vs 52% arm B would feel more concerned, p=0.001). More women in arm A also changed their preference towards treatment when the terminology was switched from ‘abnormal cells’ to ‘pre-invasive breast cancer cells’ compared to arm B. In arm A, 18% of women changed their preference to treatment while only 6% changed to watchful waiting (p=0.008). In contrast, there were no significant changes in treatment preference in arm B when the terminology was switched (9% vs 8% changed their stated preference). Conclusions In a hypothetical scenario, interest in watchful waiting for DCIS was high, and changing terminology impacted women's concern and treatment preferences. Removal of the cancer term from DCIS may assist in efforts towards reducing overtreatment. PMID:26525720

Genetic Predictors of Cardiovascular Mortality During Intensive Glycemic Control in Type 2 Diabetes: Findings From the ACCORD Clinical Trial.

PubMed

Shah, Hetal S; Gao, He; Morieri, Mario Luca; Skupien, Jan; Marvel, Skylar; Paré, Guillaume; Mannino, Gaia C; Buranasupkajorn, Patinut; Mendonca, Christine; Hastings, Timothy; Marcovina, Santica M; Sigal, Ronald J; Gerstein, Hertzel C; Wagner, Michael J; Motsinger-Reif, Alison A; Buse, John B; Kraft, Peter; Mychaleckyj, Josyf C; Doria, Alessandro

2016-11-01

To identify genetic determinants of increased cardiovascular mortality among subjects with type 2 diabetes who underwent intensive glycemic therapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. A total of 6.8 million common variants were analyzed for genome-wide association with cardiovascular mortality among 2,667 self-reported white subjects in the ACCORD intensive treatment arm. Significant loci were examined in the entire ACCORD white genetic dataset (n = 5,360) for their modulation of cardiovascular responses to glycemic treatment assignment and in a Joslin Clinic cohort (n = 422) for their interaction with long-term glycemic control on cardiovascular mortality. Two loci, at 10q26 and 5q13, attained genome-wide significance as determinants of cardiovascular mortality in the ACCORD intensive arm (P = 9.8 × 10 -9 and P = 2 × 10 -8 , respectively). A genetic risk score (GRS) defined by the two variants was a significant modulator of cardiovascular mortality response to treatment assignment in the entire ACCORD white genetic dataset. Participants with GRS = 0 experienced a fourfold reduction in cardiovascular mortality in response to intensive treatment (hazard ratio [HR] 0.24 [95% CI 0.07-0.86]), those with GRS = 1 experienced no difference (HR 0.92 [95% CI 0.54-1.56]), and those with GRS ≥2 experienced a threefold increase (HR 3.08 [95% CI 1.82-5.21]). The modulatory effect of the GRS on the association between glycemic control and cardiovascular mortality was confirmed in the Joslin cohort (P = 0.029). Two genetic variants predict the cardiovascular effects of intensive glycemic control in ACCORD. Further studies are warranted to determine whether these findings can be translated into new strategies to prevent cardiovascular complications of diabetes. © 2016 by the American Diabetes Association.

Genetic Predictors of Cardiovascular Mortality During Intensive Glycemic Control in Type 2 Diabetes: Findings From the ACCORD Clinical Trial

PubMed Central

Shah, Hetal S.; Gao, He; Morieri, Mario Luca; Skupien, Jan; Marvel, Skylar; Paré, Guillaume; Mannino, Gaia C.; Buranasupkajorn, Patinut; Mendonca, Christine; Hastings, Timothy; Marcovina, Santica M.; Sigal, Ronald J.; Gerstein, Hertzel C.; Wagner, Michael J.; Motsinger-Reif, Alison A.; Buse, John B.; Kraft, Peter; Mychaleckyj, Josyf C.

2016-01-01

OBJECTIVE To identify genetic determinants of increased cardiovascular mortality among subjects with type 2 diabetes who underwent intensive glycemic therapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS A total of 6.8 million common variants were analyzed for genome-wide association with cardiovascular mortality among 2,667 self-reported white subjects in the ACCORD intensive treatment arm. Significant loci were examined in the entire ACCORD white genetic dataset (n = 5,360) for their modulation of cardiovascular responses to glycemic treatment assignment and in a Joslin Clinic cohort (n = 422) for their interaction with long-term glycemic control on cardiovascular mortality. RESULTS Two loci, at 10q26 and 5q13, attained genome-wide significance as determinants of cardiovascular mortality in the ACCORD intensive arm (P = 9.8 × 10−9 and P = 2 × 10−8, respectively). A genetic risk score (GRS) defined by the two variants was a significant modulator of cardiovascular mortality response to treatment assignment in the entire ACCORD white genetic dataset. Participants with GRS = 0 experienced a fourfold reduction in cardiovascular mortality in response to intensive treatment (hazard ratio [HR] 0.24 [95% CI 0.07–0.86]), those with GRS = 1 experienced no difference (HR 0.92 [95% CI 0.54–1.56]), and those with GRS ≥2 experienced a threefold increase (HR 3.08 [95% CI 1.82–5.21]). The modulatory effect of the GRS on the association between glycemic control and cardiovascular mortality was confirmed in the Joslin cohort (P = 0.029). CONCLUSIONS Two genetic variants predict the cardiovascular effects of intensive glycemic control in ACCORD. Further studies are warranted to determine whether these findings can be translated into new strategies to prevent cardiovascular complications of diabetes. PMID:27527847

Explaining Away the Body: Experiences of Supernaturally Caused Touch and Touch on Non-Hand Objects within the Rubber Hand Illusion

PubMed Central

2010-01-01

Background In rubber hand illusions and full body illusions, touch sensations are projected to non-body objects such as rubber hands, dolls or virtual bodies. The robustness, limits and further perceptual consequences of such illusions are not yet fully explored or understood. A number of experiments are reported that test the limits of a variant of the rubber hand illusion. Methodology/Principal Findings A variant of the rubber hand illusion is explored, in which the real and foreign hands are aligned in personal space. The presence of the illusion is ascertained with participants' scores and temperature changes of the real arm. This generates a basic illusion of touch projected to a foreign arm. Participants are presented with further, unusual visuotactile stimuli subsequent to onset of the basic illusion. Such further visuotactile stimulation is found to generate very unusual experiences of supernatural touch and touch on a non-hand object. The finding of touch on a non-hand object conflicts with prior findings, and to resolve this conflict a further hypothesis is successfully tested: that without prior onset of the basic illusion this unusual experience does not occur. Conclusions/Significance A rubber hand illusion is found that can arise when the real and the foreign arm are aligned in personal space. This illusion persists through periods of no tactile stimulation and is strong enough to allow very unusual experiences of touch felt on a cardboard box and experiences of touch produced at a distance, as if by supernatural causation. These findings suggest that one's visual body image is explained away during experience of the illusion and they may be of further importance to understanding the role of experience in delusion formation. The findings of touch on non-hand objects may help reconcile conflicting results in this area of research. In addition, new evidence is provided that relates to the recently discovered psychologically induced temperature changes that occur during the illusion. PMID:20195378

Type of iconicity matters in the vocabulary development of signing children.

PubMed

Ortega, Gerardo; Sümer, Beyza; Özyürek, Aslı

2017-01-01

Recent research on signed as well as spoken language shows that the iconic features of the target language might play a role in language development. Here, we ask further whether different types of iconic depictions modulate children's preferences for certain types of sign-referent links during vocabulary development in sign language. Results from a picture description task indicate that lexical signs with 2 possible variants are used in different proportions by deaf signers from different age groups. While preschool and school-age children favored variants representing actions associated with their referent (e.g., a writing hand for the sign PEN), adults preferred variants representing the perceptual features of those objects (e.g., upward index finger representing a thin, elongated object for the sign PEN). Deaf parents interacting with their children, however, used action- and perceptual-based variants in equal proportion and favored action variants more than adults signing to other adults. We propose that when children are confronted with 2 variants for the same concept, they initially prefer action-based variants because they give them the opportunity to link a linguistic label to familiar schemas linked to their action/motor experiences. Our results echo findings showing a bias for action-based depictions in the development of iconic co-speech gestures suggesting a modality bias for such representations during development. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study.

PubMed

Newman, William G; Payne, Katherine; Tricker, Karen; Roberts, Stephen A; Fargher, Emily; Pushpakom, Sudeep; Alder, Jane E; Sidgwick, Gary P; Payne, Debbie; Elliott, Rachel A; Heise, Marco; Elles, Robert; Ramsden, Simon C; Andrews, Julie; Houston, J Brian; Qasim, Faeiza; Shaffer, Jon; Griffiths, Christopher E M; Ray, David W; Bruce, Ian; Ollier, William E R

2011-06-01

To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs). A total of 333 participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping. There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.59) between the two study arms. ADRs were more common in older patients (p = 0.01). There was no increase in stopping azathioprine due to ADRs in TPMT heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia. Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas TPMT heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.

Role of genetics in infection-associated arthritis.

PubMed

Benham, Helen; Robinson, Philip C; Baillet, Athan C; Rehaume, Linda M; Thomas, Ranjeny

2015-04-01

Genetic discoveries in arthritis and their associated biological pathways spanning the innate and adaptive immune system demonstrate the strong association between susceptibility to arthritis and control of exogenous organisms. The canonical theory of the aetiology of immune-mediated arthritis and other immune-mediated diseases is that the introduction of exogenous antigenic stimuli to a genetically susceptible host sets up the environment for an abnormal immune response manifesting as disease. A disruption in host-microbe homeostasis driven by disease-associated genetic variants could ultimately provide the source of exogenous antigen triggering disease development. We discuss genetic variants impacting the innate and adaptive arms of the immune system and their relationship to microbial control and arthritic disease. We go on to consider the evidence for a relationship between HLA-B27, infection and arthritis, and then emerging evidence for an interaction between microbiota and rheumatoid arthritis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Allele related mutation specific-polymerase chain reaction for rapid diagnosis of Hb New York (beta 113 (G15) Val-->Glu, beta(CD113 GTG-->GAG)).

PubMed

Viprakasit, Vip; Tachavanich, Kalaya; Suwantol, Lerlugsn; Pung-Amritt, Parichat; Chinchang, Worawut; Tanphaichitr, Voravarn S

2002-08-01

Hemoglobin New York (beta 113 (G15) Val-->Glu), a beta-globin variant, was first reported in a Chinese family living in New York. Subsequently, this abnormal hemoglobin was reported in many Chinese descendants from several groups and it was also known as Hb Kaohsiung. The subtle change in alpha1beta1 contact region apart from the heme group connecting area by Val-->Glu substitution has minor changes in both the electrophoretic mobility and stability making this hemoglobin variant difficult to distinguish from Hb A using routine hemoglobin analysis. The authors described a case of heterozygosity of Hb New York diagnosed by a molecular technique and revealed a mutation in beta(CD113 GTG-->GAG). A novel Allele Related Mutation Specific-Polymerase Chain Reaction (ARMS-PCR) for rapid diagnosis of this mutation has been proposed.

Three-sphere low-Reynolds-number swimmer with a passive elastic arm.

PubMed

Montino, Alessandro; DeSimone, Antonio

2015-05-01

One of the simplest model swimmers at low Reynolds number is the three-sphere swimmer by Najafi and Golestanian. It consists of three spheres connected by two rods which change their lengths periodically in non-reciprocal fashion. Here we investigate a variant of this model in which one rod is periodically actuated while the other is replaced by an elastic spring. We show that the competition between the elastic restoring force and the hydrodynamic drag produces a delay in the response of the passive elastic arm with respect to the active one. This leads to non-reciprocal shape changes and self-propulsion. After formulating the equations of motion, we study their solutions qualitatively and numerically. The leading-order term of the solution is computed analytically. We then address questions of optimization with respect to both actuation frequency and swimmer's geometry. Our results can provide valuable conceptual guidance in the engineering of robotic microswimmers.

Clinical comparison of automatic, noninvasive measurements of blood pressure in the forearm and upper arm.

PubMed

Schell, Kathleen; Bradley, Elisabeth; Bucher, Linda; Seckel, Maureen; Lyons, Denise; Wakai, Sandra; Bartell, Deborah; Carson, Elizabeth; Chichester, Melanie; Foraker, Teresa; Simpson, Kathleen

2005-05-01

When the upper arm (area from shoulder to elbow) is inaccessible and/or a standard-sized blood pressure cuff does not fit, some healthcare workers use the forearm to measure blood pressure. To compare automatic noninvasive measurements of blood pressure in the upper arm and forearm. A descriptive, correlational comparison study was conducted in the emergency department of a 1071-bed teaching hospital. Subjects were 204 English-speaking patients 6 to 91 years old in medically stable condition who had entered the department on foot or by wheelchair and who had no exclusions to using their left upper extremity. A Welch Allyn Vital Signs 420 series monitor was used to measure blood pressure in the left upper arm and forearm with the subject seated and the upper arm or forearm at heart level. Pearson r correlation coefficients between measurements in the upper arm and forearm were 0.88 for systolic blood pressure and 0.76 for diastolic blood pressure (P < .001 for both). Mean systolic pressures, but not mean diastolic pressures, in the upper arm and forearm differed significantly (t = 2.07, P = .04). A Bland-Altman analysis indicated that the distances between the mean values and the limits of agreement for the 2 sites ranged from 15 mm Hg (mean arterial pressure) to 18.4 mm Hg (systolic pressure). Despite strict attention to correct cuff size and placement of the upper arm or forearm at heart level, measurements of blood pressure obtained noninvasively in the arm and forearm of seated patients in stable condition are not interchangeable.

A laboratory breadboard system for dual-arm teleoperation

NASA Technical Reports Server (NTRS)

Bejczy, A. K.; Szakaly, Z.; Kim, W. S.

1990-01-01

The computing architecture of a novel dual-arm teleoperation system is described. The novelty of this system is that: (1) the master arm is not a replica of the slave arm; it is unspecific to any manipulator and can be used for the control of various robot arms with software modifications; and (2) the force feedback to the general purpose master arm is derived from force-torque sensor data originating from the slave hand. The computing architecture of this breadboard system is a fully synchronized pipeline with unique methods for data handling, communication and mathematical transformations. The computing system is modular, thus inherently extendable. The local control loops at both sites operate at 100 Hz rate, and the end-to-end bilateral (force-reflecting) control loop operates at 200 Hz rate, each loop without interpolation. This provides high-fidelity control. This end-to-end system elevates teleoperation to a new level of capabilities via the use of sensors, microprocessors, novel electronics, and real-time graphics displays. A description is given of a graphic simulation system connected to the dual-arm teleoperation breadboard system. High-fidelity graphic simulation of a telerobot (called Phantom Robot) is used for preview and predictive displays for planning and for real-time control under several seconds communication time delay conditions. High fidelity graphic simulation is obtained by using appropriate calibration techniques.

Genome-wide scans of genetic variants for psychophysiological endophenotypes: a methodological overview.

PubMed

Iacono, William G; Malone, Stephen M; Vaidyanathan, Uma; Vrieze, Scott I

2014-12-01

This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind the steps taken in the molecular genetic study design. The statistical approach included (a) biometric analysis of twin and family data, (b) heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c) genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d) follow-up analyses of candidate SNPs and genes hypothesized to have an association with each endophenotype, (e) rare variant analysis of nonsynonymous SNPs in the exome, and (f) whole genome sequencing association analysis using 27 million genetic variants. These methods were used in the accompanying empirical articles comprising this special issue, Genome-Wide Scans of Genetic Variants for Psychophysiological Endophenotypes. Copyright © 2014 Society for Psychophysiological Research.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

PubMed Central

Homburger, Julian R.; Green, Eric M.; Caleshu, Colleen; Sunitha, Margaret S.; Taylor, Rebecca E.; Ruppel, Kathleen M.; Metpally, Raghu Prasad Rao; Colan, Steven D.; Michels, Michelle; Day, Sharlene M.; Olivotto, Iacopo; Bustamante, Carlos D.; Dewey, Frederick E.; Ho, Carolyn Y.; Spudich, James A.; Ashley, Euan A.

2016-01-01

Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

78 FR 23231 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

...) Description and Quantity or Quantities of Articles or Services under Consideration for Purchase: 60 Active... equipment items, GEM-V GPS airborne receiver module, and communication security, software development... documents, U.S. Government and contract engineering and logistical personnel services, and other related...

AmeriFlux US-AR1 ARM USDA UNL OSU Woodward Switchgrass 1

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

Billesbach, Dave; Bradford, James

This is the AmeriFlux version of the carbon flux data for the site US-AR1 ARM USDA UNL OSU Woodward Switchgrass 1. Site Description - The ARM USDA UNL OSU Woodward Switchgrass 1 tower is located on public land owned by the USDA-ARS Southern Plains Range Research Station in Woodward, Oklahoma. The site is on a former native prairie that is in the process of changing to switchgrass. A second companion site (ARM USDA UNL OSU Woodward Switchgrass 2) is on a former wheat field. In Spring 2009, the former native prairie site was burned, cattle were put on the pasturemore » to graze down emergent grass, and broadleaf herbicide was sprayed. In Summer 2009, the cattle were removed from the pasture, and the site was sprayed with herbicide to kill all grass. In Spring 2010, prior to the planting of switchgrass, final herbicide was sprayed to kill cheat grass and to control broadleaf plants.« less

Defining and comparing learning actions in two simulation modalities: students training on a latex arm and each other's arms.

PubMed

Ravik, Monika; Havnes, Anton; Bjørk, Ida Torunn

2017-12-01

To explore, describe and compare learning actions that nursing students used during peripheral vein cannulation training on a latex arm or each other's arms in a clinical skills centre. Simulation-based training is thought to enhance learning and transfer of learning from simulation to the clinical setting and is commonly recommended in nursing education. What students actually are doing during simulation-based training is, however, less explored. The analysis of learning actions used during simulation-based training could contribute to development and improvement of simulation as a learning strategy in nursing education. A qualitative explorative and descriptive research design, involving content analysis of video recordings, was used. Video-supported observation of nine nursing students practicing vein cannulation was conducted in a clinical skills centre in late 2012. The students engaged in various learning actions. Students training on a latex arm used a considerably higher number of learning actions relative to those training on each other's arms. In both groups, students' learning actions consisted mainly of seeking and giving support. The teacher provided students training on each other's arms with detailed feedback regarding insertion of the cannula into the vein, while those training on a latex arm received sparse feedback from the teacher and fellow students. The teacher played an important role in facilitating nursing students' practical skill learning during simulation. The provision of support from both teachers and students should be emphasised to ensure that nursing students' learning needs are met. This study suggest that student nurses may be differently and inadequately prepared in peripheral vein cannulation in two simulation modalities used in the academic setting; training on a latex arm and on each other's arms. © 2017 John Wiley & Sons Ltd.

The SIFT hardware/software systems. Volume 2: Software listings

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.

1985-01-01

This document contains software listings of the SIFT operating system and application software. The software is coded for the most part in a variant of the Pascal language, Pascal*. Pascal* is a cross-compiler running on the VAX and Eclipse computers. The output of Pascal* is BDX-390 assembler code. When necessary, modules are written directly in BDX-390 assembler code. The listings in this document supplement the description of the SIFT system found in Volume 1 of this report, A Detailed Description.

Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases.

PubMed

Caputo, Sandrine; Benboudjema, Louisa; Sinilnikova, Olga; Rouleau, Etienne; Béroud, Christophe; Lidereau, Rosette

2012-01-01

BRCA1 and BRCA2 are the two main genes responsible for predisposition to breast and ovarian cancers, as a result of protein-inactivating monoallelic mutations. It remains to be established whether many of the variants identified in these two genes, so-called unclassified/unknown variants (UVs), contribute to the disease phenotype or are simply neutral variants (or polymorphisms). Given the clinical importance of establishing their status, a nationwide effort to annotate these UVs was launched by laboratories belonging to the French GGC consortium (Groupe Génétique et Cancer), leading to the creation of the UMD-BRCA1/BRCA2 databases (http://www.umd.be/BRCA1/ and http://www.umd.be/BRCA2/). These databases have been endorsed by the French National Cancer Institute (INCa) and are designed to collect all variants detected in France, whether causal, neutral or UV. They differ from other BRCA databases in that they contain co-occurrence data for all variants. Using these data, the GGC French consortium has been able to classify certain UVs also contained in other databases. In this article, we report some novel UVs not contained in the BIC database and explore their impact in cancer predisposition based on a structural approach.

A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination

PubMed Central

Forster, Alice S; Cornelius, Victoria; Rockliffe, Lauren; Marlow, Laura AV; Bedford, Helen; Waller, Jo

2017-01-01

Background: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. Methods: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. Results: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls’ questionnaire and 17% for the parents’. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). Conclusions: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed. PMID:28829766

Clinical descriptive measures of shoulder range of motion for a healthy, young and physically active cohort.

PubMed

Vairo, Giampietr L; Duffey, Michele L; Owens, Brett D; Cameron, Kenneth L

2012-09-10

The objective of this innovative research study was to describe clinical shoulder complex range of motion (ROM) measures for a young, healthy, and physically active population. This investigation represents a cross-sectional experiment conducted at a military academy-based sports medicine center. Military cadets with no history of shoulder complex injury were assessed within two months of enrollment in the academy; 548 men (18.8 ± 1.0 yr, 75.2 ± 12.2 kg, 178.3 ± 7.4 cm) and 74 women (18.7 ± 0.9 yr, 63.2 ± 8.9 kg, 165.2 ± 6.9 cm) participated. Descriptive measures included cross-body adduction (CAD), flexion (FLX), external rotation (ER0) with the shoulder complex in adduction and elbow flexed to 90°, internal and external rotation (IR, ER) with the shoulder complex at 90° of abduction and elbow flexed to 90° as well as arc (ARC) of IR-ER using standardized clinical quantification techniques. Bilateral and sex differences were evaluated using dependent and independent t-tests, respectively. Percentiles by arm dominance and sex were also calculated for all ROM measures. Data were normally distributed. Active and passive ROM measures indicated significant bilateral differences (P < 0.05) except for ARC. Sex differences (P < 0.05) were noted for active and passive CAD, FLX and ER0 for the dominant arm as well as active and passive CAD, FLX and ARC for the non-dominant arm. These original data provide descriptive measures for shoulder complex ROM excursions, assisting sports medicine practitioners in potentially identifying clinical deficiencies and functional outcomes following shoulder injury.

Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

PubMed

Boraska, Vesna; Day-Williams, Aaron; Franklin, Christopher S; Elliott, Katherine S; Panoutsopoulou, Kalliope; Tachmazidou, Ioanna; Albrecht, Eva; Bandinelli, Stefania; Beilin, Lawrence J; Bochud, Murielle; Cadby, Gemma; Ernst, Florian; Evans, David M; Hayward, Caroline; Hicks, Andrew A; Huffman, Jennifer; Huth, Cornelia; James, Alan L; Klopp, Norman; Kolcic, Ivana; Kutalik, Zoltán; Lawlor, Debbie A; Musk, Arthur W; Pehlic, Marina; Pennell, Craig E; Perry, John R B; Peters, Annette; Polasek, Ozren; St Pourcain, Beate; Ring, Susan M; Salvi, Erika; Schipf, Sabine; Staessen, Jan A; Teumer, Alexander; Timpson, Nicholas; Vitart, Veronique; Warrington, Nicole M; Yaghootkar, Hanieh; Zemunik, Tatijana; Zgaga, Lina; An, Ping; Anttila, Verneri; Borecki, Ingrid B; Holmen, Jostein; Ntalla, Ioanna; Palotie, Aarno; Pietiläinen, Kirsi H; Wedenoja, Juho; Winsvold, Bendik S; Dedoussis, George V; Kaprio, Jaakko; Province, Michael A; Zwart, John-Anker; Burnier, Michel; Campbell, Harry; Cusi, Daniele; Smith, George Davey; Frayling, Timothy M; Gieger, Christian; Palmer, Lyle J; Pramstaller, Peter P; Rudan, Igor; Völzke, Henry; Wichmann, H-Erich; Wright, Alan F; Zeggini, Eleftheria

2012-01-01

Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

Genome-Wide Association Study to Identify Common Variants Associated with Brachial Circumference: A Meta-Analysis of 14 Cohorts

PubMed Central

Boraska, Vesna; Day-Williams, Aaron; Franklin, Christopher S.; Elliott, Katherine S.; Panoutsopoulou, Kalliope; Tachmazidou, Ioanna; Albrecht, Eva; Bandinelli, Stefania; Beilin, Lawrence J.; Bochud, Murielle; Cadby, Gemma; Ernst, Florian; Evans, David M.; Hayward, Caroline; Hicks, Andrew A.; Huffman, Jennifer; Huth, Cornelia; James, Alan L.; Klopp, Norman; Kolcic, Ivana; Kutalik, Zoltán; Lawlor, Debbie A.; Musk, Arthur W.; Pehlic, Marina; Pennell, Craig E.; Perry, John R. B.; Peters, Annette; Polasek, Ozren; Pourcain, Beate St; Ring, Susan M.; Salvi, Erika; Schipf, Sabine; Staessen, Jan A.; Teumer, Alexander; Timpson, Nicholas; Vitart, Veronique; Warrington, Nicole M.; Yaghootkar, Hanieh; Zemunik, Tatijana; Zgaga, Lina; An, Ping; Anttila, Verneri; Borecki, Ingrid B.; Holmen, Jostein; Ntalla, Ioanna; Palotie, Aarno; Pietiläinen, Kirsi H.; Wedenoja, Juho; Winsvold, Bendik S.; Dedoussis, George V.; Kaprio, Jaakko; Province, Michael A.; Zwart, John-Anker; Burnier, Michel; Campbell, Harry; Cusi, Daniele; Davey Smith, George; Frayling, Timothy M.; Gieger, Christian; Palmer, Lyle J.; Pramstaller, Peter P.; Rudan, Igor; Völzke, Henry; Wichmann, H. -Erich; Wright, Alan F.; Zeggini, Eleftheria

2012-01-01

Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC. PMID:22479309

Description of a novel missense mutation of glucose-6-phosphate dehydrogenase gene associated with asymptomatic high enzyme deficiency.

PubMed

Minucci, Angelo; Concolino, Paola; Antenucci, Mirca; Santonocito, Concetta; Ameglio, Franco; Zuppi, Cecilia; Giardina, Bruno; Capoluongo, Ettore

2007-08-01

We report a case of an asymptomatic young subject affected by severe deficiency of Glucose 6-phosphate dehydrogenase (G6PD) activity. A novel genetic mutation (G130A) in the third exon was found. We named this novel mutation the "G6PD RIGNANO variant". These findings may contribute to a better knowledge of molecular epidemiology of the G6PD mutation and may represent an additional variant to be studied for a deep comprehension of in vivo compensation mechanisms of G6PD deficiency.

The scanning electron microscope as a tool in space biology

NASA Technical Reports Server (NTRS)

Barrett, R. A.

1983-01-01

Normal erythrocytes are disc-shaped and are referred to here descriptively as discocytes. Several morphologically variant forms occur nomally but in rather small amounts, usually less than one percent of total. It has been shown though, that spiculed variant forms referred to as echinocytes are generated in significant amounts at zero g. Normal red cells have been stressed in vitro in an effort to duplicate the observed discocyte-echinocyte transformation at zero g. The significance of this transformation to extended stay in space and some of the plausible reasons for this transformation are discussed.

Spread of Plasmids Carrying Multiple GES Variants

PubMed Central

Cuzon, Gaelle; Bogaerts, Pierre; Bauraing, Caroline; Huang, Te-Din; Glupczynski, Youri

2016-01-01

Five GES-producing Enterobacteriaceae isolates that displayed an extended-spectrum β-lactamase (ESBL) phenotype harbored two GES variants: GES-7 ESBL and GES-6 carbapenemase. In all isolates, the two GES alleles were located on the same integron that was inserted into an 80-kb IncM1 self-conjugative plasmid. Whole-genome sequencing suggested in vivo horizontal gene transfer of the plasmid along with clonal diffusion of Enterobacter cloacae. To our knowledge, this is the first description in Europe of clustered Enterobacteriaceae isolates carrying two GES β-lactamases, of which one has extended activity toward carbapenems. PMID:27216071

Tres mitos de la fonetica espanola (Three Myths of Spanish Phonetics).

ERIC Educational Resources Information Center

Dalbor, John B.

1980-01-01

Contrasts current pronunciation of some Spanish consonants with the teachings and theory of pronunciation manuals, advocating more realistic standards of instruction. Gives a detailed phonetic description of common variants of the sounds discussed, covering both Spanish and Latin American dialects. (MES)

Psychiatric Manifestations of Learning Disorders.

ERIC Educational Resources Information Center

Gever, Benson E.

1991-01-01

This article examines the descriptive influences of reading and learning disorders on personality development. It discusses the effects of biologic vulnerabilities and environmental interaction, the variant patterns of defense and symptom development at various life stages, and evidence that early development failures are key elements in later…

Fluctuation between grandiose and vulnerable narcissism.

PubMed

Gore, Whitney L; Widiger, Thomas A

2016-10-01

Current literature on narcissistic personality disorder has emphasized a distinction between grandiose and vulnerable narcissism. Some researchers have further suggested that narcissistic persons fluctuate between grandiose and vulnerable narcissism. However, this perception has been confined largely to clinical experience with no systematic research testing the hypothesis. Clinicians and clinical psychology professors in the current study identified 143 persons who fit a description of either a grandiose or a vulnerable narcissist and indicated the extent to which these persons ever demonstrated traits of the complementary variant. The results supported the fluctuation hypothesis, particularly for episodes of vulnerable narcissism in persons identified as a grandiose narcissist. Correlations of the grandiose and vulnerable narcissism traits with a brief five-factor model measure corroborated past trait descriptions of the 2 respective variants of narcissism. The results of the current study are compared with existing cross-sectional and longitudinal research, and suggestions for future research are provided. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

NASA's Asteroid Redirect Mission (ARM)

NASA Technical Reports Server (NTRS)

Abell, P. A.; Mazanek, D. D.; Reeves, D. M.; Chodas, P. W.; Gates, M. M.; Johnson, L. N.; Ticker, R. L.

2017-01-01

Mission Description and Objectives: NASA's Asteroid Redirect Mission (ARM) consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), a robotic mission to visit a large (greater than approximately 100 meters diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will explore and investigate the boulder and return to Earth with samples. The ARRM is currently planned to launch at the end of 2021 and the ARCM is scheduled for late 2026.

Analysis of Multiallelic CNVs by Emulsion Haplotype Fusion PCR.

PubMed

Tyson, Jess; Armour, John A L

2017-01-01

Emulsion-fusion PCR recovers long-range sequence information by combining products in cis from individual genomic DNA molecules. Emulsion droplets act as very numerous small reaction chambers in which different PCR products from a single genomic DNA molecule are condensed into short joint products, to unite sequences in cis from widely separated genomic sites. These products can therefore provide information about the arrangement of sequences and variants at a larger scale than established long-read sequencing methods. The method has been useful in defining the phase of variants in haplotypes, the typing of inversions, and determining the configuration of sequence variants in multiallelic CNVs. In this description we outline the rationale for the application of emulsion-fusion PCR methods to the analysis of multiallelic CNVs, and give practical details for our own implementation of the method in that context.

A Case of KCNQ2-Associated Movement Disorder Triggered by Fever.

PubMed

Dhamija, Radhika; Goodkin, Howard P; Bailey, Russell; Chambers, Chelsea; Brenton, J Nicholas

2017-12-01

The differential diagnosis of fever-induced movement disorders in childhood is broad. Whole exome sequencing has yielded new insights into those cases with a suspected genetic basis. We report the case of an 8-year-old boy with a history of neonatal seizures who presented with near-continuous hyperkinetic movements of his limbs during a febrile illness. Initial diagnostic testing did not explain his abnormalities; however, given the suspicion for a channelopathy, whole exome sequencing was performed and it demonstrated a de novo pathogenic heterozygous variant in KCNQ2. There is an expanding phenotypic spectrum of heterozygous alterations in KCNQ2; however, this report provides the first description of a pathogenic KCNQ2 variant fever-induced hyperkinetic movement disorder in childhood. We also review the literature of cases previously published with the same pathogenic variant.

A global reference for human genetic variation

PubMed Central

2016-01-01

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. PMID:26432245

In vivo study of the surgical anatomy of the axilla.

PubMed

Khan, A; Chakravorty, A; Gui, G P H

2012-06-01

Classical anatomical descriptions fail to describe variants often observed in the axilla as they are based on studies that looked at individual structures in isolation or textbooks of cadaveric dissections. The presence of variant anatomy heightens the risk of iatrogenic injury. The aim of this study was to document the nature and frequency of these anatomical variations based on in vivo peroperative surgical observations. Detailed anatomical relationships were documented prospectively during consecutive axillary dissections. Relationships between the thoracodorsal pedicle, course of the lateral thoracic vein, presence of latissimus dorsi muscle slips, variations in axillary and angular vein anatomy, and origins and branching of the intercostobrachial nerve were recorded. Among a total of 73 axillary dissections, 43 (59 per cent) revealed at least one anatomical variant. Most notable variants included aberrant courses of the thoracodorsal nerve in ten patients (14 per cent)--three variants; lateral thoracic vein in 12 patients (16 per cent)--four variants; bifid axillary veins in ten patients (14 per cent); latissimus dorsi muscle slips in four patients (5 per cent); and variants in intercostobrachial nerve origins and branching in 26 patients (36 per cent). The angular vein, a subscapular vein tributary, was found to be a constant axillary structure. Variations in axillary anatomical structures are common. Poor understanding of these variants can affect the adequacy of oncological clearance, lead to vascular injury, compromise planned microvascular procedures and result in chronic pain or numbness from nerve injury. Surgeons should be aware of the common anatomical variants to facilitate efficient and safe axillary surgery. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features

PubMed Central

Spencer, Michael D; Knight, Richard S G; Will, Robert G

2002-01-01

Objective To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob disease. Design Cohort study. Setting National surveillance system for Creutzfeldt-Jakob disease in the United Kingdom. Participants The first 100 cases of variant Creutzfeldt-Jakob disease identified in the United Kingdom. Main outcome measures The timing and nature of early psychiatric and neurological symptoms in variant Creutzfeldt-Jakob disease. Results The early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptoms, but neurological symptoms precede psychiatric symptoms in 15% of cases and are present in combination with psychiatric symptoms in 22% of cases from the onset of disease. Common early psychiatric features include dysphoria, withdrawal, anxiety, insomnia, and loss of interest. No common early neurological features exist, but a significant proportion of patients do exhibit neurological symptoms within 4 months of clinical onset, including poor memory, pain, sensory symptoms, unsteadiness of gait, and dysarthria. Conclusions Although the diagnosis of variant Creutzfeldt-Jakob disease may be impossible in the early stages of the illness, particular combinations of psychiatric and neurological features may allow early diagnosis in an appreciable proportion of patients. What is already known on this topicThe early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptomatologySome patients have early neurological features that might suggest the presence of an underlying neurological disorderWhat this study addsThis study provides a comprehensive description of the evolution of psychiatric and neurological features in variant Creutzfeldt-Jakob diseaseAn appreciable proportion of patients have early neurological symptomsA high proportion of patients have a combination of psychiatric and neurological features within four months of clinical onset that suggest the diagnosis of variant Creutzfeldt-Jakob disease PMID:12077031

Systemic lupus erythematosus in a patient with Noonan syndrome-like disorder with loose anagen hair 1: More than a chance association.

PubMed

Uehara, Tomoko; Hosogaya, Naoki; Matsuo, Nobutake; Kosaki, Kenjiro

2018-05-07

Systemic lupus erythematosus (SLE) has been reported among patients with RASopathy. Five patients have been reported: three with SHOC2 variants, one with a PTPN11 variant, and one with a KRAS variant. SHOC2 variant might represent a relatively common predisposing factor for SLE among the RASopathy genes. However, the clinical details were only reported for two patients, while information on the remaining patient appeared only in a tabular format with minimal clinical description. Here, we report a patient with a SHOC2 variant and SLE. The proband was a 28-year-old male patient with intellectual disabilities, a short stature, dysmorphic facial features, and thin hair. He developed hypertrophic cardiomyopathy and afebrile generalized seizures at the ages of 7 and 18 years, respectively. At the age of 24 years, he presented with a 3-day history of intermittent fever accompanied by right chest pain and a malar butterfly rash. He fulfilled both the American College of Rheumatology (ACR) criteria and the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE and was successfully treated with prednisolone. Medical exome sequencing identified a de novo SHOC2 variant (c.4A > G, p.S2G). The present report of a second patient who fulfills both the ACR criteria and the SLICC criteria of SLE. We suggest that the association between SHOC2 variant and SLE represents more than a chance association. In the event of fever of unknown origin in patients with constitutional SHOC2 pathogenic variant, SLE should be suspected. © 2018 Wiley Periodicals, Inc.

Prion diseases in humans: an update.

PubMed

Butler, Rob

2006-10-01

The year 2006 marks 20 years from the first identified bovine spongiform encephalitis in cows and 10 years from the first description of variant Creutzfeldt-Jakob disease in humans. The threatened epidemic in humans now appears unlikely, but psychiatrists need to be aware of recent developments in prion diseases.

Consistency of breast and arm symptoms during the first two years after breast cancer surgery.

PubMed

Wennman-Larsen, Agneta; Petersson, Lena-Marie; Saboonchi, Fredrik; Alexanderson, Kristina; Vaez, Marjan

2015-03-01

To examine the severity and development of breast and arm symptoms separately during the two years following breast cancer surgery, and to examine whether previously defined predictors of arm symptoms are associated with breast symptoms. Prospective cohort study with two-year follow-up. Three institutions in the Stockholm, Sweden, region. 645 women, aged 20-63 years, enrolled within 12 weeks of surgery for primary breast cancer. Baseline register and questionnaire data with five follow-ups were submitted to descriptive, inferential, and logistic regression analysis. Severity of breast and arm symptoms measured by the European Organisation for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire. Most participants had undergone breast-conserving 
surgery and sentinel lymph node dissection, and were scheduled for postoperative radiation therapy. Overall mean levels of breast and arm symptoms were low, but with large individual variations. At all six time points, the mean levels of breast symptoms were significantly higher than those of arm symptoms. Overall, the mean level of both types of symptoms decreased during follow-up. A body mass index (BMI) of 25 or greater and breast symptoms at eight months were associated with having breast symptoms at two years. Arm symptoms at baseline and at eight months, and radiation therapy and a BMI of 25 or greater were associated with having arm symptoms at two years. Breast symptoms show different patterns of change and are not associated with the same factors as arm symptoms. For nurses monitoring women treated for breast cancer, the results of this study provide knowledge regarding the importance of early symptom identification and long-term symptoms after treatment.

Senseless Extravagance, Shocking Gaps

ERIC Educational Resources Information Center

Weissbourd, Richard; Dodge, Trevor

2012-01-01

Although most people in the United States believe, at least theoretically, in educational equality, fewer and fewer appear to care about the resource gaps between affluent and poor schools, says Weissbourd. He illustrates these gaps with vivid descriptions of what he calls an "opulence arms race" among affluent independent schools, but…

78 FR 50045 - 36(b)(1) Arms Sales Notification

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2013-08-16

... Total $54 million (iii) Description and Quantity or Quantities of Articles or Services under... Commissions, Fee, etc: None (vii) Sensitivity of Technology Contained in the Defense Article or Defense... guidance kits in its inventory. The proposed sale of this equipment will not alter the basic military...

A Nonsense Variant in the ACADVL Gene in German Hunting Terriers with Exercise Induced Metabolic Myopathy.

PubMed

Lepori, Vincent; Mühlhause, Franziska; Sewell, Adrian C; Jagannathan, Vidhya; Janzen, Nils; Rosati, Marco; Alves de Sousa, Filipe Miguel Maximiano; Tschopp, Aurélie; Schüpbach, Gertraud; Matiasek, Kaspar; Tipold, Andrea; Leeb, Tosso; Kornberg, Marion

2018-05-04

Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1) peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD). Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C>A or p.(Tyr576*). The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, which we propose to name exercise induced metabolic myopathy (EIMM), and the identification of the first canine pathogenic ACADVL variant. Our findings provide a large animal model for a known human disease and will enable genetic testing to avoid the unintentional breeding of affected offspring. Copyright © 2018 Lepori et al.

Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia

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

Inayama, Y.; Yoneda, H.; Sakai, T.

Sixty-two patients with schizophrenia and 96 normal controls were investigated for genetic association with restriction fragment length polymorphisms (RFLPs) in the serotonin receptor genes. A positive association between the serotonin 2A receptor gene (HTR2A) and schizophrenia was found, but not between schizophrenia and the serotonin 1A receptor gene. The positive association we report here would suggest that the DNA region with susceptibility to schizophrenia lies in the HTR2A on the long arm of chromosome 13. 15 refs., 2 tabs.

Automating arm movement training following severe stroke: functional exercises with quantitative feedback in a gravity-reduced environment.

PubMed

Sanchez, Robert J; Liu, Jiayin; Rao, Sandhya; Shah, Punit; Smith, Robert; Rahman, Tariq; Cramer, Steven C; Bobrow, James E; Reinkensmeyer, David J

2006-09-01

An important goal in rehabilitation engineering is to develop technology that allows individuals with severe motor impairment to practice arm movement without continuous supervision from a rehabilitation therapist. This paper describes the development of such a system, called Therapy WREX or ("T-WREX"). The system consists of an orthosis that assists in arm movement across a large workspace, a grip sensor that detects hand grip pressure, and software that simulates functional activities. The arm orthosis is an instrumented, adult-sized version of the Wilmington Robotic Exoskeleton (WREX), which is a five degrees-of-freedom mechanism that passively counterbalances the weight of the arm using elastic bands. After providing a detailed design description of T-WREX, this paper describes two pilot studies of the system's capabilities. The first study demonstrated that individuals with chronic stroke whose arm function is compromised in a normal gravity environment can perform reaching and drawing movements while using T-WREX. The second study demonstrated that exercising the affected arm of five people with chronic stroke with T-WREX over an eight week period improved unassisted movement ability (mean change in Fugl-Meyer score was 5 points +/- 2 SD; mean change in range of motion of reaching was 10%, p < 0.001). These results demonstrate the feasibility of automating upper-extremity rehabilitation therapy for people with severe stroke using passive gravity assistance, a grip sensor, and simple virtual reality software.

Direct protein interaction underlies gene-for-gene specificity and coevolution of the flax resistance genes and flax rust avirulence genes

PubMed Central

Dodds, Peter N.; Lawrence, Gregory J.; Catanzariti, Ann-Maree; Teh, Trazel; Wang, Ching-I. A.; Ayliffe, Michael A.; Kobe, Bostjan; Ellis, Jeffrey G.

2006-01-01

Plant resistance proteins (R proteins) recognize corresponding pathogen avirulence (Avr) proteins either indirectly through detection of changes in their host protein targets or through direct R–Avr protein interaction. Although indirect recognition imposes selection against Avr effector function, pathogen effector molecules recognized through direct interaction may overcome resistance through sequence diversification rather than loss of function. Here we show that the flax rust fungus AvrL567 genes, whose products are recognized by the L5, L6, and L7 R proteins of flax, are highly diverse, with 12 sequence variants identified from six rust strains. Seven AvrL567 variants derived from Avr alleles induce necrotic responses when expressed in flax plants containing corresponding resistance genes (R genes), whereas five variants from avr alleles do not. Differences in recognition specificity between AvrL567 variants and evidence for diversifying selection acting on these genes suggest they have been involved in a gene-specific arms race with the corresponding flax R genes. Yeast two-hybrid assays indicate that recognition is based on direct R–Avr protein interaction and recapitulate the interaction specificity observed in planta. Biochemical analysis of Escherichia coli-produced AvrL567 proteins shows that variants that escape recognition nevertheless maintain a conserved structure and stability, suggesting that the amino acid sequence differences directly affect the R–Avr protein interaction. We suggest that direct recognition associated with high genetic diversity at corresponding R and Avr gene loci represents an alternative outcome of plant–pathogen coevolution to indirect recognition associated with simple balanced polymorphisms for functional and nonfunctional R and Avr genes. PMID:16731621

Differentiating primary progressive aphasias in a brief sample of connected speech

PubMed Central

Evans, Emily; O'Shea, Jessica; Powers, John; Boller, Ashley; Weinberg, Danielle; Haley, Jenna; McMillan, Corey; Irwin, David J.; Rascovsky, Katya; Grossman, Murray

2013-01-01

Objective: A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA. Methods: We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality. We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits. Results: We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant. Conclusions: These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics. PMID:23794681

Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.

PubMed

Wreesmann, Volkert B; Ghossein, Ronald A; Hezel, Michael; Banerjee, Debenranrath; Shaha, Ashok R; Tuttle, R Michael; Shah, Jatin P; Rao, Pulivarthi H; Singh, Bhuvanesh

2004-08-01

The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms. Copyright 2004 Wiley-Liss, Inc.

Neotropical Monogenoidea. 53. Gyrodactylus corydori sp. n. and redescription of Gyrodactylus anisopharynx (Gyrodactylidea: Gyrodactylidae), parasites of Corydoras spp. (Siluriformes: Callichthyidae) from southern Brazil.

PubMed

Bueno-Silva, Marlus; Boeger, Walter A

2009-03-01

Morphometric analyses are used to evaluate the taxonomic status of two sympatric variants of Gyrodactylus anisopharynx Popazoglo et Boeger, 2000 (forma "large-pharynx" and forma "small-pharynx"). The parasites were collected from the Piraquara River and the Miringuava River, State of Paraná, Brazil, between February 2005 and May 2006. A total of 132 parasites were measured from two hosts, Corydoras ehrhardti Steindachner and Corydoras paleatus (Jenyns). Eleven morphological features of the haptoral sclerites and pharynx were measured and analysed by discriminant analysis and principal components analysis. The results indicate that the observed morphological variation cannot be associated to intraspecific variation or phenotypic plasticity (P < 0.0001). Consequently, the two variants previously allocated in G. anisopharynx represent two independent species. Since the holotype was defined as the variant "large-pharynx", Gyrodactylus corydori sp. n. is proposed to accommodate specimens previously reported as "small-pharynx" variant of G. anisopharynx. Morphometric analyses showed that the hook, the anchor, and the pharyngeal bulb are significantly distinct (P < 0.0001) between G. corydori sp. n. and G. anisopharynx (s.s.). The new species is characterized by having hooks with point moderately curved, robust convex heel, convex shelf, toe concave moderately pointed with depression; deep bar with two submedial, posterior projections; anchors with robust superficial root; superficial bar with two small anterolateral projections; and male copulatory organ armed with two rows of spinelets.

75 FR 10283 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... role in the fate of stem cells. GISTs are one of the most common sarcomas of the gastrointestinal tract... applications. Patient-Derived Gastrointestinal Stromal and Paraganglioma Tumor Samples Harboring Novel Stem Cell Factor FOXD3 Variants Description of Invention: The cancer market is forecast to reach $40 billion...

How different terminology for ductal carcinoma in situ impacts women's concern and treatment preferences: a randomised comparison within a national community survey.

PubMed

McCaffery, Kirsten; Nickel, Brooke; Moynihan, Ray; Hersch, Jolyn; Teixeira-Pinto, Armando; Irwig, Les; Barratt, Alexandra

2015-11-02

There have been calls to remove 'carcinoma' from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as 'abnormal cells' versus 'pre-invasive breast cancer cells' on women's concern and treatment preferences. Community sample of Australian women (n=269) who spoke English as their main language at home. Randomised comparison within a community survey. Women considered a hypothetical scenario involving a diagnosis of DCIS described as either 'abnormal cells' (arm A) or 'pre-invasive breast cancer cells' (arm B). Within each arm, the initial description was followed by the alternative term and outcomes reassessed. Women in both arms indicated high concern, but still indicated strong initial preferences for watchful waiting (64%). There were no differences in initial concern or preferences by trial arm. However, more women in arm A ('abnormal cells' first term) indicated they would feel more concerned if given the alternative term ('pre-invasive breast cancer cells') compared to women in arm B who received the terms in the opposite order (67% arm A vs 52% arm B would feel more concerned, p=0.001). More women in arm A also changed their preference towards treatment when the terminology was switched from 'abnormal cells' to 'pre-invasive breast cancer cells' compared to arm B. In arm A, 18% of women changed their preference to treatment while only 6% changed to watchful waiting (p=0.008). In contrast, there were no significant changes in treatment preference in arm B when the terminology was switched (9% vs 8% changed their stated preference). In a hypothetical scenario, interest in watchful waiting for DCIS was high, and changing terminology impacted women's concern and treatment preferences. Removal of the cancer term from DCIS may assist in efforts towards reducing overtreatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Operational manual for two-dimensional transonic code TSFOIL

NASA Technical Reports Server (NTRS)

Stahara, S. S.

1978-01-01

This code solves the two-dimensional, transonic, small-disturbance equations for flow past lifting airfoils in both free air and various wind-tunnel environments by using a variant of the finite-difference method. A description of the theoretical and numerical basis of the code is provided, together with complete operating instructions and sample cases for the general user. In addition, a programmer's manual is also presented to assist the user interested in modifying the code. Included in the programmer's manual are a dictionary of subroutine variables in common and a detailed description of each subroutine.

Adaptive Devices for Aquatic Activities.

ERIC Educational Resources Information Center

Bradtke, Jane Silverman

1979-01-01

The article describes commercial as well as improvised and homemade equipment for teaching physically handicapped persons to swim. Descriptions address equipment for entering the pool (such as pool lifts, a transfer board, and a ramp); aids in the instructional process (kick boards, arm floats); and assorted games and materials (such as ropes,…

49 CFR 572.181 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... assembly Drawing number Head Assembly 175-1000 Neck Assembly Test/Cert 175-2000 Neck Bracket Including..., dated February 2008. (c) Weights of body segments (head, neck, upper and lower torso, arms and upper and... the convenience of the user, the added and revised text is set forth as follows: § 572.181 General...

Investigation of Millennial Students' Responses to a Shelter-in-Place Experience

ERIC Educational Resources Information Center

Johnson, Thomas C.; Frick, Melodie H.

2016-01-01

This study investigated millennial students' responses to an armed gunman threat and shelter-in-place warnings that occurred on a university campus. Using descriptive statistics and quantitative analysis, several significant differences were found for students' responses for sheltering-in-place and engaging in protective behaviors. Baxter Magolda'…

76 FR 66048 - 36(b)(1) Arms Sales Notification

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2011-10-25

.... (iii) Description and Quantity or Quantities of Articles or Services under Consideration for Purchase... High Mobility Multi-Purpose Wheeled Vehicles (HMMWVs), 1 lot AN/MPQ- 64F1 SENTINEL Radar software, 290...-Launched Advanced Medium Range Air-to-Air Missile (SL-AMRAAM) software to support Oman's Ground Based Air...

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... million Total $60 million (iii) Description and Quantity or Quantities of Articles or Services under... Technology Contained in the Defense Article or Defense Services Proposed to be Sold: See Annex attached... integrate the Helmet Mounted Cueing System. The software algorithms are the most sensitive portion of the...

78 FR 62600 - 36(b)(1) Arms Sales Notification

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2013-10-22

... million Total $68 million (iii) Description and Quantity or Quantities of Articles or Services Under... Technology Contained in the Defense Article or Defense Services Proposed To Be Sold: See Annex attached... integrate the Helmet Mounted Cueing System. The software algorithms are the most sensitive portion of the...

Analyzing octopus movements using three-dimensional reconstruction.

PubMed

Yekutieli, Yoram; Mitelman, Rea; Hochner, Binyamin; Flash, Tamar

2007-09-01

Octopus arms, as well as other muscular hydrostats, are characterized by a very large number of degrees of freedom and a rich motion repertoire. Over the years, several attempts have been made to elucidate the interplay between the biomechanics of these organs and their control systems. Recent developments in electrophysiological recordings from both the arms and brains of behaving octopuses mark significant progress in this direction. The next stage is relating these recordings to the octopus arm movements, which requires an accurate and reliable method of movement description and analysis. Here we describe a semiautomatic computerized system for 3D reconstruction of an octopus arm during motion. It consists of two digital video cameras and a PC computer running custom-made software. The system overcomes the difficulty of extracting the motion of smooth, nonrigid objects in poor viewing conditions. Some of the trouble is explained by the problem of light refraction in recording underwater motion. Here we use both experiments and simulations to analyze the refraction problem and show that accurate reconstruction is possible. We have used this system successfully to reconstruct different types of octopus arm movements, such as reaching and bend initiation movements. Our system is noninvasive and does not require attaching any artificial markers to the octopus arm. It may therefore be of more general use in reconstructing other nonrigid, elongated objects in motion.

Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines.

PubMed

Van Roy, N; Van Limbergen, H; Vandesompele, J; Van Gele, M; Poppe, B; Salwen, H; Laureys, G; Manoel, N; De Paepe, A; Speleman, F

2001-10-01

Cancer cell lines are essential gene discovery tools and have often served as models in genetic and functional studies of particular tumor types. One of the future challenges is comparison and interpretation of gene expression data with the available knowledge on the genomic abnormalities in these cell lines. In this context, accurate description of these genomic abnormalities is required. Here, we show that a combination of M-FISH with banding analysis, standard FISH, and CGH allowed a detailed description of the genetic alterations in 16 neuroblastoma cell lines. In total, 14 cryptic chromosome rearrangements were detected, including a balanced t(2;4)(p24.3;q34.3) translocation in cell line NBL-S, with the 2p24 breakpoint located at about 40 kb from MYCN. The chromosomal origin of 22 marker chromosomes and 41 cytogenetically undefined translocated segments was determined. Chromosome arm 2 short arm translocations were observed in six cell lines (38%) with and five (31%) without MYCN amplification, leading to partial chromosome arm 2p gain in all but one cell line and loss of material in the various partner chromosomes, including 1p and 11q. These 2p gains were often masked in the GGH profiles due to MYCN amplification. The commonly overrepresented region was chromosome segment 2pter-2p22, which contains the MYCN gene, and five out of eleven 2p breakpoints clustered to the interface of chromosome bands 2p16 and 2p21. In neuroblastoma cell line SJNB-12, with double minutes (dmins) but no MYCN amplification, the dmins were shown to be derived from 16q22-q23 sequences. The ATBF1 gene, an AT-binding transcription factor involved in normal neurogenesis and located at 16q22.2, was shown to be present in the amplicon. This is the first report describing the possible implication of ATBF1 in neuroblastoma cells. We conclude that a combined approach of M-FISH, cytogenetics, and CGH allowed a more complete and accurate description of the genetic alterations occurring in the investigated cell lines. Copyright 2001 Wiley-Liss, Inc.

[Clinical and morphological variants of diverticular disease in colon].

PubMed

Levchenko, S V; Lazebnik, L B; Potapova, V B; Rogozina, V A

2013-01-01

Our own results of two-stage research are presented in the article. The first stage contains the retrospective analysis of 3682 X-ray examining of large bowel which were conducted in 2002-2004 to define the structure of colon disease and to determine gender differences. The second stage is prospective research which took place from 2003 to 2012 and 486 patients with diverticular disease were regularly observed. Following parameters were estimated: dynamics of complaints, life quality, clinical symptoms. Multiple X-ray and endoscopic examining were done with estimation of quantity and size of diverticula, changes of colon mucosa, comparison of X-ray and endoscopic methods in prognosis of complications. Two basic clinical morphological variants of diverticular disease (DD) of colon are made out as a result of our research. There are IBD-like and DD with ischemic component. The variants differ by pain characteristics, presence of accompanying diseases, life quality parameters and description of colon mucosa morphological research. We suppose that different ethiopathogenetic factors of development of both variants mentioned above influence the disease prognosis and selection of treatment.

ARM Data File Standards Version: 1.0

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

Kehoe, Kenneth; Beus, Sherman; Cialella, Alice

2014-04-01

The Atmospheric Radiation Measurement (ARM) Climate Research Facility performs routine in situ and remote-sensing observations to provide a detailed and accurate description of the Earth atmosphere in diverse climate regimes. The result is a diverse data sets containing observational and derived data, currently accumulating at a rate of 30 TB of data and 150,000 different files per month (http://www.archive.arm.gov/stats/storage2.html). Continuing the current processing while scaling this to even larger sizes is extremely important to the ARM Facility and requires consistent metadata and data standards. The standards described in this document will enable development of automated analysis and discovery tools formore » the ever-growing volumes of data. It also will enable consistent analysis of the multiyear data, allow for development of automated monitoring and data health status tools, and facilitate development of future capabilities for delivering data on demand that can be tailored explicitly to user needs. This analysis ability will only be possible if the data follows a minimum set of standards. This document proposes a hierarchy that includes required and recommended standards.« less

A robotic workstation for stroke rehabilitation of the upper extremity using FES.

PubMed

Freeman, C T; Hughes, A-M; Burridge, J H; Chappell, P H; Lewin, P L; Rogers, E

2009-04-01

An experimental test facility is developed for use by stroke patients in order to improve sensory-motor function of their upper limb. Subjects are seated at the workstation and their task is to repeatedly follow reaching trajectories that are projected onto a target above their arm. To do this they use voluntary control with the addition of electrical stimulation mediated by advanced control schemes applied to muscles in their impaired shoulder and arm. Full details of the design of the workstation and its periphery systems are given, together with a description of its use during the treatment of stroke patients.

Traction-drive, seven-degree-of-freedom telerobot arm: A concept for manipulaton in space

NASA Technical Reports Server (NTRS)

Kuban, D. P.; Williams, D. M.

1987-01-01

As man seeks to expand his dominion into new environments, the demand increases for machines that perform useful functions in remote locations. This new concept for manipulation in space is based on knowledge and experience gained from manipulator systems developed to meet the needs of remote nuclear applications. It merges the best characteristics of teleoperation and robotic technologies. The design goals for the telerobot, a mechanical description, and technology areas that must be addressed for successful implementation are presented and discussed. The concept incorporates mechanical traction drives, redundant kinematics, and modular arm subelements to provide a backlash-free manipulator capable of obstacle avoidance.

Removal of central obscuration and spider arm effects with beam-shaping coronagraphy

NASA Astrophysics Data System (ADS)

Abe, L.; Murakami, N.; Nishikawa, J.; Tamura, M.

2006-05-01

This paper describes a method for removing the effect of a centrally obscured aperture with additional spider arms in arbitrary geometrical configurations. The proposed method is based on a two-stage process where the light beam is first shaped to remove the central obscuration and spider arms, in order to feed a second, highly efficient coronagraph. The beam-shaping stage is a combination of a diffraction mask in the first focal plane and a complex amplitude filter located in the conjugate pupil. This paper specifically describes the case of using Lyot occulting masks and circular phase-shifting masks as diffracting components. The basic principle of the method is given along with an analytical description and numerical simulations. Substantial improvement in the performance of high-contrast coronagraphs can be obtained with this method, even if the beam-shaping filter is not perfectly manufactured.

A comprehensive global genotype-phenotype database for rare diseases.

PubMed

Trujillano, Daniel; Oprea, Gabriela-Elena; Schmitz, Yvonne; Bertoli-Avella, Aida M; Abou Jamra, Rami; Rolfs, Arndt

2017-01-01

The ability to discover genetic variants in a patient runs far ahead of the ability to interpret them. Databases with accurate descriptions of the causal relationship between the variants and the phenotype are valuable since these are critical tools in clinical genetic diagnostics. Here, we introduce a comprehensive and global genotype-phenotype database focusing on rare diseases. This database (CentoMD ® ) is a browser-based tool that enables access to a comprehensive, independently curated system utilizing stringent high-quality criteria and a quickly growing repository of genetic and human phenotype ontology (HPO)-based clinical information. Its main goals are to aid the evaluation of genetic variants, to enhance the validity of the genetic analytical workflow, to increase the quality of genetic diagnoses, and to improve evaluation of treatment options for patients with hereditary diseases. The database software correlates clinical information from consented patients and probands of different geographical backgrounds with a large dataset of genetic variants and, when available, biomarker information. An automated follow-up tool is incorporated that informs all users whenever a variant classification has changed. These unique features fully embedded in a CLIA/CAP-accredited quality management system allow appropriate data quality and enhanced patient safety. More than 100,000 genetically screened individuals are documented in the database, resulting in more than 470 million variant detections. Approximately, 57% of the clinically relevant and uncertain variants in the database are novel. Notably, 3% of the genetic variants identified and previously reported in the literature as being associated with a particular rare disease were reclassified, based on internal evidence, as clinically irrelevant. The database offers a comprehensive summary of the clinical validity and causality of detected gene variants with their associated phenotypes, and is a valuable tool for identifying new disease genes through the correlation of novel genetic variants with specific, well-defined phenotypes.

The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

PubMed Central

Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

2014-01-01

Background Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. Objectives To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Methods Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Results Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. Conclusions No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally. PMID:24988074

The effect of the hemochromatosis (HFE) genotype on lead load and iron metabolism among lead smelter workers.

PubMed

Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

2014-01-01

Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

Neuroprosthetic Decoder Training as Imitation Learning.

PubMed

Merel, Josh; Carlson, David; Paninski, Liam; Cunningham, John P

2016-05-01

Neuroprosthetic brain-computer interfaces function via an algorithm which decodes neural activity of the user into movements of an end effector, such as a cursor or robotic arm. In practice, the decoder is often learned by updating its parameters while the user performs a task. When the user's intention is not directly observable, recent methods have demonstrated value in training the decoder against a surrogate for the user's intended movement. Here we show that training a decoder in this way is a novel variant of an imitation learning problem, where an oracle or expert is employed for supervised training in lieu of direct observations, which are not available. Specifically, we describe how a generic imitation learning meta-algorithm, dataset aggregation (DAgger), can be adapted to train a generic brain-computer interface. By deriving existing learning algorithms for brain-computer interfaces in this framework, we provide a novel analysis of regret (an important metric of learning efficacy) for brain-computer interfaces. This analysis allows us to characterize the space of algorithmic variants and bounds on their regret rates. Existing approaches for decoder learning have been performed in the cursor control setting, but the available design principles for these decoders are such that it has been impossible to scale them to naturalistic settings. Leveraging our findings, we then offer an algorithm that combines imitation learning with optimal control, which should allow for training of arbitrary effectors for which optimal control can generate goal-oriented control. We demonstrate this novel and general BCI algorithm with simulated neuroprosthetic control of a 26 degree-of-freedom model of an arm, a sophisticated and realistic end effector.

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials.

PubMed

Papandonatos, George D; Pan, Qing; Pajewski, Nicholas M; Delahanty, Linda M; Peter, Inga; Erar, Bahar; Ahmad, Shafqat; Harden, Maegan; Chen, Ling; Fontanillas, Pierre; Wagenknecht, Lynne E; Kahn, Steven E; Wing, Rena R; Jablonski, Kathleen A; Huggins, Gordon S; Knowler, William C; Florez, Jose C; McCaffery, Jeanne M; Franks, Paul W

2015-12-01

Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2-4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism×treatment interaction (P = 4.3 × 10(-3)). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 10(-4)). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Association between CFH, CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular age-related macular degeneration.

PubMed

Cobos, Estefania; Recalde, Sergio; Anter, Jaouad; Hernandez-Sanchez, Maria; Barreales, Carla; Olavarrieta, Leticia; Valverde, Alicia; Suarez-Figueroa, Marta; Cruz, Fernando; Abraldes, Maximino; Pérez-Pérez, Julian; Fernández-Robredo, Patricia; Arias, Luis; García-Layana, Alfredo

2018-03-01

We sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response to ranibizumab in neovascular age-related macular degeneration (AMD). A total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from six different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors (gender, smoking habit and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT) and fluid criteria (fluid/no fluid measured by OCT). Hypertension was the environmental factor with the strongest poor response association with ranibizumab in the anatomical measure after the loading phase (p = 0.0004; OR 3.7; 95% CI, 2.4-5.8) and after 12 months of treatment (p = 10 -5 ; OR 2.3; 95% CI, 1.5-3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a good response, while rs12603486 and rs1136287 (SERPINF1) were associated with a poor response. The protective genotype of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048). All these data suggest that genetics play an important role in treatment response in AMD patients. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A numerical investigation of flow around octopus-like arms: near-wake vortex patterns and force development.

PubMed

Kazakidi, A; Vavourakis, V; Tsakiris, D P; Ekaterinaris, J A

2015-01-01

The fluid dynamics of cephalopods has so far received little attention in the literature, due to their complexity in structure and locomotion. The flow around octopuses, in particular, can be complicated due to their agile and dexterous arms, which frequently display some of the most diverse mechanisms of motion. The study of this flow amounts to a specific instance of the hydrodynamics problem for rough tapered cylinder geometries. The outstanding manipulative and locomotor skills of octopuses could inspire the development of advanced robotic arms, able to operate in fluid environments. Our primary aim was to study the hydrodynamic characteristics of such bio-inspired robotic models and to derive the hydrodynamic force coefficients as a concise description of the vortical flow effects. Utilizing computational fluid dynamic methods, the coefficients were computed on realistic morphologies of octopus-like arm models undergoing prescribed solid-body movements; such motions occur in nature for short durations in time, e.g. during reaching movements and exploratory behaviors. Numerical simulations were performed on translating, impulsively rotating, and maneuvering arms, around which the flow field structures were investigated. The results reveal in detail the generation of complex vortical flow structures around the moving arms. Hydrodynamic forces acting on a translating arm depend on the angle of incidence; forces generated during impulsive rotations of the arms are independent of their exact morphology and the angle of rotation; periodic motions based on a slow recovery and a fast power stroke are able to produce considerable propulsive thrust while harmonic motions are not. Parts of these results have been employed in bio-inspired models of underwater robotic mechanisms. This investigation may further assist elucidating the hydrodynamics underlying aspects of octopus locomotion and exploratory behaviors.

Variant of Rett syndrome and CDKL5 gene: clinical and autonomic description of 10 cases.

PubMed

Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt; Calabrese, Olga; Felloni, Beatrice; Scusa, Maria Flora; Di Marco, Pietro; Borelli, Paolo; Bonuccelli, Ubaldo; Julu, Peter O O; Nielsen, Jytte Bieber; Morin, Bodil; Hansen, Stig; Gobbi, Giuseppe; Visconti, Paola; Pintaudi, Maria; Edvige, Veneselli; Romanelli, Anna; Bianchi, Fabrizio; Casarano, Manuela; Battini, Roberta; Cioni, Giovanni; Ariani, Francesca; Renieri, Alessandra; Benincasa, Alberto; Delamont, Robert S; Zappella, Michele

2012-02-01

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A non-equilibrium neutral model for analysing cultural change.

PubMed

Kandler, Anne; Shennan, Stephen

2013-08-07

Neutral evolution is a frequently used model to analyse changes in frequencies of cultural variants over time. Variants are chosen to be copied according to their relative frequency and new variants are introduced by a process of random mutation. Here we present a non-equilibrium neutral model which accounts for temporally varying population sizes and mutation rates and makes it possible to analyse the cultural system under consideration at any point in time. This framework gives an indication whether observed changes in the frequency distributions of a set of cultural variants between two time points are consistent with the random copying hypothesis. We find that the likelihood of the existence of the observed assemblage at the end of the considered time period (expressed by the probability of the observed number of cultural variants present in the population during the whole period under neutral evolution) is a powerful indicator of departures from neutrality. Further, we study the effects of frequency-dependent selection on the evolutionary trajectories and present a case study of change in the decoration of pottery in early Neolithic Central Europe. Based on the framework developed we show that neutral evolution is not an adequate description of the observed changes in frequency. Copyright © 2013 Elsevier Ltd. All rights reserved.

Plasma Letrozole Concentrations in Postmenopausal Women With Breast Cancer Are Associated With CYP2A6 Genetic Variants, Body Mass Index, and Age

PubMed Central

Desta, Z; Kreutz, Y; Nguyen, AT; Li, L; Skaar, T; Kamdem, LK; Henry, NL; Hayes, DF; Storniolo, AM; Stearns, V; Hoffmann, E; Tyndale, RF; Flockhart, DA

2013-01-01

The associations between plasma letrozole concentrations and CYP2A6 and CYP3A5 genetic variants were tested in the Exemestane and Letrozole Pharmacogenomics (ELPH) trial. ELPH is a multicenter, open-label prospective clinical trial in women randomly assigned (n ≈ 250 in each arm) to receive 2 years of treatment with either oral letrozole (2.5 mg/day) or oral exemestane (25 mg/day). CYP2A6 and CYP3A showed effects on letrozole metabolism in vitro. DNA samples were genotyped for variants in the CYP2A6 and CYP3A5 genes. plasma letrozole concentrations showed high interpatient variability (>10-fold) and were associated significantly with CYP2A6 genotypes (P < 0.0001), body mass index (BMI) (P < 0.0001), and age (P = 0.0035). However, CYP3A5 genotypes showed no association with plasma letrozole concentrations. These data suggest that CYP2A6 is the principal clearance mechanism for letrozole in vivo. CYP2A6 metabolic status, along with BMI and age, may serve as a biomarker of the efficacy of letrozole treatment or a predictor of adverse effects. PMID:21975350

Simultaneous and Continuous Estimation of Shoulder and Elbow Kinematics from Surface EMG Signals

PubMed Central

Zhang, Qin; Liu, Runfeng; Chen, Wenbin; Xiong, Caihua

2017-01-01

In this paper, we present a simultaneous and continuous kinematics estimation method for multiple DoFs across shoulder and elbow joint. Although simultaneous and continuous kinematics estimation from surface electromyography (EMG) is a feasible way to achieve natural and intuitive human-machine interaction, few works investigated multi-DoF estimation across the significant joints of upper limb, shoulder and elbow joints. This paper evaluates the feasibility to estimate 4-DoF kinematics at shoulder and elbow during coordinated arm movements. Considering the potential applications of this method in exoskeleton, prosthetics and other arm rehabilitation techniques, the estimation performance is presented with different muscle activity decomposition and learning strategies. Principle component analysis (PCA) and independent component analysis (ICA) are respectively employed for EMG mode decomposition with artificial neural network (ANN) for learning the electromechanical association. Four joint angles across shoulder and elbow are simultaneously and continuously estimated from EMG in four coordinated arm movements. By using ICA (PCA) and single ANN, the average estimation accuracy 91.12% (90.23%) is obtained in 70-s intra-cross validation and 87.00% (86.30%) is obtained in 2-min inter-cross validation. This result suggests it is feasible and effective to use ICA (PCA) with single ANN for multi-joint kinematics estimation in variant application conditions. PMID:28611573

Deciphering the Hidden Informational Content of Protein Sequences

PubMed Central

Liu, Ming; Hua, Qing-xin; Hu, Shi-Quan; Jia, Wenhua; Yang, Yanwu; Saith, Sunil Evan; Whittaker, Jonathan; Arvan, Peter; Weiss, Michael A.

2010-01-01

Protein sequences encode both structure and foldability. Whereas the interrelationship of sequence and structure has been extensively investigated, the origins of folding efficiency are enigmatic. We demonstrate that the folding of proinsulin requires a flexible N-terminal hydrophobic residue that is dispensable for the structure, activity, and stability of the mature hormone. This residue (PheB1 in placental mammals) is variably positioned within crystal structures and exhibits 1H NMR motional narrowing in solution. Despite such flexibility, its deletion impaired insulin chain combination and led in cell culture to formation of non-native disulfide isomers with impaired secretion of the variant proinsulin. Cellular folding and secretion were maintained by hydrophobic substitutions at B1 but markedly perturbed by polar or charged side chains. We propose that, during folding, a hydrophobic side chain at B1 anchors transient long-range interactions by a flexible N-terminal arm (residues B1–B8) to mediate kinetic or thermodynamic partitioning among disulfide intermediates. Evidence for the overall contribution of the arm to folding was obtained by alanine scanning mutagenesis. Together, our findings demonstrate that efficient folding of proinsulin requires N-terminal sequences that are dispensable in the native state. Such arm-dependent folding can be abrogated by mutations associated with β-cell dysfunction and neonatal diabetes mellitus. PMID:20663888

Patterns of Weakness, Classification of Motor Neuron Disease & Clinical Diagnosis of Sporadic ALS

PubMed Central

Statland, Jeffrey M.; Barohn, Richard J.; McVey, April L.; Katz, Jonathan; Dimachkie, Mazen M.

2015-01-01

Synopsis When approaching the patient with suspected motor neuron disease (MND) the pattern of weakness on exam helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing, in the absence of other abnormalities on neuroimaging or serological testing. MNDs exist on a spectrum: from a pure lower motor neuron; to mixed upper and lower motor neuron; to a pure upper motor neuron variant in addition to regional variants restricted to the arms, legs or bulbar region. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic (~85%), which is invariably fatal. The only FDA approved treatments for ALS are riluzole, which prolongs life by about 3 months, and dextromethorphan/quinidine which provides symptomatic relief for pseudobulbar affect (inappropriate bouts of laughter or crying). Here we describe a pattern approach to identifying motor neuron disease, and clinical features of sporadic ALS. PMID:26515618

Three-dimensional circumferential liposuction of the overweight or obese upper arm.

PubMed

Hong, Yoon Gi; Sim, Hyung Bo; Lee, Mu Young; Seo, Sang Won; Chang, Choong Hyun; Yeo, Kwan Koo; Kim, June-kyu

2012-06-01

Due to recent trends in liposuction, anatomic consideration of the body's fatty layers is essential. Based on this knowledge, a circumferential approach to achieving maximal aesthetic results is highlighted. In the upper arm, aspiration of fat from only the posterolateral region can result in skin flaccidity and disharmony of the overall balance of the upper arm contour. Different suction techniques were applied depending on the degree of fat accumulation. If necessary, the operation area was extended around the axillary and scapular regions to overcome the limitations of the traditional method and to achieve optimal effects. To maximize skin contracture and redraping, the authors developed three-dimensional circumferential liposuction (3D-CL) based on two concepts: circumferential aspiration of the upper arm, to which was applied different fluid infiltration and liposuction techniques in three anatomic compartments (anteromedial, anterolateral, and posterolateral), and extension of liposuction to the periaxillar and parascarpular areas. A total of 57 female patients underwent liposuction of their excess arm fat using this technique. The authors achieved their aesthetic goals of a straightened inferior brachial border and a more slender body contour. Complications occurred for five patients including irregularity, incision-site scar, and transient pigmentation. Through 3D-CL, the limitations of traditional upper arm liposuction were overcome, and a slender arm contour with a straightened inferior brachial border was produced. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at http://www.springer.com/00266.

Reporting of analyses from randomized controlled trials with multiple arms: a systematic review.

PubMed

Baron, Gabriel; Perrodeau, Elodie; Boutron, Isabelle; Ravaud, Philippe

2013-03-27

Multiple-arm randomized trials can be more complex in their design, data analysis, and result reporting than two-arm trials. We conducted a systematic review to assess the reporting of analyses in reports of randomized controlled trials (RCTs) with multiple arms. The literature in the MEDLINE database was searched for reports of RCTs with multiple arms published in 2009 in the core clinical journals. Two reviewers extracted data using a standardized extraction form. In total, 298 reports were identified. Descriptions of the baseline characteristics and outcomes per group were missing in 45 reports (15.1%) and 48 reports (16.1%), respectively. More than half of the articles (n = 171, 57.4%) reported that a planned global test comparison was used (that is, assessment of the global differences between all groups), but 67 (39.2%) of these 171 articles did not report details of the planned analysis. Of the 116 articles reporting a global comparison test, 12 (10.3%) did not report the analysis as planned. In all, 60% of publications (n = 180) described planned pairwise test comparisons (that is, assessment of the difference between two groups), but 20 of these 180 articles (11.1%) did not report the pairwise test comparisons. Of the 204 articles reporting pairwise test comparisons, the comparisons were not planned for 44 (21.6%) of them. Less than half the reports (n = 137; 46%) provided baseline and outcome data per arm and reported the analysis as planned. Our findings highlight discrepancies between the planning and reporting of analyses in reports of multiple-arm trials.

Molecular and morphological description of Meloidogyne arenaria from traveler’s tree (Ravenala madagascariensis)

USDA-ARS?s Scientific Manuscript database

An unusual variant of Meloidogyne arenaria was discovered on roots of a traveler’s tree (Ravenala madagascariensis) intended for display at a public arboretum in Pennsylvania. The population aroused curiosity by the lack of visible galling on the roots of the infected plant. Morphometrics of the pop...

[Comparative description and retrospective analisis of modern methods of surgical wounds closure for intraoperative prophylaxis of development of pathologic cutaneous cicatrices].

PubMed

Stavyts'kyĭ, S O; Avetikov, D S; Lokes, K P; Rozkolupa, O O; Boĭko, I V

2014-05-01

The experience of application of various methods of closure was presented for the head and neck cutaneous wound surfaces after elective operative interventions. The variant of the postoperative results estimation and optimization of the wounds healing by primary closure was proposed.

Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network Model of Cognitive Development

ERIC Educational Resources Information Center

Thomas, Michael S. C.; Forrester, Neil A.; Ronald, Angelica

2016-01-01

In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such…

Osteogenesis Imperfecta: A Review with Clinical Examples

PubMed Central

van Dijk, F.S.; Cobben, J.M.; Kariminejad, A.; Maugeri, A.; Nikkels, P.G.J.; van Rijn, R.R.; Pals, G.

2011-01-01

Osteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures, with a severity ranging from subtle increase in fracture frequency to prenatal fractures. The first scientific description of OI dates from 1788. Since then, important milestones in OI research and treatment have, among others, been the classification of OI into 4 types (the ‘Sillence classification’), the discovery of defects in collagen type I biosynthesis as a cause of most cases of OI and the use of bisphosphonate therapy. Furthermore, in the past 5 years, it has become clear that OI comprises a group of heterogeneous disorders, with an estimated 90% of cases due to a causative variant in the COL1A1 or COL1A2 genes and with the remaining 10% due to causative recessive variants in the 8 genes known so far, or in other currently unknown genes. This review aims to highlight the current knowledge around the history, epidemiology, pathogenesis, clinical/radiological features, management, and future prospects of OI. The text will be illustrated with clinical descriptions, including radiographs and, where possible, photographs of patients with OI. PMID:22570641

Transforming Mechanized Reconnaissance: How the Armored Brigade Combat Team (ABCT) Cavalry Squadron Should be Structured for Reconnaissance and Security Operations in the Near Future

DTIC Science & Technology

2014-06-13

Squadron ( BFV /HMMWV, Current) .................................................. 93 Description...Evaluation Criteria ........................................................ 106 Comparison to Validation Criteria: ABCT Cavalry Squadron ( BFV /HMMWV...Brigade Combat Team BFV Bradley Fighting Vehicle BRT Brigade Reconnaissance Troop CAB Combined Arms Battalion CFV Cavalry Fighting Vehicle FM

76 FR 72180 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-22

...) Description and Quantity or Quantities of Articles or Services under Consideration for Purchase: 20 AIM-9X-2.... (vii) Sensitivity of Technology Contained in the Defense Article or Defense Services Proposed to be... Helmet Mounted Cueing System. The software algorithms are the most sensitive portion of the AIM-9X-2...

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

Bartholomew, M. J.

To improve the quantitative description of precipitation processes in climate models, the Atmospheric Radiation Measurement (ARM) Climate Research Facility deployed rain gauges located near disdrometers (DISD and VDIS data streams). This handbook deals specifically with the rain gauges that make the observations for the RAIN data stream. Other precipitation observations are made by the surface meteorology instrument suite (i.e., MET data stream).

Exercise for Well or Community Living Older Adults.

ERIC Educational Resources Information Center

Bennett, John P.

This set of instructions is designed for use by instructors in aerobic dance, although the instructions can also be used by individuals for an exercise program. Descriptions are given of specific exercises for the head and neck, shoulders, arms, legs, and chest and trunk. Routines for a complete aerobic dance session (warm-up, aerobic, and…

Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP) - pure coincidence?

PubMed Central

Döcker, Dennis; Schubach, Max; Menzel, Moritz; Spaich, Christiane; Gabriel, Heinz-Dieter; Zenker, Martin; Bartholdi, Deborah; Biskup, Saskia

2015-01-01

Megalencephaly-capillary malformation (MCAP) syndrome is an overgrowth syndrome that is diagnosed by clinical criteria. Recently, somatic and germline variants in genes that are involved in the PI3K-AKT pathway (AKT3, PIK3R2 and PIK3CA) have been described to be associated with MCAP and/or other related megalencephaly syndromes. We performed trio-exome sequencing in a 6-year-old boy and his healthy parents. Clinical features were macrocephaly, cutis marmorata, angiomata, asymmetric overgrowth, developmental delay, discrete midline facial nevus flammeus, toe syndactyly and postaxial polydactyly—thus, clearly an MCAP phenotype. Exome sequencing revealed a pathogenic de novo germline variant in the PTPN11 gene (c.1529A>G; p.(Gln510Arg)), which has so far been associated with Noonan, as well as LEOPARD syndrome. Whole-exome sequencing (>100 × coverage) did not reveal any alteration in the known megalencephaly genes. However, ultra-deep sequencing results from saliva (>1000 × coverage) revealed a 22% mosaic variant in PIK3CA (c.2740G>A; p.(Gly914Arg)). To our knowledge, this report is the first description of a PTPN11 germline variant in an MCAP patient. Data from experimental studies show a complex interaction of SHP2 (gene product of PTPN11) and the PI3K-AKT pathway. We hypothesize that certain PTPN11 germline variants might drive toward additional second-hit alterations. PMID:24939587

Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP)--pure coincidence?

PubMed

Döcker, Dennis; Schubach, Max; Menzel, Moritz; Spaich, Christiane; Gabriel, Heinz-Dieter; Zenker, Martin; Bartholdi, Deborah; Biskup, Saskia

2015-03-01

Megalencephaly-capillary malformation (MCAP) syndrome is an overgrowth syndrome that is diagnosed by clinical criteria. Recently, somatic and germline variants in genes that are involved in the PI3K-AKT pathway (AKT3, PIK3R2 and PIK3CA) have been described to be associated with MCAP and/or other related megalencephaly syndromes. We performed trio-exome sequencing in a 6-year-old boy and his healthy parents. Clinical features were macrocephaly, cutis marmorata, angiomata, asymmetric overgrowth, developmental delay, discrete midline facial nevus flammeus, toe syndactyly and postaxial polydactyly--thus, clearly an MCAP phenotype. Exome sequencing revealed a pathogenic de novo germline variant in the PTPN11 gene (c.1529A>G; p.(Gln510Arg)), which has so far been associated with Noonan, as well as LEOPARD syndrome. Whole-exome sequencing (>100 × coverage) did not reveal any alteration in the known megalencephaly genes. However, ultra-deep sequencing results from saliva (>1000 × coverage) revealed a 22% mosaic variant in PIK3CA (c.2740G>A; p.(Gly914Arg)). To our knowledge, this report is the first description of a PTPN11 germline variant in an MCAP patient. Data from experimental studies show a complex interaction of SHP2 (gene product of PTPN11) and the PI3K-AKT pathway. We hypothesize that certain PTPN11 germline variants might drive toward additional second-hit alterations.

Assessment of the Accountability and Control of Arms, Ammunition, and Explosives (AA&E) Provided to the Security Forces of Afghanistan

DTIC Science & Technology

2009-09-11

Corps to verify weapons and ammunition accountability. It conducted a serial number inventory of 67 weapons, including ten M16 rifles, 40 AK47 ...11. Mossberg M590A1 pump 12 gauge Former Warsaw Pact Weapons (FWP) 1. AK47 rifle and variants ( AK47 , AK74, AMD65, VZ58, AKMS) 2. RPK light machine...recorded as EL 4910  AK47 : 30 counted o Serial No. IA0499 recorded as IA0489  VZ58: 90 counted o 2 weapons were in the wrong boxes

Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia

PubMed Central

Moore, Daniel J.; Onoufriadis, Alexandros; Shoemark, Amelia; Simpson, Michael A.; zur Lage, Petra I.; de Castro, Sandra C.; Bartoloni, Lucia; Gallone, Giuseppe; Petridi, Stavroula; Woollard, Wesley J.; Antony, Dinu; Schmidts, Miriam; Didonna, Teresa; Makrythanasis, Periklis; Bevillard, Jeremy; Mongan, Nigel P.; Djakow, Jana; Pals, Gerard; Lucas, Jane S.; Marthin, June K.; Nielsen, Kim G.; Santoni, Federico; Guipponi, Michel; Hogg, Claire; Antonarakis, Stylianos E.; Emes, Richard D.; Chung, Eddie M.K.; Greene, Nicholas D.E.; Blouin, Jean-Louis; Jarman, Andrew P.; Mitchison, Hannah M.

2013-01-01

Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.Val16Gly (c.47T>G) homozygote individuals, whose cilia retained a stiff and slowed beat. In mice, Zmynd10 mRNA is restricted to regions containing motile cilia. In a Drosophila model of PCD, Zmynd10 is exclusively expressed in cells with motile cilia: chordotonal sensory neurons and sperm. In these cells, P-element-mediated gene silencing caused IDA and ODA defects, proprioception deficits, and sterility due to immotile sperm. Drosophila Zmynd10 with an equivalent c.47T>G (p.Val16Gly) missense change rescued mutant male sterility less than the wild-type did. Tagged Drosophila ZMYND10 is localized primarily to the cytoplasm, and human ZMYND10 interacts with LRRC6, another cytoplasmically localized protein altered in PCD. Using a fly model of PCD, we conclude that ZMYND10 is a cytoplasmic protein required for IDA and ODA assembly and that its variants cause ciliary dysmotility and PCD with laterality defects. PMID:23891471

Broad chromosomal domains of histone modification patterns in C. elegans

PubMed Central

Liu, Tao; Rechtsteiner, Andreas; Egelhofer, Thea A.; Vielle, Anne; Latorre, Isabel; Cheung, Ming-Sin; Ercan, Sevinc; Ikegami, Kohta; Jensen, Morten; Kolasinska-Zwierz, Paulina; Rosenbaum, Heidi; Shin, Hyunjin; Taing, Scott; Takasaki, Teruaki; Iniguez, A. Leonardo; Desai, Arshad; Dernburg, Abby F.; Kimura, Hiroshi; Lieb, Jason D.; Ahringer, Julie; Strome, Susan; Liu, X. Shirley

2011-01-01

Chromatin immunoprecipitation identifies specific interactions between genomic DNA and proteins, advancing our understanding of gene-level and chromosome-level regulation. Based on chromatin immunoprecipitation experiments using validated antibodies, we define the genome-wide distributions of 19 histone modifications, one histone variant, and eight chromatin-associated proteins in Caenorhabditis elegans embryos and L3 larvae. Cluster analysis identified five groups of chromatin marks with shared features: Two groups correlate with gene repression, two with gene activation, and one with the X chromosome. The X chromosome displays numerous unique properties, including enrichment of monomethylated H4K20 and H3K27, which correlate with the different repressive mechanisms that operate in somatic tissues and germ cells, respectively. The data also revealed striking differences in chromatin composition between the autosomes and between chromosome arms and centers. Chromosomes I and III are globally enriched for marks of active genes, consistent with containing more highly expressed genes, compared to chromosomes II, IV, and especially V. Consistent with the absence of cytological heterochromatin and the holocentric nature of C. elegans chromosomes, markers of heterochromatin such as H3K9 methylation are not concentrated at a single region on each chromosome. Instead, H3K9 methylation is enriched on chromosome arms, coincident with zones of elevated meiotic recombination. Active genes in chromosome arms and centers have very similar histone mark distributions, suggesting that active domains in the arms are interspersed with heterochromatin-like structure. These data, which confirm and extend previous studies, allow for in-depth analysis of the organization and deployment of the C. elegans genome during development. PMID:21177964

Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene.

PubMed

Backer, Julie De; Braverman, Alan C

2018-05-01

Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Normal magnetic resonance imaging anatomy of the ankle & foot.

PubMed

Arnold, George; Vohra, Saifuddin; Marcantonio, David; Doshi, Shashin

2011-08-01

This article discusses anatomic relationships, anatomic variants, and MRI protocols that pertain to the foot and ankle. MR images with detailed anatomic description form the cornerstone of this article. The superb image quality will facilitate learning normal imaging anatomy, as well as conceptualizing spatial relationships of anatomic structures. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular Characteristics of Hb New York [β113(G15)Val→Glu, HBB: c.341T>A] in Thailand.

PubMed

Chaibunruang, Attawut; Singha, Kritsada; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Fucharoen, Supan

2018-01-01

Hb New York or Hb Kaohsiung [β113(G15)Val→Glu (GTG>GAG), HBB: c.341T>A] has been considered a rare β hemoglobin (Hb) variant found originally in an Iranian woman and later in diverse populations but its genetic origin has not been elucidated. Here we report molecular and hematological descriptions of this variant found in the Thai population. Among 5643 subjects referred for hemoglobinopathy investigation during January 2015 to September 2017, 183 (3.2%) were found to carry several Hb variants, including β chain variants (n = 135, 2.4%), α chain variants (n = 33, 0.6%), Hb Lepore-Hollandia (NG_000007.3: g.63290_70702del) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del) (δβ hybrid Hb) (n = 12, 0.2%) and δ chain variants (n = 3, 0.05%). Of patients with β chain variants, six with normal high performance liquid chromatography (HPLC) patterns, had an abnormal Hb in zone 11 of capillary electrophoresis (CE), the amounts of which ranged from 29.6-45.4% with normal levels of Hb A 2 and Hb F. DNA analysis identified a heterozygous Hb New York mutation in all cases. Further screening of α-thalassemia (α-thal) identified coinheritance of α + - and α 0 -thal in two of them who had reduced levels of Hb New York. Haplotype analysis suggested that the Thai Hb New York was likely associated with a single β-globin haplotype [+ - - - - + +], indicating that it was of the same origin. Hematological findings and simple DNA assay based on allele-specific polymerase chain reaction (PCR) for rapid detection of Hb New York are presented.

Understanding Nuclear Weapons and Arms Control: A Guide to the Issues. Instructor's Manual.

ERIC Educational Resources Information Center

Zahka, William J.; Mayers, Teena Karsa

Intended for teachers of secondary and college level students, this instructor's guide presents an overview of materials covered in the student text, followed by four categories of examination questions and teaching aids. The guide reflects the format of the student text and is divided into four sections. A brief description is provided of each…

49 CFR 572.5 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... M080—Right leg assembly SA 150 M081—Left leg assembly SA 150 M010—Head assembly SA 150 M020—Neck... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 50th Percentile Male § 572... grouped by component assemblies under the following nine headings: SA 150 M070—Right arm assembly SA 150...

Physical Fitness Test Battery for Mentally Retarded Children (Trainable and Educable).

ERIC Educational Resources Information Center

Fait, Hollis F.

A physical fitness test battery for educable and trainable mentally handicapped children is presented. Instructions are given for administering the test; descriptions are given of the seven test items, including the 25 yard run, bent arm hang, leg lift, static balance, thrust, and 300 yard run-walk. Rationale for the items and factors in…

Use of the DEKA Arm for amputees with brachial plexus injury: A case series.

PubMed

Resnik, Linda; Fantini, Christopher; Latlief, Gail; Phillips, Samuel; Sasson, Nicole; Sepulveda, Eve

2017-01-01

Patients with upper limb amputation and brachial plexus injuries have high rates of prosthesis rejection. Study purpose is to describe experiences of subjects with transhumeral amputation and brachial plexus injury, who were fit with, and trained to use, a DEKA Arm. This was a mixed-methods study utilizing qualitative (e.g. interview, survey) and quantitative data (e.g. self-report and performance measures). Subject 1, a current prosthesis user, had a shoulder arthrodesis. Subject 2, not a prosthesis user, had a subluxed shoulder. Both were trained in laboratory and participated in a trial of home use. Descriptive analyses of processes and outcomes were conducted. Subject 1 was fitted with the transhumeral configuration (HC) DEKA Arm using a compression release stabilized socket. He had 12 hours of prosthetic training and participated in all home study activities. Subject 1 had improved dexterity and prosthetic satisfaction with the DEKA Arm and reported better quality of life (QOL) at the end of participation. Subject 2 was fit with the shoulder configuration (SC) DEKA Arm using a modified X-frame socket. He had 30 hours of training and participated in 3 weeks of home activities. He reported less functional disability at the end of training as compared to baseline, but encountered personal problems and exacerbation of PTSD symptoms and withdrew from home use portion at 3 weeks. Both subjects reported functional benefits from use, and expressed a desire to receive a DEKA Arm in the future. This paper reported on two different strategies for prosthetic fitting and their outcomes. The advantages and limitations of each approach were discussed. Use of both the HC and SC DEKA Arm for patients with TH amputation and brachial plexus injury was reported. Lessons learned may be instructive to clinicians considering prosthetic choices for future cases.

A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

PubMed

Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

2016-01-01

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus. Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian immunodeficiency virus [SIV]) if its activity is not counteracted by the viral Vif protein. Here we investigate the ability of 7 naturally occurring variants of feline APOBEC3, APOBEC3Z3 (A3Z3), to inhibit FIV replication. Interestingly, one feline A3Z3 variant is dominant, restrictive, and naturally resistant to FIV Vif-mediated degradation. Phylogenetic analyses revealed that the ancestral change that generated this variant could have been caused by positive Darwinian selection, presumably due to an ancestral FIV infection. The experimental-phylogenetic investigation sheds light on the evolutionary history of the domestic cat, which was likely influenced by lentiviral infection. Copyright © 2015 Yoshikawa et al.

eMelanoBase: an online locus-specific variant database for familial melanoma.

PubMed

Fung, David C Y; Holland, Elizabeth A; Becker, Therese M; Hayward, Nicholas K; Bressac-de Paillerets, Brigitte; Mann, Graham J

2003-01-01

A proportion of melanoma-prone individuals in both familial and non-familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1alpha, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A-p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A-related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model-view-controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.edu.au:8080/melanoma.html. Copyright 2002 Wiley-Liss, Inc.

[Lymphogranuloma venereum: new serovariant L2b and old "groove sign"].

PubMed

de Lavaissière, M; Nougué, J

2013-08-01

An ongoing lymphogranuloma venereum (LGV) outbreak has been reported in several European countries since 2003, related to a new variant L2b. This serovar appears to affect men who have sex with men (MSM), most of them being co-infected with the Human Immunodeficiency Virus (HIV). The secondary stage of LGV may involve lymph nodes and the inguinal form has sometimes been described on each side of the inguinal ligament thus named the "groove sign". We report the case of LGV serovariant L2b acquired by an heterosexual intercourse in an HIV seronegative patient who presented with an inguinal lymph node and a "groove sign". This is an uncommon but suggestive sign of LGV and we suggest that the clinical presentation of L2b LGV might not be so different than other variants and than the 20th century authors' description. Such a new Chlamydia trachomatis variant may circulate in other populations than MSM in Europe and clinical awareness must prevail.

Hb Mozhaisk [β92(F8)His→Arg; HBB: c.278A>G] as a De Novo Mutation in a Child of Mixed Ethnic Origins.

PubMed

Benzoni, Elena; Giannone, Valentina; Michetti, Laura; Seia, Manuela; Cavalleri, Laura; Curcio, Cristina

Approximately 150 variants described in the HbVar database have been found to be unstable and about 80.0% of these are on the β-globin gene. We describe the case of a 3-year-old child who presented at the emergency room with fever and asthenia. Hematological data suggested severe hemolytic anemia. Sequencing of the β-globin gene revealed the mutation HBB: c.278A>G at codon 92 in a heterozygous state, reported as Hb Mozhaisk in the HbVar database. Other family members did not have Hb Mozhaisk, thus, this variant is due to a de novo mutation. Because of the rarity of this globin variant, we believe it is important to report similar cases, to have a more complete phenotype description of the pathology and define an adequate reproductive risk for couples, considering the dominant inheritance pattern (hence an inheritance risk of 50.0%).

Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

PubMed Central

Barohn, Richard J.; Katz, Jonathan

2014-01-01

Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge regarding pathogenesis, diagnosis and management continues to expand, resulting in improved opportunities for identification and treatment. PMID:23642723

Co-evolutionary interactions between host resistance and pathogen avirulence genes in rice-Magnaporthe oryzae pathosystem.

PubMed

Singh, Pankaj Kumar; Ray, Soham; Thakur, Shallu; Rathour, Rajeev; Sharma, Vinay; Sharma, Tilak Raj

2018-06-01

Rice and Magnaporthe oryzae constitutes an ideal pathosystem for studying host-pathogen interaction in cereals crops. There are two alternative hypotheses, viz. Arms race and Trench warfare, which explain the co-evolutionary dynamics of hosts and pathogens which are under continuous confrontation. Arms race proposes that both R- and Avr- genes of host and pathogen, respectively, undergo positive selection. Alternatively, trench warfare suggests that either R- or Avr- gene in the pathosystem is under balanced selection intending to stabilize the genetic advantage gained over the opposition. Here, we made an attempt to test the above-stated hypotheses in rice-M. oryzae pathosystem at loci of three R-Avr gene pairs, Piz-t-AvrPiz-t, Pi54-AvrPi54 and Pita-AvrPita using allele mining approach. Allele mining is an efficient way to capture allelic variants existing in the population and to study the selective forces imposed on the variants during evolution. Results of nucleotide diversity, neutrality statistics and phylogenetic analyses reveal that Piz-t, Pi54 and AvrPita are diversified and under positive selection at their corresponding loci, while their counterparts, AvrPiz-t, AvrPi54 and Pita are conserved and under balancing selection, in nature. These results imply that rice-M. oryzae populations are engaged in a trench warfare at least at the three R/Avr loci studied. It is a maiden attempt to study the co-evolution of three R-Avr gene pairs in this pathosystem. Knowledge gained from this study will help in understanding the evolutionary dynamics of host-pathogen interaction in a better way and will also aid in developing new durable blast resistant rice varieties in future. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroprosthetic Decoder Training as Imitation Learning

PubMed Central

Merel, Josh; Paninski, Liam; Cunningham, John P.

2016-01-01

Neuroprosthetic brain-computer interfaces function via an algorithm which decodes neural activity of the user into movements of an end effector, such as a cursor or robotic arm. In practice, the decoder is often learned by updating its parameters while the user performs a task. When the user’s intention is not directly observable, recent methods have demonstrated value in training the decoder against a surrogate for the user’s intended movement. Here we show that training a decoder in this way is a novel variant of an imitation learning problem, where an oracle or expert is employed for supervised training in lieu of direct observations, which are not available. Specifically, we describe how a generic imitation learning meta-algorithm, dataset aggregation (DAgger), can be adapted to train a generic brain-computer interface. By deriving existing learning algorithms for brain-computer interfaces in this framework, we provide a novel analysis of regret (an important metric of learning efficacy) for brain-computer interfaces. This analysis allows us to characterize the space of algorithmic variants and bounds on their regret rates. Existing approaches for decoder learning have been performed in the cursor control setting, but the available design principles for these decoders are such that it has been impossible to scale them to naturalistic settings. Leveraging our findings, we then offer an algorithm that combines imitation learning with optimal control, which should allow for training of arbitrary effectors for which optimal control can generate goal-oriented control. We demonstrate this novel and general BCI algorithm with simulated neuroprosthetic control of a 26 degree-of-freedom model of an arm, a sophisticated and realistic end effector. PMID:27191387

Clinical and genetic features of cervical dystonia in a large multicenter cohort

PubMed Central

Vemula, Satya R.; Xiao, Jianfeng; Thompson, Misty M.; Perlmutter, Joel S.; Wright, Laura J.; Jinnah, H.A.; Rosen, Ami R.; Hedera, Peter; Comella, Cynthia L.; Weissbach, Anne; Junker, Johanna; Jankovic, Joseph; Barbano, Richard L.; Reich, Stephen G.; Rodriguez, Ramon L.; Berman, Brian D.; Chouinard, Sylvain; Severt, Lawrence; Agarwal, Pinky; Stover, Natividad P.

2016-01-01

Objective: To characterize the clinical and genetic features of cervical dystonia (CD). Methods: Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A. Results: The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in THAP1, TOR1A, and GNAL were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of TOR1A. Synonymous and noncoding SVs in THAP1 and GNAL were identified in 4% of the cohort. Conclusions: Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions to the pathogenesis of CD. PMID:27123488

Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells

PubMed Central

Shrestha, Roshan L.; Ahn, Grace S.; Staples, Mae I.; Sathyan, Kizhakke M.; Karpova, Tatiana S.; Foltz, Daniel R.; Basrai, Munira A.

2017-01-01

Chromosomal instability (CIN) is a hallmark of many cancers and a major contributor to tumorigenesis. Centromere and kinetochore associated proteins such as the evolutionarily conserved centromeric histone H3 variant CENP-A, associate with centromeric DNA for centromere function and chromosomal stability. Stringent regulation of cellular CENP-A levels prevents its mislocalization in yeast and flies to maintain genome stability. CENP-A overexpression and mislocalization are observed in several cancers and reported to be associated with increased invasiveness and poor prognosis. We examined whether there is a direct relationship between mislocalization of overexpressed CENP-A and CIN using HeLa and chromosomally stable diploid RPE1 cell lines as model systems. Our results show that mislocalization of overexpressed CENP-A to chromosome arms leads to chromosome congression defects, lagging chromosomes, micronuclei formation and a delay in mitotic exit. CENP-A overexpressing cells showed altered localization of centromere and kinetochore associated proteins such as CENP-C, CENP-T and Nuf2 leading to weakened native kinetochores as shown by reduced interkinetochore distance and CIN. Importantly, our results show that mislocalization of CENP-A to chromosome arms is one of the major contributors for CIN as depletion of histone chaperone DAXX prevents CENP-A mislocalization and rescues the reduced interkinetochore distance and CIN phenotype in CENP-A overexpressing cells. In summary, our results establish that CENP-A overexpression and mislocalization result in a CIN phenotype in human cells. This study provides insights into how overexpression of CENP-A may contribute to CIN in cancers and underscore the importance of understanding the pathways that prevent CENP-A mislocalization for genome stability. PMID:28596481

Touch sensors and control.

NASA Technical Reports Server (NTRS)

Hill, J. W.; Sword, A. J.

1973-01-01

Description of the equipment employed and results obtained in experiments with tactile feedback and different levels of automatic control. In the experiments described tactile feedback was investigated by incorporating a touch sensing and touch display system into a teleoperator, while the levels of automatic control were investigated by incorporating supervisory control features in the teleoperator control system. In particular, a hand contact system which senses and reproduces to the operator the contact between the end-effector and the object being touched or manipulated is described, as well as a jaw contact system which senses and reproduces to the operator the shape and location of the object held in the remote jaws, and an arm control system consisting of a control station where the operator controls the motion of the arm by transmitting commands, a remote station that accepts the commands and uses them, and a communications link that limits information flow. In addition, an algorithmic language for remote manipulation is described, and the desired features that an automatic arm controller should possess are reviewed.

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

PubMed Central

Qiu, Jian-Wu; Deng, Mei; Cheng, Ying; Atif, Raza-Muhammad; Lin, Wei-Xia; Guo, Li; Li, Hua; Song, Yuan-Zong

2017-01-01

Sodium taurocholate cotransporting polypeptide (NTCP) is encoded by the gene SLC10A1 and expressed in the basolateral membrane of the hepatocyte, functioning to uptake bile acids from plasma. Although SLC10A1 has been cloned and NTCP function studied intensively for years, clinical description of NTCP deficiency remains rather limited. This study reported the genotypic and phenotypic features of two neonatal patients with NTCP deficiency. They both presented with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia, and harbored the SLC10A1 variants c.800C>T (p.S267F) and c.263T>C (p.I88T). On genetic analysis of the two family trios, the latter missense variant was detected in trans with the former, a reported loss-of-function variant. Having not been reported in any databases, the c.263T>C (p.I88T) variant demonstrated an allele frequency of 0.67% (1/150) in healthy controls. Moreover, this variant involved a relatively conservative amino acid, and was predicted to be pathogenic or deleterious by changing the conformation of the NTCP molecule. In conclusion, the novel variant c.263T>C (p.I88T) in this study enriched the SLC10A1 mutation spectrum; the clinical findings lent support to the primary role of NTCP in hepatic bile acid clearance, and suggested that NTCP deficiency might be a contributing factor for the development of neonatal indirect hyperbilirubinemia. PMID:29290974

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia.

PubMed

Qiu, Jian-Wu; Deng, Mei; Cheng, Ying; Atif, Raza-Muhammad; Lin, Wei-Xia; Guo, Li; Li, Hua; Song, Yuan-Zong

2017-12-05

Sodium taurocholate cotransporting polypeptide (NTCP) is encoded by the gene SLC10A1 and expressed in the basolateral membrane of the hepatocyte, functioning to uptake bile acids from plasma. Although SLC10A1 has been cloned and NTCP function studied intensively for years, clinical description of NTCP deficiency remains rather limited. This study reported the genotypic and phenotypic features of two neonatal patients with NTCP deficiency. They both presented with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia, and harbored the SLC10A1 variants c.800C>T (p.S267F) and c.263T>C (p.I88T). On genetic analysis of the two family trios, the latter missense variant was detected in trans with the former, a reported loss-of-function variant. Having not been reported in any databases, the c.263T>C (p.I88T) variant demonstrated an allele frequency of 0.67% (1/150) in healthy controls. Moreover, this variant involved a relatively conservative amino acid, and was predicted to be pathogenic or deleterious by changing the conformation of the NTCP molecule. In conclusion, the novel variant c.263T>C (p.I88T) in this study enriched the SLC10A1 mutation spectrum; the clinical findings lent support to the primary role of NTCP in hepatic bile acid clearance, and suggested that NTCP deficiency might be a contributing factor for the development of neonatal indirect hyperbilirubinemia.

Molecular cytogenetic analysis consistently identifies translocations involving chromosomes 1, 2 and 15 in five embryonal rhabdomyosarcoma cell lines and a PAX-FOXO1A fusion gene negative alveolar rhabdomyosarcoma cell line.

PubMed

Roberts, I; Gordon, A; Wang, R; Pritchard-Jones, K; Shipley, J; Coleman, N

2001-01-01

Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays skeletal muscle differentiation. Two main histological variants are recognised, alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent chromosome translocations characteristic of ARMS have been reported, no such cytogenetic abnormality has yet been described in ERMS. We have used multiple colour chromosome painting to obtain composite karyotypes for five ERMS cell lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ hybridisation (M-FISH) using series of seven colour paint sets generated to examine specific abnormalities, and comparative genomic hybridisation (CGH). This approach enabled us to obtain karyotypes of the cell lines in greater detail than previously possible. Several recurring cytogenetic abnormalities were demonstrated, including translocations involving chromosomes 1 and 15 and chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1 and 15 have previously been recorded in two primary cases of ERMS by conventional cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of ERMS tumourigenesis and may enable the development of novel approaches to the clinical management of this tumour. Copyright 2002 S. Karger AG, Basel

Controllable molecular motors engineered from myosin and RNA

NASA Astrophysics Data System (ADS)

Omabegho, Tosan; Gurel, Pinar S.; Cheng, Clarence Y.; Kim, Laura Y.; Ruijgrok, Paul V.; Das, Rhiju; Alushin, Gregory M.; Bryant, Zev

2018-01-01

Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems1 or in living cells2. Previously, synthetic nucleic acid motors3-5 and modified natural protein motors6-10 have been developed in separate complementary strategies to achieve tunable and controllable motor function. Integrating protein and nucleic-acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number and composition of tethered protein motors11-15. Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport and can be dynamically controlled using programmed transitions in the lever arm structure7,9. We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy and structural probing16. Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement17 reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10-20 nm s-1. Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals.

Valuing EQ-5D-5L health states 'in context' using a discrete choice experiment.

PubMed

Cole, Amanda; Shah, Koonal; Mulhern, Brendan; Feng, Yan; Devlin, Nancy

2018-05-01

In health state valuation studies, health states are typically presented as a series of sentences, each describing a health dimension and severity 'level'. Differences in the severity levels can be subtle, and confusion about which is 'worse' can lead to logically inconsistent valuation data. A solution could be to mimic the way patients self-report health, where the ordinal structure of levels is clear. We develop and test the feasibility of presenting EQ-5D-5L health states in the 'context' of the entire EQ-5D-5L descriptive system. An online two-arm discrete choice experiment was conducted in the UK (n = 993). Respondents were randomly allocated to a control (standard presentation) or 'context' arm. Each respondent completed 16 paired comparison tasks and feedback questions about the tasks. Differences across arms were assessed using regression analyses. Presenting health states 'in context' can significantly reduce the selection of logically dominated health states, particularly for labels 'severe' and 'extreme' (χ 2  = 46.02, p < 0.001). Preferences differ significantly between arms (likelihood ratio statistic = 42.00, p < 0.05). Comparing conditional logit modeling results, coefficients are ordered as expected for both arms, but the magnitude of decrements between levels is larger for the context arm. Health state presentation is a key consideration in the design of valuation studies. Presenting health states 'in context' affects valuation data and reduces logical inconsistencies. Our results could have implications for other valuation tasks such as time trade-off, and for the valuation of other preference-based measures.

Site scientific mission plan for the Southern Great Plains CART site, January-June 1995

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

Schneider, J.M.; Lamb, P.J.; Sisterson, D.L.

1994-12-01

The Southern Great Plains (SGP) Cloud and Radiation Testbed (CART) site is designed to help satisfy the data needs of the Atmospheric Measurement (ARM) Program Science Team. This document defines the scientific priorities for site activities during the six months beginning on January 1, 1995, and also looks forward in lesser detail to subsequent six-month periods. The primary purpose of this Site Scientific Mission Plan is to provide guidance for the development of plans for site operations. It also provides information on current plans to the ARM functional teams (Management Team, Experiment Support Team [EST], Operations Team, Data Management Teammore » [DMT], Instrument Team [IT], and Campaign Team) and serves to disseminate the plans more generally within the ARM Program and among the members of the Science Team. This document includes a description of the operational status of the site and the primary envisaged site activities, together with information concerning approved and proposed Intensive Observation Periods (IOPs). Amendments will be prepared and distributed whenever the content changes by more than 30% within a six-month period. The primary users of this document are the site operator, the site scientist, the Science Team through the ARM Program Science Director, The ARM Program Experiment Center, and the aforementioned ARM Program functional teams. This plan is a living document that will be updated and reissued every six months as the observational facilities are developed, tested, and augmented and as priorities are adjusted in response to developments in scientific planning and understanding.« less

Compressed-sensing-based content-driven hierarchical reconstruction: Theory and application to C-arm cone-beam tomography

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

Langet, Hélène; Laboratoire des Signaux et Systèmes, CentraleSupélec, Gif-sur-Yvette F-91192; Center for Visual Computing, CentraleSupélec, Châtenay-Malabry F-92295

2015-09-15

Purpose: This paper addresses the reconstruction of x-ray cone-beam computed tomography (CBCT) for interventional C-arm systems. Subsampling of CBCT is a significant issue with C-arms due to their slow rotation and to the low frame rate of their flat panel x-ray detectors. The aim of this work is to propose a novel method able to handle the subsampling artifacts generally observed with analytical reconstruction, through a content-driven hierarchical reconstruction based on compressed sensing. Methods: The central idea is to proceed with a hierarchical method where the most salient features (high intensities or gradients) are reconstructed first to reduce the artifactsmore » these features induce. These artifacts are addressed first because their presence contaminates less salient features. Several hierarchical schemes aiming at streak artifacts reduction are introduced for C-arm CBCT: the empirical orthogonal matching pursuit approach with the ℓ{sub 0} pseudonorm for reconstructing sparse vessels; a convex variant using homotopy with the ℓ{sub 1}-norm constraint of compressed sensing, for reconstructing sparse vessels over a nonsparse background; homotopy with total variation (TV); and a novel empirical extension to nonlinear diffusion (NLD). Such principles are implemented with penalized iterative filtered backprojection algorithms. For soft-tissue imaging, the authors compare the use of TV and NLD filters as sparsity constraints, both optimized with the alternating direction method of multipliers, using a threshold for TV and a nonlinear weighting for NLD. Results: The authors show on simulated data that their approach provides fast convergence to good approximations of the solution of the TV-constrained minimization problem introduced by the compressed sensing theory. Using C-arm CBCT clinical data, the authors show that both TV and NLD can deliver improved image quality by reducing streaks. Conclusions: A flexible compressed-sensing-based algorithmic approach is proposed that is able to accommodate for a wide range of constraints. It is successfully applied to C-arm CBCT images that may not be so well approximated by piecewise constant functions.« less

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound.

PubMed

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-08-01

Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

PubMed Central

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-01-01

Background Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era where tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesize that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Study Design Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (Arm 1) versus SLNB (Arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Results 68 subjects were enrolled in the pilot phase of the trial (34 subjects in Arm 1, no further staging; 32 subjects in Arm 2, SLNB, and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40-80) in Arm 1 and 59 years (range 31-81) in Arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1-32). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (> 2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Conclusions Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. PMID:27212005

Shark island pedicle flap for repair of combined nasal ala-perialar defects.

PubMed

Cvancara, Joseph L; Wentzell, J Michael

2006-05-01

The combined nasal ala-perialar defect involving the concave intersection of the lateral nasal ala, nasal sidewall, cheek, and upper cutaneous lip is a problem for reconstructive surgery. During repair of combined cheek and nose defects, it is important not to blunt the alar facial sulcus. Defects involving these adjacent cosmetic units can be repaired by using combination procedures such as a flap/graft. Our purpose is to introduce, describe, and illustrate a one-stage flap repair descriptively named the "shark" island pedicle flap (SIPF). The SIPF was developed for a specific combined nasal ala-perialar defect. This reconstruction restores the natural contours, preserves cosmetic boundaries, and eliminates the need for pexing sutures and graft/flap combinations. The SIPF is an island pedicle flap with a superior arm that rotates 90 degrees into the wound. This arm repairs the alar portion of the defect. The advancing island pedicle flap repairs the alar facial sulcus. The 90 degrees rotation of the superior arm forces the alar portion of the flap to tilt 90 degrees relative to the remaining body of the flap, forming an inverted cone of redundancy. Natural re-creation of the lateral ala and the alar facial sulcus results. Illustrative examples with a descriptive technique are provided for the SIPF. A well-planned SIPF reconstruction can provide exceptional cosmetic and functional results. Cutaneous reconstructive surgeons will find the SIPF useful and reproducible in their armamentarium for single-stage aesthetic and functional repair of a specific combined lateral ala-adjacent perialar tissue defect.

Genetic insights into age-related macular degeneration: Controversies addressing Risk, Causality, and Therapeutics

PubMed Central

Gorin, Michael B.

2012-01-01

Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews.(Chen et al., 2010b; Deangelis et al., 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al., 2011) Large meta analysis of AMD GWAS has added new loci and variants to this collection.(Chen et al., 2010a; Kopplin et al., 2010; Yu et al., 2011) This paper will focus on the ongoing controversies that are confronting AMD genetics at this time, rather than attempting to summarize this field, which has exploded in the past 5 years. PMID:22561651

A Short Note on the Derivation of the Atmospheric Transfer Function for a Communications Channel and its Connection to Associated Propagation Parameters

NASA Technical Reports Server (NTRS)

Manning, Robert M.

2004-01-01

The systems engineering description of a wideband communications channel is provided which is based upon the fundamental propagation aspects of the problem. In particular, the well known time variant description of a channel is formulated from the basic multiple scattering processes that occur in a random propagation medium. Such a connection is required if optimal processing methods are to be applied to mitigate the deleterious random fading and multipathing of the channel. An example is given which demonstrates how the effective bandwidth of the channel is diminished due to atmospheric propagation impairments.

Split-core heat-pipe reactors for out-of-pile thermionic power systems.

NASA Technical Reports Server (NTRS)

Niederauer, G.; Lantz, E.; Breitweiser, R.

1971-01-01

Description of the concept of splitting a heat-pipe reactor for out-of-core thermionics into two identical halves and using the resulting center gap for reactivity control. Short Li-W reactor heat pipes penetrate the axial reflectors and form a heat exchanger with long heat pipes which wind through the shield to the thermionic diodes. With one reactor half anchored to the shield, the other is attached to a long arm with a pivot behind the shield and swings through a small arc for reactivity control. A safety shim prevents large reactivity inputs, and a fueled control arm drive shaft acts as a power stabilizer. Reactors fueled with U-235C and with U-233C have been studied.-

Characteristics of microstrip muscle-loaded single-arm Archimedean spiral antennas as investigated by FDTD numerical computations.

PubMed

Jacobsen, Svein; Rolfsnes, Hans Olav; Stauffer, Paul R

2005-02-01

The radiation characteristics and mode of operation of single-arm, groundplane backed, Archimedean spiral antennas are investigated by means of conformal finite difference time domain numerical analysis. It is shown that this antenna type may be categorized as a well-matched, broadband, circularly polarized traveling wave structure that can be fed directly by nonbalanced coaxial networks. The study further concentrates on relevant design and description features parameterized in terms of measures like radiation efficiency, sensing depth, directivity, and axial ratio of complementary polarizations. We document that an antenna of only 30-mm transverse size produces circularly polarized waves in a two-octave frequency span (2-8 GHz) with acceptable radiation efficiency (76%-94%) when loaded by muscle-like tissue.

Telerobotic controller development

NASA Technical Reports Server (NTRS)

Otaguro, W. S.; Kesler, L. O.; Land, Ken; Rhoades, Don

1987-01-01

To meet NASA's space station's needs and growth, a modular and generic approach to robotic control which provides near-term implementation with low development cost and capability for growth into more autonomous systems was developed. The method uses a vision based robotic controller and compliant hand integrated with the Remote Manipulator System arm on the Orbiter. A description of the hardware and its system integration is presented.

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

Bartholomew, Mary Jane

To improve the quantitative description of precipitation processes in climate models, the U.S. Department of Energy (DOE)’s Atmospheric Radiation Measurement (ARM) Climate Research Facility deploys several types of rain gauges (MET, RAIN, and optical rain gauge [ORG] datastreams) as well as disdrometers (DISD and VDIS datastreams) at the Southern Great Plains (SGP) Site. This handbook deals specifically with the independent analog ORG (i.e., the ORG datastream).

Mexican waves in an excitable medium.

PubMed

Farkas, I; Helbing, D; Vicsek, T

2002-09-12

The Mexican wave, or La Ola, which rose to fame during the 1986 World Cup in Mexico, surges through the rows of spectators in a stadium as those in one section leap to their feet with their arms up, and then sit down again as the next section rises to repeat the motion. To interpret and quantify this collective human behaviour, we have used a variant of models that were originally developed to describe excitable media such as cardiac tissue. Modelling the reaction of the crowd to attempts to trigger the wave reveals how this phenomenon is stimulated, and may prove useful in controlling events that involve groups of excited people.

DNA Fragmentation Factor 45 (DFF45) Gene at 1p36.2 Is Homozygously Deleted and Encodes Variant Transcripts in Neuroblastoma Cell Line1

PubMed Central

Yang, Hong Wei; Chen, Ying Zhang; Piao, Hui Ying; Takita, Junko; Soeda, Eiichi; Hayashi, Yasuhide

2001-01-01

Abstract Recently, loss of heterozygosity (LOH) studies suggest that more than two tumor suppressor genes lie on the short arm of chromosome 1 (1p) in neuroblastoma (NB). To identify candidate tumor suppressor genes in NB, we searched for homozygous deletions in 20 NB cell lines using a high-density STS map spanning chromosome 1p36, a common LOH region in NB. We found that the 45-kDa subunit of the DNA fragmentation factor (DFF45) gene was homozygously deleted in an NB cell line, NB-1. DFF45 is the chaperon of DFF40, and both molecules are necessary for caspase 3 to induce apoptosis. DFF35, a splicing variant of DFF45, is an inhibitor of DFF40. We examined 20 NB cell lines for expression and mutation of DFF45 gene by reverse transcription (RT)-polymerase chain reaction (PCR) and RT-PCR-single-strand conformation polymorphism. Some novel variant transcripts of the DFF45 gene were found in NB cell lines, but not in normal adrenal gland and peripheral blood. These variants may not serve as chaperons of DFF40, but as inhibitors like DFF35, thus disrupting the balance between DFF45 and DFF40. No mutations of the DFF45 gene were found in any NB cell line, suggesting that the DFF45 is not a tumor suppressor gene for NB. However, homozygous deletion of the DFF45 gene in the NB-1 cell line may imply the presence of unknown tumor suppressor genes in this region. PMID:11420752

HTR1B gene variants associate with the susceptibility of Raynauds' phenomenon in workers exposed hand-arm vibration.

PubMed

Chen, Qingsong; Lang, Li; Xiao, Bin; Lin, Hansheng; Yang, Aichu; Li, Hongling; Tang, Shichuan; Huang, Hanlin

2016-10-05

To explore whether polymorphic variants of the HTR1B gene are associated with the susceptibility of Raynauds' Phenomenon (RP) coursed by vibration. 148 subjects exposed to vibration for more than 2 years were classified into either induced white finger (VWF) group (n = 72), or non-VWF group (n = 76). Vibration exposure levels were measured and assessed following ISO 5349-1:2001 protocol. All workers were genotyped by sequencing for the single nucleotide polymorphisms (SNPs) in the 5'-flanking and coding region of HTR1B. Genetic characteristics and linkage disequilibrium (LD) were analyzed with Haploview. Serum serotonin levels of each subject were detected using ELISA. The association between the susceptibility of vascular damage and genotype was analyzed via logistic regression. 7 known SNPs were obtained and their allele frequencies were inserted into the Hardy-Weinberg equilibrium. rs6297 variant genotype had an increased risk of VWF compared with wild genotype (OR = 2.14, 95% CI = 1.04- 4.58, P < 0.05). rs6298 mutant type (AG+GG) was found to have a significant interaction on vibration exposure LN(CEI), accounting for VWF occurrence. LN(5-HT) level is significantly different between the VWF group (x¯±s= 1.99±1.09 ng/mL) and the non-VWF group (x¯±s= 2.72±1.47 ng/mL). Serotonin levels may affect the progression of secondary RP. Polymorphic variants of the HTR1B gene are associated with the susceptibility of secondary RP in vibration-exposed occupational populations of Chinese Han people.

Simultaneous Genotyping of the rs4762 and rs699 Polymorphisms in Angiotensinogen Gene and Correlation with Iranian CAD Patients with Novel Hexa-primer ARMS-PCR

PubMed Central

KHATAMI, Mehri; HEIDARI, Mohammad Mehdi; HADADZADEH, Mehdi; SCHEIBER-MOJDEHKAR, Barbara; BITARAF SANI, Morteza; HOUSHMAND, Massoud

2017-01-01

Background: A significant role of Renin-angiotensin system (RAS) genetic variants in the pathogenesis of essential hypertension and cardiovascular diseases has been proved. This study aimed to develop a new, fast and cheap method for the simultaneous detection of two missense single nucleotide polymorphisms (T207M or rs4762 and M268T orrs699) of angiotensinogen (AGT) in single-step Multiplex Hexa-Primer Amplification Refractory Mutation System - polymerase chain reaction (H-ARMS-PCR). Methods: In this case-control study, 148 patients with coronary artery disease (CAD) and 135 controls were included. The patients were referred to cardiac centers in Afshar Hospital (Yazd, Iran) from 2012 to 2015. Two sets of inner primer (for each SNP) and one set outer primer pairs were designed for genotyping of rs4762 and rs699 in single tube H-ARMS-PCR. Direct sequencing of all samples was also performed to assess the accuracy of this method. DNA sequencing method validated the results of single tube H-ARMS-PCR. Results: We found full accordance for genotype adscription by sequencing method. The frequency of the AGT T521 and C702 alleles was significantly higher in CAD patients than in the control group (OR: 0.551, 95% CI: 0.359–0.846, P=0.008 and OR: 0.629, 95% CI: 0.422–0.936, P=0.028, respectively). Conclusion: This is the first work describing a rapid, low-cost, high-throughput simultaneous detection of rs4762 and rs699 polymorphisms in AGT gene, used in large clinical studies. PMID:28828324

Contextual Multi-armed Bandits under Feature Uncertainty

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

Yun, Seyoung; Nam, Jun Hyun; Mo, Sangwoo

We study contextual multi-armed bandit problems under linear realizability on rewards and uncertainty (or noise) on features. For the case of identical noise on features across actions, we propose an algorithm, coined NLinRel, having O(T⁷/₈(log(dT)+K√d)) regret bound for T rounds, K actions, and d-dimensional feature vectors. Next, for the case of non-identical noise, we observe that popular linear hypotheses including NLinRel are impossible to achieve such sub-linear regret. Instead, under assumption of Gaussian feature vectors, we prove that a greedy algorithm has O(T²/₃√log d)regret bound with respect to the optimal linear hypothesis. Utilizing our theoretical understanding on the Gaussian case,more » we also design a practical variant of NLinRel, coined Universal-NLinRel, for arbitrary feature distributions. It first runs NLinRel for finding the ‘true’ coefficient vector using feature uncertainties and then adjust it to minimize its regret using the statistical feature information. We justify the performance of Universal-NLinRel on both synthetic and real-world datasets.« less

Text-mined phenotype annotation and vector-based similarity to improve identification of similar phenotypes and causative genes in monogenic disease patients.

PubMed

Saklatvala, Jake R; Dand, Nick; Simpson, Michael A

2018-05-01

The genetic diagnosis of rare monogenic diseases using exome/genome sequencing requires the true causal variant(s) to be identified from tens of thousands of observed variants. Typically a virtual gene panel approach is taken whereby only variants in genes known to cause phenotypes resembling the patient under investigation are considered. With the number of known monogenic gene-disease pairs exceeding 5,000, manual curation of personalized virtual panels using exhaustive knowledge of the genetic basis of the human monogenic phenotypic spectrum is challenging. We present improved probabilistic methods for estimating phenotypic similarity based on Human Phenotype Ontology annotation. A limitation of existing methods for evaluating a disease's similarity to a reference set is that reference diseases are typically represented as a series of binary (present/absent) observations of phenotypic terms. We evaluate a quantified disease reference set, using term frequency in phenotypic text descriptions to approximate term relevance. We demonstrate an improved ability to identify related diseases through the use of a quantified reference set, and that vector space similarity measures perform better than established information content-based measures. These improvements enable the generation of bespoke virtual gene panels, facilitating more accurate and efficient interpretation of genomic variant profiles from individuals with rare Mendelian disorders. These methods are available online at https://atlas.genetics.kcl.ac.uk/~jake/cgi-bin/patient_sim.py. © 2018 Wiley Periodicals, Inc.

Language change in a multiple group society

NASA Astrophysics Data System (ADS)

Pop, Cristina-Maria; Frey, Erwin

2013-08-01

The processes leading to change in languages are manifold. In order to reduce ambiguity in the transmission of information, agreement on a set of conventions for recurring problems is favored. In addition to that, speakers tend to use particular linguistic variants associated with the social groups they identify with. The influence of other groups propagating across the speech community as new variant forms sustains the competition between linguistic variants. With the utterance selection model, an evolutionary description of language change, Baxter [Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.73.046118 73, 046118 (2006)] have provided a mathematical formulation of the interactions inside a group of speakers, exploring the mechanisms that lead to or inhibit the fixation of linguistic variants. In this paper, we take the utterance selection model one step further by describing a speech community consisting of multiple interacting groups. Tuning the interaction strength between groups allows us to gain deeper understanding about the way in which linguistic variants propagate and how their distribution depends on the group partitioning. Both for the group size and the number of groups we find scaling behaviors with two asymptotic regimes. If groups are strongly connected, the dynamics is that of the standard utterance selection model, whereas if their coupling is weak, the magnitude of the latter along with the system size governs the way consensus is reached. Furthermore, we find that a high influence of the interlocutor on a speaker's utterances can act as a counterweight to group segregation.

PNPLA3 expression and its impact on the liver: current perspectives

PubMed Central

Bruschi, Francesca Virginia; Tardelli, Matteo; Claudel, Thierry; Trauner, Michael

2017-01-01

A single-nucleotide polymorphism occurring in the sequence of the human patatin-like phospholipase domain-containing 3 gene (PNPLA3), known as I148M variant, is one of the best characterized and deeply investigated variants in several clinical scenarios, because of its tight correlation with increased risk for developing hepatic steatosis and more aggressive part of the disease spectrum, such as nonalcoholic steatohepatitis, advanced fibrosis and cirrhosis. Further, the I148M variant is positively associated with alcoholic liver diseases, chronic hepatitis C–related cirrhosis and hepatocellular carcinoma. The native gene encodes for a protein that has not yet a fully defined role in liver lipid metabolism and, according to recent observations, seems to be divergently regulated among distinct liver cells type, such as hepatic stellate cells. Therefore, the aim of this review is to collect the latest data regarding PNPLA3 expression in human liver and to analyze the impact of its genetic variant in human hepatic pathologies. Moreover, a description of the current biochemical and metabolic data pertaining to PNPLA3 function in both animal models and in vitro studies is summarized to allow a better understanding of the relevant pathophysiological role of this enzyme in the progression of hepatic diseases. PMID:29158695

Cloaca--Historical aspects and terminology.

PubMed

Peña, Alberto

2016-04-01

This is a summary of the milestones in the history of the treatment of cloacal malformations. It is based in a comprehensive literature review of the subject, from the early times, followed by a description of the evolution of the surgical maneuvers that were created, to be able to deal with the different anatomical variants of this complex congenital malformation. Copyright © 2016 Elsevier Inc. All rights reserved.

Defense Trade. Clarification and More Comprehensive Oversight of Export Exemptions Certified by DOD Are Needed

DTIC Science & Technology

2007-09-01

Identified in DTSA Guidelines for Military Service Certification and ITAR Exemption Description 8 Table 2: GAO Analysis of DOD Exemption... DTSA Defense Technology Security Administration ITAR International Traffic in Arms Regulations NATO North Atlantic Treaty Organization This is...and friendly nations. To clarify exemption use, DOD’s Defense Technology Security Administration ( DTSA )—which is responsible for developing and

Using the MEDiPORT humanoid robot to reduce procedural pain and distress in children with cancer: A pilot randomized controlled trial.

PubMed

Jibb, Lindsay A; Birnie, Kathryn A; Nathan, Paul C; Beran, Tanya N; Hum, Vanessa; Victor, J Charles; Stinson, Jennifer N

2018-06-12

Subcutaneous port needle insertions are painful and distressing for children with cancer. The interactive MEDiPORT robot has been programmed to implement psychological strategies to decrease pain and distress during this procedure. This study assessed the feasibility of a future MEDiPORT trial. The secondary aim was to determine the preliminary effectiveness of MEDiPORT in reducing child pain and distress during subcutaneous port accesses. This 5-month pilot randomized controlled trial used a web-based service to randomize 4- to 9-year-olds with cancer to the MEDiPORT cognitive-behavioral arm (robot using evidence-based cognitive-behavioral interventions) or active distraction arm (robot dancing and singing) while a nurse conducted a needle insertion. We assessed accrual and retention; technical difficulties; outcome measure completion by children, parents, and nurses; time taken to complete the study and clinical procedure; and child-, parent-, and nurse-rated acceptability. Descriptive analyses, with exploratory inferential testing of child pain and distress data, were used to address study aims. Forty children were randomized across study arms. Most (85%) eligible children participated and no children withdrew. Technical difficulties were more common in the cognitive-behavioral arm. Completion times for the study and needle insertion were acceptable and >96% of outcome measure items were completed. Overall, MEDiPORT and the study were acceptable to participants. There was no difference in pain between arms, but distress during the procedure was less pronounced in the active distraction arm. The MEDiPORT study appears feasible to implement as an adequately-powered effectiveness-assessing trial following modifications to the intervention and study protocol. ClinicalTrials.gov NCT02611739. © 2018 Wiley Periodicals, Inc.

Loss of Productivity Due to Neck/Shoulder Symptoms and Hand/Arm Symptoms: Results from the PROMO-Study

PubMed Central

IJmker, Stefan; Blatter, Birgitte M.; de Korte, Elsbeth M.

2007-01-01

Introduction The objective of the present study is to describe the extent of productivity loss among computer workers with neck/shoulder symptoms and hand/arm symptoms, and to examine associations between pain intensity, various physical and psychosocial factors and productivity loss in computer workers with neck/shoulder and hand/arm symptoms. Methods A cross-sectional design was used. The study population consisted of 654 computer workers with neck/shoulder or hand/arm symptoms from five different companies. Descriptive statistics were used to describe the occurrence of self-reported productivity loss. Logistic regression analyses were used to examine the associations. Results In 26% of all the cases reporting symptoms, productivity loss was involved, the most often in cases reporting both symptoms (36%). Productivity loss involved sickness absence in 11% of the arm/hand cases, 32% of the neck/shoulder cases and 43% of the cases reporting both symptoms. The multivariate analyses showed statistically significant odds ratios for pain intensity (OR: 1.26; CI: 1.12–1.41), for high effort/no low reward (OR: 2.26; CI: 1.24–4.12), for high effort/low reward (OR: 1.95; CI: 1.09–3.50), and for low job satisfaction (OR: 3.10; CI: 1.44–6.67). Physical activity in leisure time, full-time work and overcommitment were not associated with productivity loss. Conclusion In most computer workers with neck/shoulder symptoms or hand/arm symptoms productivity loss derives from a decreased performance at work and not from sickness absence. Favorable psychosocial work characteristics might prevent productivity loss in symptomatic workers. PMID:17636455

Are we armed with the right data? Pooled individual data review of biomarkers in people with severe upper limb impairment after stroke.

PubMed

Hayward, Kathryn S; Schmidt, Julia; Lohse, Keith R; Peters, Sue; Bernhardt, Julie; Lannin, Natasha A; Boyd, Lara A

2017-01-01

To build an understanding of the neurobiology underpinning arm recovery in people with severe arm impairment due to stroke, we conducted a pooled individual data systematic review to: 1) characterize brain biomarkers; 2) determine relationship(s) between biomarkers and motor outcome; and 3) establish relationship(s) between biomarkers and motor recovery. Three electronic databases were searched up to October 2, 2015. Eligible studies included adults with severe arm impairment after stroke. Descriptive statistics were calculated to characterize brain biomarkers, and pooling of individual patient data was performed using mixed-effects linear regression to examine relationships between brain biomarkers and motor outcome and recovery. Thirty-eight articles including individual data from 372 people with severe arm impairment were analysed. The majority of individuals were in the chronic (> 6 months) phase post stroke (51%) and had a subcortical stroke (49%). The presence of a motor evoked potential (indexed by transcranial magnetic stimulation) was the only biomarker related to better motor outcome ( p  = 0.02). There was no relationship between motor outcome and stroke volume (cm 3 ), location (cortical, subcortical, mixed) or side (left vs. right), and corticospinal tract asymmetry index (extracted from diffusion weighted imaging). Only one study had longitudinal data, thus no data pooling was possible to address change over time (preventing our third objective). Based on the available evidence, motor evoked potentials at rest were the only biomarker that predicted motor outcome in individuals with severe arm impairment following stroke. Given that few biomarkers emerged, this review highlights the need to move beyond currently known biomarkers and identify new indices with sufficient variability and sensitivity to guide recovery models in individuals with severe motor impairments following stroke. CRD42015026107.

Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.

PubMed

Bridge, Julia A; Liu, Jian; Qualman, Stephen J; Suijkerbuijk, Ron; Wenger, Gail; Zhang, Ji; Wan, Xiaoying; Baker, K Scott; Sorensen, Poul; Barr, Frederic G

2002-03-01

In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas. Copyright 2002 Wiley-Liss, Inc.

Kinematic model for the space-variant image motion of star sensors under dynamical conditions

NASA Astrophysics Data System (ADS)

Liu, Chao-Shan; Hu, Lai-Hong; Liu, Guang-Bin; Yang, Bo; Li, Ai-Jun

2015-06-01

A kinematic description of a star spot in the focal plane is presented for star sensors under dynamical conditions, which involves all necessary parameters such as the image motion, velocity, and attitude parameters of the vehicle. Stars at different locations of the focal plane correspond to the slightly different orientation and extent of motion blur, which characterize the space-variant point spread function. Finally, the image motion, the energy distribution, and centroid extraction are numerically investigated using the kinematic model under dynamic conditions. A centroid error of eight successive iterations <0.002 pixel is used as the termination criterion for the Richardson-Lucy deconvolution algorithm. The kinematic model of a star sensor is useful for evaluating the compensation algorithms of motion-blurred images.

Morphological Analysis of Bronchial Arteries and Variants with Computed Tomography Angiography.

PubMed

Esparza-Hernández, Claudia Nallely; Ramírez-González, Juan Manuel; Cuéllar-Lozano, Rolando Alberto; Morales-Avalos, Rodolfo; González-Arocha, Carla Sofía; Martínez-González, Brenda; Quiroga-Garza, Alejandro; Pinales-Razo, Ricardo; Elizondo-Riojas, Guillermo; Elizondo-Omaña, Rodrigo Enrique; Guzmán-López, Santos

2017-01-01

The aim of our study was to determine the prevalence of anatomical variants of bronchial arteries using computed tomographic angiography in a population of northeastern Mexico. An observational, transversal, descriptive, comparative, retrospective study was performed using 139 imaging studies of Mexican patients in which we evaluated the following parameters from the left and right bronchial arteries: artery origin, branching pattern, arterial ostium, vertebral level of origin, diameter, and mediastinal trajectory. The anatomies of the bronchial arteries were similar in both genders, except distribution for vertebral origin level ( p   0.006) and the diameter ( p   0.013). Left and right arteries were similar, except for the mediastinal trajectory in reference to the esophagus ( p < 0.001) as well as the arterial diameter ( p < 0.001) and lumen diameter.

The PHOBOS detector at RHIC

NASA Astrophysics Data System (ADS)

Back, B. B.; Baker, M. D.; Barton, D. S.; Basilev, S.; Baum, R.; Betts, R. R.; Białas, A.; Bindel, R.; Bogucki, W.; Budzanowski, A.; Busza, W.; Carroll, A.; Ceglia, M.; Chang, Y.-H.; Chen, A. E.; Coghen, T.; Connor, C.; Czyż, W.; Dabrowski, B.; Decowski, M. P.; Despet, M.; Fita, P.; Fitch, J.; Friedl, M.; Gałuszka, K.; Ganz, R.; Garcia, E.; George, N.; Godlewski, J.; Gomes, C.; Griesmayer, E.; Gulbrandsen, K.; Gushue, S.; Halik, J.; Halliwell, C.; Haridas, P.; Hayes, A.; Heintzelman, G. A.; Henderson, C.; Hollis, R.; Hołyński, R.; Hofman, D.; Holzman, B.; Johnson, E.; Kane, J.; Katzy, J.; Kita, W.; Kotuła, J.; Kraner, H.; Kucewicz, W.; Kulinich, P.; Law, C.; Lemler, M.; Ligocki, J.; Lin, W. T.; Manly, S.; McLeod, D.; Michałowski, J.; Mignerey, A.; Mülmenstädt, J.; Neal, M.; Nouicer, R.; Olszewski, A.; Pak, R.; Park, I. C.; Patel, M.; Pernegger, H.; Plesko, M.; Reed, C.; Remsberg, L. P.; Reuter, M.; Roland, C.; Roland, G.; Ross, D.; Rosenberg, L.; Ryan, J.; Sanzgiri, A.; Sarin, P.; Sawicki, P.; Scaduto, J.; Shea, J.; Sinacore, J.; Skulski, W.; Steadman, S. G.; Stephans, G. S. F.; Steinberg, P.; Straczek, A.; Stodulski, M.; Strek, M.; Stopa, Z.; Sukhanov, A.; Surowiecka, K.; Tang, J.-L.; Teng, R.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Verdier, R.; Wadsworth, B.; Wolfs, F. L. H.; Wosiek, B.; Woźniak, K.; Wuosmaa, A. H.; Wysłouch, B.; Zalewski, K.; Żychowski, P.; Phobos Collaboration

2003-03-01

This manuscript contains a detailed description of the PHOBOS experiment as it is configured for the Year 2001 running period. It is capable of detecting charged particles over the full solid angle using a multiplicity detector and measuring identified charged particles near mid-rapidity in two spectrometer arms with opposite magnetic fields. Both of these components utilize silicon pad detectors for charged particle detection. The minimization of material between the collision vertex and the first layers of silicon detectors allows for the detection of charged particles with very low transverse momenta, which is a unique feature of the PHOBOS experiment. Additional detectors include a time-of-flight wall which extends the particle identification range for one spectrometer arm, as well as sets of scintillator paddle and Cherenkov detector arrays for event triggering and centrality selection.

Neurology of anomia in the semantic variant of primary progressive aphasia

PubMed Central

Rogalski, Emily; Wieneke, Christina; Cobia, Derin; Rademaker, Alfred; Thompson, Cynthia; Weintraub, Sandra

2009-01-01

The semantic variant of primary progressive aphasia (PPA) is characterized by the combination of word comprehension deficits, fluent aphasia and a particularly severe anomia. In this study, two novel tasks were used to explore the factors contributing to the anomia. The single most common factor was a blurring of distinctions among members of a semantic category, leading to errors of overgeneralization in word–object matching tasks as well as in word definitions and object descriptions. This factor was more pronounced for natural kinds than artifacts. In patients with the more severe anomias, conceptual maps were more extensively disrupted so that inter-category distinctions were as impaired as intra-category distinctions. Many objects that could not be named aloud could be matched to the correct word in patients with mild but not severe anomia, reflecting a gradual intensification of the semantic factor as the naming disorder becomes more severe. Accurate object descriptions were more frequent than accurate word definitions and all patients experienced prominent word comprehension deficits that interfered with everyday activities but no consequential impairment of object usage or face recognition. Magnetic resonance imaging revealed three characteristics: greater atrophy of the left hemisphere; atrophy of anterior components of the perisylvian language network in the superior and middle temporal gyri; and atrophy of anterior components of the face and object recognition network in the inferior and medial temporal lobes. The left sided asymmetry and perisylvian extension of the atrophy explains the more profound impairment of word than object usage and provides the anatomical basis for distinguishing the semantic variant of primary progressive aphasia from the partially overlapping group of patients that fulfil the widely accepted diagnostic criteria for semantic dementia. PMID:19506067

Neurology of anomia in the semantic variant of primary progressive aphasia.

PubMed

Mesulam, Marsel; Rogalski, Emily; Wieneke, Christina; Cobia, Derin; Rademaker, Alfred; Thompson, Cynthia; Weintraub, Sandra

2009-09-01

The semantic variant of primary progressive aphasia (PPA) is characterized by the combination of word comprehension deficits, fluent aphasia and a particularly severe anomia. In this study, two novel tasks were used to explore the factors contributing to the anomia. The single most common factor was a blurring of distinctions among members of a semantic category, leading to errors of overgeneralization in word-object matching tasks as well as in word definitions and object descriptions. This factor was more pronounced for natural kinds than artifacts. In patients with the more severe anomias, conceptual maps were more extensively disrupted so that inter-category distinctions were as impaired as intra-category distinctions. Many objects that could not be named aloud could be matched to the correct word in patients with mild but not severe anomia, reflecting a gradual intensification of the semantic factor as the naming disorder becomes more severe. Accurate object descriptions were more frequent than accurate word definitions and all patients experienced prominent word comprehension deficits that interfered with everyday activities but no consequential impairment of object usage or face recognition. Magnetic resonance imaging revealed three characteristics: greater atrophy of the left hemisphere; atrophy of anterior components of the perisylvian language network in the superior and middle temporal gyri; and atrophy of anterior components of the face and object recognition network in the inferior and medial temporal lobes. The left sided asymmetry and perisylvian extension of the atrophy explains the more profound impairment of word than object usage and provides the anatomical basis for distinguishing the semantic variant of primary progressive aphasia from the partially overlapping group of patients that fulfil the widely accepted diagnostic criteria for semantic dementia.

The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

PubMed

Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

2016-06-01

Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of Constitutional and Replication Stress-Induced Genome Structural Variation by SNP Array and Mate-Pair Sequencing

PubMed Central

Arlt, Martin F.; Ozdemir, Alev Cagla; Birkeland, Shanda R.; Lyons, Robert H.; Glover, Thomas W.; Wilson, Thomas E.

2011-01-01

Copy-number variants (CNVs) are a major source of genetic variation in human health and disease. Previous studies have implicated replication stress as a causative factor in CNV formation. However, existing data are technically limited in the quality of comparisons that can be made between human CNVs and experimentally induced variants. Here, we used two high-resolution strategies—single nucleotide polymorphism (SNP) arrays and mate-pair sequencing—to compare CNVs that occur constitutionally to those that arise following aphidicolin-induced DNA replication stress in the same human cells. Although the optimized methods provided complementary information, sequencing was more sensitive to small variants and provided superior structural descriptions. The majority of constitutional and all aphidicolin-induced CNVs appear to be formed via homology-independent mechanisms, while aphidicolin-induced CNVs were of a larger median size than constitutional events even when mate-pair data were considered. Aphidicolin thus appears to stimulate formation of CNVs that closely resemble human pathogenic CNVs and the subset of larger nonhomologous constitutional CNVs. PMID:21212237

Theoretical description of RESPIRATION-CP

NASA Astrophysics Data System (ADS)

Nielsen, Anders B.; Tan, Kong Ooi; Shankar, Ravi; Penzel, Susanne; Cadalbert, Riccardo; Samoson, Ago; Meier, Beat H.; Ernst, Matthias

2016-02-01

We present a quintuple-mode operator-based Floquet approach to describe arbitrary amplitude modulated cross polarization experiments under magic-angle spinning (MAS). The description is used to analyze variants of the RESPIRATION approach (RESPIRATIONCP) where recoupling conditions and the corresponding first-order effective Hamiltonians are calculated, validated numerically and compared to experimental results for 15N-13C coherence transfer in uniformly 13C,15N-labeled alanine and in uniformly 2H,13C,15N-labeled (deuterated and 100% back-exchanged) ubiquitin at spinning frequencies of 16.7 and 90.9 kHz. Similarities and differences between different implementations of the RESPIRATIONCP sequence using either CW irradiation or small flip-angle pulses are discussed.

Refinement of Optimal Work Envelope for Extra-Vehicular Activity (EVA) Suit Operations

NASA Technical Reports Server (NTRS)

Jaramillo, Marcos A.; Angermiller, Bonnie L.; Morency, Richard M.; Rajululu, Sudhakar L.

2008-01-01

The purpose of the Extravehicular Mobility Unit (EMU) Work Envelope study is to determine and revise the work envelope defined in NSTS 07700 "System Description and Design Data - Extravehicular Activities" [1], arising from an action item as a result of the Shoulder Injury Tiger Team findings. The aim of this study is to determine a common work envelope that will encompass a majority of the crew population while minimizing the possibility of shoulder and upper arm injuries. There will be approximately two phases of testing: arm sweep analysis to be performed in the Anthropometry and Biomechanics Facility (ABF), and torso lean testing to be performed on the Precision Air Bearing Facility (PABF). NSTS 07700 defines the preferred work envelope arm reach in terms of maximum reach, and defines the preferred work envelope torso flexibility of a crewmember to be a net 45 degree backwards lean [1]. This test served two functions: to investigate the validity of the standard discussed in NSTS 07700, and to provide recommendations to update this standard if necessary.

Lake Sturgeon, Acipenser fulvescens, movements in Rainy Lake, Minnesota and Ontario

USGS Publications Warehouse

Adams, W.E.; Kallemeyn, L.W.; Willis, D.W.

2006-01-01

Rainy Lake, Minnesota-Ontario, contains a native population of Lake Sturgeon (Acipenser fulvescens) that has gone largely unstudied. The objective of this descriptive study was to summarize generalized Lake Sturgeon movement patterns through the use of biotelemetry. Telemetry data reinforced the high utilization of the Squirrel Falls geographic location by Lake Sturgeon, with 37% of the re-locations occurring in that area. Other spring aggregations occurred in areas associated with Kettle Falls, the Pipestone River, and the Rat River, which could indicate spawning activity. Movement of Lake Sturgeon between the Seine River and the South Arm of Rainy Lake indicates the likelihood of one integrated population on the east end of the South Arm. The lack of re-locations in the Seine River during the months of September and October may have been due to Lake Sturgeon moving into deeper water areas of the Seine River and out of the range of radio telemetry gear or simply moving back into the South Arm. Due to the movements between Minnesota and Ontario, coordination of management efforts among provincial, state, and federal agencies will be important.

Voluntary control of arm movement in athetotic patients

PubMed Central

Neilson, Peter D.

1974-01-01

Visual tracking tests have been employed to provide a quantitative description of voluntary control of arm movement in a group of patients suffering from athetoid cerebral palsy. Voluntary control was impaired in all patients in a characteristic manner. Maximum velocity and acceleration of arm movement were reduced to about 30-50% of their values in normal subjects and the time lag of the response to a visual stimulus was two or three times greater than in normals. Tracking transmission characteristics indicated a degree of underdamping which was not presnet in normal or spastic patients. This underdamping could be responsible for a low frequency (0·3-0·6 Hz) transient oscillation in elbow-angle movements associated with sudden voluntary movement. The maximum frequency at which patients could produce a coherent tracking response was only 50% of that in normal subjects and the relationship between the electromyogram and muscle contraction indicated that the mechanical load on the biceps muscle was abnormal, possibly due to increased stiffness of joint movement caused by involuntary activity in agonist and antagonist muscles acting across the joint. Images PMID:4362243

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

Palanisamy, Giri

The U.S. Department of Energy (DOE)’s Atmospheric Radiation Measurement (ARM) Climate Research Facility performs routine in situ and remote-sensing observations to provide a detailed and accurate description of the Earth atmosphere in diverse climate regimes. The result is a huge archive of diverse data sets containing observational and derived data, currently accumulating at a rate of 30 terabytes (TB) of data and 150,000 different files per month (http://www.archive.arm.gov/stats/). Continuing the current processing while scaling this to even larger sizes is extremely important to the ARM Facility and requires consistent metadata and data standards. The standards described in this document willmore » enable development of automated analysis and discovery tools for the ever growing data volumes. It will enable consistent analysis of the multiyear data, allow for development of automated monitoring and data health status tools, and allow future capabilities of delivering data on demand that can be tailored explicitly for the user needs. This analysis ability will only be possible if the data follows a minimum set of standards. This document proposes a hierarchy of required and recommended standards.« less

Use of the DEKA Arm for amputees with brachial plexus injury: A case series

PubMed Central

Fantini, Christopher; Latlief, Gail; Phillips, Samuel; Sasson, Nicole; Sepulveda, Eve

2017-01-01

Objective Patients with upper limb amputation and brachial plexus injuries have high rates of prosthesis rejection. Study purpose is to describe experiences of subjects with transhumeral amputation and brachial plexus injury, who were fit with, and trained to use, a DEKA Arm. Methods This was a mixed-methods study utilizing qualitative (e.g. interview, survey) and quantitative data (e.g. self-report and performance measures). Subject 1, a current prosthesis user, had a shoulder arthrodesis. Subject 2, not a prosthesis user, had a subluxed shoulder. Both were trained in laboratory and participated in a trial of home use. Descriptive analyses of processes and outcomes were conducted. Results Subject 1 was fitted with the transhumeral configuration (HC) DEKA Arm using a compression release stabilized socket. He had 12 hours of prosthetic training and participated in all home study activities. Subject 1 had improved dexterity and prosthetic satisfaction with the DEKA Arm and reported better quality of life (QOL) at the end of participation. Subject 2 was fit with the shoulder configuration (SC) DEKA Arm using a modified X-frame socket. He had 30 hours of training and participated in 3 weeks of home activities. He reported less functional disability at the end of training as compared to baseline, but encountered personal problems and exacerbation of PTSD symptoms and withdrew from home use portion at 3 weeks. Both subjects reported functional benefits from use, and expressed a desire to receive a DEKA Arm in the future. Discussion This paper reported on two different strategies for prosthetic fitting and their outcomes. The advantages and limitations of each approach were discussed. Conclusion Use of both the HC and SC DEKA Arm for patients with TH amputation and brachial plexus injury was reported. Lessons learned may be instructive to clinicians considering prosthetic choices for future cases. PMID:28628623

A systematic review of the etiopathogenesis of Kienböck's disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration.

PubMed

Stahl, Stéphane; Stahl, Adelana Santos; Meisner, Christoph; Rahmanian-Schwarz, Afshin; Schaller, Hans-Eberhard; Lotter, Oliver

2012-11-21

We systematically reviewed etiological factors of Kienböck's disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck's disease (KD) in the European Listing of Occupational Diseases. We searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria. A total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration. A systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand-arm vibration is a risk factor for KD.

The PNPLA3 I148M variant is associated with transaminase elevations in type 2 diabetes patients treated with basal insulin peglispro.

PubMed

Pillai, S; Duvvuru, S; Bhatnagar, P; Foster, W; Farmen, M; Shankar, S; Harris, C; Bastyr, E; Hoogwerf, B; Haupt, A

2018-05-22

Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials. Magnetic resonance imaging assessments of LFC were conducted in a subset of patients (n=296). Analyses showed α-corrected significant increases in change from baseline in AST (P=0.0004) and nominal increases in ALT (P=0.019), and LFC (P=0.035) for PNPLA3 (148M/M) genotypes in the BIL arm at 26 weeks but no significant associations in GL. PNPLA3 (148M/M) was also associated with increases in total cholesterol (P=0.014) and low-density lipoprotein cholesterol (P=0.005) but not with hemoglobin A1c or TG. T2D patients with the PNPLA3 (148M/M) genotype treated with BIL may be more susceptible to increased liver fat deposition. The current data provide further insights into the biological role of PNPLA3 in lipid metabolism.

Supernumerary heads to biceps brachii muscle and Asian population history.

PubMed

Techataweewan, N; Toomsan, Y; Maneenin, C; Tungsrithong, N; Tayles, N

2016-12-01

Supernumerary heads of biceps brachii are one of the most common anatomic variants in the muscular system and appear to develop under genetic control and vary in prevalence among populations. Variation in prevalence and morphology therefore has the potential to contribute to understanding of human population history. Until now, there has been no publication of the prevalence of the variant in Southeast Asian populations. The aim of this research is to document the prevalence and morphology of the variant in a sample of Thai cadavers and to consider the significance of the findings. The method used was dissection of arms of 162 donated cadavers at Khon Kaen University, Thailand. The sample showed high prevalence of third heads of biceps brachii in 35% of cadavers, compared with the prevalence of up to 25% reported in large samples worldwide. The sample also showed equal prevalence in males and females and one-third present bilaterally. This pattern is similar to that found in East Asia, and very different from the low prevalence found in South Asia. The morphology of the supernumerary heads does not appear to be different from elsewhere in the world based on the minimal comparable data available in the literature. The Southeast-East Asian pattern of prevalence is consistent with current theories of population history in the region and suggests anatomical variation of the postcranial soft tissues may ultimately contribute to understanding of past human migrations. Copyright © 2016 Elsevier GmbH. All rights reserved.

[Prevalence of hemoglobinopathies in pregnant women in the Lanzarote health sanitary area].

PubMed

Calvo-Villas, J M; Zapata Ramos, M F; Cuesta Tovar, J; de la Iglesia Iñigo, S; Ropero Gradilla, P; Carreter de Granda, E; Sicilia Guillén, F

2006-05-01

The aim of this study is to analyze the global prevalence of carriers of heterozygous hemoglobinopathies among pregnant women settled in Lanzarote. A epidemiologic cross-sectional observational investigation was undertaken to study the prevalence of hemoglobinopathies in 2,436 pregnant women in Lanzarote. The techniques of primary screening were hemoglobin electrophoresis on cellulose acetate at alkaline pH for the detection of hemoglobin variants, and the quantification of HbA2 and HbF for the diagnosis of b thalassemia trait. The study to confirm the diagnosis of structural hemoglobinopathies was based on hemoglobin electrophoresis on citrate agar at acid pH, isolectric focusing and high-performance liquid chromatography (HPLC). The molecular characterization of b thalassemia trait (HbA2 >3.5%) was carried out by techniques using a real time PCR procedure with specific fluorescently labelled hybridization probes and allele-specific amplification (PCR-ARMS). The global prevalence of hemoglobinopathies was 11.90 corresponding to 9.44 for structural hemoglobinopathies and 2.46 for heterozygous b thalassemias. A variant hemoglobin was detected on 23 women and the distribution was as follows: thirteen carriers of hemoglobin S, seven HbC trait, two HbD trait and one "unstable" hemoglobin. 82.6% of the variant hemoglobins found were from migrant population from Africa and America. The high prevalence of carriers of structural hemoglobinopathies in Lanzarote justifies the initiation of programs for screening for hemoglobinopathies to prevent the emergence of severe states causing disease.

Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel

PubMed Central

Houle, David; Márquez, Eladio J.

2015-01-01

We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r2 ≥ 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SNPs is also common when minor allele frequency (MAF) is low: 37% of SNPs with MAF < 0.1 are highly correlated with SNPs more than 100 kb distant. Although SNPs within regions with polymorphic inversions are highly correlated with somewhat larger numbers of SNPs, and these correlated SNPs are on average farther away, the probability that a SNP in such regions is highly correlated with at least one other SNP is very similar to SNPs outside inversions. Previous karyotyping of the DGRP lines has been inconsistent, and we used LD and genotype to investigate these discrepancies. When previous studies agreed on inversion karyotype, our analysis was almost perfectly concordant with those assignments. In discordant cases, and for inversion heterozygotes, our results suggest errors in two previous analyses or discordance between genotype and karyotype. Heterozygosities of chromosome arms are, in many cases, surprisingly highly correlated, suggesting strong epsistatic selection during the inbreeding and maintenance of the DGRP lines. PMID:26068573

Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

PubMed

Houle, David; Márquez, Eladio J

2015-06-10

We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r(2) ≥ 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SNPs is also common when minor allele frequency (MAF) is low: 37% of SNPs with MAF < 0.1 are highly correlated with SNPs more than 100 kb distant. Although SNPs within regions with polymorphic inversions are highly correlated with somewhat larger numbers of SNPs, and these correlated SNPs are on average farther away, the probability that a SNP in such regions is highly correlated with at least one other SNP is very similar to SNPs outside inversions. Previous karyotyping of the DGRP lines has been inconsistent, and we used LD and genotype to investigate these discrepancies. When previous studies agreed on inversion karyotype, our analysis was almost perfectly concordant with those assignments. In discordant cases, and for inversion heterozygotes, our results suggest errors in two previous analyses or discordance between genotype and karyotype. Heterozygosities of chromosome arms are, in many cases, surprisingly highly correlated, suggesting strong epsistatic selection during the inbreeding and maintenance of the DGRP lines. Copyright © 2015 Houle and Márquez.

First description of NOD2 variant associated with defective neutrophil responses in a woman with granulomatous mastitis related to corynebacteria.

PubMed

Bercot, Béatrice; Kannengiesser, Caroline; Oudin, Claire; Grandchamp, Bernard; Sanson-le Pors, Marie-José; Mouly, Stéphane; Elbim, Carole

2009-09-01

We report the first case of granulomatous mastitis due to Corynebacterium kroppenstedtii linked to strongly impaired neutrophil responses to Nod2 agonist and a single nucleotide polymorphism within the NOD2 gene (SNP13 [Leu1007fsinsC]) in a heterozygous state. These findings provided the first demonstration of impaired Nod2 function associated with corynebacterial infection.

Development of Laboratory Investigations in Disorders of Sex Development.

PubMed

Audí, Laura; Camats, Núria; Fernández-Cancio, Mónica; Granada, María L

2018-01-01

Scientific knowledge to understand the biological basis of sex development was prompted by the observation of variants different from the 2 most frequent body types, and this became one of the fields first studied by modern pediatric endocrinology. The clinical observation was supported by professionals working in different areas of laboratory sciences which led to the description of adrenal and gonadal steroidogenesis, the enzymes involved, and the different deficiencies. Steroid hormone measurements evolved from colorimetry to radioimmunoassay (RIA) and automated immunoassays, although gas and liquid chromatography coupled to mass spectrometry are now the gold standard techniques for steroid measurements. Peptide hormones and growth factors were purified, and their measurement evolved from RIA to automated immunoassays. Hormone action mechanisms were described, and their specific receptors were characterized and assayed in experimental materials and in patient tissues and cell cultures. The discovery of the genetic basis for variant sex developments began with the description of the sex chromosomes. Molecular technology allowed cloning of genes coding for the different proteins involved in sex determination and development. Experimental animal models aided in verifying the roles of proteins and also suggested new genes to be investigated. New candidate genes continue to be described based on experimental models and on next-generation sequencing of patient DNAs. © 2017 S. Karger AG, Basel.

The United States Army 1995 Modernization Plan. Force 21

DTIC Science & Technology

1995-04-06

being modified to support the requirements and new dangers of our changing times. It is often said that we study history so as not to repeat thu...intuitive sense of battle gained from study and expertise. Training remains the key to modem, combat-ready Light Forces. Effective modemization and...Devices, Simulators and Simulations (TADSS) Light Forces training is supported by the Combined Arms Training Strategy (CATS). CATS is a descriptive

Manufacturing process applications team (MATEAM). [technology transfer in the areas of machine tools and robots

NASA Technical Reports Server (NTRS)

1979-01-01

The transfer of NASA technology to the industrial sector is reported. Presentations to the machine tool and robot industries and direct technology transfers of the Adams Manipulator arm, a-c motor control, and the bolt tension monitor are discussed. A listing of proposed RTOP programs with strong potential is included. A detailed description of the rotor technology available to industry is given.

Description of Officers and Enlisted Personnel in the U.S. Armed Forces. A Reference for Military Manpower Analysis.

ERIC Educational Resources Information Center

Doering, Zahava D.; And Others

As part of a project to improve the quality of survey data and to link survey data to policy formulation and research needs in the military, a study was made of more than 54,000 men and women military officers and enlisted personnel in 1978-79. The survey sought information about their personal preferences and attitudes, past behavior, and career…

Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study.

PubMed

Meisel, Cornelia; Sadowski, Carolin Eva; Kohlstedt, Daniela; Keller, Katja; Stäritz, Franziska; Grübling, Nannette; Becker, Kerstin; Mackenroth, Luisa; Rump, Andreas; Schröck, Evelin; Arnold, Norbert; Wimberger, Pauline; Kast, Karin

2017-05-01

Determination of mutation status of BRCA1 and BRCA2 has become part of the clinical routine. However, the spectrum of genetic variants differs between populations. The aim of this study was to deliver a comprehensive description of all detected variants. In families fulfilling one of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) criteria for genetic testing, one affected was chosen for analysis. DNA of blood lymphocytes was amplified by PCR and prescreened by DHPLC. Aberrant fragments were sequenced. All coding exons and splice sites of BRCA1 and BRCA2 were analyzed. Screening for large rearrangements in both genes was performed by MLPA. Of 523 index patients, 121 (23.1%) were found to carry a pathogenic or likely pathogenic (class 4/5) mutation. A variant of unknown significance (VUS) was detected in 73/523 patients (13.9%). Two mutations p.Gln1756Profs*74 and p.Cys61Gly comprised 42.3% (n = 33/78) of all detected pathogenic mutations in BRCA1. Most of the other mutations were unique mutations. The most frequently detected mutation in BRCA2 was p.Val1283Lys (13.9%; n = 6/43). Altogether, 101 different neutral genetic variants were counted in BRCA1 (n = 35) and in BRCA2 (n = 66). The two most frequently detected mutations are founder mutations in Poland and Czech Republic. More similarities seem to be shared with our direct neighbor countries compared to other European countries. For comparison of the extended genotype, a shared database is needed.

MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease.

PubMed

Shen, Lishuang; Diroma, Maria Angela; Gonzalez, Michael; Navarro-Gomez, Daniel; Leipzig, Jeremy; Lott, Marie T; van Oven, Mannis; Wallace, Douglas C; Muraresku, Colleen Clarke; Zolkipli-Cunningham, Zarazuela; Chinnery, Patrick F; Attimonelli, Marcella; Zuchner, Stephan; Falk, Marni J; Gai, Xiaowu

2016-06-01

MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web portal (https://mseqdr.org) integrates community knowledge from expert-curated databases with genomic and phenotype data shared by clinicians and researchers. MSeqDR also functions as a centralized application server for Web-based tools to analyze data across both mitochondrial and nuclear DNA, including investigator-driven whole exome or genome dataset analyses through MSeqDR-Genesis. MSeqDR-GBrowse genome browser supports interactive genomic data exploration and visualization with custom tracks relevant to mtDNA variation and mitochondrial disease. MSeqDR-LSDB is a locus-specific database that currently manages 178 mitochondrial diseases, 1,363 genes associated with mitochondrial biology or disease, and 3,711 pathogenic variants in those genes. MSeqDR Disease Portal allows hierarchical tree-style disease exploration to evaluate their unique descriptions, phenotypes, and causative variants. Automated genomic data submission tools are provided that capture ClinVar compliant variant annotations. PhenoTips will be used for phenotypic data submission on deidentified patients using human phenotype ontology terminology. The development of a dynamic informed patient consent process to guide data access is underway to realize the full potential of these resources. © 2016 WILEY PERIODICALS, INC.

MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease

PubMed Central

Shen, Lishuang; Diroma, Maria Angela; Gonzalez, Michael; Navarro-Gomez, Daniel; Leipzig, Jeremy; Lott, Marie T.; van Oven, Mannis; Wallace, Douglas C.; Muraresku, Colleen Clarke; Zolkipli-Cunningham, Zarazuela; Chinnery, Patrick F.; Attimonelli, Marcella; Zuchner, Stephan

2016-01-01

MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web portal (https://mseqdr.org) integrates community knowledge from expert-curated databases with genomic and phenotype data shared by clinicians and researchers. MSeqDR also functions as a centralized application server for Web-based tools to analyze data across both mitochondrial and nuclear DNA, including investigator-driven whole exome or genome dataset analyses through MSeqDR-Genesis. MSeqDR-GBrowse supports interactive genomic data exploration and visualization with custom tracks relevant to mtDNA variation and disease. MSeqDR-LSDB is a locus specific database that currently manages 178 mitochondrial diseases, 1,363 genes associated with mitochondrial biology or disease, and 3,711 pathogenic variants in those genes. MSeqDR Disease Portal allows hierarchical tree-style disease exploration to evaluate their unique descriptions, phenotypes, and causative variants. Automated genomic data submission tools are provided that capture ClinVar-compliant variant annotations. PhenoTips is used for phenotypic data submission on de-identified patients using human phenotype ontology terminology. Development of a dynamic informed patient consent process to guide data access is underway to realize the full potential of these resources. PMID:26919060

Venomics of the Australian eastern brown snake (Pseudonaja textilis): Detection of new venom proteins and splicing variants.

PubMed

Viala, Vincent Louis; Hildebrand, Diana; Trusch, Maria; Fucase, Tamara Mieco; Sciani, Juliana Mozer; Pimenta, Daniel Carvalho; Arni, Raghuvir K; Schlüter, Hartmut; Betzel, Christian; Mirtschin, Peter; Dunstan, Nathan; Spencer, Patrick Jack

2015-12-01

The eastern brown snake is the predominant cause of snakebites in mainland Australia. Its venom induces defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia. Cardiovascular collapse has been described as an early cause of death in patients, but, so far, the mechanisms involved have not been fully identified. In the present work, we analysed the venome of Pseudonaja textilis by combining high throughput proteomics and transcriptomics, aiming to further characterize the components of this venom. The combination of these techniques in the analysis and identification of toxins, venom proteins and putative toxins allowed the sequence description and the identification of the following: prothrombinase coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and "acidic PLA2", three-finger toxins (3FTx) and the Kunitz-type protease inhibitor textilinin, venom metalloproteinase, C-type lectins, cysteine rich secretory proteins, calreticulin, dipeptidase 2, as well as evidences of Heloderma lizard peptides. Deep data-mining analysis revealed the secretion of a new transcript variant of venom coagulation factor 5a and the existence of a splicing variant of PLA2 modifying the UTR and signal peptide from a same mature protein. The transcriptome revealed the diversity of transcripts and mutations, and also indicates that splicing variants can be an important source of toxin variation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Family studies to find rare high risk variants in migraine.

PubMed

Hansen, Rikke Dyhr; Christensen, Anne Francke; Olesen, Jes

2017-12-01

Migraine has long been known as a common complex disease caused by genetic and environmental factors. The pathophysiology and the specific genetic susceptibility are poorly understood. Common variants only explain a small part of the heritability of migraine. It is thought that rare genetic variants with bigger effect size may be involved in the disease. Since migraine has a tendency to cluster in families, a family approach might be the way to find these variants. This is also indicated by identification of migraine-associated loci in classical linkage-analyses in migraine families. A single migraine study using a candidate-gene approach was performed in 2010 identifying a rare mutation in the TRESK potassium channel segregating in a large family with migraine with aura, but this finding has later become questioned. The technologies of next-generation sequencing (NGS) now provides an affordable tool to investigate the genetic variation in the entire exome or genome. The family-based study design using NGS is described in this paper. We also review family studies using NGS that have been successful in finding rare variants in other common complex diseases in order to argue the promising application of a family approach to migraine. PubMed was searched to find studies that looked for rare genetic variants in common complex diseases through a family-based design using NGS, excluding studies looking for de-novo mutations, or using a candidate-gene approach and studies on cancer. All issues from Nature Genetics and PLOS genetics 2014, 2015 and 2016 (UTAI June) were screened for relevant papers. Reference lists from included and other relevant papers were also searched. For the description of the family-based study design using NGS an in-house protocol was used. Thirty-two successful studies, which covered 16 different common complex diseases, were included in this paper. We also found a single migraine study. Twenty-three studies found one or a few family specific variants (less than five), while other studies found several possible variants. Not all of them were genome wide significant. Four studies performed follow-up analyses in unrelated cases and controls and calculated odds ratios that supported an association between detected variants and risk of disease. Studies of 11 diseases identified rare variants that segregated fully or to a large degree with the disease in the pedigrees. It is possible to find rare high risk variants for common complex diseases through a family-based approach. One study using a family approach and NGS to find rare variants in migraine has already been published but with strong limitations. More studies are under way.

POINTER: Portable Intelligent Trainer for External Robotics

NASA Technical Reports Server (NTRS)

Kuiper, Hilbert; Rikken, Patrick J.

1994-01-01

Intelligent tutoring systems (ITS's) play an increasing role in training and education of people with different levels of skill and knowledge. As compared to conventional computer based training (CBT) an ITS provides more tailored instruction by trying to mimic the teaching behavior of a human instructor as much as possible and is therefore much more flexible. This paper starts with an introduction to ITS's, followed by the description of an ITS for training of an (astronaut) operator in monitoring and controlling robotic arm procedures. The robotic arm will be used for exchange of equipment between a space station and a space plane involving critical and accurate movements of the robotic arm. The ITS for this application, called Pointer, is developed by TNO Physics and Electronics Laboratory and is based upon an existing ITS that includes procedural training. Pointer has been developed on a workstation whereas the target platform was a portable computer. Therefore, a lot of attention had to be paid to scaling effects and keeping up with user friendliness of the much smaller user interface. Although the learning domain was the control of a robotic arm, it is clear that use of intelligent training technologies on a portable computer has many other applications (payload operations, operation control rooms, etc.). Training can occur at any time and place in an attractive and cost effective way.

Real-time portable system for fabric defect detection using an ARM processor

NASA Astrophysics Data System (ADS)

Fernandez-Gallego, J. A.; Yañez-Puentes, J. P.; Ortiz-Jaramillo, B.; Alvarez, J.; Orjuela-Vargas, S. A.; Philips, W.

2012-06-01

Modern textile industry seeks to produce textiles as little defective as possible since the presence of defects can decrease the final price of products from 45% to 65%. Automated visual inspection (AVI) systems, based on image analysis, have become an important alternative for replacing traditional inspections methods that involve human tasks. An AVI system gives the advantage of repeatability when implemented within defined constrains, offering more objective and reliable results for particular tasks than human inspection. Costs of automated inspection systems development can be reduced using modular solutions with embedded systems, in which an important advantage is the low energy consumption. Among the possibilities for developing embedded systems, the ARM processor has been explored for acquisition, monitoring and simple signal processing tasks. In a recent approach we have explored the use of the ARM processor for defects detection by implementing the wavelet transform. However, the computation speed of the preprocessing was not yet sufficient for real time applications. In this approach we significantly improve the preprocessing speed of the algorithm, by optimizing matrix operations, such that it is adequate for a real time application. The system was tested for defect detection using different defect types. The paper is focused in giving a detailed description of the basis of the algorithm implementation, such that other algorithms may use of the ARM operations for fast implementations.

Ecchymosis and/or haematoma formation after prophylactic administration of subcutaneous enoxaparin in the abdomen or arm of the critically ill patient.

PubMed

Jareño-Collado, R; Sánchez-Sánchez, M M; Fraile-Gamo, M P; García-Crespo, N; Barba-Aragón, S; Bermejo-García, H; Sánchez-Izquierdo, R; Sánchez-Muñoz, E I; López-López, A; Arias-Rivera, S

Ecchymosis and/or haematoma are the most common adverse events after subcutaneous administration of low molecular weight heparin. There is no strong recommendation as to the puncture site. To evaluate the adverse events, ecchymosis and/or haematoma after the administration of prophylactic subcutaneous enoxaparin in the abdomen vs the arm in the critically ill patient. A randomised, two-arm clinical trial (injection in the abdomen vs the arm), performed between July 2014 and January 2017, in an 18-bed, polyvalent intensive care unit. Patients receiving prophylactic enoxaparin, admitted >72h, with no liver or haematological disorders, a body mass index (BMI) >18.5, not pregnant, of legal age and with no skin lesions which would impede assessment were included. We excluded patients who died or who were transferred to another hospital before completing the evaluation. We gathered demographic and clinical variables, and the onset of ecchymosis and/or haematomas at the injection site after 12, 24, 48 and 72hours. A descriptive analysis was undertaken, with group comparison and logistic regression. The study was approved by the ethics committee with the signed consent of patients/families. 301 cases (11 excluded): 149 were injected in the abdomen vs 141 in the arm. There were no significant differences in demographic and clinical variables, BMI, enoxaparin dose or antiplatelet administration [ecchymosis, abdomen vs arm, n(%): 66(44) vs 72(51), P=.25] [haematoma abdomen vs arm, n(%): 9(6) vs 14(10), P=.2]. Statistical significance was found in the size of the haematomas after 72h: [area of haematoma (mm 2 ) abdomen vs arm, median (IQR): 2(1-5.25) vs 20(5.25-156), P=.027]. In our patient cohort, prophylactic subcutaneous enoxaparin administered in the abdomen causes fewer haematomas after 72hours, than when administered in the arm. The incidence rate of ecchymosis and haematoma was lower than the published incidence in critically ill patients, although patients receiving anti-platelet agents present a higher risk of injury. No relationship was observed in relation to BMI. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

Standard Mutation Nomenclature in Molecular Diagnostics

PubMed Central

Ogino, Shuji; Gulley, Margaret L.; den Dunnen, Johan T.; Wilson, Robert B.

2007-01-01

To translate basic research findings into clinical practice, it is essential that information about mutations and variations in the human genome are communicated easily and unequivocally. Unfortunately, there has been much confusion regarding the description of genetic sequence variants. This is largely because research articles that first report novel sequence variants do not often use standard nomenclature, and the final genomic sequence is compiled over many separate entries. In this article, we discuss issues crucial to clear communication, using examples of genes that are commonly assayed in clinical laboratories. Although molecular diagnostics is a dynamic field, this should not inhibit the need for and movement toward consensus nomenclature for accurate reporting among laboratories. Our aim is to alert laboratory scientists and other health care professionals to the important issues and provide a foundation for further discussions that will ultimately lead to solutions. PMID:17251329

Subtelomeric deletion of 12p: Description of a third case and review.

PubMed

Macdonald, A H; Rodríguez, L; Aceña, I; Martínez-Fernández, M L; Sánchez-Izquierdo, D; Zuazo, E; Martínez-Frías, M L

2010-06-01

Only 12 cases with a cytogenetically visible deletion of the short arm of chromosome 12 (12p) have been reported so far. The difference in clinical features observed in these patients indicates that there is no distinct phenotype associated with this short arm deletion, although the existence of a del(12p) syndrome was previously suggested. Besides those 12 reports, only two patients have been described with a subtelomeric 12p deletion; both present in the same family in which the son showed a mild phenotype of moderate mental retardation and behavioral problems and his carrier mother had no apparent phenotype. In this article, we describe the third known patient with a subtelomeric 12p deletion in a young boy with mental retardation and microcephaly, and review the literature. (c) 2010 Wiley-Liss, Inc.

Artificial Metalloproteins Containing Co 4O 4Cubane Active Sites

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

Olshansky, Lisa; Huerta-Lavorie, Raul; Nguyen, Andy I.

Artificial metalloproteins (ArMs) containing Co 4O 4 cubane active sites were constructed via biotin-streptavidin technology. Stabilized by hydrogen bonds (H-bonds), terminal and cofacial Co III-OH 2 moieties are observed crystallographically in a series of immobilized cubane sites. Solution electrochemistry provided correlations of oxidation potential and pH. For variants containing Ser and Phe adjacent to the metallocofactor, 1e -/1H + chemistry predominates until pH 8, above which the oxidation becomes pH-independent. Installation of Tyr proximal to the Co 4O 4 active site provided a single H-bond to one of a set of cofacial Co III-OH 2 groups. With this variant, multi-emore » - /multi-H + chemistry is observed, along with a change in mechanism at pH 9.5 that is consistent with Tyr deprotonation. Finally, with structural similarities to both the oxygen-evolving complex of photosystem II (H-bonded Tyr) and to thin film water oxidation catalysts (Co 4O 4 core), these findings bridge synthetic and biological systems for water oxidation, highlighting the importance of secondary sphere interactions in mediating multi-e - /multi-H + reactivity.« less

CD4-Negative Variant of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm With a Novel PBRM1 Mutation in an 11-Year-Old Girl.

PubMed

Yigit, Nuri; Suarez, Luisa Fernanda; Roth, Lisa Giulino; Orazi, Attilio; Tam, Wayne

2017-05-01

We report a rare case of CD4- cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a novel PBRM1 mutation. An 11-year-old girl presented with an enlarged mass on her left arm and underwent an incisional biopsy. Histopathologic examination and immunohistochemistry studies showed a monotonous proliferation of blasts that were CD4-, CD56+, and CD123+. There was no evidence of leukemic dissemination. Next-generation sequencing detected PBRM1 and CIC gene abnormalities. We confirmed and validated a novel PBRM1 mutation by conventional polymerase chain reaction and Sanger sequencing. CD4- variant of BPDCN may be mistaken for myeloid sarcoma or extramedullary lymphoblastic leukemia/lymphoma because of their overlapping morphologic and immunophenotypic features; thus, a careful clinicopathologic evaluation is essential to reach the correct diagnosis. PBRM1 mutation seems to be a driver event in this case. Our study underscores the importance of alterations in chromatin remodeling in the pathogenesis of BPDCN. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss.

PubMed

Amiri Jahromi, Rakhshan; Nasiri, Mahboobeh; Jahromi, Athar Rasekh

2017-01-01

This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran. 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease. These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.

Artificial Metalloproteins Containing Co 4O 4Cubane Active Sites

DOE PAGES

Olshansky, Lisa; Huerta-Lavorie, Raul; Nguyen, Andy I.; ...

2018-02-05

Artificial metalloproteins (ArMs) containing Co 4O 4 cubane active sites were constructed via biotin-streptavidin technology. Stabilized by hydrogen bonds (H-bonds), terminal and cofacial Co III-OH 2 moieties are observed crystallographically in a series of immobilized cubane sites. Solution electrochemistry provided correlations of oxidation potential and pH. For variants containing Ser and Phe adjacent to the metallocofactor, 1e -/1H + chemistry predominates until pH 8, above which the oxidation becomes pH-independent. Installation of Tyr proximal to the Co 4O 4 active site provided a single H-bond to one of a set of cofacial Co III-OH 2 groups. With this variant, multi-emore » - /multi-H + chemistry is observed, along with a change in mechanism at pH 9.5 that is consistent with Tyr deprotonation. Finally, with structural similarities to both the oxygen-evolving complex of photosystem II (H-bonded Tyr) and to thin film water oxidation catalysts (Co 4O 4 core), these findings bridge synthetic and biological systems for water oxidation, highlighting the importance of secondary sphere interactions in mediating multi-e - /multi-H + reactivity.« less

Age-related macular degeneration: genome-wide association studies to translation.

PubMed

Black, James R M; Clark, Simon J

2016-04-01

In recent years, genome-wide association studies (GWAS), which are able to analyze the contribution to disease of genetic variations that are common within a population, have attracted considerable investment. Despite identifying genetic variants for many conditions, they have been criticized for yielding data with minimal clinical utility. However, in this regard, age-related macular degeneration (AMD), the most common form of blindness in the Western world, is a striking exception. Through GWAS, common genetic variants at a number of loci have been discovered. Two loci in particular, including genes of the complement cascade on chromosome 1 and the ARMS2/HTRA1 genes on chromosome 10, have been shown to convey significantly increased susceptibility to developing AMD. Today, although it is possible to screen individuals for a genetic predisposition to the disease, effective interventional strategies for those at risk of developing AMD are scarce. Ongoing research in this area is nonetheless promising. After providing brief overviews of AMD and common disease genetics, we outline the main recent advances in the understanding of AMD, particularly those made through GWAS. Finally, the true merit of these findings and their current and potential translational value is examined.Genet Med 18 4, 283-289.

Mutation of Dcdc2 in mice leads to impairments in auditory processing and memory ability.

PubMed

Truong, D T; Che, A; Rendall, A R; Szalkowski, C E; LoTurco, J J; Galaburda, A M; Holly Fitch, R

2014-11-01

Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and is associated with specific difficulties in phonological and rapid auditory processing (RAP), visual attention and working memory. Genetic variants in Doublecortin domain-containing protein 2 (DCDC2) have been associated with dyslexia, impairments in phonological processing and in short-term/working memory. The purpose of this study was to determine whether sensory and behavioral impairments can result directly from mutation of the Dcdc2 gene in mice. Several behavioral tasks, including a modified pre-pulse inhibition paradigm (to examine auditory processing), a 4/8 radial arm maze (to assess/dissociate working vs. reference memory) and rotarod (to examine sensorimotor ability and motor learning), were used to assess the effects of Dcdc2 mutation. Behavioral results revealed deficits in RAP, working memory and reference memory in Dcdc2(del2/del2) mice when compared with matched wild types. Current findings parallel clinical research linking genetic variants of DCDC2 with specific impairments of phonological processing and memory ability. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Scalable and Versatile Genome Editing Using Linear DNAs with Microhomology to Cas9 Sites in Caenorhabditis elegans

PubMed Central

Paix, Alexandre; Wang, Yuemeng; Smith, Harold E.; Lee, Chih-Yung S.; Calidas, Deepika; Lu, Tu; Smith, Jarrett; Schmidt, Helen; Krause, Michael W.; Seydoux, Geraldine

2014-01-01

Homology-directed repair (HDR) of double-strand DNA breaks is a promising method for genome editing, but is thought to be less efficient than error-prone nonhomologous end joining in most cell types. We have investigated HDR of double-strand breaks induced by CRISPR-associated protein 9 (Cas9) in Caenorhabditis elegans. We find that HDR is very robust in the C. elegans germline. Linear repair templates with short (∼30–60 bases) homology arms support the integration of base and gene-sized edits with high efficiency, bypassing the need for selection. Based on these findings, we developed a systematic method to mutate, tag, or delete any gene in the C. elegans genome without the use of co-integrated markers or long homology arms. We generated 23 unique edits at 11 genes, including premature stops, whole-gene deletions, and protein fusions to antigenic peptides and GFP. Whole-genome sequencing of five edited strains revealed the presence of passenger variants, but no mutations at predicted off-target sites. The method is scalable for multi-gene editing projects and could be applied to other animals with an accessible germline. PMID:25249454

Design of trials for interrupting the transmission of endemic pathogens.

PubMed

Silkey, Mariabeth; Homan, Tobias; Maire, Nicolas; Hiscox, Alexandra; Mukabana, Richard; Takken, Willem; Smith, Thomas A

2016-06-06

Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up. A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor-baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial. Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial. The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors.

Impact of demographic, genetic, and bioimpedance factors on gestational weight gain and birth weight in a Romanian population

PubMed Central

Mărginean, Claudiu; Mărginean, Cristina Oana; Bănescu, Claudia; Meliţ, Lorena; Tripon, Florin; Iancu, Mihaela

2016-01-01

Abstract The present study had 2 objectives, first, to investigate possible relationships between increased gestational weight gain and demographic, clinical, paraclinical, genetic, and bioimpedance (BIA) characteristics of Romanian mothers, and second, to identify the influence of predictors (maternal and newborns characteristics) on our outcome birth weight (BW). We performed a cross-sectional study on 309 mothers and 309 newborns from Romania, divided into 2 groups: Group I—141 mothers with high gestational weight gain (GWG) and Group II—168 mothers with normal GWG, that is, control group. The groups were evaluated regarding demographic, anthropometric (body mass index [BMI], middle upper arm circumference, tricipital skinfold thickness, weight, height [H]), clinical, paraclinical, genetic (interleukin 6 [IL-6]: IL-6 -174G>C and IL-6 -572C>G gene polymorphisms), and BIA parameters. We noticed that fat mass (FM), muscle mass (MM), bone mass (BM), total body water (TBW), basal metabolism rate (BMR) and metabolic age (P < 0.001), anthropometric parameters (middle upper arm circumference, tricipital skinfold thickness; P < 0.001/P = 0.001) and hypertension (odds ratio = 4.65, 95% confidence interval: 1.27–17.03) were higher in mothers with high GWG. BW was positively correlated with mothers’ FM (P < 0.001), TBW (P = 0.001), BMR (P = 0.02), while smoking was negatively correlated with BW (P = 0.04). Variant genotype (GG+GC) of the IL-6 -572C>G polymorphism was higher in the control group (P = 0.042). We observed that high GWG may be an important predictor factor for the afterward BW, being positively correlated with FM, TBW, BMR, metabolic age of the mothers, and negatively with the mother's smoking status. Variant genotype (GG+GC) of the IL-6 -572C>G gene polymorphism is a protector factor against obesity in mothers. All the variables considered explained 14.50% of the outcome variance. PMID:27399105

Impact of demographic, genetic, and bioimpedance factors on gestational weight gain and birth weight in a Romanian population: A cross-sectional study in mothers and their newborns: the Monebo study (STROBE-compliant article).

PubMed

Mărginean, Claudiu; Mărginean, Cristina Oana; Bănescu, Claudia; Meliţ, Lorena; Tripon, Florin; Iancu, Mihaela

2016-07-01

The present study had 2 objectives, first, to investigate possible relationships between increased gestational weight gain and demographic, clinical, paraclinical, genetic, and bioimpedance (BIA) characteristics of Romanian mothers, and second, to identify the influence of predictors (maternal and newborns characteristics) on our outcome birth weight (BW).We performed a cross-sectional study on 309 mothers and 309 newborns from Romania, divided into 2 groups: Group I-141 mothers with high gestational weight gain (GWG) and Group II-168 mothers with normal GWG, that is, control group.The groups were evaluated regarding demographic, anthropometric (body mass index [BMI], middle upper arm circumference, tricipital skinfold thickness, weight, height [H]), clinical, paraclinical, genetic (interleukin 6 [IL-6]: IL-6 -174G>C and IL-6 -572C>G gene polymorphisms), and BIA parameters.We noticed that fat mass (FM), muscle mass (MM), bone mass (BM), total body water (TBW), basal metabolism rate (BMR) and metabolic age (P < 0.001), anthropometric parameters (middle upper arm circumference, tricipital skinfold thickness; P < 0.001/P = 0.001) and hypertension (odds ratio = 4.65, 95% confidence interval: 1.27-17.03) were higher in mothers with high GWG. BW was positively correlated with mothers' FM (P < 0.001), TBW (P = 0.001), BMR (P = 0.02), while smoking was negatively correlated with BW (P = 0.04). Variant genotype (GG+GC) of the IL-6 -572C>G polymorphism was higher in the control group (P = 0.042).We observed that high GWG may be an important predictor factor for the afterward BW, being positively correlated with FM, TBW, BMR, metabolic age of the mothers, and negatively with the mother's smoking status. Variant genotype (GG+GC) of the IL-6 -572C>G gene polymorphism is a protector factor against obesity in mothers. All the variables considered explained 14.50% of the outcome variance.

The TRIGA Reactor Facility at the Armed Forces Radiobiology Research Institute: A Simplified Technical Description.

DTIC Science & Technology

1986-05-01

COUNT Technical FROM_ TO May 1986 20 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18. SUBJECT TERMS iConitinue on reverse if neceasary and identify by...Reactor, Modes of Operation, The AFRRI Reactor, Exposure Facilities, and Cerenkov Radiation. I- 20 DISTRISUTIONIAVAILABILITY OF ABSTRACT 21. ABSTRACT...6 Exposure Facilities 12 Cerenkov Radiation 17 Acoessiofl For NTIS GRA&I DT.C TABUnamnnounced [] UusnriOfltond -. By IZ Distribution/ Availability

Predictors of Hand-Foot Syndrome and Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized Clinical Trial.

PubMed

Yap, Yoon-Sim; Kwok, Li-Lian; Syn, Nicholas; Chay, Wen Yee; Chia, John Whay Kuang; Tham, Chee Kian; Wong, Nan Soon; Lo, Soo Kien; Dent, Rebecca Alexandra; Tan, Sili; Mok, Zuan Yu; Koh, King Xin; Toh, Han Chong; Koo, Wen Hsin; Loh, Marie; Ng, Raymond Chee Hui; Choo, Su Pin; Soong, Richie Chuan Teck

2017-11-01

Hand-foot syndrome (HFS) is a common adverse effect of capecitabine treatment. To compare the incidence and time to onset of grade 2 or greater HFS in patients receiving pyridoxine vs placebo and to identify biomarkers predictive of HFS. This single-center, randomized double-blind, placebo-controlled phase 3 trial conducted at National Cancer Centre Singapore assessed whether oral pyridoxine could prevent the onset of grade 2 or higher HFS in 210 patients scheduled to receive single-agent capecitabine chemotherapy for breast, colorectal, and other cancers. Patients were randomized to receive concurrent pyridoxine (200 mg) or placebo daily for a maximum of 8 cycles of capecitabine, with stratification by sex and use in adjuvant or neoadjuvant vs palliative setting. Patients were withdrawn from the study on development of grade 2 or higher HFS or cessation of capecitabine. Primary end point was the incidence of grade 2 or higher HFS in patients receiving pyridoxine. Secondary end points included the time to onset (days) of grade 2 or higher HFS and identification of biomarkers predictive of HFS, including baseline folate and vitamin B12 levels, as well as genetic polymorphisms with genome-wide arrays. In this cohort of 210 patients (median [range] age, 58 [26-82] years; 162 women) grade 2 or higher HFS occurred in 33 patients (31.4%) in the pyridoxine arm vs 39 patients (37.1%) in the placebo arm (P = .38). The median time to onset of grade 2 or higher HFS was not reached in both arms. In univariate analysis, the starting dose of capecitabine (odds ratio [OR], 1.99; 95% CI, 1.32-3.00; P = .001), serum folate levels (OR, 1.27; 95% CI, 1.10-1.47; P = .001), and red blood cell folate levels (OR, 1.25; 95% CI, 1.08-1.44; P = .003) were associated with increased risk of grade 2 or higher HFS. In multivariate analyses, serum folate (OR, 1.30; 95% CI, 1.12-1.52; P < .001) and red blood cell folate (OR, 1.28; 95% CI, 1.10-1.49; P = .001) were the only significant predictors of grade 2 or higher HFS. Grade 2 or higher HFS was associated with 300 DNA variants at genome-wide significance (P < 5 × 10-8), including a novel DPYD variant (rs75267292; P = 1.57 × 10-10), and variants in the MACF1 (rs183324967, P = 4.80 × 10-11; rs148221738, P = 5.73 × 10-10) and SPRY2 (rs117876855, P < 1.01 × 10-8; rs139544515, P = 1.30 × 10-8) genes involved in wound healing. Pyridoxine did not significantly prevent or delay the onset of grade 2 or higher HFS. Serum and red blood cell folate levels are independent predictors of HFS. clinicaltrials.gov Identifier: NCT00486213.

Use of Video to Facilitate End-of-Life Discussions With Patients With Cancer: A Randomized Controlled Trial

PubMed Central

El-Jawahri, Areej; Podgurski, Lisa M.; Eichler, April F.; Plotkin, Scott R.; Temel, Jennifer S.; Mitchell, Susan L.; Chang, Yuchiao; Barry, Michael J.; Volandes, Angelo E.

2010-01-01

Purpose To determine whether the use of a goals-of-care video to supplement a verbal description can improve end-of-life decision making for patients with cancer. Methods Fifty participants with malignant glioma were randomly assigned to either a verbal narrative of goals-of-care options at the end of life (control), or a video after the same verbal narrative (intervention) in this randomized controlled trial. The video depicts three levels of medical care: life-prolonging care (cardiopulmonary resuscitation [CPR], ventilation), basic care (hospitalization, no CPR), and comfort care (symptom relief). The primary study outcome was participants' preferences for end-of-life care. The secondary outcome was participants' uncertainty regarding decision making (score range, 3 to 15; higher score indicating less uncertainty). Participants' comfort level with the video was also measured. Results Fifty participants were randomly assigned to either the verbal narrative (n = 27) or video (n = 23). After the verbal description, 25.9% of participants preferred life-prolonging care, 51.9% basic care, and 22.2% comfort care. In the video arm, no participants preferred life-prolonging care, 4.4% preferred basic care, 91.3% preferred comfort care, and 4.4% were uncertain (P < .0001). The mean uncertainty score was higher in the video group than in the verbal group (13.7 v 11.5, respectively; P < .002). In the intervention arm, 82.6% of participants reported being very comfortable watching the video. Conclusion Compared with participants who only heard a verbal description, participants who viewed a goals-of-care video were more likely to prefer comfort care and avoid CPR, and were more certain of their end-of-life decision making. Participants reported feeling comfortable watching the video. PMID:19949010

A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528.

PubMed

Dy, Grace K; Mandrekar, Sumithra J; Nelson, Garth D; Meyers, Jeffrey P; Adjei, Araba A; Ross, Helen J; Ansari, Rafat H; Lyss, Alan P; Stella, Philip J; Schild, Steven E; Molina, Julian R; Adjei, Alex A

2013-01-01

The purpose of this study was to assess the safety and efficacy of gemcitabine and carboplatin with (arm A) or without (arm B) daily oral cediranib as first-line therapy for advanced non-small-cell lung cancer. A lead-in phase to determine the tolerability of gemcitabine 1000 mg/m on days 1 and 8, and carboplatin on day 1 at area under curve 5 administered every 21 days with cediranib 45 mg once daily was followed by a 2 (A):1 (B) randomized phase II study. The primary end point was confirmed overall response rate (ORR) with 6-month progression-free survival (PFS6) rate in arm A as secondary end point. Polymorphisms in genes encoding cediranib targets and transport were correlated with treatment outcome. On the basis of the safety assessment, cediranib 30 mg daily was used in the phase II portion. A total of 58 and 29 evaluable patients were accrued to arms A and B. Patients in A experienced more grade 3+ nonhematologic adverse events, 71% versus 45% (p = 0.01). The ORR was 19% (A) versus 20% (B) (p = 1.0). PFS6 in A was 48% (95% confidence interval: 35%-62%), thus meeting the protocol-specified threshold of at least 40%. The median overall survival was 12.0 versus 9.9 months (p = 0.10). FGFR1 rs7012413, FGFR2 rs2912791, and VEGFR3 rs11748431 polymorphisms were significantly associated with decreased overall survival (hazard ratio 2.78-5.01, p = 0.0002-0.0095). The trial did not meet its primary end point of ORR but met its secondary end point of PFS6. The combination with cediranib 30 mg daily resulted in increased toxicity. Pharmacogenetic analysis revealed an association of FGFR and VEGFR variants with survival.

Biomechanically Induced and Controller Coupled Oscillations Experienced on the F-16XL Aircraft During Rolling Maneuvers

NASA Technical Reports Server (NTRS)

Smith, John W.; Montgomery, Terry

1996-01-01

During rapid rolling maneuvers, the F-16 XL aircraft exhibits a 2.5 Hz lightly damped roll oscillation, perceived and described as 'roll ratcheting.' This phenomenon is common with fly-by-wire control systems, particularly when primary control is derived through a pedestal-mounted side-arm controller. Analytical studies have been conducted to model the nature of the integrated control characteristics. The analytical results complement the flight observations. A three-degree-of-freedom linearized set of aerodynamic matrices was assembled to simulate the aircraft plant. The lateral-directional control system was modeled as a linear system. A combination of two second-order transfer functions was derived to couple the lateral acceleration feed through effect of the operator's arm and controller to the roll stick force input. From the combined systems, open-loop frequency responses and a time history were derived, describing and predicting an analogous in-flight situation. This report describes the primary control, aircraft angular rate, and position time responses of the F-16 XL-2 aircraft during subsonic and high-dynamic-pressure rolling maneuvers. The analytical description of the pilot's arm and controller can be applied to other aircraft or simulations to assess roll ratcheting susceptibility.

Towards automatic Markov reliability modeling of computer architectures

NASA Technical Reports Server (NTRS)

Liceaga, C. A.; Siewiorek, D. P.

1986-01-01

The analysis and evaluation of reliability measures using time-varying Markov models is required for Processor-Memory-Switch (PMS) structures that have competing processes such as standby redundancy and repair, or renewal processes such as transient or intermittent faults. The task of generating these models is tedious and prone to human error due to the large number of states and transitions involved in any reasonable system. Therefore model formulation is a major analysis bottleneck, and model verification is a major validation problem. The general unfamiliarity of computer architects with Markov modeling techniques further increases the necessity of automating the model formulation. This paper presents an overview of the Automated Reliability Modeling (ARM) program, under development at NASA Langley Research Center. ARM will accept as input a description of the PMS interconnection graph, the behavior of the PMS components, the fault-tolerant strategies, and the operational requirements. The output of ARM will be the reliability of availability Markov model formulated for direct use by evaluation programs. The advantages of such an approach are (a) utility to a large class of users, not necessarily expert in reliability analysis, and (b) a lower probability of human error in the computation.

A novel thromboxane A2 receptor N42S variant results in reduced surface expression and platelet dysfunction.

PubMed

Nisar, Shaista P; Lordkipanidzé, Marie; Jones, Matthew L; Dawood, Ban; Murden, Sherina; Cunningham, Margaret R; Mumford, Andrew D; Wilde, Jonathan T; Watson, Steve P; Mundell, Stuart J; Lowe, Gillian C

2014-05-05

A small number of thromboxane receptor variants have been described in patients with a bleeding history that result in platelet dysfunction. We have identified a patient with a history of significant bleeding, who expresses a novel heterozygous thromboxane receptor variant that predicts an asparagine to serine substitution (N42S). This asparagine is conserved across all class A GPCRs, suggesting a vital role for receptor structure and function.We investigated the functional consequences of the TP receptor heterozygous N42S substitution by performing platelet function studies on platelet-rich plasma taken from the patient and healthy controls. We investigated the N42S mutation by expressing the wild-type (WT) and mutant receptor in human embryonic kidney (HEK) cells. Aggregation studies showed an ablation of arachidonic acid responses in the patient, whilst there was right-ward shift of the U46619 concentration response curve (CRC). Thromboxane generation was unaffected. Calcium mobilisation studies in cells lines showed a rightward shift of the U46619 CRC in N42S-expressing cells compared to WT. Radioligand binding studies revealed a reduction in BMax in platelets taken from the patient and in N42S-expressing cells, whilst cell studies confirmed poor surface expression. We have identified a novel thromboxane receptor variant, N42S, which results in platelet dysfunction due to reduced surface expression. It is associated with a significant bleeding history in the patient in whom it was identified. This is the first description of a naturally occurring variant that results in the substitution of this highly conserved residue and confirms the importance of this residue for correct GPCR function.

Descriptive Cadaveric Study Comparing the Accuracy of Ultrasound Versus Fluoroscopic Guidance for First Sacral Transforaminal Injections: A Comparison Study.

PubMed

Thompson, Bradley F; Pingree, Matthew J; Qu, Wenchun; Murthy, Naveen S; Lachman, Nirusha; Hurdle, Mark Friedrich

2018-04-01

Ultrasound is rarely used for guiding lumbosacral epidural steroid injections due to its technical limitations. For example, sonographic imaging lacks the ability to confirm epidural spread and identify vascular uptake. The perceived risk that these limitations pose to human subjects has precluded any large scale clinical trials to date. To compare the accuracy of ultrasound versus fluoroscopic guidance for first sacral transforaminal epidural injections. Cadaveric comparative study using dichotomous outcomes. A fluoroscopy suite and anatomic laboratory at an academic medical center. Four unembalmed adult human cadavers with no history of spinal surgery. Eight sites were injected twice by one interventionalist, using fluoroscopic and ultrasound guidance. In the fluoroscopy arm, contrast spread was assessed using computed tomography. In the ultrasound arm, latex spread was assessed using gross anatomic dissection. Any visible evidence of epidural spread constituted a positive result. Comparison of the success of obtaining epidural contrast flow was the primary outcome measure. Secondary outcome measures included average duration, rate of intravascular uptake, and quantity of intravascular uptake. All injections performed in both the ultrasound arm and the fluoroscopy arm had positive epidural spread. The average duration was 3.03 minutes with fluoroscopy and 4.76 minutes with ultrasound. The rate of intravascular uptake was 37.5% with fluoroscopy and 50% with ultrasound. Within the ultrasound arm, greater intravascular spread and duration variability were recorded. Although ultrasonography can provide reliable image guidance for cannulating the first sacral foramen in cadavers, it would have limited clinical utility due to its inability to visualize relevant neurovascular structures deep to the osseus roof and exclude intravascular uptake. IV. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Model-Observation "Data Cubes" for the DOE Atmospheric Radiation Measurement Program's LES ARM Symbiotic Simulation and Observation (LASSO) Workflow

NASA Astrophysics Data System (ADS)

Vogelmann, A. M.; Gustafson, W. I., Jr.; Toto, T.; Endo, S.; Cheng, X.; Li, Z.; Xiao, H.

2015-12-01

The Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facilities' Large-Eddy Simulation (LES) ARM Symbiotic Simulation and Observation (LASSO) Workflow is currently being designed to provide output from routine LES to complement its extensive observations. The modeling portion of the LASSO workflow is presented by Gustafson et al., which will initially focus on shallow convection over the ARM megasite in Oklahoma, USA. This presentation describes how the LES output will be combined with observations to construct multi-dimensional and dynamically consistent "data cubes", aimed at providing the best description of the atmospheric state for use in analyses by the community. The megasite observations are used to constrain large-eddy simulations that provide a complete spatial and temporal coverage of observables and, further, the simulations also provide information on processes that cannot be observed. Statistical comparisons of model output with their observables are used to assess the quality of a given simulated realization and its associated uncertainties. A data cube is a model-observation package that provides: (1) metrics of model-observation statistical summaries to assess the simulations and the ensemble spread; (2) statistical summaries of additional model property output that cannot be or are very difficult to observe; and (3) snapshots of the 4-D simulated fields from the integration period. Searchable metrics are provided that characterize the general atmospheric state to assist users in finding cases of interest, such as categorization of daily weather conditions and their specific attributes. The data cubes will be accompanied by tools designed for easy access to cube contents from within the ARM archive and externally, the ability to compare multiple data streams within an event as well as across events, and the ability to use common grids and time sampling, where appropriate.

Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene.

PubMed

Thonberg, Håkan; Chiang, Huei-Hsin; Lilius, Lena; Forsell, Charlotte; Lindström, Anna-Karin; Johansson, Charlotte; Björkström, Jenny; Thordardottir, Steinunn; Sleegers, Kristel; Van Broeckhoven, Christine; Rönnbäck, Annica; Graff, Caroline

2017-06-09

Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. The majority of AD cases are sporadic, while up to 5% are families with an early onset AD (EOAD). Mutations in one of the three genes: amyloid beta precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) can be disease causing. However, most EOAD families do not carry mutations in any of these three genes, and candidate genes, such as the sortilin-related receptor 1 (SORL1), have been suggested to be potentially causative. To identify AD causative variants, we performed whole-exome sequencing on five individuals from a family with EOAD and a missense variant, p.Arg1303Cys (c.3907C > T) was identified in SORL1 which segregated with disease and was further characterized with immunohistochemistry on two post mortem autopsy cases from the same family. In a targeted re-sequencing effort on independent index patients from 35 EOAD-families, a second SORL1 variant, c.3050-2A > G, was found which segregated with the disease in 3 affected and was absent in one unaffected family member. The c.3050-2A > G variant is located two nucleotides upstream of exon 22 and was shown to cause exon 22 skipping, resulting in a deletion of amino acids Gly1017- Glu1074 of SORL1. Furthermore, a third SORL1 variant, c.5195G > C, recently identified in a Swedish case control cohort included in the European Early-Onset Dementia (EU EOD) consortium study, was detected in two affected siblings in a third family with familial EOAD. The finding of three SORL1-variants that segregate with disease in three separate families with EOAD supports the involvement of SORL1 in AD pathology. The cause of these rare monogenic forms of EOAD has proven difficult to find and the use of exome and genome sequencing may be a successful route to target them.

MRI Proton Density Fat Fraction Is Robust Across the Biologically Plausible Range of Triglyceride Spectra in Adults With Nonalcoholic Steatohepatitis

PubMed Central

Hong, Cheng William; Mamidipalli, Adrija; Hooker, Jonathan C.; Hamilton, Gavin; Wolfson, Tanya; Chen, Dennis H.; Dehkordy, Soudabeh Fazeli; Middleton, Michael S.; Reeder, Scott B.; Loomba, Rohit; Sirlin, Claude B.

2017-01-01

Background Proton density fat fraction (PDFF) estimation requires spectral modeling of the hepatic triglyceride (TG) signal. Deviations in the TG spectrum may occur, leading to bias in PDFF quantification. Purpose To investigate the effects of varying six-peak TG spectral models on PDFF estimation bias. Study Type Retrospective secondary analysis of prospectively acquired clinical research data. Population Forty-four adults with biopsy-confirmed nonalcoholic steatohepatitis. Field Strength/Sequence Confounder-corrected chemical-shift-encoded 3T MRI (using a 2D multiecho gradient-recalled echo technique with magnitude reconstruction) and MR spectroscopy. Assessment In each patient, 61 pairs of colocalized MRI-PDFF and MRS-PDFF values were estimated: one pair used the standard six-peak spectral model, the other 60 were six-peak variants calculated by adjusting spectral model parameters over their biologically plausible ranges. MRI-PDFF values calculated using each variant model and the standard model were compared, and the agreement between MRI-PDFF and MRS-PDFF was assessed. Statistical Tests MRS-PDFF and MRI-PDFF were summarized descriptively. Bland–Altman (BA) analyses were performed between PDFF values calculated using each variant model and the standard model. Linear regressions were performed between BA biases and mean PDFF values for each variant model, and between MRI-PDFF and MRS-PDFF. Results Using the standard model, mean MRS-PDFF of the study population was 17.9±8.0% (range: 4.1–34.3%). The difference between the highest and lowest mean variant MRI-PDFF values was 1.5%. Relative to the standard model, the model with the greatest absolute BA bias overestimated PDFF by 1.2%. Bias increased with increasing PDFF (P < 0.0001 for 59 of the 60 variant models). MRI-PDFF and MRS-PDFF agreed closely for all variant models (R2=0.980, P < 0.0001). Data Conclusion Over a wide range of hepatic fat content, PDFF estimation is robust across the biologically plausible range of TG spectra. Although absolute estimation bias increased with higher PDFF, its magnitude was small and unlikely to be clinically meaningful. Level of Evidence 3 Technical Efficacy Stage 2 PMID:28851124

Pure Erythroleukemia (Variant Acute Myeloid Leukemia-vAML-M6) with Deletion of Chromosome 20, Mainly Presenting as Late Erythroblasts, a Unique Case Report with Review of Literature.

PubMed

Rasool, Javid; Geelani, Sajad; Khursheed; Yasir; Lone, Mohd Suhail; Shaban, Mohd

2014-03-01

Acute erythroleukemia is characterized by a predominant immature erythroid population and accounts for approximately 2-5 % of all cases of acute leukemia. Two subtypes are recognized based on the presence or absence of a significant myeloid component: erythroleukemia and pure erythroid leukemia. Erythroleukemia is predominantly a disease of adults, while pure erythroid leukemia can be seen in any age including children. Here is a case of pure erythroleukemia presenting mainly as late erythroblasts which was diagnosed on bone marrow examination, cytochemistry and was confirmed on immunophenotyping. Possibly this is the only case so for demonstrating deletion of long arm of chromosome 20 in pure erythroleukemia.

Numerical dispersion compensation for Partial Coherence Interferometry and Optical Coherence Tomography.

PubMed

Fercher, A; Hitzenberger, C; Sticker, M; Zawadzki, R; Karamata, B; Lasser, T

2001-12-03

Dispersive samples introduce a wavelength dependent phase distortion to the probe beam. This leads to a noticeable loss of depth resolution in high resolution OCT using broadband light sources. The standard technique to avoid this consequence is to balance the dispersion of the sample byarrangingadispersive materialinthereference arm. However, the impact of dispersion is depth dependent. A corresponding depth dependent dispersion balancing technique is diffcult to implement. Here we present a numerical dispersion compensation technique for Partial Coherence Interferometry (PCI) and Optical Coherence Tomography (OCT) based on numerical correlation of the depth scan signal with a depth variant kernel. It can be used a posteriori and provides depth dependent dispersion compensation. Examples of dispersion compensated depth scan signals obtained from microscope cover glasses are presented.

Sunni and Shi’a Terrorism: Differences that Matter

DTIC Science & Technology

2008-12-29

of the Alawite variant, Ayatollah Khomeini quickly adopted the fledgling  Hezbollah movement by  financing  it, arming it and providing it religious...thought provoking, they are  ultimately unconvincing. At best, the evidence suggests that Shi’a expatriate communities tend to  finance  terrorist‐linked...Shi’a‐extremists in Lebanon. This makes them akin to Irish expatriate  communities  financing  Irish Republican Army terror against Great Britain in the

[The boundary ranges of the free flight of particles of gunpowder and metals in shots from a hand firearm].

PubMed

Popov, V L; Isakov, V D; Krivozheĭko, A G

1990-01-01

On the basis of equations of external ballistics and probability theory the largest possible distances of free (independent) flight of gunshot powder and metal particles having different forms and sizes were calculated. Experimental control of the calculated data for different types of battle and sports hand fire-arms was carried out. The correspondence of the calculated data to maximal free (independent) particle flight in blank shots was stated. In experiments with cartridges equipped with bullets the distances of free particle flight were significantly lesser (by 53-65%) which may be connected with effect of gunshot projectile on the process of particle distribution. Reversed adapted formulas and calculation variants are presented.

A systematic review of the etiopathogenesis of Kienböck's disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration

PubMed Central

2012-01-01

Background We systematically reviewed etiological factors of Kienböck’s disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck’s disease (KD) in the European Listing of Occupational Diseases. Methods We searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria. Results A total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration. Conclusions A systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand-arm vibration is a risk factor for KD. PMID:23171057

Field guide to the Mesozoic accretionary complex along Turnagain Arm and Kachemak Bay, south-central Alaska

USGS Publications Warehouse

Bradley, Dwight C.; Kusky, Timothy M.; Karl, Susan M.; Haeussler, Peter J.

1997-01-01

Turnagain Arm, just east of Anchorage, provides a readily accessible, world-class cross section through a Mesozoic accretionary wedge. Nearly continuous exposures along the Seward Highway, the Alaska Railroad, and the shoreline of Turnagain Arm display the two main constituent units of the Chugach terrane: the McHugh Complex and Valdez Group. In this paper we describe seven bedrock geology stops along Turnagain Arm, and two others in the Chugach Mountains just to the north (Stops 1-7 and 9), which will be visited as part of the May, 1997 field trip of the Alaska Geological Society. Outcrops along Turnagain Arm have already been described in two excellent guidebook articles (Clark, 1981; Winkler and others 1984), both of which remain as useful and valid today as when first published. Since the early 1980's, studies along Turnagain Arm have addressed radiolarian ages of chert and conodont ages of limestone in the McHugh Complex (Nelson and others, 1986, 1987); geochemistry of basalt in the McHugh Complex (Nelson and Blome, 1991); post-accretion brittle faulting (Bradley and Kusky, 1990; Kusky and others, 1997); and the age and tectonic setting of gold mineralization (Haeussler and others, 1995). Highlights of these newer findings will described both in the text below, and in the stop descriptions.Superb exposures along the southeastern shore of Kachemak Bay show several other features of the McHugh Complex that are either absent or less convincing along Turnagain Arm. While none of these outcrops can be reached via the main road network, they are still reasonably accessible - all are within an hour by motorboat from Homer, seas permitting. Here, we describe seven outcrops along the shore of Kachemak Bay that we studied between 1989 and 1993 during geologic mapping of the Seldovia 1:250,000- scale quadrangle. These outcrops (Stops 61-67) will not be part of the 1997 itinerary, but are included here tor the benefit of those who may wish to visit them later.

Maladaptively high and low openness: the case for experiential permeability.

PubMed

Piedmont, Ralph L; Sherman, Martin F; Sherman, Nancy C

2012-12-01

The domain of Openness within the Five-Factor Model (FFM) has received inconsistent support as a source for maladaptive personality functioning, at least when the latter is confined to the disorders of personality included within the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, ). However, an advantage of the FFM relative to the DSM-IV-TR is that the former was developed to provide a reasonably comprehensive description of general personality structure. Rather than suggest that the FFM is inadequate because the DSM-IV-TR lacks much representation of Openness, it might be just as reasonable to suggest that the DSM-IV-TR is inadequate because it lacks an adequate representation of maladaptive variants of both high and low Openness. This article discusses the development and validation of a measure of these maladaptive variants, the Experiential Permeability Inventory. © 2012 The Authors. Journal of Personality © 2012, Wiley Periodicals, Inc.

Spermatocytic seminoma: review of the literature and description of a new case of the anaplastic variant.

PubMed

Lombardi, Mariano; Valli, Mirca; Brisigotti, Massimo; Rosai, Juan

2011-02-01

The aims of this paper were to review the literature of Spermatocytic Seminoma (SS) updating its clinico-pathological features and to present a new case of the exceptionally rare variant of this tumor known as anaplastic which only five cases have been reported. Many studies have confirmed that SS is a distinct neoplasm both clinically and pathologically from classical Seminoma and it differs from the latter especially in regard to behavior, characterized by an almost complete inability to metastasize with only very few convincing examples described with metastatic behavior. There is general agreement that orchidectomy is sufficient therapy for SS and that surveillance following surgery is the preferred management option. Surprisingly, the presence of an anaplastic component does not seem to impact on this excellent prognosis. Very different is the case of sarcomatous transformation, for which further therapy after orchiectomy is advisable.

Nonsingular bouncing cosmology: Consistency of the effective description

NASA Astrophysics Data System (ADS)

Koehn, Michael; Lehners, Jean-Luc; Ovrut, Burt

2016-05-01

We explicitly confirm that spatially flat nonsingular bouncing cosmologies make sense as effective theories. The presence of a nonsingular bounce in a spatially flat universe implies a temporary violation of the null energy condition, which can be achieved through a phase of ghost condensation. We calculate the scale of strong coupling and demonstrate that the ghost-condensate bounce remains trustworthy throughout, and that all perturbation modes within the regime of validity of the effective description remain under control. For this purpose we require the perturbed action up to third order in perturbations, which we calculate in both flat and co-moving gauge—since these two gauges allow us to highlight different physical aspects. Our conclusion is that there exist healthy descriptions of nonsingular bouncing cosmologies providing a viable resolution of the big-bang singularities in cosmological models. Our results also suggest a variant of ekpyrotic cosmology, in which entropy perturbations are generated during the contracting phase, but are only converted into curvature perturbations after the bounce.

A Process Algebraic Approach to Software Architecture Design

NASA Astrophysics Data System (ADS)

Aldini, Alessandro; Bernardo, Marco; Corradini, Flavio

Process algebra is a formal tool for the specification and the verification of concurrent and distributed systems. It supports compositional modeling through a set of operators able to express concepts like sequential composition, alternative composition, and parallel composition of action-based descriptions. It also supports mathematical reasoning via a two-level semantics, which formalizes the behavior of a description by means of an abstract machine obtained from the application of structural operational rules and then introduces behavioral equivalences able to relate descriptions that are syntactically different. In this chapter, we present the typical behavioral operators and operational semantic rules for a process calculus in which no notion of time, probability, or priority is associated with actions. Then, we discuss the three most studied approaches to the definition of behavioral equivalences - bisimulation, testing, and trace - and we illustrate their congruence properties, sound and complete axiomatizations, modal logic characterizations, and verification algorithms. Finally, we show how these behavioral equivalences and some of their variants are related to each other on the basis of their discriminating power.

Application of TREECS to Small Arms Firing Ranges at Fort Leonard Wood, MO

DTIC Science & Technology

2013-12-01

edited as necessary. The crop management factors (C) of the Universal Soil Loss Equation ( USLE ) were adjusted based upon the land-use description...ranges from approximately 750 to 1,150 feet above sea level near the northeastern installation boundary. The soils located at FLW are formed in the...official U.S. Department of Agriculture (USDA) soil types have been identified at FLW: Clarksville Gravelly Loam, Lebanon Silt Loam, and Huntington Loam

Artificial Intelligence Applied to the Command, Control, Communications, and Intelligence of the U.S. Central Command.

DTIC Science & Technology

1983-06-06

Command, Control, Communications, and Intelligence presented by the Armed Forced Communications Electronics Association and the perusal of many ...A great deal was also learned from the knowledgeable and helpful USAWC faculty and SSI staff as well as the curriculum which provided many insights to...actually an _ umbrella-label covering many disciplines. Thus, after a definition of Al, descriptions of a selection of its subfields will follow to set the

How completely are physiotherapy interventions described in reports of randomised trials?

PubMed

Yamato, Tiê P; Maher, Chris G; Saragiotto, Bruno T; Hoffmann, Tammy C; Moseley, Anne M

2016-06-01

Incomplete descriptions of interventions are a common problem in reports of randomised controlled trials. To date no study has evaluated the completeness of the descriptions of physiotherapy interventions. To evaluate the completeness of the descriptions of physiotherapy interventions in a random sample of reports of randomised controlled trials (RCTs). A random sample of 200 reports of RCTs from the PEDro database. We included full text papers, written in English, and reporting trials with two arms. We included trials evaluating any type of physiotherapy interventions and subdisciplines. The methodological quality was evaluated using the PEDro scale and completeness of intervention description using the Template for Intervention Description and Replication (TIDieR) checklist. The proportion and 95% confidence interval were calculated for intervention and control groups, and used to present the relationship between completeness and methodological quality, and subdisciplines. Completeness of intervention reporting in physiotherapy RCTs was poor. For intervention groups, 46 (23%) trials did not describe at least half of the items. Reporting was worse for control groups, 149 (75%) trials described less than half of the items. There was no clear difference in the completeness across subdisciplines or methodological quality. Our sample were restricted to trials published in English in 2013. Descriptions of interventions in physiotherapy RCTs are typically incomplete. Authors and journals should aim for more complete descriptions of interventions in physiotherapy trials. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.

PubMed

Elsayed, Liena E O; Mohammed, Inaam N; Hamed, Ahlam A A; Elseed, Maha A; Johnson, Adam; Mairey, Mathilde; Mohamed, Hassab Elrasoul S A; Idris, Mohamed N; Salih, Mustafa A M; El-Sadig, Sarah M; Koko, Mahmoud E; Mohamed, Ashraf Y O; Raymond, Laure; Coutelier, Marie; Darios, Frédéric; Siddig, Rayan A; Ahmed, Ahmed K M A; Babai, Arwa M A; Malik, Hiba M O; Omer, Zulfa M B M; Mohamed, Eman O E; Eltahir, Hanan B; Magboul, Nasr Aldin A; Bushara, Elfatih E; Elnour, Abdelrahman; Rahim, Salah M Abdel; Alattaya, Abdelmoneim; Elbashir, Mustafa I; Ibrahim, Muntaser E; Durr, Alexandra; Audhya, Anjon; Brice, Alexis; Ahmed, Ammar E; Stevanin, Giovanni

2016-01-01

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

PubMed Central

Elsayed, Liena E O; Mohammed, Inaam N; Hamed, Ahlam A A; Elseed, Maha A; Johnson, Adam; Mairey, Mathilde; Mohamed, Hassab Elrasoul S A; Idris, Mohamed N; Salih, Mustafa A M; El-sadig, Sarah M; Koko, Mahmoud E; Mohamed, Ashraf Y O; Raymond, Laure; Coutelier, Marie; Darios, Frédéric; Siddig, Rayan A; Ahmed, Ahmed K M A; Babai, Arwa M A; Malik, Hiba M O; Omer, Zulfa M B M; Mohamed, Eman O E; Eltahir, Hanan B; Magboul, Nasr Aldin A; Bushara, Elfatih E; Elnour, Abdelrahman; Rahim, Salah M Abdel; Alattaya, Abdelmoneim; Elbashir, Mustafa I; Ibrahim, Muntaser E; Durr, Alexandra; Audhya, Anjon; Brice, Alexis; Ahmed, Ammar E; Stevanin, Giovanni

2017-01-01

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance. PMID:27601211

[Psychoactive Drug Use by Youth in a Post Armed-Conflict Region].

PubMed

Díaz, Carlos Gantiva; Ramírez, Nohelia Hewitt; Maldonado, Anderssen Vera; Varela, Adriana Angarita; Baños, Arturo Parado; Puerto, Angélica Guillén

2012-06-01

There are no studies in Colombia on the use of psychoactive substances (PAS) by post armed-conflict population to serve as guide for prevention programs and to account for the potential impact armed conflict may have upon this area. To describe the use of PAS in young students in a post-conflict region. A quantitative-descriptive study involving the totality of students of the township of Viotá, Department of Cundinamarca, Colombia (1,304 participants). The World Health Survey for Schoolchildren was applied. Alcohol is the substance with the highest percentage of lifetime prevalence; during the last month, it was observed that the highest percentage of people start PAS use between the age of 8 and 13, while 42% of youngsters have experienced at least one drunkenness episode. It was found that 43.4% have been exposed to alcohol in their families while 35.1% were exposed to tobacco at school or in their neighborhoods. 84.5% stated their intention to continue consuming tobacco during the next year. Results show lower consumption percentages in comparison to school youngsters in Bogotá, Colombia, which may indicate that the armed conflict has not increased consumption levels in this population. Based on the results, certain elements to be taken into account are proposed for the implementation of prevention programs with this population. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Interactive evolution of camouflage.

PubMed

Reynolds, Craig

2011-01-01

This article presents an abstract computation model of the evolution of camouflage in nature. The 2D model uses evolved textures for prey, a background texture representing the environment, and a visual predator. A human observer, acting as the predator, is shown a cohort of 10 evolved textures overlaid on the background texture. The observer clicks on the five most conspicuous prey to remove ("eat") them. These lower-fitness textures are removed from the population and replaced with newly bred textures. Biological morphogenesis is represented in this model by procedural texture synthesis. Nested expressions of generators and operators form a texture description language. Natural evolution is represented by genetic programming (GP), a variant of the genetic algorithm. GP searches the space of texture description programs for those that appear least conspicuous to the predator.

History of Entomopathogenic Nematology

PubMed Central

Poinar, G. O.; Grewal, P. S.

2012-01-01

The history of entomopathogenic nematology is briefly reviewed. Topic selections include early descriptions of members of Steinernema and Heterorhabditis, how only morphology was originally used to distinguish between the species; descriptions of the symbiotic bacteria and elucidating their role in the nematode- insect complex, including antibiotic properties, phase variants, and impeding host defense responses. Other topics include early solutions regarding production, storage, field applications and the first commercial sales of entomopathogenic nematodes in North America. Later studies centered on how the nematodes locate insect hosts, their effects on non-target organisms and susceptibility of the infective juveniles to soil microbes. While the goals of early workers was to increase the efficacy of entomopathogenic nematodes for pest control, the increasing use of Heterorhabditis and Photorhabdus as genetic models in molecular biology is noted. PMID:23482453

NATO Scientific and Technical Information Service (NSTIS): functional description. Final report

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

Molholm, K.N.; Blados, W.N.; Bulca, C.

1987-08-01

This report provides a functional description of the requirements for a NATO Scientific and Technical Information Service (NSTIS). The user requirements and much of the background information in this report were derived primarily from interviews with more than 60 NATO Headquarters staff members between 2 March and 25 March 1987. In addition, representatives of the Supreme Headquarters Applied Powers Europe (SHAPE) Technical Centre (STC), the Supreme Allied Commander Atlantic (Anti-Submarine Warfare Research) Centre (SACLANTCEN), the NATO Communications and Information Systems Agency (NACISA), The Advisory Group for Aerospace Research and Development (AGARD), the U.S. Defense Technical Information Center (DTIC), and themore » Technical Documentation Center for the Armed Forces in the Netherlands (TDCK), were interviewed, either in person or by telephone.« less

Glucose-6-phosphate dehydrogenase deficiency among malaria patients of Honduras: a descriptive study of archival blood samples.

PubMed

Zúñiga, Miguel Á; Mejía, Rosa E; Sánchez, Ana L; Sosa-Ochoa, Wilfredo H; Fontecha, Gustavo A

2015-08-07

The frequency of deficient variants of glucose-6-phosphate dehydrogenase (G6PDd) is particularly high in areas where malaria is endemic. The administration of antirelapse drugs, such as primaquine, has the potential to trigger an oxidative event in G6PD-deficient individuals. According to Honduras´ national scheme, malaria treatment requires the administration of chloroquine and primaquine for both Plasmodium vivax and Plasmodium falciparum infections. The present study aimed at investigating for the first time in Honduras the frequency of the two most common G6PDd variants. This was a descriptive study utilizing 398 archival DNA samples of patients that had been diagnosed with malaria due to P. vivax, P. falciparum, or both. The most common allelic variants of G6PD: G6PD A+(376G) and G6PD A-(376G/202A) were assessed by two molecular methods (PCR-RFLP and a commercial kit). The overall frequency of G6PD deficient genotypes was 16.08%. The frequency of the "African" genotype A- (Class III) was 11.9% (4.1% A- hemizygous males; 1.5% homozygous A- females; and 6.3% heterozygous A- females). A high frequency of G6PDd alleles was observed in samples from malaria patients residing in endemic regions of Northern Honduras. One case of Santamaria mutation (376G/542T) was detected. Compared to other studies in the Americas, as well as to data from predictive models, the present study identified a higher-than expected frequency of genotype A- in Honduras. Considering that the national standard of malaria treatment in the country includes primaquine, further research is necessary to ascertain the risk of PQ-triggered haemolytic reactions in sectors of the population more likely to carry G6PD mutations. Additionally, consideration should be given to utilizing point of care technologies to detect this genetic disorder prior administration of 8-aminoquinoline drugs, either primaquine or any new drug available in the near future.

Mode Theory of Multi-Armed Spiral Antennas and Its Application to Electronic Warfare Antennas

NASA Astrophysics Data System (ADS)

Radway, Matthew J.

Since their invention about 55 years ago, spiral antennas have earned a reputation for providing stable impedance and far-field patterns over multi-decade frequency ranges. For the first few decades these antennas were researched for electronic warfare receiving applications, primarily in the 2-18 GHz range. This research was often done under conditions of secrecy, and often by private contractors who did not readily share their research, and now have been defunct for decades. Even so, the body of literature on the two-armed variant of these antennas is rich, often leading non-specialists to the misconception that these antennas are completely understood. Furthermore, early work was highly experimental in nature, and was conducted before modern data collection and postprocessing capabilities were widespread, which limited the range of the studies. Recent research efforts have focused on extending the application of spirals into new areas, as well as applying exotic materials to `improve' their performance and reduce their size. While interesting results have been obtained, in most instances these were incomplete, often compromising the frequency independent nature of these antennas. This thesis expands the role of the multi-armed spiral outside of its traditional niche of receive-only monopulse direction finding. As a first step, careful study of the spiral-antenna mode theory is undertaken with particular attention paid to the concepts of mode filtering and modal decomposition. A technique for reducing the modal impedance of high arm-count spirals is introduced. The insights gained through this theoretical study are first used to improve the far-field performance of the coiled-arm spiral antenna. Specifically, expanding the number of arms on a coiled arm spiral from two to four while providing proper excitation enables dramatically improved broadside axial ratio and azimuthal pattern uniformity. The multiarming technique is then applied to the design of an antenna with exceptionally stable and clean radiation patterns without use of an absorbing cavity. The multiarming technique allows the spiral to retain its pattern integrity at frequencies well below those of comparable two-armed spiral antennas. A quadrifilar helix-type of end-loading is applied to the end of the spiral, resulting in dramatically-improved low-frequency gain. Careful application of resistive end-loading allows good impedance matching at frequencies as low as one-half of the Mode 1 cutoff frequency, while providing acceptable radiation efficiency due to effective use of the available antenna volume. A novel dual-layering technique for reducing the spiral's modal impedance is presented, allowing the antenna to present a good impedance match to a 50 ohm system. The third application of mode theory has been to exploit the wideband multi-mode capability of the multi-armed spiral antenna to implement a simple wide-band radiation pattern nulling technique on a multi-armed spiral antenna. It is shown that wideband nulling is possible and that, in contrast to traditional array antennas, grating lobes do not appear even over extremely wide bandwidths. Simple techniques for addressing the phenomenon of null rotation with frequency are discussed. Finally, mode theory has been used to analyze beamformer non-idealities. This has led to the revelation that the spectral distribution of beamformer errors is at least as important as the magnitude of those errors. Proper choice of beamformer topology can result in noticeable improvement in the antenna performance.

Role of the ρ meson in the description of pion electroproduction experiments

NASA Astrophysics Data System (ADS)

Faessler, Amand; Gutsche, Thomas; Lyubovitskij, Valery E.; Obukhovsky, Igor T.

2007-08-01

We study the p(e,e'π+)n reaction in the framework of an effective Lagrangian approach including nucleon, π and ρ meson degrees of freedom and show the importance of the ρ-meson t-pole contribution to σT, the transverse part of cross section. We test two different field representations of the ρ meson, vector and tensor, and find that the tensor representation of the ρ meson is more reliable in the description of the existing data. In particular, we show that the ρ-meson t-pole contribution, including the interference with an effective nonlocal contact term, sufficiently improves the description of the recent JLab data at invariant mass W≲2.2 GeV and Q2≲2.5 GeV2/c2. A “soft” variant of the strong πNN and ρNN form factors is also found to be compatible with these data. On the basis of the successful description of both the σL and σT parts of the cross section we discuss the importance of taking into account the σT data when extracting the charge pion form factor Fπ from σL.

Randomness Testing of the Advanced Encryption Standard Finalist Candidates

DTIC Science & Technology

2000-03-28

Excursions Variant 18 168-185 Rank 1 7 Serial 2 186-187 Spectral DFT 1 8 Lempel - Ziv Compression 1 188 Aperiodic Templates 148 9-156 Linear Complexity...256 bits) for each of the algorithms , for a total of 80 different data sets10. These data sets were selected based on the belief that they would be...useful in evaluating the randomness of cryptographic algorithms . Table 2 lists the eight data types. For a description of the data types, see Appendix

The Human Variome Project (HVP) 2009 Forum "Towards Establishing Standards".

PubMed

Howard, Heather J; Horaitis, Ourania; Cotton, Richard G H; Vihinen, Mauno; Dalgleish, Raymond; Robinson, Peter; Brookes, Anthony J; Axton, Myles; Hoffmann, Robert; Tuffery-Giraud, Sylvie

2010-03-01

The May 2009 Human Variome Project (HVP) Forum "Towards Establishing Standards" was a round table discussion attended by delegates from groups representing international efforts aimed at standardizing several aspects of the HVP: mutation nomenclature, description and annotation, clinical ontology, means to better characterize unclassified variants (UVs), and methods to capture mutations from diagnostic laboratories for broader distribution to the medical genetics research community. Methods for researchers to receive credit for their effort at mutation detection were also discussed. (c) 2010 Wiley-Liss, Inc.

Complementation of Myelodysplastic Syndrome Clones with Lentivirus Expression Libraries

DTIC Science & Technology

2012-07-01

Description HRAS Homo sapiens v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), transcript 1 CDC25C Homo sapiens cell division cycle 25...homolog C (CDC25C), transcript variant 1 MYC Homo sapiens v-myc myeloctomatosis viral oncogene homolog (avian) (MYC) MAP3K7 Homo sapiens mitogen...activated protein kinase kinase kinase 7 (MAP3K7) MAP3K8 Homo sapiens mitogen-activated protein kinase kinase kinase 8 (MAP3K8) SF3B1 Homo sapiens splicing

Complementation of Myelodysplastic Syndrome Clones with Lentivirus Expression Libraries

DTIC Science & Technology

2013-01-01

Description HRAS Homo sapiens v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), transcript 1 CDC25C Homo sapiens cell division cycle 25...homolog C (CDC25C), transcript variant 1 MYC Homo sapiens v-myc myeloctomatosis viral oncogene homolog (avian) (MYC) MAP3K7 Homo sapiens mitogen...activated protein kinase kinase kinase 7 (MAP3K7) MAP3K8 Homo sapiens mitogen-activated protein kinase kinase kinase 8 (MAP3K8) SF3B1 Homo sapiens

Non-Lethal Weapons and Future Peace Enforcement Operations (Les armes non letales dans les operations d’imposition de la paix)

DTIC Science & Technology

2004-11-01

Principles and System Description Chemical agents may be used to immobilise vehicles. They act on the tyres , the optics and sensors (windscreen, video...lenses, mirrors etc), the engine and the fuel. For example, the following means of action may be mentioned: • • • • The tyres : glue, solvents...liquid metal embrittlement (LME) chemicals have the ability to dissolve metals, plastics, rubber , glass, etc. The use of all chemical agents must be

Experimental and Demonstration Manpower Project for Recruitment, Training, Placement and Followup of Rejected Armed Forces Volunteers in Baltimore, Maryland and Washington, D.C., March 1, 1965 to June 30, 1966. Final Report.

ERIC Educational Resources Information Center

National Committee for Children and Youth, Washington, DC.

This report contains an analysis of the efforts in 1965 and 1966 of the National Committee for Children and Youth (NCCY) to help the youth in Baltimore and Washington, D.C. who failed to meet the educational requirements for military enlistment. A description of the program includes: (1) background of the NCCY, (2) intake and followup process, (3)…

Description of Officers and Enlisted Personnel in the U.S. Armed Forces: A Reference for Military Manpower Analysis.

DTIC Science & Technology

1982-03-01

FINANCIAL STATUS AND PARTICIPATION IN THE CIVILIAN LABOR FORCE OF MILITARY PERSONNEL AND THEIR SPOUSES .... 264 IX. MILITARY COMPENSATION AND BENEFITS...effects of rotation and assignment location on military personnel and their households (Section VII). Section VIII deals with the financial status and...Response rate 58.3 58.6 71.7 71.3 62.2 12 number of questionnaires fielded was not adjusted to account for persons who had been separated from the

High efficiency conical scanner for earth resources applications

NASA Technical Reports Server (NTRS)

Bates, J. C.; Dumas, H. J., Jr.

1975-01-01

A description is given of a six-arm conical scanner which was selected to provide a continuous line-of-sight scan. Two versions of the instrument are considered. The two versions differ in their weight. The weight of the heavy version is 600 lbs. A light weight design which employs beryllium and aluminum optical components weighs only 350 lbs. A multiplexer and analog-to-digital converter are to be incorporated into the design. Questions of instrument performance are also discussed.

Air Force Operational Medicine: Using the Enterprise Estimating Supplies Program to Develop Materiel Solutions for the Thoracic/Vascular Surgery Team (FFGKT)

DTIC Science & Technology

2010-11-10

asset, including combat wounds, non-battle injuries , and illnesses. International Classification of Diseases, Ninth Revision (ICD-9) coded patient...patient conditions and the frequency at which they would present. The resulting illness and injury frequencies characterize the expected patient...The scenario is shown in Table 1. Table 1 Thoracic/Vascular Scenario ICD-9 ICD-9 description No. patients 903.9 INJURY ARM VESSEL NOS 2 904.8

Analysis of protein-altering variants in telomerase genes and their association with MUC5B common variant status in patients with idiopathic pulmonary fibrosis: a candidate gene sequencing study.

PubMed

Dressen, Amy; Abbas, Alexander R; Cabanski, Christopher; Reeder, Janina; Ramalingam, Thirumalai R; Neighbors, Margaret; Bhangale, Tushar R; Brauer, Matthew J; Hunkapiller, Julie; Reeder, Jens; Mukhyala, Kiran; Cuenco, Karen; Tom, Jennifer; Cowgill, Amy; Vogel, Jan; Forrest, William F; Collard, Harold R; Wolters, Paul J; Kropski, Jonathan A; Lancaster, Lisa H; Blackwell, Timothy S; Arron, Joseph R; Yaspan, Brian L

2018-06-08

Idiopathic pulmonary fibrosis (IPF) risk has a strong genetic component. Studies have implicated variations at several loci, including TERT, surfactant genes, and a single nucleotide polymorphism at chr11p15 (rs35705950) in the intergenic region between TOLLIP and MUC5B. Patients with IPF who have risk alleles at rs35705950 have longer survival from the time of IPF diagnosis than do patients homozygous for the non-risk allele, whereas patients with shorter telomeres have shorter survival times. We aimed to assess whether rare protein-altering variants in genes regulating telomere length are enriched in patients with IPF homozygous for the non-risk alleles at rs35705950. Between Nov 1, 2014, and Nov 1, 2016, we assessed blood samples from patients aged 40 years or older and of European ancestry with sporadic IPF from three international phase 3 clinical trials (INSPIRE, CAPACITY, ASCEND), one phase 2 study (RIFF), and US-based observational studies (Vanderbilt Clinical Interstitial Lung Disease Registry and the UCSF Interstitial Lung Disease Clinic registry cohorts) at the Broad Institute (Cambridge, MA, USA) and Human Longevity (San Diego, CA, USA). We also assessed blood samples from non-IPF controls in several clinical trials. We did whole-genome sequencing to assess telomere length and identify rare protein-altering variants, stratified by rs35705950 genotype. We also assessed rare functional variation in TERT exons and compared telomere length and disease progression across genotypes. We assessed samples from 1510 patients with IPF and 1874 non-IPF controls. 30 (3%) of 1046 patients with an rs35705950 risk allele had a rare protein-altering variant in TERT compared with 34 (7%) of 464 non-risk allele carriers (odds ratio 0·40 [95% CI 0·24-0·66], p=0·00039). Subsequent analyses identified enrichment of rare protein-altering variants in PARN and RTEL1, and rare variation in TERC in patients with IPF compared with controls. We expanded our study population to provide a more accurate estimation of rare variant frequency in these four loci, and to calculate telomere length. The proportion of patients with at least one rare variant in TERT, PARN, TERC, or RTEL1 was higher in patients with IPF than in controls (149 [9%] of 1739 patients vs 205 [2%] of 8645 controls, p=2·44 × 10 -8 ). Patients with IPF who had a variant in any of the four identified telomerase component genes had telomeres that were 3·69-16·10% shorter than patients without a variant in any of the four genes and had an earlier mean age of disease onset than patients without one or more variants (65·1 years [SD 7·8] vs 67·1 years [7·9], p=0·004). In the placebo arms of clinical trials, shorter telomeres were significantly associated with faster disease progression (1·7% predicted forced vital capacity per kb per year, p=0·002). Pirfenidone had treatment benefit regardless of telomere length (p=4·24 × 10 -8 for telomere length lower than the median, p=0·0044 for telomere length greater than the median). Rare protein-altering variants in TERT, PARN, TERC, and RTEL1 are enriched in patients with IPF compared with controls, and, in the case of TERT, particularly in individuals without a risk allele at the rs35705950 locus. This suggests that multiple genetic factors contribute to sporadic IPF, which might implicate distinct mechanisms of pathogenesis and disease progression. Genentech, National Institutes of Health, Francis Family Foundation, Pulmonary Fibrosis Foundation, Nina Ireland Program for Lung Health, US Department of Veterans Affairs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetic Analysis of Aspartate Aminotransferase Isozymes from Hybrids between DROSOPHILA MELANOGASTER and DROSOPHILA SIMULANS and Mutagen-Induced Isozyme Variants

PubMed Central

Grell, E. H.

1976-01-01

The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster for which naturally occurring electrophoretic variants were not found. There is an electrophoretic difference between D. melanogaster and D. simulans. Since the F 1 hybrid offspring of these species are sterile, a genetic analysis of the ordinary type cannot be done on differences between the two species. A method was devised to make "partial hybrids" in which one chromosome arm is homozygous for melanogaster genes in an otherwise hybrid background. By using this method, Got1 was localized to 2R and Got2 to 2L. Once a gene can be assigned to a chromosome, it may be followed in crossing schemes and mutations from mutagen treatments may be looked for. At the locus of Got1 a mutation with low activity was recovered and designated Got1lo. It was located at a genetic map position of 75 on 2R. A Got2 mutant with a greater migration to the anode was recovered and designated Got2 J. It was located at a genetic map position of 3.0, and in the salivary chromosome was between 22B1 and 22B4 inclusive. PMID:823072

SNPase-ARMS qPCR: Ultrasensitive Mutation-Based Detection of Cell-Free Tumor DNA in Melanoma Patients

PubMed Central

Stadler, Julia; Eder, Johanna; Pratscher, Barbara; Brandt, Sabine; Schneller, Doris; Müllegger, Robert; Vogl, Claus; Trautinger, Franz; Brem, Gottfried; Burgstaller, Joerg P.

2015-01-01

Cell-free circulating tumor DNA in the plasma of cancer patients has become a common point of interest as indicator of therapy options and treatment response in clinical cancer research. Especially patient- and tumor-specific single nucleotide variants that accurately distinguish tumor DNA from wild type DNA are promising targets. The reliable detection and quantification of these single-base DNA variants is technically challenging. Currently, a variety of techniques is applied, with no apparent “gold standard”. Here we present a novel qPCR protocol that meets the conditions of extreme sensitivity and specificity that are required for detection and quantification of tumor DNA. By consecutive application of two polymerases, one of them designed for extreme base-specificity, the method reaches unprecedented sensitivity and specificity. Three qPCR assays were tested with spike-in experiments, specific for point mutations BRAF V600E, PTEN T167A and NRAS Q61L of melanoma cell lines. It was possible to detect down to one copy of tumor DNA per reaction (Poisson distribution), at a background of up to 200 000 wild type DNAs. To prove its clinical applicability, the method was successfully tested on a small cohort of BRAF V600E positive melanoma patients. PMID:26562020

Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize.

PubMed

Liu, Yalin; Su, Handong; Pang, Junling; Gao, Zhi; Wang, Xiu-Jie; Birchler, James A; Han, Fangpu

2015-03-17

The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity.

Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize

PubMed Central

Liu, Yalin; Su, Handong; Pang, Junling; Gao, Zhi; Wang, Xiu-Jie; Birchler, James A.; Han, Fangpu

2015-01-01

The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity. PMID:25733907

Preventive Neuromuscular Training for Young Female Athletes: Comparison of Coach and Athlete Compliance Rates

PubMed Central

Sugimoto, Dai; Mattacola, Carl G.; Bush, Heather M.; Thomas, Staci M.; Foss, Kim D. Barber; Myer, Gregory D.; Hewett, Timothy E.

2017-01-01

Context: Fewer athletic injuries and lower anterior cruciate ligament injury incidence rates were noted in studies of neuromuscular-training (NMT) interventions that had high compliance rates. However, several groups have demonstrated that preventive NMT interventions were limited by low compliance rates. Objective: To descriptively analyze coach and athlete compliance with preventive NMT and compare the compliance between study arms as well as among school levels and sports. Design: Randomized, controlled clinical trial. Setting: Middle and high school athletic programs. Participants or Other Participants: A total of 52 teams, comprising 547 female athletes, were randomly assigned to the experimental or control group and followed for 1 athletic season. Intervention(s): The experimental group (n = 30 teams [301 athletes]: 12 basketball teams [125 athletes], 6 soccer teams [74 athletes], and 12 volleyball teams [102 athletes]) participated in an NMT program aimed at reducing traumatic knee injuries through a trunk-stabilization and hip-strengthening program. The control group (n = 22 teams [246 athletes]: 11 basketball teams [116 athletes], 5 soccer teams [68 athletes], and 6 volleyball teams [62 athletes]) performed a resistive rubber-band running program. Main Outcome Measure(s): Compliance with the assigned intervention protocols (3 times per week during the preseason [mean = 3.4 weeks] and 2 times per week in-season [mean = 11.9 weeks] of coaches [coach compliance] and athletes [athlete compliance]) was measured descriptively. Using an independent t test, we compared coach and athlete compliance between the study arms. A 2-way analysis of variance was calculated to compare differences between coach and athlete compliance by school level (middle and high schools) and sport (basketball, soccer, and volleyball). Results: The protocols were completed at a mean rate of 1.3 ± 1.1 times per week during the preseason and 1.2 ± 0.5 times per week in-season. A total of 88.4% of athletes completed 2/3 of the intervention sessions. Coach compliance was greater in the experimental group than in the control group (P = .014). Coach compliance did not differ by sport but was greater at the high school than the middle school (P = .001) level. Athlete compliance did not differ by study arm, sport, or school level. Conclusions: Athletes received instruction in about 50% of each protocol. Nearly 90% of athletes performed more than 2/3 of the assigned NMT interventions. The assigned intervention was performed more often in the experimental arm compared with the control arm. Coaches at the high school level complied with the given protocol more than middle school coaches did. Athletes complied well with the protocol, but coaches did not, especially at the middle school level. PMID:27977300

Preventive Neuromuscular Training for Young Female Athletes: Comparison of Coach and Athlete Compliance Rates.

PubMed

Sugimoto, Dai; Mattacola, Carl G; Bush, Heather M; Thomas, Staci M; Foss, Kim D Barber; Myer, Gregory D; Hewett, Timothy E

2017-01-01

 Fewer athletic injuries and lower anterior cruciate ligament injury incidence rates were noted in studies of neuromuscular-training (NMT) interventions that had high compliance rates. However, several groups have demonstrated that preventive NMT interventions were limited by low compliance rates.  To descriptively analyze coach and athlete compliance with preventive NMT and compare the compliance between study arms as well as among school levels and sports.  Randomized, controlled clinical trial.  Middle and high school athletic programs. Participants or Other Participants: A total of 52 teams, comprising 547 female athletes, were randomly assigned to the experimental or control group and followed for 1 athletic season.  The experimental group (n = 30 teams [301 athletes]: 12 basketball teams [125 athletes], 6 soccer teams [74 athletes], and 12 volleyball teams [102 athletes]) participated in an NMT program aimed at reducing traumatic knee injuries through a trunk-stabilization and hip-strengthening program. The control group (n = 22 teams [246 athletes]: 11 basketball teams [116 athletes], 5 soccer teams [68 athletes], and 6 volleyball teams [62 athletes]) performed a resistive rubber-band running program.  Compliance with the assigned intervention protocols (3 times per week during the preseason [mean = 3.4 weeks] and 2 times per week in-season [mean = 11.9 weeks] of coaches [coach compliance] and athletes [athlete compliance]) was measured descriptively. Using an independent t test, we compared coach and athlete compliance between the study arms. A 2-way analysis of variance was calculated to compare differences between coach and athlete compliance by school level (middle and high schools) and sport (basketball, soccer, and volleyball).  The protocols were completed at a mean rate of 1.3 ± 1.1 times per week during the preseason and 1.2 ± 0.5 times per week in-season. A total of 88.4% of athletes completed 2/3 of the intervention sessions. Coach compliance was greater in the experimental group than in the control group (P = .014). Coach compliance did not differ by sport but was greater at the high school than the middle school (P = .001) level. Athlete compliance did not differ by study arm, sport, or school level.  Athletes received instruction in about 50% of each protocol. Nearly 90% of athletes performed more than 2/3 of the assigned NMT interventions. The assigned intervention was performed more often in the experimental arm compared with the control arm. Coaches at the high school level complied with the given protocol more than middle school coaches did. Athletes complied well with the protocol, but coaches did not, especially at the middle school level.

Correlations between Angular Velocities in Selected Joints and Velocity of Table Tennis Racket during Topspin Forehand and Backhand

PubMed Central

Bańkosz, Ziemowit; Winiarski, Sławomir

2018-01-01

The aim of this study was to determine the correlations between angular velocities in individual joints and racket velocity for different topspin forehand and backhand strokes in table tennis. Ten elite female table tennis players participated, presenting different kinds of topspin forehands and backhands – after a no-spin ball (FH1, BH1), after a backspin ball (FH2, BH2) and “heavy” topspin (FH3, BH3). Range of motion was measured with the BTS Smart-E (BTS Bioengineering, Milan, Italy) motion analysis system with a specially developed marker placement protocol for the upper body parts and an acoustic sensor attached to the racket to identify ball-racket contact. In forehand strokes angular velocities of internal arm rotation and adduction in shoulder joint correlated with racket velocity. Racket velocity was correlated with angular velocities (hip extension on the playing side; hip flexion on the opposite side; ankle flexion) in the case of a topspin forehand performed with maximal force –”heavy” topspin (FH3). In backhand strokes the velocities of arm abduction and shoulder girdle rotation towards the playing side correlated with racket velocity. The angular velocity of internal arm rotation and adduction in shoulder joint may be important components of a coordinated stroke, whilst angular velocity can substantially affect the racket speed when one is changing the type of stroke. Key points The aim of this study was to calculate correlations between racket velocity and the angular velocities of individual joints and for variants of topspin forehand and backhand strokes in table tennis. A novel model was used to estimate range of motion (specially developed placement protocol for upper body markers and identification of a ball-racket contact using an acoustic sensor attached to the racket). In forehand strokes angular velocities of internal arm rotation and adduction in shoulder joint were correlated with racket velocity. Correlations between racket velocity and the angular velocities of playing- and non-playing-side hip extension and ankle flexion were found in topspin forehands. In topspin backhands abduction of the arm had the greatest impact on the racket speed. The results can be used directly to improve training of table tennis techniques, especially topspin strokes. PMID:29769835

Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.

PubMed

Li, Jonathan Z; Chapman, Brad; Charlebois, Patrick; Hofmann, Oliver; Weiner, Brian; Porter, Alyssa J; Samuel, Reshmi; Vardhanabhuti, Saran; Zheng, Lu; Eron, Joseph; Taiwo, Babafemi; Zody, Michael C; Henn, Matthew R; Kuritzkes, Daniel R; Hide, Winston; Wilson, Cara C; Berzins, Baiba I; Acosta, Edward P; Bastow, Barbara; Kim, Peter S; Read, Sarah W; Janik, Jennifer; Meres, Debra S; Lederman, Michael M; Mong-Kryspin, Lori; Shaw, Karl E; Zimmerman, Louis G; Leavitt, Randi; De La Rosa, Guy; Jennings, Amy

2014-01-01

The impact of raltegravir-resistant HIV-1 minority variants (MVs) on raltegravir treatment failure is unknown. Illumina sequencing offers greater throughput than 454, but sequence analysis tools for viral sequencing are needed. We evaluated Illumina and 454 for the detection of HIV-1 raltegravir-resistant MVs. A5262 was a single-arm study of raltegravir and darunavir/ritonavir in treatment-naïve patients. Pre-treatment plasma was obtained from 5 participants with raltegravir resistance at the time of virologic failure. A control library was created by pooling integrase clones at predefined proportions. Multiplexed sequencing was performed with Illumina and 454 platforms at comparable costs. Illumina sequence analysis was performed with the novel snp-assess tool and 454 sequencing was analyzed with V-Phaser. Illumina sequencing resulted in significantly higher sequence coverage and a 0.095% limit of detection. Illumina accurately detected all MVs in the control library at ≥0.5% and 7/10 MVs expected at 0.1%. 454 sequencing failed to detect any MVs at 0.1% with 5 false positive calls. For MVs detected in the patient samples by both 454 and Illumina, the correlation in the detected variant frequencies was high (R2 = 0.92, P<0.001). Illumina sequencing detected 2.4-fold greater nucleotide MVs and 2.9-fold greater amino acid MVs compared to 454. The only raltegravir-resistant MV detected was an E138K mutation in one participant by Illumina sequencing, but not by 454. In participants of A5262 with raltegravir resistance at virologic failure, baseline raltegravir-resistant MVs were rarely detected. At comparable costs to 454 sequencing, Illumina demonstrated greater depth of coverage, increased sensitivity for detecting HIV MVs, and fewer false positive variant calls.

A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia

PubMed Central

Duriez, Bénédicte; Duquesnoy, Philippe; Escudier, Estelle; Bridoux, Anne-Marie; Escalier, Denise; Rayet, Isabelle; Marcos, Elisabeth; Vojtek, Anne-Marie; Bercher, Jean-François; Amselem, Serge

2007-01-01

Thioredoxins belong to a large family of enzymatic proteins that function as general protein disulfide reductases, therefore participating in several cellular processes via redox-mediated reactions. So far, none of the 18 members of this family has been involved in human pathology. Here we identified TXNDC3, which encodes a thioredoxin–nucleoside diphosphate kinase, as a gene implicated in primary ciliary dyskinesia (PCD), a genetic condition characterized by chronic respiratory tract infections, left–right asymmetry randomization, and male infertility. We show that the disease, which segregates as a recessive trait, results from the unusual combination of the following two transallelic defects: a nonsense mutation and a common intronic variant found in 1% of control chromosomes. This variant affects the ratio of two physiological TXNDC3 transcripts: the full-length isoform and a novel isoform, TXNDC3d7, carrying an in-frame deletion of exon 7. In vivo and in vitro expression data unveiled the physiological importance of TXNDC3d7 (whose expression was reduced in the patient) and the corresponding protein that was shown to bind microtubules. PCD is known to result from defects of the axoneme, an organelle common to respiratory cilia, embryonic nodal cilia, and sperm flagella, containing dynein arms, with, to date, the implication of genes encoding dynein proteins. Our findings, which identify a another class of molecules involved in PCD, disclose the key role of TXNDC3 in ciliary function; they also point to an unusual mechanism underlying a Mendelian disorder, which is an SNP-induced modification of the ratio of two physiological isoforms generated by alternative splicing. PMID:17360648

TGFβ1 genetic variants are associated with an increased risk of acute brucellosis.

PubMed

Sepanjnia, Adel; Eskandari-Nasab, Ebrahim; Moghadampour, Mehdi; Tahmasebi, Arezoo; Dahmardeh, Fatemeh

2015-07-01

Cytokines play a critical role in the regulation of the immune response against brucellosis infection, and mediate production of many pro- and anti-inflammatory signals. Transforming growth factor-beta 1 (TGFβ1), a powerful suppressive cytokine, inhibits macrophage activation and modulates T-cell function, and plays crucial roles in regulation of microbial replication and host responses to brucella. The association of three polymorphisms in the TGFβ1 gene (-509 C/T [rs1800469], + 868 C/T [rs1800470], and + 913 G/C [rs1800471]) in promoter, codons 10 and 25, respectively, with brucellosis infection was evaluated. This case-control study was performed on a total of 281 Iranian subjects including 153 patients with active brucellosis and 128 age- and sex-matched healthy individuals as controls. Genotyping for the TGFβ1 -509 C/T and + 868 C/T variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Also, the + 913 G/C polymorphism was genotyped using an allele-specific PCR. The results demonstrated that the TGFβ1 + 868 C/T mutant homozygote genotype (TT vs CC), was a risk factor for developing brucellosis in the co-dominant and recessive models (odds ratio (OR) = 2.60, p = 0.023; OR = 2.602, p = 0.014, respectively). Additionally, the diplotype analyses revealed that TGFβ1 codon 10 and 25 diplotype, TT/GG, was associated with an increased risk of brucellosis (OR = 2.49, p = 0.038). Other TGFβ1 variants did not increase the risk of brucellosis infection. Our findings propose that TGFβ1 + 868 TT genotype and TT/GG diplotype may confer increased risk of brucellosis in the examined population.

Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program

PubMed Central

Florez, J. C.; Jablonski, K. A.; McAteer, J.; Sandhu, M. S.; Wareham, N. J.; Barroso, I.; Franks, P. W.; Altshuler, D.; Knowler, W. C.

2008-01-01

Aims/hypothesis Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with type 2 diabetes. We therefore examined the effects of these variants on diabetes incidence and response to interventions in the Diabetes Prevention Program (DPP), in which a lifestyle intervention or metformin treatment was compared with placebo. Methods We genotyped the WFS1 SNPs rs10010131, rs752 854 and rs734312 (H611R) in 3,548 DPP participants and performed Cox regression analysis using genotype, intervention and their interactions as predictors of diabetes incidence. We also evaluated the effect of these SNPs on insulin resistance and beta cell function at 1 year. Results Although none of the three SNPs was associated with diabetes incidence in the overall cohort, white homozygotes for the previously reported protective alleles appeared less likely to develop diabetes in the lifestyle arm. Examination of the publicly available Diabetes Genetics Initiative genome-wide association dataset revealed that rs10012946, which is in strong linkage disequilibrium with the three WFS1 SNPs (r2=0.88–1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75–0.97, p=0.026). In the DPP, we noted a trend towards increased insulin secretion in carriers of the protective variants, although for most SNPs this was seen as compensatory for the diminished insulin sensitivity. Conclusions/interpretation The previously reported protective effect of select WFS1 alleles may be magnified by a lifestyle intervention. These variants appear to confer an improvement in beta cell function. PMID:18060660

The effect of position on the percentage of body mass supported during traditional and modified push-up variants.

PubMed

Suprak, David N; Dawes, Jay; Stephenson, Mark D

2011-02-01

The push-up is a popular upper-extremity weight-bearing exercise. However, limited information is available regarding its effectiveness. Much of the past research has focused on muscle activation levels, whereas very little has examined the forces encountered during push-up variants. The purpose of the present study was to examine the effect of position within the range of motion on the percentage of body mass (BM) supported by the upper extremities during the traditional and modified (knees-down) push-up. Twenty-eight highly strength-trained male subjects were positioned with their hands on a force platform in 4 static positions, consisting of the up and down position in both the traditional and modified push-up exercise. The performance measures included the average vertical ground reaction force (GRF), expressed as a percentage of BM, supported in each of the 4 static positions and the percentage of change between the up and down positions in each push-up exercise. In both the traditional and modified push-ups, subjects supported less weight in the up vs. the down position. The percentage change in % BM from the up to the down position was greater in the modified push-up variant. The pattern of resistances to the push-up exercises observed in this study may be a result of differing moment arms between the support surface contact point (knees or feet) and the hands. These results may be useful in prescribing programs for strengthening and/or rehabilitation for both the prime movers and stabilizers of the upper extremity. Further, range of motion may need to be altered to accommodate strength differences in beginners and clients rehabilitating from injury.

Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease.

PubMed

Masud, Rizwan; Qureshi, Irfan Zia

2011-09-01

Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.

Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study.

PubMed

Hein, Alexander; Lambrechts, Diether; von Minckwitz, Gunter; Häberle, Lothar; Eidtmann, Holger; Tesch, Hans; Untch, Michael; Hilfrich, Jörn; Schem, Christian; Rezai, Mahdi; Gerber, Bernd; Dan Costa, Serban; Blohmer, Jens-Uwe; Schwedler, Kathrin; Kittel, Kornelia; Fehm, Tanja; Kunz, Georg; Beckmann, Matthias W; Ekici, Arif B; Hanusch, Claus; Huober, Jens; Liedtke, Cornelia; Mau, Christine; Moisse, Matthieu; Müller, Volkmar; Nekljudova, Valentina; Peuteman, Gilian; Rack, Brigitte; Rübner, Matthias; Van Brussel, Thomas; Wang, Liewei; Weinshilboum, Richard M; Loibl, Sibylle; Fasching, Peter A

2015-12-15

Studies assessing the effect of bevacizumab (BEV) on breast cancer (BC) outcome have shown different effects on progression-free and overall survival, suggesting that a subgroup of patients may benefit from this treatment. Unfortunately, no biomarkers exist to identify these patients. Here, we investigate whether single nucleotide polymorphisms (SNPs) in VEGF pathway genes correlate with pathological complete response (pCR) in the neoadjuvant GeparQuinto trial. HER2-negative patients were randomized into treatment arms receiving either BEV combined with standard chemotherapy or chemotherapy alone. In a pre-planned biomarker study, DNA was collected from 729 and 724 patients, respectively from both treatment arms, and genotyped for 125 SNPs. Logistic regression assessed interaction between individual SNPs and both treatment arms to predict pCR. Five SNPs may be associated with a better response to BEV, but none of them remained significant after correction for multiple testing. The two SNPs most strongly associated, rs833058 and rs699947, were located upstream of the VEGF-A promoter. Odds ratios for the homozygous common, heterozygous and homozygous rare rs833058 genotypes were 2.36 (95% CI, 1.49-3.75), 1.20 (95% CI, 0.88-1.64) and 0.61 (95% CI, 0.34-1.12). Notably, some SNPs in VEGF-A exhibited a more pronounced effect in the triple-negative subgroup. Several SNPs in VEGF-A may be associated with improved pCR when receiving BEV in the neoadjuvant setting. Although none of the observed effects survived correction for multiple testing, our observations are consistent with previous studies on BEV efficacy in BC. Further research is warranted to clarify the predictive value of these markers. © 2015 UICC.

Genome-wide Association Mapping of Qualitatively Inherited Traits in a Germplasm Collection.

PubMed

Bandillo, Nonoy B; Lorenz, Aaron J; Graef, George L; Jarquin, Diego; Hyten, David L; Nelson, Randall L; Specht, James E

2017-07-01

Genome-wide association (GWA) has been used as a tool for dissecting the genetic architecture of quantitatively inherited traits. We demonstrate here that GWA can also be highly useful for detecting many major genes governing categorically defined phenotype variants that exist for qualitatively inherited traits in a germplasm collection. Genome-wide association mapping was applied to categorical phenotypic data available for 10 descriptive traits in a collection of ∼13,000 soybean [ (L.) Merr.] accessions that had been genotyped with a 50,000 single nucleotide polymorphism (SNP) chip. A GWA on a panel of accessions of this magnitude can offer substantial statistical power and mapping resolution, and we found that GWA mapping resulted in the identification of strong SNP signals for 24 classical genes as well as several heretofore unknown genes controlling the phenotypic variants in those traits. Because some of these genes had been cloned, we were able to show that the narrow GWA mapping SNP signal regions that we detected for the phenotypic variants had chromosomal bp spans that, with just one exception, overlapped the bp region of the cloned genes, despite local variation in SNP number and nonuniform SNP distribution in the chip set. Copyright © 2017 Crop Science Society of America.

Quantitative application of the primary progressive aphasia consensus criteria.

PubMed

Wicklund, Meredith R; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Whitwell, Jennifer L; Josephs, Keith A

2014-04-01

To determine how well the consensus criteria could classify subjects with primary progressive aphasia (PPA) using a quantitative speech and language battery that matches the test descriptions provided by the consensus criteria. A total of 105 participants with a neurodegenerative speech and language disorder were prospectively recruited and underwent neurologic, neuropsychological, and speech and language testing and MRI in this case-control study. Twenty-one participants with apraxia of speech without aphasia served as controls. Select tests from the speech and language battery were chosen for application of consensus criteria and cutoffs were employed to determine syndromic classification. Hierarchical cluster analysis was used to examine participants who could not be classified. Of the 84 participants, 58 (69%) could be classified as agrammatic (27%), semantic (7%), or logopenic (35%) variants of PPA. The remaining 31% of participants could not be classified. Of the unclassifiable participants, 2 clusters were identified. The speech and language profile of the first cluster resembled mild logopenic PPA and the second cluster semantic PPA. Gray matter patterns of loss of these 2 clusters of unclassified participants also resembled mild logopenic and semantic variants. Quantitative application of consensus PPA criteria yields the 3 syndromic variants but leaves a large proportion unclassified. Therefore, the current consensus criteria need to be modified in order to improve sensitivity.

Low-Rank Correction Methods for Algebraic Domain Decomposition Preconditioners

DOE PAGES

Li, Ruipeng; Saad, Yousef

2017-08-01

This study presents a parallel preconditioning method for distributed sparse linear systems, based on an approximate inverse of the original matrix, that adopts a general framework of distributed sparse matrices and exploits domain decomposition (DD) and low-rank corrections. The DD approach decouples the matrix and, once inverted, a low-rank approximation is applied by exploiting the Sherman--Morrison--Woodbury formula, which yields two variants of the preconditioning methods. The low-rank expansion is computed by the Lanczos procedure with reorthogonalizations. Numerical experiments indicate that, when combined with Krylov subspace accelerators, this preconditioner can be efficient and robust for solving symmetric sparse linear systems. Comparisonsmore » with pARMS, a DD-based parallel incomplete LU (ILU) preconditioning method, are presented for solving Poisson's equation and linear elasticity problems.« less

TPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group.

PubMed

Wray, Lisa; Vujkovic, Marijana; McWilliams, Thomas; Cannon, Shannon; Devidas, Meenakshi; Stork, Linda; Aplenc, Richard

2014-11-01

Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well as by MTHFR genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was not associated with SOS risk. These suggest that germline genetic variation in TPMT and MTHFR do not significantly alter SOS risk in patients exposed to thioguanine. © 2014 Wiley Periodicals, Inc.

Low-Rank Correction Methods for Algebraic Domain Decomposition Preconditioners

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

Li, Ruipeng; Saad, Yousef

This study presents a parallel preconditioning method for distributed sparse linear systems, based on an approximate inverse of the original matrix, that adopts a general framework of distributed sparse matrices and exploits domain decomposition (DD) and low-rank corrections. The DD approach decouples the matrix and, once inverted, a low-rank approximation is applied by exploiting the Sherman--Morrison--Woodbury formula, which yields two variants of the preconditioning methods. The low-rank expansion is computed by the Lanczos procedure with reorthogonalizations. Numerical experiments indicate that, when combined with Krylov subspace accelerators, this preconditioner can be efficient and robust for solving symmetric sparse linear systems. Comparisonsmore » with pARMS, a DD-based parallel incomplete LU (ILU) preconditioning method, are presented for solving Poisson's equation and linear elasticity problems.« less

Biomechanics of youth windmill softball pitching.

PubMed

Werner, Sherry L; Guido, John A; McNeice, Ryan P; Richardson, Jasper L; Delude, Neil A; Stewart, Gregory W

2005-04-01

Limited research attention has been paid to the potentially harmful windmill softball pitch. No information is available regarding lower extremity kinetics in softball pitching. The stresses on the throwing arm of youth windmill pitchers are clinically significant and similar to those found for college softball pitchers. Descriptive laboratory study. Three-dimensional, high-speed (240-Hz) video and stride foot force plate (1200 Hz) data were collected on fastballs from 53 youth softball pitchers. Kinematic parameters related to pitching mechanics and resultant kinetics on the throwing-arm elbow and shoulder joints were calculated. Kinetic parameters were compared to those reported for baseball pitchers. Elbow and shoulder joint loads were similar to those found for baseball pitchers and college softball pitchers. Shoulder distraction stress averaged 94% body weight for the youth pitchers. Stride foot ground reaction force patterns were not similar to those reported for baseball pitchers. Vertical and braking force components under the stride foot were in excess of body weight. Excessive distraction stress and joint torques at the throwing-arm elbow and shoulder are similar to those found in baseball pitchers, which suggests that windmill softball pitchers are at risk for overuse injuries. Normative information regarding upper and lower extremity kinematics and kinetics for 12- to 19-year-old softball pitchers has been established.

Gender differences between muscle activation and onset timing of the four subdivisions of trapezius during humerothoracic elevation.

PubMed

Szucs, Kimberly A; Borstad, John D

2013-12-01

The aim of this study was to provide a description of gender differences of the normal muscle activation patterns of the four subdivisions of the trapezius (clavicular, descending, transverse, ascending) during arm elevation. Surface EMG was collected from these four subdivisions from twenty-two healthy subjects (12 females, 10 males) during arm elevation in the scapular plane. Percent activation (RMS) of each subdivision was compared between genders across arm angles and elevation phase and onset time of each subdivision was compared between genders. Females demonstrated significantly higher % activation levels for each subdivision (p<.05), except transverse trapezius (p=.36). A statistically significant difference for onset time was observed between gender for the descending trapezius, with a slower onset time for females (p<.05). Findings from this study support the theory that subdivisions within descending trapezius are preferentially activated and demonstrate that gender differences are present within the fourth subdivision of trapezius. As subjects were without shoulder pathology, the observed gender differences may be explained by normal motor control variations. However, as coordinated activation of trapezius is required for normal shoulder motion, it is recommended to include all four subdivisions of trapezius and address gender differences in future studies. Copyright © 2013 Elsevier B.V. All rights reserved.

[Population dynamics and armed violence in Colombia, 1985-2010].

PubMed

Salaya, Hernán Eduardo; Rodríguez, Jesús

2014-09-01

Describe changes in the population structure of Colombia's municipalities in relation to internal displacement in response to armed violence. A descriptive ecological study was carried out. Secondary sources were consulted, taken from the Consolidated Registry of Displaced Population and from the National Administrative Department of Statistics, to calculate expulsion and reception rates for population displaced by violence from 2002 to 2010. Based on these rates, four groups were created of municipalities in the extreme quartile for each rate during the entire period, which were classified as high expulsion, low expulsion, high reception, and low reception. Subsequently, population pyramids and structure indicators were constructed for each group of municipalities for two comparative reference years (1985 and 2010). Municipalities with high expulsion or reception rates experienced a slower epidemiological transition, with lower mean ages and aging indices. The high expulsion group had the least regression, based on the Sundbärg index. In the high reception group, the masculinity ratio decreased the most, especially among the economically active population, and it had the highest population growth. Population dynamics in Colombia have been affected by armed violence and changes in these dynamics are not uniform across the country, leading to important social, economic, and cultural consequences. This study is useful for decision-making and public policy making.

Controversies in Narcissism.

PubMed

Miller, Joshua D; Lynam, Donald R; Hyatt, Courtland S; Campbell, W Keith

2017-05-08

There has been a surge in interest in and research on narcissism and narcissistic personality disorder (NPD). Despite or because of this increased attention, there are several areas of substantial debate that surround the construct, including descriptions of grandiose and vulnerable dimensions or variants, questions regarding the existence of a consensual description, central versus peripheral features of narcissism, distinctions between normal and pathological narcissism, possible etiological factors, the role of self-esteem in narcissism, where narcissism should be studied, how it can be assessed, and its representation in diagnostic nosologies. We suggest that a failure to distinguish between grandiose (i.e., overtly immodest, self-centered, entitled, domineering) and vulnerable (e.g., self-centered, distrustful, neurotic, introverted) presentations of narcissism has led to a less cohesive and coherent literature and that trait-based models of personality and personality disorder can bring greater clarity to many of these important debates.

New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

PubMed

Pilliod, Julie; Moutton, Sébastien; Lavie, Julie; Maurat, Elise; Hubert, Christophe; Bellance, Nadège; Anheim, Mathieu; Forlani, Sylvie; Mochel, Fanny; N'Guyen, Karine; Thauvin-Robinet, Christel; Verny, Christophe; Milea, Dan; Lesca, Gaëtan; Koenig, Michel; Rodriguez, Diana; Houcinat, Nada; Van-Gils, Julien; Durand, Christelle M; Guichet, Agnès; Barth, Magalie; Bonneau, Dominique; Convers, Philippe; Maillart, Elisabeth; Guyant-Marechal, Lucie; Hannequin, Didier; Fromager, Guillaume; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Valence, Stéphanie; Charles, Perrine; Berquin, Patrick; Rooryck, Caroline; Bouron, Julie; Brice, Alexis; Lacombe, Didier; Rossignol, Rodrigue; Stevanin, Giovanni; Benard, Giovanni; Burglen, Lydie; Durr, Alexandra; Goizet, Cyril; Coupry, Isabelle

2015-12-01

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in the SACS gene. SACS encodes sacsin, a protein whose function remains unknown, despite the description of numerous protein domains and the recent focus on its potential role in the regulation of mitochondrial physiology. This study aimed to identify new mutations in a large population of ataxic patients and to functionally analyze their cellular effects in the mitochondrial compartment. A total of 321 index patients with spastic ataxia selected from the SPATAX network were analyzed by direct sequencing of the SACS gene, and 156 patients from the ATAXIC project presenting with congenital ataxia were investigated either by targeted or whole exome sequencing. For functional analyses, primary cultures of fibroblasts were obtained from 11 patients carrying either mono- or biallelic variants, including 1 case harboring a large deletion encompassing the entire SACS gene. We identified biallelic SACS variants in 33 patients from SPATAX, and in 5 nonprogressive ataxia patients from ATAXIC. Moreover, a drastic and recurrent alteration of the mitochondrial network was observed in 10 of the 11 patients tested. Our results permit extension of the clinical and mutational spectrum of ARSACS patients. Moreover, we suggest that the observed mitochondrial network anomalies could be used as a trait biomarker for the diagnosis of ARSACS when SACS molecular results are difficult to interpret (ie, missense variants and heterozygous truncating variant). Based on our findings, we propose new diagnostic definitions for ARSACS using clinical, genetic, and cellular criteria. © 2015 American Neurological Association.

Novel mutation in the CHST6 gene causes macular corneal dystrophy in a black South African family.

PubMed

Carstens, Nadia; Williams, Susan; Goolam, Saadiah; Carmichael, Trevor; Cheung, Ming Sin; Büchmann-Møller, Stine; Sultan, Marc; Staedtler, Frank; Zou, Chao; Swart, Peter; Rice, Dennis S; Lacoste, Arnaud; Paes, Kim; Ramsay, Michèle

2016-07-20

Macular corneal dystrophy (MCD) is a rare autosomal recessive disorder that is characterized by progressive corneal opacity that starts in early childhood and ultimately progresses to blindness in early adulthood. The aim of this study was to identify the cause of MCD in a black South African family with two affected sisters. A multigenerational South African Sotho-speaking family with type I MCD was studied using whole exome sequencing. Variant filtering to identify the MCD-causal mutation included the disease inheritance pattern, variant minor allele frequency and potential functional impact. Ophthalmologic evaluation of the cases revealed a typical MCD phenotype and none of the other family members were affected. An average of 127 713 variants per individual was identified following exome sequencing and approximately 1.2 % were not present in any of the investigated public databases. Variant filtering identified a homozygous E71Q mutation in CHST6, a known MCD-causing gene encoding corneal N-acetyl glucosamine-6-O-sulfotransferase. This E71Q mutation results in a non-conservative amino acid change in a highly conserved functional domain of the human CHST6 that is essential for enzyme activity. We identified a novel E71Q mutation in CHST6 as the MCD-causal mutation in a black South African family with type I MCD. This is the first description of MCD in a black Sub-Saharan African family and therefore contributes valuable insights into the genetic aetiology of this disease, while improving genetic counselling for this and potentially other MCD families.

Description of the LASSO Alpha 1 Release

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

Gustafson, William I.; Vogelmann, Andrew M.; Cheng, Xiaoping

The Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility began a pilot project in May 2015 to design a routine, high-resolution modeling capability to complement ARM’s extensive suite of measurements. This modeling capability has been named the Large-Eddy Simulation (LES) ARM Symbiotic Simulation and Observation (LASSO) project. The availability of LES simulations with concurrent observations will serve many purposes. LES helps bridge the scale gap between DOE ARM observations and models, and the use of routine LES adds value to observations. It provides a self-consistent representation of the atmosphere and a dynamical context for the observations. Further,more » it elucidates unobservable processes and properties. LASSO will generate a simulation library for researchers that enables statistical approaches beyond a single-case mentality. It will also provide tools necessary for modelers to reproduce the LES and conduct their own sensitivity experiments. Many different uses are envisioned for the combined LASSO LES and observational library. For an observationalist, LASSO can help inform instrument remote-sensing retrievals, conduct Observation System Simulation Experiments (OSSEs), and test implications of radar scan strategies or flight paths. For a theoretician, LASSO will help calculate estimates of fluxes and co-variability of values, and test relationships without having to run the model yourself. For a modeler, LASSO will help one know ahead of time which days have good forcing, have co-registered observations at high-resolution scales, and have simulation inputs and corresponding outputs to test parameterizations. Further details on the overall LASSO project are available at http://www.arm. gov/science/themes/lasso.« less

[Proposed neotype Streptomyces ruber (Krainsky, 1914) Waksman et Henrici, 1948].

PubMed

Kuznetsov, V D; Filippova, S N; Poltorak, V A

1987-01-01

Culture 78 was proposed as a neotype of Streptomyces ruber. It was isolated from the soils of the Baikal region and was closest, in its taxonomic properties, to the original description of the species [13] whose representative had been lost. Cultures from different microbial collections designated as S. ruber were shown to be unlike the original description. The neotype had the following taxononic properties: the cell wall of type I; spiral sporophores with extended spirals having 2-3 coils; oval spores with a smooth envelope; greyish pink aerial and dark-red substrate mycelia; a red pigment not passing into the medium; slow gelatin liquefaction and milk peptonization; weak starch hydrolysis; assimilation of glucose, xylose, rammose, fructose, and inositol; weak growth on arabinose, raffinose and mannitol, but not on sucrose; no formation of melanoid pigments; synthesis of riboflavin and prodigiosin pigments; inhibition of Gram-positive bacterial and acid-resistant mycobacterial growth; no inhibition of yeast and fungal growth. The culture was sensitive to streptomycin, neomycin, gentamycin, monomycin, tetracycline,erythromycin, oleandomycin, lincomycin, ristomycin, levomycetin, polymyxin and fusidin, but resistant in penicillin. The population was composed of six variants [3]: main, faded, asporogenic red, asporogenic yellow, asporogenic white and nocardia-like. The latter two were not capable of riboflavin and prodigiosin formation. The asporogenic yellow variant was a monosynthetic organism: it formed riboflavin, but could not synthesize prodigiosin. The neotype of S. ruber 78 is deposited withthe national Collection of Microorganisms (the reference number is VKM A-611).

Clinical effectiveness of decongestive treatments on excess arm volume and patient-centered outcomes in women with early breast cancer-related arm lymphedema: a systematic review

PubMed Central

Jeffs, Eunice; Ream, Emma; Taylor, Cath; Bick, Debra

2018-01-01

ABSTRACT Objective: To identify the effect of decongestive lymphedema treatment on excess arm volume or patient-centered outcomes in women presenting within either 12 months or a mean nine months of developing arm lymphedema following breast cancer treatment. Introduction: Lymphedema is a common consequence of breast cancer treatment requiring life-long treatment to reduce symptoms and prevent complications. Currently, evidence to inform the optimal decongestive lymphedema treatment package is lacking. Inclusion criteria: The review included studies on women who received lymphedema treatment within either 12 months or a mean of nine months of developing unilateral breast cancer-related arm lymphedema. The intervention was any decongestive lymphedema treatment delivered with the purpose of reducing arm lymphedema, compared to another form of lymphedema treatment (whether self or practitioner-administered), placebo or no treatment. The clinical outcome was excess arm volume; patient-centered outcomes were health-related quality of life, arm heaviness, arm function, patient-perceived benefit and satisfaction with treatment. Experimental study designs were eligible, including randomized and non-randomized controlled trials, quasi-experimental, prospective and retrospective before and after studies were considered. Methods: A three-step search strategy was utilized to find published and unpublished studies. The search identified studies published from the inception of each database to July 6, 2016. Reference lists were scanned to identify further eligible studies. Studies were critically appraised using appropriate standardized critical appraisal instruments from the Joanna Briggs Institute. Details describing each study and treatment results regarding outcomes of interest were extracted from papers included in the review using appropriate standardized data extraction tools from the Joanna Briggs Institute. Due to heterogeneity in included studies, results for similar outcome measures were not pooled in statistical meta-analysis. A narrative and tabular format was used to synthesize results from identified and included studies. Results: Seven studies reporting results for outcomes of interest were critically appraised and included in the review: five randomized controlled trials and two descriptive (uncontrolled) studies. Reported outcomes included excess arm volume (five studies), health-related quality of life (three studies), arm heaviness (one study), arm function (two studies) and patient-perceived benefit (two studies). There was some evidence that decongestive treatments were effective for women presenting within either 12 months or a mean of nine months of developing breast cancer-related arm lymphedema, but the wide range of data prevented comparison of treatment findings which limited our ability to answer the review questions. Conclusions: Weak evidence (grade B) for the impact of decongestive lymphedema treatment on women with early lymphedema (i.e. less than 12 months duration of BCRL symptoms) did not allow any conclusions to be drawn about the most effective treatment to be offered when these women first present for treatment. Findings provided no justification to support change to current practice. Future primary research needs to focus on the most effective treatment for women when they first present with lymphedema symptoms, e.g. treatment provided within 12 months of developing symptoms. Studies should be adequately powered and recruit women exclusively with less than 12 months duration of breast cancer-related lymphedema symptoms, provide longer follow-up to monitor treatment effect over time, with comparable treatment protocols, outcome measures and reporting methods. PMID:29419623

Quantification of upper limb position sense using an exoskeleton and a virtual reality display.

PubMed

Deblock-Bellamy, Anne; Batcho, Charles Sebiyo; Mercier, Catherine; Blanchette, Andreanne K

2018-03-16

Proprioceptive sense plays a significant role in the generation and correction of skilled movements and, consequently, in most activities of daily living. We developed a new proprioception assessment protocol that enables the quantification of elbow position sense without using the opposite arm, involving active movement of the evaluated limb or relying on working memory. The aims of this descriptive study were to validate this assessment protocol by quantifying the elbow position sense of healthy adults, before using it in individuals who sustained a stroke, and to investigate its test-retest reliability. Elbow joint position sense was quantified using a robotic device and a virtual reality system. Two assessments were performed, by the same evaluator, with a one-week interval. While the participant's arms and hands were occluded from vision, the exoskeleton passively moved the dominant arm from an initial to a target position. Then, a virtual arm representation was projected on a screen placed over the participant's arm. This virtual representation and the real arm were not perfectly superimposed, however. Participants had to indicate verbally the relative position of their arm (more flexed or more extended; two-alternative forced choice paradigm) compared to the virtual representation. Each participant completed a total of 136 trials, distributed in three phases. The angular differences between the participant's arm and the virtual representation ranged from 1° to 27° and changed pseudo-randomly across trials. No feedback about results was provided to the participants during the task. A discrimination threshold was statistically extracted from a sigmoid curve fit representing the relationship between the angular difference and the percentage of successful trials. Test-retest reliability was evaluated with 3 different complementary approaches, i.e. a Bland-Altman analysis, an intraclass correlation coefficient (ICC) and a standard error of measurement (SEm). Thirty participants (24.6 years old; 17 males, 25 right-handed) completed both assessments. The mean discrimination thresholds were 7.0 ± 2.4 (mean ± standard deviation) and 5.9 ± 2.1 degrees for the first and the second assessment session, respectively. This small difference between assessments was significant (- 1.1 ± 2.2 degrees), however. The assessment protocol was characterized by a fair to good test-retest reliability (ICC = 0.47). This study demonstrated the potential of this assessment protocol to objectively quantify elbow position sense in healthy individuals. Futures studies will validate this protocol in older adults and in individuals who sustained a stroke.

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis

PubMed Central

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-01-01

Introduction Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Methods Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. Ethics and dissemination A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. Trial registration number NCT023528702; Pre-results. PMID:27072573

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis.

PubMed

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-04-12

Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. NCT023528702; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

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

Verlander, P.C.; Kaporis, A.G.; Qian, L.

1994-09-01

Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutationsmore » are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.« less

Recurrent (2;2) and (2;8) Translocations in Rhabdomyosarcoma without the Canonical PAX-FOXO1 fuse PAX3 to Members of the Nuclear Receptor Transcriptional Coactivator (NCOA) Family

PubMed Central

Sumegi, Janos; Streblow, Renae; Frayer, Robert W.; Cin, Paola Dal; Rosenberg, Andrew; Meloni-Ehrig, Aurelia; Bridge, Julia A.

2009-01-01

The fusion oncoproteins PAX3-FOXO1 [t(2;13)(q35;q14)] and PAX7-FOXO1 [t(1;13)(p36;q14)] typify alveolar rhabdomyosarcoma (ARMS); however, 20-30% of cases lack these specific translocations. In this study, cytogenetic and/or molecular characterization to include FISH, RT-PCR and sequencing analyses of five rhabdomyosarcomas [four ARMS and one embryonal rhabdomyosarcoma (ERMS)] with novel, recurrent t(2;2)(p23;q35) or t(2;8)(q35;q13) revealed that these non-canonical translocations fuse PAX3 to NCOA1 or NCOA2 respectively. The PAX3-NCOA1 and PAX3-NCOA2 transcripts encode chimeric proteins composed of the paired-box and homeodomain DNA-binding domains of PAX3, and the CID domain, the Q-rich region and the AD2 domain of NCOA1 or NCOA2. To investigate the biological function of these recurrent variant translocations, the coding regions of PAX3-NCOA1 and PAX3-NCOA2 cDNA constructs were introduced into expression vectors with tetracycline-regulated expression. Both fusion proteins showed transforming activity in the soft agar assay. Deletion of the AD2 portion of the PAX3-NCOA fusion proteins reduced the transforming activity of each chimeric protein. Similarly, but with greater impact, CID domain deletion fully abrogated the transforming activity of the chimeric protein. These studies: (1) expand our knowledge of PAX3 variant translocations in RMS with identification of a novel PAX3-NCOA2 fusion; (2) show that both PAX3-NCOA1 and PAX3-NCOA2 represent recurrent RMS rearrangements; (3) confirm the transforming activity of both translocation events and demonstrate the essentiality of intact AD2 and CID domains for optimal transforming activity; and, (5) provide alternative approaches (FISH and RT-PCR) for detecting PAX-NCOA fusions in nondividing cells of RMS. The latter could potentially be utilized as aids in diagnostically challenging cases. PMID:19953635

Trajectory control of an articulated robot with a parallel drive arm based on splines under tension

NASA Astrophysics Data System (ADS)

Yi, Seung-Jong

Today's industrial robots controlled by mini/micro computers are basically simple positioning devices. The positioning accuracy depends on the mathematical description of the robot configuration to place the end-effector at the desired position and orientation within the workspace and on following the specified path which requires the trajectory planner. In addition, the consideration of joint velocity, acceleration, and jerk trajectories are essential for trajectory planning of industrial robots to obtain smooth operation. The newly designed 6 DOF articulated robot with a parallel drive arm mechanism which permits the joint actuators to be placed in the same horizontal line to reduce the arm inertia and to increase load capacity and stiffness is selected. First, the forward kinematic and inverse kinematic problems are examined. The forward kinematic equations are successfully derived based on Denavit-Hartenberg notation with independent joint angle constraints. The inverse kinematic problems are solved using the arm-wrist partitioned approach with independent joint angle constraints. Three types of curve fitting methods used in trajectory planning, i.e., certain degree polynomial functions, cubic spline functions, and cubic spline functions under tension, are compared to select the best possible method to satisfy both smooth joint trajectories and positioning accuracy for a robot trajectory planner. Cubic spline functions under tension is the method selected for the new trajectory planner. This method is implemented for a 6 DOF articulated robot with a parallel drive arm mechanism to improve the smoothness of the joint trajectories and the positioning accuracy of the manipulator. Also, this approach is compared with existing trajectory planners, 4-3-4 polynomials and cubic spline functions, via circular arc motion simulations. The new trajectory planner using cubic spline functions under tension is implemented into the microprocessor based robot controller and motors to produce combined arc and straight-line motion. The simulation and experiment show interesting results by demonstrating smooth motion in both acceleration and jerk and significant improvements of positioning accuracy in trajectory planning.

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

PubMed Central

Cornel, Anthony J; Brisco, Katherine K; Tadei, Wanderli P; Secundino, Nágila FC; Rafael, Miriam S; Galardo, Allan KR; Medeiros, Jansen F; Pessoa, Felipe AC; Ríos-Velásquez, Claudia M; Lee, Yoosook; Pimenta, Paulo FP; Lanzaro, Gregory C

2016-01-01

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies. PMID:27223867

Altering the N-terminal arms of the polymerase manager protein UmuD modulates protein interactions.

PubMed

Murison, David A; Ollivierre, Jaylene N; Huang, Qiuying; Budil, David E; Beuning, Penny J

2017-01-01

Escherichia coli cells that are exposed to DNA damaging agents invoke the SOS response that involves expression of the umuD gene products, along with more than 50 other genes. Full-length UmuD is expressed as a 139-amino-acid protein, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The N-terminal arms of UmuD are dynamic and contain recognition sites for multiple partner proteins. Cleavage of UmuD to UmuD' dramatically affects the function of the protein and activates UmuC for translesion synthesis (TLS) by forming DNA Polymerase V. To probe the roles of the N-terminal arms in the cellular functions of the umuD gene products, we constructed additional N-terminal truncated versions of UmuD: UmuD 8 (UmuD Δ1-7) and UmuD 18 (UmuD Δ1-17). We found that the loss of just the N-terminal seven (7) amino acids of UmuD results in changes in conformation of the N-terminal arms, as determined by electron paramagnetic resonance spectroscopy with site-directed spin labeling. UmuD 8 is cleaved as efficiently as full-length UmuD in vitro and in vivo, but expression of a plasmid-borne non-cleavable variant of UmuD 8 causes hypersensitivity to UV irradiation, which we determined is the result of a copy-number effect. UmuD 18 does not cleave to form UmuD', but confers resistance to UV radiation. Moreover, removal of the N-terminal seven residues of UmuD maintained its interactions with the alpha polymerase subunit of DNA polymerase III as well as its ability to disrupt interactions between alpha and the beta processivity clamp, whereas deletion of the N-terminal 17 residues resulted in decreases in binding to alpha and in the ability to disrupt the alpha-beta interaction. We find that UmuD 8 mimics full-length UmuD in many respects, whereas UmuD 18 lacks a number of functions characteristic of UmuD.

Differential splicing of oncogenes and tumor suppressor genes in African and Caucasian American populations: contributing factor in prostate cancer disparities

DTIC Science & Technology

2017-12-01

exhibited enhanced activation of the PI3K/AKT pathway compared to the same lines over-expressing the CA- enriched long (-L) variant PIK3CD-L (retains...demonstrate that FGFR3-S: i) encodes a more aggressive oncogenic signaling protein compared to CA-enriched FGFR3-L (retains exon 14) as defined by in vitro...into PCa cell lines for in vitro and in vivo investigations completed in Year 1 (see description below). 3 FIGURE 1. Full-length cDNA

The management of esophageal achalasia: from diagnosis to surgical treatment.

PubMed

Dobrowolsky, Adrian; Fisichella, P Marco

2014-03-01

The goal of this review is to illustrate our approach to patients with achalasia in terms of preoperative evaluation and surgical technique. Indications, patient selection and management are herein discussed. Specifically, we illustrate the pathogenetic theories and diagnostic algorithm with current up-to-date techniques to diagnose achalasia and its manometric variants. Finally, we focus on the therapeutic approaches available today: medical and surgical. A special emphasis is given on the surgical treatment of achalasia and we provide the reader with a detailed description of our pre and postoperative management.

DITTY - a computer program for calculating population dose integrated over ten thousand years

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

Napier, B.A.; Peloquin, R.A.; Strenge, D.L.

The computer program DITTY (Dose Integrated Over Ten Thousand Years) was developed to determine the collective dose from long term nuclear waste disposal sites resulting from the ground-water pathways. DITTY estimates the time integral of collective dose over a ten-thousand-year period for time-variant radionuclide releases to surface waters, wells, or the atmosphere. This document includes the following information on DITTY: a description of the mathematical models, program designs, data file requirements, input preparation, output interpretations, sample problems, and program-generated diagnostic messages.

Kissing nevus of the penis: a case report and dermatoscopic findings*

PubMed Central

Godinho, Nivea; Nai, Gisele Alborghetti; Schaefer, Arnaldo Luiz Flávio; Schaefer, Luiza Vasconcelos

2017-01-01

Divided nevus, also known as kissing nevus, is a rare variant of congenital melanocytic nevi in which there are two adjacent nevi in areas of the body that undergo embryonic cleavage. The original description of this type of lesion was on the eyelid. The location on the penis is even rarer, with only 17 case reports in the literature so far, and only one of them described the dermoscopic findings. We report the case of a patient with divided nevus of the penis and its clinical, dermoscopic and histopathological features. PMID:29267459

Jerky periods: myoclonus occurring solely during menses.

PubMed

Buijink, Arthur W G; Gelauff, Jeannette M; van der Salm, Sandra M A; Tijssen, Marina A J; van Rootselaar, Anne-Fleur

2013-01-01

In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. This appears to be the first description of myoclonus appearing only during menses. We suggest a cortical origin for myoclonus.

[Tumour of the right lung vertex that produced a Pancoast syndrome: description of a case].

PubMed

Hermida Péreza, J A; Bermejo Hernández, A; Hernández Guerra, J S; Arroyo Diaz, R

2012-03-01

We describe a clinical case of an 80 year-old woman, with a history of Alzheimer's disease, who presented with right shoulder pain, numbness and decreased strength in the right arm, with right eye ptosis, cough and dysphagia. The chest X-Ray and thoracic-abdominal computed tomography scan showed a large mass in the upper lobe and apex of the right lung, supraclavicular metastatic lymph nodes. In the fine needle aspiration biopsy: poorly differentiated non-small cell carcinoma. She was referred to Oncology to start chemotherapy treatment.

KALI - An environment for the programming and control of cooperative manipulators

NASA Technical Reports Server (NTRS)

Hayward, Vincent; Hayati, Samad

1988-01-01

A design description is given of a controller for cooperative robots. The background and motivation for multiple arm control are discussed. A set of programming primitives which permit a programmer to specify cooperative tasks are described. Motion primitives specify asynchronous motions, master/slave motions, and cooperative motions. In the context of cooperative robots, trajectory generation issues are discussed and the authors' implementation briefly described. The relations between programming and control in the case of multiple robots are examined. The allocation of various tasks among a multiprocessor computer is described.

Contemporary Leadership and Doctrine: The Utility of Analyzing the Outcome of Thucydides’ The Peloponnesian War Via Clausewitz’s Concepts as Articulated in On War

DTIC Science & Technology

2001-04-03

Corps doctrine. This made clear to me iii the danger of concentrating on emerging technology during doctrine development, while simultaneously de ...is, but introduces his work as an "inquiry" ( historia ). Herodotus clearly believes in the intervention of the gods in his description of historical...He begins the war as a general in the Athenian armed forces. During the eighth year of the war, the Spartan commander, Brasidas, gains access to the

Descriptive Study of a Military Pain Clinic

DTIC Science & Technology

1996-09-13

Neuropathy 6 10 Postherpatic Neuralgia (PHN) 5 9 Headache 3 5 Occipital Neuralgia 3 5 Shoulder/Hand/Arm pain 3 5 Migraine 2 4 Reflex Sympathetic...34"lhesi. o vomiting o OTHER: I I O OTHER:I I o hyporp"U’. D OTHEFI : D no.,na I I Rwimtl fIIoch o C.rvieo!t1o,.cic Sympathetic ;:] Occipital Nerve bloc k...and postherpatic neuralgia at 9 percent (Tab le 5). Other diagnoses were recorded for fewer than 10 percent of the patients during the 14 month

Localized diabatization applied to excitons in molecular crystals

NASA Astrophysics Data System (ADS)

Jin, Zuxin; Subotnik, Joseph E.

2017-06-01

Traditional ab initio electronic structure calculations of periodic systems yield delocalized eigenstates that should be understood as adiabatic states. For example, excitons are bands of extended states which superimpose localized excitations on every lattice site. However, in general, in order to study the effects of nuclear motion on exciton transport, it is standard to work with a localized description of excitons, especially in a hopping regime; even in a band regime, a localized description can be helpful. To extract localized excitons from a band requires essentially a diabatization procedure. In this paper, three distinct methods are proposed for such localized diabatization: (i) a simple projection method, (ii) a more general Pipek-Mezey localization scheme, and (iii) a variant of Boys diabatization. Approaches (i) and (ii) require localized, single-particle Wannier orbitals, while approach (iii) has no such dependence. These methods should be very useful for studying energy transfer through solids with ab initio calculations.

Can Nomenclature for the Body be Explained by Embodiment Theories?

PubMed

Majid, Asifa; van Staden, Miriam

2015-10-01

According to widespread opinion, the meaning of body part terms is determined by salient discontinuities in the visual image; such that hands, feet, arms, and legs, are natural parts. If so, one would expect these parts to have distinct names which correspond in meaning across languages. To test this proposal, we compared three unrelated languages-Dutch, Japanese, and Indonesian-and found both naming systems and boundaries of even basic body part terms display variation across languages. Bottom-up cues alone cannot explain natural language semantic systems; there simply is not a one-to-one mapping of the body semantic system to the body structural description. Although body parts are flexibly construed across languages, body parts semantics are, nevertheless, constrained by non-linguistic representations in the body structural description, suggesting these are necessary, although not sufficient, in accounting for aspects of the body lexicon. Copyright © 2015 Cognitive Science Society, Inc.

A literature review of studies evaluating gluteus maximus and gluteus medius activation during rehabilitation exercises.

PubMed

Reiman, Michael P; Bolgla, Lori A; Loudon, Janice K

2012-05-01

Recently, clinicians have focused much attention on the importance of hip strength for the rehabilitation of not only patients with low back pain but also lower extremity pathology. Properly designing a rehabilitation program for the gluteal muscles requires careful consideration of biomechanical principles, such as length of the external moment arm, gravity, and subject positioning. Understanding the anatomy and function of these muscles also is essential. Electromyography (EMG) provides a useful means to determine muscle activation levels during specific exercises. Descriptions of specific exercises, as they relate to the gluteal muscles, are described. The specific performance of these exercises, the reliability of such EMG measures, and descriptive figures are also detailed. Of utmost importance to practicing clinicians is the interpretation of such data and how it can be best used in exercise prescription when formulating a treatment plan.

Oral lichen planus: An overview

PubMed Central

Krupaa, R. Jayasri; Sankari, S. Leena; Masthan, K. M. K.; Rajesh, E.

2015-01-01

Lichen planus is an immunologically mediated mucocutaneous disease that is triggered by varied etiological agents. The oral lichenoid reaction is considered a variant of the disease that needs to be clearly diagnosed as a separate entity from oral lichen planus and treated. They follow a strict cause-effector relationship, protocols that suggest the differentiation. Lichen planus has varied clinical forms in the oral mucosa and cutaneously that has different prognosis. This condition also arises in association with various other systemic conditions such as hypertension, diabetes mellitus. There have been cases reported in the esophagus, larynx, scalp, nail, cutaneous areas, especially arms and wrists, trunk. There is reported malignant transformation that essentiates careful examination, treatment protocol and regular follow-up sessions. This article throws light on the disease condition of oral lichen planus and oral lichenoid reaction that is essential for the differentiation and treatment. PMID:26015696

Hot Topics in Pharmacogenetics of Age-Related Macular Degeneration.

PubMed

Schwartz, Stephen G; Brantley, Milam A; Kovach, Jaclyn L; Grzybowski, Andrzej

2017-01-01

Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lichen Planus Pigmentosus: The Controversial Consensus

PubMed Central

Ghosh, Aparajita; Coondoo, Arijit

2016-01-01

A pigmented variant of lichen planus (LP) was first reported from India in 1974 by Bhutani et al. who coined the term LP pigmentosus (LPP) to give a descriptive nomenclature to it. LP has a number of variants, one of which is LPP. This disease has also later been reported from the Middle East, Latin America, Korea, and Japan, especially in people with darker skin. It has an insidious onset. Initially, small, black or brown macules appear on sun-exposed areas. They later merge to form large hyperpigmented patches. The disease principally affects the sun-exposed areas of the body such as the face, trunk, and upper extremities. The oral mucosa may rarely be involved. However, the palms, soles, and nails are not affected. Histologically, the epidermis is atrophic along with vacuolar degeneration of basal cell layer. The dermis exhibits incontinence of pigment with scattered melanophages and a sparse follicular or perivascular infiltrate. There is a considerable similarity in histopathological findings between LPP and erythema dyschromicum perstans. However, there are immunologic and clinical differences between the two. These observations have led to a controversy regarding the identity of the two entities. While some dermatologists consider them to be the same, others have opined that the two should be considered as distinctly different diseases. A number of associations such as hepatitis C virus infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic syndrome have been reported with LPP. A rare variant, LPP inversus, with similar clinical and histopathological findings was reported in 2001. As opposed to LPP, this variant occurs in covered intertriginous locations such as groins and axillae and mostly affects white-skinned persons. PMID:27688435

Does the type of renal artery anatomic variant determine the diameter of the main vessel supplying a kidney? A study based on CT data with a particular focus on the presence of multiple renal arteries.

PubMed

Majos, Marcin; Stefańczyk, Ludomir; Szemraj-Rogucka, Zofia; Elgalal, Marcin; De Caro, Raffaele; Macchi, Veronica; Polguj, Michał

2018-04-01

An in-depth knowledge of renal vascular anatomy is essential when planning many surgical procedures; however, a few data exists regarding renal artery diameter. The aim of this study was to assess this morphological feature and to investigate whether a correlation exists between renal artery diameter and the type of arterial supply, with a particular emphasis on variant anatomy and the presence of multiple renal arteries. Computed tomography angiography (CTA) studies of 248 patients, i.e., a total of 496 kidneys, were evaluated. The mean age of the patients was 66.4 ± 15.01 years. Renal artery diameter was measured based on the type of arterial blood supply. The frequency of occurrence of three anatomic variants of renal arterial supply was established: single renal artery (RA) 43.35%, single artery with prehilar branching (pRA) 37.30%, and multiple renal artery (mRA) 19.35%. The diameter of single renal arteries, with either prehilar or hilar branching, was significantly larger than when multiple arteries were present. A detailed analysis of just the mRA variant demonstrated that the diameter of the renal arteries in men was larger (p = 0.012) than those in women and that there was no difference in diameter with regard to the side of the body (p = 0.219). The classification described in our study containing a detailed description of renal artery diameter. It may be helpful in clinical practice, especially for transplantologists, surgeons, and vascular surgeons.

Concomitant expression of far upstream element (FUSE) binding protein (FBP) interacting repressor (FIR) and its splice variants induce migration and invasion of non-small cell lung cancer (NSCLC) cells.

PubMed

Müller, Benedikt; Bovet, Michael; Yin, Yi; Stichel, Damian; Malz, Mona; González-Vallinas, Margarita; Middleton, Alistair; Ehemann, Volker; Schmitt, Jennifer; Muley, Thomas; Meister, Michael; Herpel, Esther; Singer, Stephan; Warth, Arne; Schirmacher, Peter; Drasdo, Dirk; Matthäus, Franziska; Breuhahn, Kai

2015-11-01

Transcription factors integrate a variety of oncogenic input information, facilitate tumour growth and cell dissemination, and therefore represent promising therapeutic target structures. Because over-expression of DNA-interacting far upstream element binding protein (FBP) supports non-small cell lung cancer (NSCLC) migration, we asked whether its repressor, FBP-interacting repressor (FIR) is functionally inactivated and how FIR might affect NSCLC cell biology. Different FIR splice variants were highly expressed in the majority of NSCLCs, with the highest levels in tumours carrying genomic gains of chromosome 8q24.3, which contained the FIR gene locus. Nuclear FIR expression was significantly enriched at the invasion front of primary NSCLCs, but this did not correlate with tumour cell proliferation. FIR accumulation was associated with worse patient survival and tumour recurrence; in addition, FIR over-expression significantly correlated with lymph node metastasis in squamous cell carcinomas (SCCs). In vitro, we applied newly developed methods and modelling approaches for the quantitative and time-resolved description of the pro-migratory and pro-invasive capacities of SCC cells. siRNA-mediated silencing of all FIR variants significantly reduced the speed and directional movement of tumour cells in all phases of migration. Furthermore, sprouting efficiency and single cell invasiveness were diminished following FIR inhibition. Interestingly, the silencing of FIR isoforms lacking exon 2 (FIR(Δexon2)) alone was sufficient to reduce lateral migration and invasion. In summary, by using scale-spanning data derived from primary human tissues, quantitative cellular analyses and mathematical modelling, we have demonstrated that concomitant over-expression of FIR and its splice variants drives NSCLC migration and dissemination. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology

PubMed Central

Brannon, A. Rose; Haake, Scott M.; Hacker, Kathryn E.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E.; Rathmell, W. Kimryn

2011-01-01

Background Clear cell renal cell carcinoma (ccRCC) displays molecular and histologic heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multigene expression profiles, but it is unclear whether these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histologic descriptions or gender. Objective Determine whether additional subtypes of ccRCC exist and whether these subtypes are related to von Hippel-Lindau (VHL) inactivation, hypoxia-inducible factor (HIF) 1 and 2 expression, tumor histology, or gender. Design, setting, and participants Six large, publicly available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. Measurements Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. Results and limitations Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed that correlated strongly with a wild type (WT) VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by the potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. Conclusions The ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified that may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that it could have implications regarding current treatments and future drug development. PMID:22030119

Guillain-Barré Syndrome.

PubMed

Wijdicks, Eelco F M; Klein, Christopher J

2017-03-01

Guillain-Barré syndrome is an acute inflammatory immune-mediated polyradiculoneuropathy presenting typically with tingling, progressive weakness, and pain. Variants and formes frustes may complicate recognition. The best known variant is the sensory ataxic form of Miller Fisher syndrome, which also affects the oculomotor nerves and the brain stem. Divergent pathologic mechanisms lead to demyelinating, axonal, or mixed demyelinating-axonal damage. In the demyelinating form, yet to be identified antigens are inferred by complement activation, myelin destruction, and macrophage-activated cleanup. In the axonal and Miller Fisher variants, gangliosides (GM1, GD1a, GQ1b) are targeted by immunoglobulins and share antigenic epitopes with some bacterial and viral antigens. Campylobacter jejuni infection is associated with an axonal-onset variant; affected patients commonly experience more rapid deterioration. Many other antecedent infectious agents have been recognized including the most recently identified, Zika virus. Supportive care remains the mainstay of therapy. Plasma exchange or intravenous immunoglobin hastens recovery. Combination immunotherapy is not more effective, and the efficacy of prolonged immunotherapy is unproven. One in 3 patients will have deterioration severe enough to require prolonged intensive care monitoring or mechanical ventilation. Full recovery is often seen; most patients regain ambulation, even in severe cases, but disability remains in up to 10% and perhaps more. Numerous challenges remain including early identification and control of infectious triggers, improved access of modern neurointensive care worldwide, and translating our understanding of pathogenesis into meaningful preventive or assistive therapies. This review provides a historical perspective at the centenary of the first description of the syndrome, insights into its pathogenesis, triage, initial immunotherapy, and management in the intensive care unit. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Subunit compositions of Arabidopsis RNA polymerases I and III reveal Pol I- and Pol III-specific forms of the AC40 subunit and alternative forms of the C53 subunit

DOE PAGES

Ream, Thomas S.; Haag, Jeremy R.; Pontvianne, Frederic; ...

2015-05-02

Using affinity purification and mass spectrometry, we identified the subunits of Arabidopsis thaliana multisubunit RNA Polymerases I and III (abbreviated as Pol I and Pol III), providing the first description of their physical compositions in plants. AC40 and AC19 subunits are typically common to Pol I (a.k.a. Pol A) and Pol III (a.k.a. Pol C) and are encoded by single genes whose mutation, in humans, is a cause of the craniofacial disorder, Treacher-Collins Syndrome. Surprisingly, A. thaliana, and related species, express two distinct AC40 paralogs, one of which assembles into Pol I and the other of which assembles into Polmore » III. Changes at eight amino acid positions correlate with this functional divergence of Pol I and Pol III-specific AC40 paralogs. Two genes encode homologs of the yeast C53 subunit, and either variant can assemble into Pol III. By contrast, only one of two potential C17 variants, and one of two potential C31 variants were detected in Pol III. We introduce a new nomenclature system for plant Pol I and Pol III subunits in which the twelve subunits that are structurally and functionally homologous among Pols I through V are assigned equivalent numbers.« less

Subunit compositions of Arabidopsis RNA polymerases I and III reveal Pol I- and Pol III-specific forms of the AC40 subunit and alternative forms of the C53 subunit

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

Ream, Thomas S.; Haag, Jeremy R.; Pontvianne, Frederic

Using affinity purification and mass spectrometry, we identified the subunits of Arabidopsis thaliana multisubunit RNA Polymerases I and III (abbreviated as Pol I and Pol III), providing the first description of their physical compositions in plants. AC40 and AC19 subunits are typically common to Pol I (a.k.a. Pol A) and Pol III (a.k.a. Pol C) and are encoded by single genes whose mutation, in humans, is a cause of the craniofacial disorder, Treacher-Collins Syndrome. Surprisingly, A. thaliana, and related species, express two distinct AC40 paralogs, one of which assembles into Pol I and the other of which assembles into Polmore » III. Changes at eight amino acid positions correlate with this functional divergence of Pol I and Pol III-specific AC40 paralogs. Two genes encode homologs of the yeast C53 subunit, and either variant can assemble into Pol III. By contrast, only one of two potential C17 variants, and one of two potential C31 variants were detected in Pol III. We introduce a new nomenclature system for plant Pol I and Pol III subunits in which the twelve subunits that are structurally and functionally homologous among Pols I through V are assigned equivalent numbers.« less

Quantitative application of the primary progressive aphasia consensus criteria

PubMed Central

Wicklund, Meredith R.; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Whitwell, Jennifer L.

2014-01-01

Objective: To determine how well the consensus criteria could classify subjects with primary progressive aphasia (PPA) using a quantitative speech and language battery that matches the test descriptions provided by the consensus criteria. Methods: A total of 105 participants with a neurodegenerative speech and language disorder were prospectively recruited and underwent neurologic, neuropsychological, and speech and language testing and MRI in this case-control study. Twenty-one participants with apraxia of speech without aphasia served as controls. Select tests from the speech and language battery were chosen for application of consensus criteria and cutoffs were employed to determine syndromic classification. Hierarchical cluster analysis was used to examine participants who could not be classified. Results: Of the 84 participants, 58 (69%) could be classified as agrammatic (27%), semantic (7%), or logopenic (35%) variants of PPA. The remaining 31% of participants could not be classified. Of the unclassifiable participants, 2 clusters were identified. The speech and language profile of the first cluster resembled mild logopenic PPA and the second cluster semantic PPA. Gray matter patterns of loss of these 2 clusters of unclassified participants also resembled mild logopenic and semantic variants. Conclusions: Quantitative application of consensus PPA criteria yields the 3 syndromic variants but leaves a large proportion unclassified. Therefore, the current consensus criteria need to be modified in order to improve sensitivity. PMID:24598709

The XBabelPhish MAGE-ML and XML translator.

PubMed

Maier, Don; Wymore, Farrell; Sherlock, Gavin; Ball, Catherine A

2008-01-18

MAGE-ML has been promoted as a standard format for describing microarray experiments and the data they produce. Two characteristics of the MAGE-ML format compromise its use as a universal standard: First, MAGE-ML files are exceptionally large - too large to be easily read by most people, and often too large to be read by most software programs. Second, the MAGE-ML standard permits many ways of representing the same information. As a result, different producers of MAGE-ML create different documents describing the same experiment and its data. Recognizing all the variants is an unwieldy software engineering task, resulting in software packages that can read and process MAGE-ML from some, but not all producers. This Tower of MAGE-ML Babel bars the unencumbered exchange of microarray experiment descriptions couched in MAGE-ML. We have developed XBabelPhish - an XQuery-based technology for translating one MAGE-ML variant into another. XBabelPhish's use is not restricted to translating MAGE-ML documents. It can transform XML files independent of their DTD, XML schema, or semantic content. Moreover, it is designed to work on very large (> 200 Mb.) files, which are common in the world of MAGE-ML. XBabelPhish provides a way to inter-translate MAGE-ML variants for improved interchange of microarray experiment information. More generally, it can be used to transform most XML files, including very large ones that exceed the capacity of most XML tools.

Important issues in the justification of a control treatment in paediatric drug trials.

PubMed

Kelly, Lauren E; Davies, Elin Haf; Saint-Raymond, Agnes; Tomasi, Paolo; Offringa, Martin

2016-10-01

The value of comparative effectiveness trials in informing clinical and policy decisions depends heavily on the choice of control arm (comparator). Our objective is to identify challenges in comparator reasoning and to determine justification criteria for selecting a control arm in paediatric clinical trials. A literature search was completed to identify existing sources of guidance on comparator selection. Subsequently, we reviewed a randomly selected sample of comparators selected for paediatric investigation plans (PIPs) adopted by the Paediatric Committee of the European Medicines Agency in 2013. We gathered descriptive information and evaluated their review process to identify challenges and compromises between regulators and sponsors with regard to the selection of the comparator. A tool to help investigators justify the selection of active controls and placebo arms was developed using the existing literature and empirical data. Justifying comparator selection was a challenge in 28% of PIPs. The following challenging paediatric issues in the decision-making process were identified: use of off-label medications as comparators, ethical and safe use of placebo, duration of placebo use, an undefined optimal dosing strategy, lack of age-appropriate safety and efficacy data, and drug dosing not supported by extrapolation of safety/efficacy evidence from other populations. In order to generate trials that will inform clinical decision-making and support marketing authorisations, researchers must systemically and transparently justify their selection of the comparator arm for their study. This report highlights key areas for justification in the choice of comparator in paediatric clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The validity and clinical utility of the Disabilities of the Arm Shoulder and Hand questionnaire for hand injuries in developing country contexts: A systematic review.

PubMed

de Klerk, Susan; Buchanan, Helen; Jerosch-Herold, Christina

Systematic review. The Disabilities of the Arm Shoulder and Hand Questionnaire has multiple language versions from many countries around the world. In addition there is extensive research evidence of its psychometric properties. The purpose of this study was to systematically review the evidence available on the validity and clinical utility of the Disabilities of the Arm Shoulder and Hand as a measure of activity and participation in patients with musculoskeletal hand injuries in developing country contexts. We registered the review with international prospective register of systematic reviews prior to conducting a comprehensive literature search and extracting descriptive data. Two reviewers independently assessed methodological quality with the Consensus-Based Standards for the Selection of Health Measurement Instruments critical appraisal tool, the checklist to operationalize measurement characteristics of patient-rated outcome measures and the multidimensional model of clinical utility. Fourteen studies reporting 12 language versions met the eligibility criteria. Two language versions (Persian and Turkish) had an overall rating of good, and one (Thai) had an overall rating of excellent for cross-cultural validity. The remaining 9 language versions had an overall poor rating for cross-cultural validity. Content and construct validity and clinical utility yielded similar results. Poor quality ratings for validity and clinical utility were due to insufficient documentation of results and inadequate psychometric testing. With the increase in migration and globalization, hand therapists are likely to require a range of culturally adapted and translated versions of the Disabilities of the Arm Shoulder and Hand. Recommendations include rigorous application and reporting of cross-cultural adaptation, appropriate psychometric testing, and testing of clinical utility in routine clinical practice. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Randomized phase II study of sequential carboplatin plus paclitaxel and gefitinib in chemotherapy-naïve patients with advanced or metastatic non-small-cell lung cancer: Long-term follow-up results.

PubMed

Kubo, Emi; Yamamoto, Noboru; Nokihara, Hiroshi; Fujiwara, Yutaka; Horinouchi, Hidehito; Kanda, Shintaro; Goto, Yasushi; Ohe, Yuichiro

2017-01-01

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of their EGFR mutation status. A total of 97 patients meeting this description were randomly assigned to arm A (carboplatin and paclitaxel followed by gefitinib; n=49) or B (gefitinib followed by carboplatin and paclitaxel; n=48) from June, 2003 to October, 2005. Carboplatin and paclitaxel were administered in 4 cycles every 3 weeks; gefitinib was continued until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival; the secondary endpoints were response rate and adverse event prevalence. The median overall follow-up was 65.1 months (range, 28.7-75.1 months). The major toxicities were hematological (carboplatin and paclitaxel) or skin rash, diarrhea and hepatic dysfunction (gefitinib). Interstitial lung disease was observed in 1 patient from each arm. In arms A and B, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34.8 and 26.5%, 33.3 and 35.7%, and 18.8 and 17.2 months, respectively. Arm A was selected for a subsequent phase III study.

Angular position, range of motion and velocity of arm elevation: a study of consistency of performance.

PubMed

García-Alsina, Joan; García Almazan, Concepción; Moranta Mesquida, José; Pleguezuelos Cobo, Eulogio

2005-11-01

To define the normal range, velocity and consistency of the movement of active arm elevation with humerus in neutral or in external rotation using a simplified kinematic model. Nine normal volunteers and the non-involved side of twenty five patients with unilateral shoulder lesion participated. A 3D optoelectronic tracking system was used to register the movement of raising the arm from the normal upright position to maximal elevation in a repetitive way. Peak humeral position, range of movement, velocity of motion and consistency of cycles were analyzed. Descriptive statistics, correlation between variables and with sex, age and side are presented, including differences between performances of movement done in neutral or external rotation. Data of the six variables were: maximal abduction 142 degrees [137.4-147.0], range of motion 118.1 degrees [112-124], maximal velocity 238 degrees/s [209-265]; mean velocity 113 degrees/s [96-130]; coefficient of variation of maximal angular abduction was 2.2% [1.7-2.7]; coefficient of variation of maximal velocity 8.6% [7.3-9.9]. No significant differences were observed either on side, sex or between the shoulder of normal volunteers or that of the patients with opposite shoulder lesions. Participants older than 45 years old showed only a significant slightly lower average velocity. The study confirms the weak association between dependent (biomechanical) and independent variables. As it is described here, analysis of arm elevation has not been previously studied and shows that has a good consistency in angular position, velocity and repeatability of motion in normal conditions which permits a picture of the overall performance of the shoulder.

Collaborative Research: Using ARM Observations to Evaluate GCM Cloud Statistics for Development of Stochastic Cloud-Radiation Parameterizations

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

Shen, Samuel S. P.

2013-09-01

The long-range goal of several past and current projects in our DOE-supported research has been the development of new and improved parameterizations of cloud-radiation effects and related processes, using ARM data, and the implementation and testing of these parameterizations in global models. The main objective of the present project being reported on here has been to develop and apply advanced statistical techniques, including Bayesian posterior estimates, to diagnose and evaluate features of both observed and simulated clouds. The research carried out under this project has been novel in two important ways. The first is that it is a key stepmore » in the development of practical stochastic cloud-radiation parameterizations, a new category of parameterizations that offers great promise for overcoming many shortcomings of conventional schemes. The second is that this work has brought powerful new tools to bear on the problem, because it has been an interdisciplinary collaboration between a meteorologist with long experience in ARM research (Somerville) and a mathematician who is an expert on a class of advanced statistical techniques that are well-suited for diagnosing model cloud simulations using ARM observations (Shen). The motivation and long-term goal underlying this work is the utilization of stochastic radiative transfer theory (Lane-Veron and Somerville, 2004; Lane et al., 2002) to develop a new class of parametric representations of cloud-radiation interactions and closely related processes for atmospheric models. The theoretical advantage of the stochastic approach is that it can accurately calculate the radiative heating rates through a broken cloud layer without requiring an exact description of the cloud geometry.« less

Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations

PubMed Central

Yang, Tian; Jia, Zhonglin; Bryant-Pike, Whitney; Chandrasekhar, Anand; Murray, Jeffrey C; Fritzsch, Bernd; Bassuk, Alexander G

2014-01-01

Palate development is shaped by multiple molecular signaling pathways, including the Wnt pathway. In mice and humans, mutations in both the canonical and noncanonical arms of the Wnt pathway manifest as cleft palate, one of the most common human birth defects. Like the palate, numerous studies also link different Wnt signaling perturbations to varying degrees of limb malformation; for example, shortened limbs form in mutations of Ror2,Vangl2looptail and, in particular, Wnt5a. We recently showed the noncanonical Wnt/planar cell polarity (PCP) signaling molecule Prickle1 (Prickle like 1) also stunts limb growth in mice. We now expanded these studies to the palate and show that Prickle1 is also required for palate development, like Wnt5a and Ror2. Unlike in the limb, the Vangl2looptail mutation only aggravates palate defects caused by other mutations. We screened Filipino cleft palate patients and found PRICKLE1 variants, both common and rare, at an elevated frequency. Our results reveal that in mice and humans PRICKLE1 directs palate morphogenesis; our results also uncouple Prickle1 function from Vangl2 function. Together, these findings suggest mouse and human palate development is guided by PCP-Prickle1 signaling that is probably not downstream of Vangl2. PMID:24689077

Linkage of osteoporosis to chromosome 20p12 and association to BMP2.

PubMed

Styrkarsdottir, Unnur; Cazier, Jean-Baptiste; Kong, Augustine; Rolfsson, Ottar; Larsen, Helene; Bjarnadottir, Emma; Johannsdottir, Vala D; Sigurdardottir, Margret S; Bagger, Yu; Christiansen, Claus; Reynisdottir, Inga; Grant, Struan F A; Jonasson, Kristjan; Frigge, Michael L; Gulcher, Jeffrey R; Sigurdsson, Gunnar; Stefansson, Kari

2003-12-01

Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 x 10(-7)), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.

Mosaic isochromosome 15q and maternal uniparental isodisomy for chromosome 15 in a patient with morbid obesity and variant PWS-like phenotype.

PubMed

Wang, Jia-Chi; Vaccarello-Cruz, Mary; Ross, Leslie; Owen, Renius; Pratt, Victoria M; Lightman, Katherine; Liu, Yan; Hafezi, Katayoun; Cherif, Dhia; Sahoo, Trilochan

2013-07-01

Angelman and Prader-Willi syndromes are reciprocal imprinting disorders caused by loss of maternally or paternally expressed genes, respectively, within 15q11.2-q13. Angelman syndrome (AS; OMIM 105830) is a neurodevelopmental disorder and is due to the loss of maternally expressed UBE3A gene. Prader-Willi syndrome (PWS; OMIM 176270) is a clinically distinct disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13. Recently published data strongly suggest a role for the paternally expressed small nucleolar RNA (snoRNA) cluster, SNORD116, in PWS etiology. Uniparental disomy (UPD) 15 is one of the important causes of PWS and AS. Interestingly, balanced and unbalanced chromosomal aberrations in the form of Robertsonian translocation, isochromosomes, supernumerary marker chromosomes and copy number variations have been strongly linked with the occurrence of UPD. Here we report on a very unique case with a mosaic isochromosome for the entire long arm of 15, that is, i(15)(q10), resulting in mosaic uniparental isodisomy for 15q and with no copy number alterations. This is the first report of UPD15 constituted by a mosaic, but copy number neutral chromosomal rearrangement in a patient with a variant PWS-like phenotype. Copyright © 2013 Wiley Periodicals, Inc.

Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector

PubMed Central

Bowles, Dawn E; McPhee, Scott WJ; Li, Chengwen; Gray, Steven J; Samulski, Jade J; Camp, Angelique S; Li, Juan; Wang, Bing; Monahan, Paul E; Rabinowitz, Joseph E; Grieger, Joshua C; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Xiao, Xiao; Samulski, R Jude

2012-01-01

Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer. PMID:22068425

A Study of relationship between frailty and physical performance in elderly women.

PubMed

Jeoung, Bog Ja; Lee, Yang Chool

2015-08-01

Frailty is a disorder of multiple inter-related physiological systems. It is unclear whether the level of physical performance factors can serve as markers of frailty and a sign. The purpose of this study was to examine the relationship between frailty and physical performance in elderly women. One hundred fourteen elderly women participated in this study, their aged was from 65 to 80. We were measured 6-min walk test, grip-strength, 30-sec arm curl test, 30-sec chair stand test, 8 foot Up- and Go, Back scratch, chair sit and reach, unipedal stance, BMI, and the frailty with questionnaire. The collected data were analyzed by descriptive statistics, frequencies, correlation analysis, ANOVA, and simple liner regression using the IBM 21. SPSS program. In results, statistic tests showed that there were significant differences between frailty and 6-min walk test, 30-sec arm curl test, 30-sec chair stand test, grip-strength, Back scratch, and BMI. However, we did not find significant differences between frailty and 8 foot Up- and Go, unipedal stance. When the subjects were divided into five groups according to physical performance level, subjects with high 6-min walk, 30-sec arm curl test, chair sit and reach test, and high grip strength had low score frailty. Physical performance factors were strongly associated with decreased frailty, suggesting that physical performance improvements play an important role in preventing or reducing the frailty.

A Canadian Electric-Arm Prosthesis for Children

PubMed Central

Nicholls, Peter B.; Stevenson, David A.; Sherman, E. David; Lippay, Andrew L.; Gingras, Gustave

1967-01-01

The thalidomide tragedy in Canada initiated new efforts to produce functional prosthetic appliances for very young amputees. In 1962, the Rehabilitation Institute of Montreal began to fit 36 babies with adapted conventional and gas-operated devices. Practical experience with the Soviet prosthesis proved the feasibility of myoelectric control, and indicated the possibility of using skin electrodes over an active muscle for control purposes in children. We obtained assistance from the Northern Electric Company, whose research laboratories produced the prototype arms described in this report. An all-electric prosthetic system was developed which carries out four different movements driven by a single motor. Function is effected by switches, but a myoelectric control system could be readily adapted without major changes. In the description of our needs for the proposed arm, we asked for modular construction and a minimum service life of one year between major repairs. Details of design and performance are outlined in this report. Initial clinical experience indicates that the prosthesis is completely accepted by the young patient, in spite of its excessive weight and inconvenient control. Four powered joints give the child greater functional freedom. In future we plan to fit an older child and will study more bilateral installations in the next 14 months. After further use, study and improvement, this device will become a useful prosthesis. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:6021562

Magneto-inductive skin sensor for robot collision avoidance: A new development

NASA Technical Reports Server (NTRS)

Chauhan, D. S.; Dehoff, Paul H.

1989-01-01

Safety is a primary concern for robots operating in space. The tri-mode sensor addresses that concern by employing a collision avoidance/management skin around the robot arms. This rf-based skin sensor is at present a dual mode (proximity and tactile). The third mode, pyroelectric, will complement the other two. The proximity mode permits the robot to sense an intruding object, to range the object, and to detect the edges of the object. The tactile mode permits the robot to sense when it has contacted an object, where on the arm it has made contact, and provides a three-dimensional image of the shape of the contact impression. The pyroelectric mode will be added to permit the robot arm to detect the proximity of a hot object and to add sensing redundancy to the two other modes. The rf-modes of the sensing skin are presented. These modes employ a highly efficient magnetic material (amorphous metal) in a sensing technique. This results in a flexible sensor array which uses a primarily inductive configuration to permit both capacitive and magnetoinductive sensing of object; thus optimizing performance in both proximity and tactile modes with the same sensing skin. The fundamental operating principles, design particulars, and theoretical models are provided to aid in the description and understanding of this sensor. Test results are also given.

Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering.

PubMed

Barnes, Melissa D; Winkler, Marisa L; Taracila, Magdalena A; Page, Malcolm G; Desarbre, Eric; Kreiswirth, Barry N; Shields, Ryan K; Nguyen, Minh-Hong; Clancy, Cornelius; Spellberg, Brad; Papp-Wallace, Krisztina M; Bonomo, Robert A

2017-10-31

The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in Escherichia coli and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn "traps" β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i) the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii) the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii) E166 is displaced by 2 Å when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases. IMPORTANCE Antibiotic resistance is emerging at unprecedented rates and threatens to reach crisis levels. One key mechanism of resistance is the breakdown of β-lactam antibiotics by β-lactamase enzymes. KPC-2 is a β-lactamase that inactivates carbapenems and β-lactamase inhibitors (e.g., clavulanate) and is prevalent around the world, including in the United States. Resistance to the new antibiotic ceftazidime-avibactam, which was designed to overcome KPC resistance, had already emerged within a year. Using protein engineering, we uncovered a mechanism by which resistance to this new drug emerges, which could arm scientists with the ability to forestall such resistance to future drugs. Copyright © 2017 Barnes et al.

Hand-Eye Calibration of Robonaut

NASA Technical Reports Server (NTRS)

Nickels, Kevin; Huber, Eric

2004-01-01

NASA's Human Space Flight program depends heavily on Extra-Vehicular Activities (EVA's) performed by human astronauts. EVA is a high risk environment that requires extensive training and ground support. In collaboration with the Defense Advanced Research Projects Agency (DARPA), NASA is conducting a ground development project to produce a robotic astronaut's assistant, called Robonaut, that could help reduce human EVA time and workload. The project described in this paper designed and implemented a hand-eye calibration scheme for Robonaut, Unit A. The intent of this calibration scheme is to improve hand-eye coordination of the robot. The basic approach is to use kinematic and stereo vision measurements, namely the joint angles self-reported by the right arm and 3-D positions of a calibration fixture as measured by vision, to estimate the transformation from Robonaut's base coordinate system to its hand coordinate system and to its vision coordinate system. Two methods of gathering data sets have been developed, along with software to support each. In the first, the system observes the robotic arm and neck angles as the robot is operated under external control, and measures the 3-D position of a calibration fixture using Robonaut's stereo cameras, and logs these data. In the second, the system drives the arm and neck through a set of pre-recorded configurations, and data are again logged. Two variants of the calibration scheme have been developed. The full calibration scheme is a batch procedure that estimates all relevant kinematic parameters of the arm and neck of the robot The daily calibration scheme estimates only joint offsets for each rotational joint on the arm and neck, which are assumed to change from day to day. The schemes have been designed to be automatic and easy to use so that the robot can be fully recalibrated when needed such as after repair, upgrade, etc, and can be partially recalibrated after each power cycle. The scheme has been implemented on Robonaut Unit A and has been shown to reduce mismatch between kinematically derived positions and visually derived positions from a mean of 13.75cm using the previous calibration to means of 1.85cm using a full calibration and 2.02cm using a suboptimal but faster daily calibration. This improved calibration has already enabled the robot to more accurately reach for and grasp objects that it sees within its workspace. The system has been used to support an autonomous wrench-grasping experiment and significantly improved the workspace positioning of the hand based on visually derived wrench position. estimates.

NOTE: On the need to revise the arm structure in stylized anthropomorphic phantoms in lateral photon irradiation geometry

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lee, Choonik; Lee, Jai-Ki

2006-11-01

Distributions of radiation absorbed dose within human anatomy have been estimated through Monte Carlo radiation transport techniques implemented for two different classes of computational anthropomorphic phantoms: (1) mathematical equation-based stylized phantoms and (2) tomographic image-based voxel phantoms. Voxel phantoms constructed from tomographic images of real human anatomy have been actively developed since the late 1980s to overcome the anatomical approximations necessary with stylized phantoms, which themselves have been utilized since the mid 1960s. However, revisions of stylized phantoms have also been pursued in parallel to the development of voxel phantoms since voxel phantoms (1) are initially restricted to the individual-specific anatomy of the person originally imaged, (2) must be restructured on an organ-by-organ basis to conform to reference individual anatomy and (3) cannot easily represent very fine anatomical structures and tissue layers that are thinner than the voxel dimensions of the overall phantom. Although efforts have been made to improve the anatomic realism of stylized phantoms, most of these efforts have been limited to attempts to alter internal organ structures. Aside from the internal organs, the exterior shapes, and especially the arm structures, of stylized phantoms are also far from realistic descriptions of human anatomy, and may cause dosimetry errors in the calculation of organ-absorbed doses for external irradiation scenarios. The present study was intended to highlight the need to revise the existing arm structure within stylized phantoms by comparing organ doses of stylized adult phantoms with those from three adult voxel phantoms in the lateral photon irradiation geometry. The representative stylized phantom, the adult phantom of the Oak Ridge National Laboratory (ORNL) series and two adult male voxel phantoms, KTMAN-2 and VOXTISS8, were employed for Monte Carlo dose calculation, and data from another voxel phantom, VIP-Man, were obtained from literature sources. The absorbed doses for lungs, oesophagus, liver and kidneys that could be affected by arm structures in the lateral irradiation geometry were obtained for both classes of phantoms in lateral monoenergetic photon irradiation geometries. As expected, those organs in the ORNL phantoms received apparently higher absorbed doses than those in the voxel phantoms. The overestimation is mainly attributed to the relatively poor representation of the arm structure in the ORNL phantom in which the arm bones are embedded within the regions describing the phantom's torso. The results of this study suggest that the overestimation of organ doses, due to unrealistic arm representation, should be taken into account when stylized phantoms are employed for equivalent or effective dose estimates, especially in the case of an irradiation scenario with dominating lateral exposure. For such a reason, the stylized phantom arm structure definition should be revised in order to obtain more realistic evaluations.

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

PubMed

André, Thierry; Vernerey, Dewi; Mineur, Laurent; Bennouna, Jaafar; Desrame, Jérôme; Faroux, Roger; Fratte, Serge; Hug de Larauze, Marine; Paget-Bailly, Sophie; Chibaudel, Benoist; Bez, Jeremie; Dauba, Jérôme; Louvet, Christophe; Lepere, Céline; Dupuis, Olivier; Becouarn, Yves; Mabro, May; Egreteau, Joëlle; Bouche, Olivier; Deplanque, Gaël; Ychou, Marc; Galais, Marie Pierre; Ghiringhelli, François; Dourthe, Louis Marie; Bachet, Jean-Baptiste; Khalil, Ahmed; Bonnetain, Franck; de Gramont, Aimery; Taieb, Julien

2018-05-20

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Sustainable reduction of antibiotic-induced antimicrobial resistance (ARena) in German ambulatory care: study protocol of a cluster randomised trial.

PubMed

Kamradt, Martina; Kaufmann-Kolle, Petra; Andres, Edith; Brand, Tonia; Klingenberg, Anja; Glassen, Katharina; Poß-Doering, Regina; Uhlmann, Lorenz; Hees, Katharina; Weber, Dorothea; Gutscher, Andreas; Wambach, Veit; Szecsenyi, Joachim; Wensing, Michel

2018-02-05

Despite many initiatives to enhance the rational use of antibiotics, there remains substantial room for improvement. The overall aim of this study is to optimise the appropriate use of antibiotics in German ambulatory care in patients with acute non-complicated infections (respiratory tract infections, such as bronchitis, sinusitis, tonsillitis and otitis media), community-acquired pneumonia and non-complicated cystitis, in order to counter the advancing antimicrobial resistance development. A three-armed cluster randomised trial will be conducted in 14 practice networks in two German federal states (Bavaria and North Rhine-Westphalia) and an added cohort that reflects standard care. The trial is accompanied by a process evaluation. Each arm will receive a different set of implementation strategies. Arm A receives a standard set, comprising of e-learning on communication with patients and quality circles with data-based feedback for physicians, information campaigns for the public, patient information material and performance-based additional reimbursement. Arm B receives this standard set plus e-learning on communication with patients and quality circles with data-based feedback tailored for non-physician health professionals of the practice team and information material for tablet computers (culture sensitive). Arm C receives the standard set as well as a computerised decision support system and quality circles in local multidisciplinary groups. The study aims to recruit 193 practices which will provide data on 23,934 patients each year (47,867 patients in total). The outcome evaluation is based on claims data and refers to established indicators of the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). Primary and secondary outcomes relate to prescribing of antibiotics, which will be analysed in multivariate regression models. The process evaluation is based on interviews with surveys among physicians, non-physician health professionals of the practice team and stakeholders. A patient survey is conducted in one of the study arms. Interview data will be qualitatively analysed using thematic framework analysis. Survey data of physicians, non-physician health professionals of the practice team and patients will use descriptive and exploratory statistics for analysis. The ARena trial will examine the effectiveness of large scale implementation strategies and explore their delivery in routine practice. ISRCTN, ISRCTN58150046 . Registered 24 August 2017.

Models of optical quantum computing

NASA Astrophysics Data System (ADS)

Krovi, Hari

2017-03-01

I review some work on models of quantum computing, optical implementations of these models, as well as the associated computational power. In particular, we discuss the circuit model and cluster state implementations using quantum optics with various encodings such as dual rail encoding, Gottesman-Kitaev-Preskill encoding, and coherent state encoding. Then we discuss intermediate models of optical computing such as boson sampling and its variants. Finally, we review some recent work in optical implementations of adiabatic quantum computing and analog optical computing. We also provide a brief description of the relevant aspects from complexity theory needed to understand the results surveyed.

Hierarchical hybrid control of manipulators: Artificial intelligence in large scale integrated circuits

NASA Technical Reports Server (NTRS)

Greene, P. H.

1972-01-01

Both in practical engineering and in control of muscular systems, low level subsystems automatically provide crude approximations to the proper response. Through low level tuning of these approximations, the proper response variant can emerge from standardized high level commands. Such systems are expressly suited to emerging large scale integrated circuit technology. A computer, using symbolic descriptions of subsystem responses, can select and shape responses of low level digital or analog microcircuits. A mathematical theory that reveals significant informational units in this style of control and software for realizing such information structures are formulated.

Radiometric liquid level gauge with linear-detection (in German)

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

Glaeser, M.; Emmelmann, K.P.

1973-09-01

A description is given of a radiometric liquid level gauge with linear detection. It consists of a set of radioactive sources (e.g., /sup 137/Cs) with quadratic graduation in their activities, of a scintillation counter with electronic back-up unit and of a slender tube. The tube, sources and scintillation counter form a compact snd easily transportsble liquid level gauge. It is-especially adapted for liquid level measurements in slender, difficulty accessible and opaque containers. The device supplements the different methods for liquid level measurement with a new variant which is adopted for many cases in practice. (auth)

Nonthermal steady states after an interaction quench in the Falicov-Kimball model.

PubMed

Eckstein, Martin; Kollar, Marcus

2008-03-28

We present the exact solution of the Falicov-Kimball model after a sudden change of its interaction parameter using nonequilibrium dynamical mean-field theory. For different interaction quenches between the homogeneous metallic and insulating phases the system relaxes to a nonthermal steady state on time scales on the order of variant Planck's over 2pi/bandwidth, showing collapse and revival with an approximate period of h/interaction if the interaction is large. We discuss the reasons for this behavior and provide a statistical description of the final steady state by means of generalized Gibbs ensembles.

Interdisciplinary Management of a Perforated Aneurysmal Arteria Lusoria: A Case Report.

PubMed

Rouman, Mina; Petrovitch, Alexander; Gey, Eva-Maria; Kuntze, Thomas

2017-01-01

Background  An aberrant right subclavian artery (RSA) or arteria lusoria is the most common congenital abnormality of the aortic arch with an incidence of 0.3 to 3.0%. Case Description  We report a case of a perforated aneurysmal aberrant RSA, managed using a hybrid approach. Conclusion  In emergency cases with acute bleeding, we recommend an endovascular approach to avoid the lethal sequel of arterial leakage. Whenever possible, the pulsatile blood flow to the right arm should be restored. Management should be tailored to the nature of the aneurysmal aberrant RSA, patient's comorbidities, and concomitant lesions.

Issues in advanced automation for manipulator control

NASA Technical Reports Server (NTRS)

Bejczy, A. K.

1976-01-01

This paper provides a brief description and analysis of the main issues in advanced autonomous control of manipulators as seen from a system point of view. The nature of manipulation is analyzed at some depth. A general multilevel structure is outlined for manipulator control organization which includes the human operator at the top level of the control structure. Different approaches to the development of advanced automation of mechanical arms are summarized. Recent work in the JPL teleoperator project is described, including control system, force/torque sensor, and control software development. Some results from control experiments are summarized.

A unified teleoperated-autonomous dual-arm robotic system

NASA Technical Reports Server (NTRS)

Hayati, Samad; Lee, Thomas S.; Tso, Kam Sing; Backes, Paul G.; Lloyd, John

1991-01-01

A description is given of complete robot control facility built as part of a NASA telerobotics program to develop a state-of-the-art robot control environment for performing experiments in the repair and assembly of spacelike hardware to gain practical knowledge of such work and to improve the associated technology. The basic architecture of the manipulator control subsystem is presented. The multiarm Robot Control C Library (RCCL), a key software component of the system, is described, along with its implementation on a Sun-4 computer. The system's simulation capability is also described, and the teleoperation and shared control features are explained.

MWRRET Value-Added Product: The Retrieval of Liquid Water Path and Precipitable Water Vapor from Microwave Radiometer (MWR) Datasets

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

KL Gaustad; DD Turner

2007-09-30

This report provides a short description of the Atmospheric Radiation Measurement (ARM) microwave radiometer (MWR) RETrievel (MWRRET) Value-Added Product (VAP) algorithm. This algorithm utilizes complimentary physical and statistical retrieval methods and applies brightness temperature offsets to reduce spurious liquid water path (LWP) bias in clear skies resulting in significantly improved precipitable water vapor (PWV) and LWP retrievals. We present a general overview of the technique, input parameters, output products, and describe data quality checks. A more complete discussion of the theory and results is given in Turner et al. (2007b).

Analytical model for three-dimensional Mercedes-Benz water molecules.

PubMed

Urbic, T

2012-06-01

We developed a statistical model which describes the thermal and volumetric properties of water-like molecules. A molecule is presented as a three-dimensional sphere with four hydrogen-bonding arms. Each water molecule interacts with its neighboring waters through a van der Waals interaction and an orientation-dependent hydrogen-bonding interaction. This model, which is largely analytical, is a variant of a model developed before for a two-dimensional Mercedes-Benz model of water. We explored properties such as molar volume, density, heat capacity, thermal expansion coefficient, and isothermal compressibility as a function of temperature and pressure. We found that the volumetric and thermal properties follow the same trends with temperature as in real water and are in good general agreement with Monte Carlo simulations, including the density anomaly, the minimum in the isothermal compressibility, and the decreased number of hydrogen bonds upon increasing the temperature.

Analytical model for three-dimensional Mercedes-Benz water molecules

NASA Astrophysics Data System (ADS)

Urbic, T.

2012-06-01

We developed a statistical model which describes the thermal and volumetric properties of water-like molecules. A molecule is presented as a three-dimensional sphere with four hydrogen-bonding arms. Each water molecule interacts with its neighboring waters through a van der Waals interaction and an orientation-dependent hydrogen-bonding interaction. This model, which is largely analytical, is a variant of a model developed before for a two-dimensional Mercedes-Benz model of water. We explored properties such as molar volume, density, heat capacity, thermal expansion coefficient, and isothermal compressibility as a function of temperature and pressure. We found that the volumetric and thermal properties follow the same trends with temperature as in real water and are in good general agreement with Monte Carlo simulations, including the density anomaly, the minimum in the isothermal compressibility, and the decreased number of hydrogen bonds upon increasing the temperature.

Signing on for dirty work: Taking stock of a public psychiatry project from the inside.

PubMed

Pope, Leah G; Cubellis, Lauren; Hopper, Kim

2016-08-01

As applied anthropologists used to working at arm's length from public psychiatry, we step out of the daily grind to take stock of the challenges of taking on ethnography entrained-harnessed to the implementation of a new program. These include the loss of critical distance, the struggles to negotiate locally viable forms of authority and relevance, the necessity of sustaining a Janus-faced relation with principal players, the urgency of seeing time-sensitive information converted into corrective feedback, and the undeniable attraction of being part of "committed work" with game-changing potential. In so doing, we rework the terms of witnessing and revive an old alternative: that documentary dirty work be reclaimed as a variant of public anthropology, one that transforms the work of application from mere afterthought to integral part of the original inquiry. © The Author(s) 2016.

Analytical model for three-dimensional Mercedes-Benz water molecules

PubMed Central

Urbic, T.

2013-01-01

We developed a statistical model which describes the thermal and volumetric properties of water-like molecules. A molecule is presented as a three-dimensional sphere with four hydrogen-bonding arms. Each water molecule interacts with its neighboring waters through a van der Waals interaction and an orientation-dependent hydrogen-bonding interaction. This model, which is largely analytical, is a variant of a model developed before for a two-dimensional Mercedes-Benz model of water. We explored properties such as molar volume, density, heat capacity, thermal expansion coefficient, and isothermal compressibility as a function of temperature and pressure. We found that the volumetric and thermal properties follow the same trends with temperature as in real water and are in good general agreement with Monte Carlo simulations, including the density anomaly, the minimum in the isothermal compressibility, and the decreased number of hydrogen bonds upon increasing the temperature. PMID:23005100

[Cutaneous leishmaniasis caused by Leishmania mexicana in Durango, Mexico: first clinical case report].

PubMed

Pérez-Vega, Jorge Humberto; López-Moreno, Carmina Yanett; López-Valenzuela, José Angel; Rendón-Maldonado, José Guadalupe; López-Moreno, Héctor Samuel

2009-01-01

Leishmanisis is a parasitic diseases caused by intracellular protozoan of Leishmania genus. These parasites are transmitted by the bite of phlebotomine flies. Leishmanises are classified in different clinic variants: cutaneous localized or diffuse, mucocutaneous and visceral. In Mexico, the leishmanisis are distributed in several states, however Durango was considered free of leishmaniasis. A 9 year old male patient with an ulcerated pruriginous node of circular shape, 13 x 18 mm diameter, localized in the back of the right arm with 6 months progression. The patient was a permanent resident of Durango, Mexico. Histopathology evidenced macrophages infected with amastigotes. The PCR-RFLP result was consistent with Leishmania mexicana. Treatment with glucantime was satisfactory. Here we report the first clinical case of leishmanisis cutaneous localized caused by Leishmania mexicana from Durango, Mexico in a 9 years old male, confirming the increasing propagation of this protozoan parasite in Mexico.

Phi-value analysis of apo-azurin folding: comparison between experiment and theory.

PubMed

Zong, Chenghang; Wilson, Corey J; Shen, Tongye; Wolynes, Peter G; Wittung-Stafshede, Pernilla

2006-05-23

Pseudomonas aeruginosa azurin is a 128-residue beta-sandwich metalloprotein; in vitro kinetic experiments have shown that it folds in a two-state reaction. Here, we used a variational free energy functional to calculate the characteristics of the transition state ensemble (TSE) for folding of the apo-form of P. aeruginosa azurin and investigate how it responds to thermal and mutational changes. The variational method directly yields predicted chevron plots for wild-type and mutant apo-forms of azurin. In parallel, we performed in vitro kinetic-folding experiments on the same set of azurin variants using chemical perturbation. Like the wild-type protein, all apo-variants fold in apparent two-state reactions both in calculations and in stopped-flow mixing experiments. Comparisons of phi (phi) values determined from the experimental and theoretical chevron parameters reveal an excellent agreement for most positions, indicating a polarized, highly structured TSE for folding of P. aeruginosa apo-azurin. We also demonstrate that careful analysis of side-chain interactions is necessary for appropriate theoretical description of core mutants.

Integration of the blaNDM-1 carbapenemase gene into Proteus genomic island 1 (PGI1-PmPEL) in a Proteus mirabilis clinical isolate.

PubMed

Girlich, Delphine; Dortet, Laurent; Poirel, Laurent; Nordmann, Patrice

2015-01-01

To decipher the mechanisms and their associated genetic determinants responsible for β-lactam resistance in a Proteus mirabilis clinical isolate. The entire genetic structure surrounding the β-lactam resistance genes was characterized by PCR, gene walking and DNA sequencing. Genes encoding the carbapenemase NDM-1 and the ESBL VEB-6 were located in a 38.5 kb MDR structure, which itself was inserted into a new variant of the Proteus genomic island 1 (PGI1). This new PGI1-PmPEL variant of 64.4 kb was chromosomally located, as an external circular form in the P. mirabilis isolate, suggesting potential mobility. This is the first known description of the bla(NDM-1) gene in a genomic island structure, which might further enhance the spread of the bla(NDM-1) carbapenemase gene among enteric pathogens. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Normal and variant anatomy of the nasal tip.

PubMed

Ketcham, Amy S; Dobratz, Eric J

2012-04-01

A thorough understanding of nasal tip anatomy is a prerequisite to understanding the nuances of restructuring the nasal tip. The three-dimensional structural anatomy of the nasal tip is complex. Additionally, the interrelationship between these structures determines the ultimate form and function of the nasal tip. As a result, alteration of one structure in the tip will often lead to change in other portions of the nasal tip. This dynamic concept of anatomy in the nasal tip makes proper alteration of the nasal tip one of the most challenging tasks faced by a rhinoplasty surgeon. This article provides a fundamental knowledge of the normal anatomy of the tip structures and how their interaction with each other determines the shape and support of the lower portion of the nose. It also provides a description of some common variants of tip anatomy that cause patients to seek consultation for rhinoplasty. A proper understanding of the concepts presented provides a foundation to build on as the reader continues to explore the "nuances of the nasal tip." Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hashimoto thyroiditis: a century later.

PubMed

Ahmed, Rania; Al-Shaikh, Safa; Akhtar, Mohammed

2012-05-01

More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized. The most recently recognized variant is immunoglobulin G4(+) HT, which may occur as isolated thyroid limited disease or as part of a generalized Ig4-related sclerosing disease. The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. HT is frequently associated with papillary thyroid carcinoma and may indeed be a risk factor for developing this type of cancer. The relationship between thyroid lymphoma and HT on the other hand appears well established.

[Differential diagnosis of Dandy-Walker syndrome different presentations].

PubMed

Tobías-González, Pablo; Gil Mira, Mar; Valero de Bernabé, Javier; Zapardiel, Ignacio

2012-08-01

Dandy-Walker syndrome is a set of abnormalities of the posterior fossa including three modalities: classic Dandy-Walker malformation, Dandy-Walker variant and mega-cisterna magna. Our objective is clarify the differential diagnosis among these entities. Descriptive and retrospective study of Dandy-Walker cases diagnosed at our Department during the last five years plus a review of the related Medical literature. Three cases of Dandy-Walker modalities are reported: one case of classic Dandy-Walker malformation, one case of Dandy-Walker variant, and one case of false Dandy-Walker. In the first two cases the patients underwent legal abortion, whereas in the last one a healthy male newborn was delivered in the week 38 of gestation. Malformations in the posterior fossa, including Dandy-Walker syndrome, are still a challenge in prenatal diagnosis. Technical developments in imaging, such as in three-dimensional sonography and magnetic resonance, allow higher resolution and multiplanar images for an easier diagnose. There is a high rate of false positive, particularly before the 18th week of gestation. It is advisable not to establish a final diagnose before that week.

Evaluation of the Systematic Status of Geographical Variations in Arcuphantes hibanus (Arachnida: Araneae: Linyphiidae), with Descriptions of Two New Species.

PubMed

Nakano, Takafumi; Ihara, Yoh; Kumasaki, Yusuke; Baba, Yuki G; Tomikawa, Ko

2017-08-01

The systematic status of geographical variants of Arcuphantes hibanus Saito, 1992 belonging to the A. longiscapus species group, indigenous to western Honshu and Shikoku, Japan, was evaluated using morphological and molecular data. Two species, A. enmusubi Ihara, Nakano and Tomikawa, sp. nov. and A. occidentalis Ihara, Nakano and Tomikawa, sp. nov., are described, and A. hibanus is redescribed with redefinition of its taxonomic status. These three species are diagnosed by the characteristics of paracymbium, pseudolamella, and epigynal basal part. Phylogenetic trees obtained with mitochondrial cytochrome c oxidase subunit I and 16S rRNA markers showed that the variants are mutually genetically highly diverged. However, the mtDNA phylogenies failed to recover the monophyly of A. hibanus redefined herein. Contrary to the mtDNA phylogenetic analyses, a neighbor-network analysis of nuclear internal transcribed spacer 1 sequences of A. hibanus, A. enmusubi and A. occidentalis spiders showed that each of them forms a cluster. The results of mitochondrial and nuclear DNA analyses in each of the three species are briefly discussed, along with their taxonomic identities.

Coinheritance of a novel mutation on the HBA1 gene: c.187delG (p.W62fsX66) [codon 62 (-G) (α1)] with the α212 patchwork allele and Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T].

PubMed

Scheps, Karen G; De Paula, Silvia M; Bitsman, Alicia R; Freigeiro, Daniel H; Basack, F Nora; Pennesi, Sandra P; Varela, Viviana

2013-01-01

We describe a novel frameshift mutation on the HBA1 gene (c.187delG), causative of α-thalassemia (α-thal) in a Black Cuban family with multiple sequence variants in the HBA genes and the Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T] mutation. The deletion of the first base of codon 62 resulted in a frameshift at amino acid 62 with a putative premature termination codon (PTC) at amino acid 66 on the same exon (p.W62fsX66), which most likely triggers nonsense mediated decay of the resulting mRNA. This study also presents the first report of the α212 patchwork allele in Latin America and the description of two new sequence variants in the HBA2 region (c.-614G>A in the promoter region and c.95+39 C>T on the first intron).

The application of active side arm controllers in helicopters

NASA Technical Reports Server (NTRS)

Knorr, R.; Melz, C.; Faulkner, A.; Obermayer, M.

1993-01-01

Eurocopter Deutschland (ECD) started simulation trials to investigate the particular problems of Side Arm Controllers (SAC) applied to helicopters. Two simulation trials have been performed. In the first trial, the handling characteristics of a 'passive' SAC and the basic requirements for the application of an 'active' SAC were evaluated in pilot-in-the-loop simulations, performing the tasks in a realistic scenario representing typical phases of a transport mission. The second simulation trial investigated the general control characteristics of the 'active' in comparison to the 'passive' control principle. A description of the SACs developed by ECD and the principle of the 'passive' and 'active' control concept is given, as well as specific ratings for the investigated dynamic and ergonomic parameters effecting SAC characteristics. The experimental arrangements, as well as the trials procedures of both simulation phases, are described and the results achieved are discussed emphasizing the advantages of the 'active' as opposed to the 'passive' SAC concept. This also includes the presentation of some critical aspects still to be improved and proposals to solve them.

Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease.

PubMed

Kuhlman, Kate Ryan; Chiang, Jessica J; Horn, Sarah; Bower, Julienne E

2017-09-01

Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Automatic specification of reliability models for fault-tolerant computers

NASA Technical Reports Server (NTRS)

Liceaga, Carlos A.; Siewiorek, Daniel P.

1993-01-01

The calculation of reliability measures using Markov models is required for life-critical processor-memory-switch structures that have standby redundancy or that are subject to transient or intermittent faults or repair. The task of specifying these models is tedious and prone to human error because of the large number of states and transitions required in any reasonable system. Therefore, model specification is a major analysis bottleneck, and model verification is a major validation problem. The general unfamiliarity of computer architects with Markov modeling techniques further increases the necessity of automating the model specification. Automation requires a general system description language (SDL). For practicality, this SDL should also provide a high level of abstraction and be easy to learn and use. The first attempt to define and implement an SDL with those characteristics is presented. A program named Automated Reliability Modeling (ARM) was constructed as a research vehicle. The ARM program uses a graphical interface as its SDL, and it outputs a Markov reliability model specification formulated for direct use by programs that generate and evaluate the model.

Description of larvae of two closely related species Cassida palaestina Reiche, 1858 and Cassida rubiginosa Müller, 1776 (Coleoptera: Chrysomelidae: Cassidinae).

PubMed

Swiętojańska, Jolanta; Moradian, Hossein; Borowiec, Lech; Ostovan, Hadi

2013-11-29

Larvae of two closely related species Cassida palaestina Reiche, 1858 and Cassida rubiginosa Müller, 1776 are described in detail including SEM microstructures. First instars are extremely similar with no clear diagnostic characters, larvae of Cassida palaestina are slightly more contrastingly coloured than larvae of C. rubiginosa, the latter having darker scoli, basal part of supra-anal processes and legs. Last instars differ in very subtle but constant characters: lateral scoli of C. palaestina are slightly shorter than those of C. rubiginosa, in C. palaestina tops of the lateral branches are armed apically with an elongate cauliflower-shaped sensillum while in C. rubiginosa tops of the lateral branches are more often armed with a pointed seta than with an elongate cauliflower-shaped sensillum, and cauliflower-shaped sensilla on tergites are less elongate in C. palaestina than in C. rubiginosa. These differences accompanied by distinguishing characters of adults and their distribution range indicate that both taxa are probably vicariant species with partial parapatric occurrence. Centaurea behen is a new host plant for C. palaestina.

Improved Arctic Cloud and Aerosol Research and Model Parameterizations

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

Kenneth Sassen

2007-03-01

In this report are summarized our contributions to the Atmospheric Measurement (ARM) program supported by the Department of Energy. Our involvement commenced in 1990 during the planning stages of the design of the ARM Cloud and Radiation Testbed (CART) sites. We have worked continuously (up to 2006) on our ARM research objectives, building on our earlier findings to advance our knowledge in several areas. Below we summarize our research over this period, with an emphasis on the most recent work. We have participated in several aircraft-supported deployments at the SGP and NSA sites. In addition to deploying the Polarization Diversitymore » Lidar (PDL) system (Sassen 1994; Noel and Sassen 2005) designed and constructed under ARM funding, we have operated other sophisticated instruments W-band polarimetric Doppler radar, and midinfrared radiometer for intercalibration and student training purposes. We have worked closely with University of North Dakota scientists, twice co-directing the Citation operations through ground-to-air communications, and serving as the CART ground-based mission coordinator with NASA aircraft during the 1996 SUCCESS/IOP campaign. We have also taken a leading role in initiating case study research involving a number of ARM coinvestigators. Analyses of several case studies from these IOPs have been reported in journal articles, as we show in Table 1. The PDL has also participated in other major field projects, including FIRE II and CRYSTAL-FACE. In general, the published results of our IOP research can be divided into two categories: comprehensive cloud case study analyses to shed light on fundamental cloud processes using the unique CART IOP measurement capabilities, and the analysis of in situ data for the testing of remote sensing cloud retrieval algorithms. One of the goals of the case study approach is to provide sufficiently detailed descriptions of cloud systems from the data-rich CART environment to make them suitable for application to cloud modeling groups, such as the GEWEX Cloud Simulation Study (GCSS) Cirrus Working Groups. In this paper we summarize our IOP-related accomplishments.« less

Perspectives of health care professionals on the facilitators and barriers to the implementation of a stroke rehabilitation guidelines cluster randomized controlled trial.

PubMed

Munce, Sarah E P; Graham, Ian D; Salbach, Nancy M; Jaglal, Susan B; Richards, Carol L; Eng, Janice J; Desrosiers, Johanne; MacKay-Lyons, Marilyn; Wood-Dauphinee, Sharon; Korner-Bitensky, Nicol; Mayo, Nancy E; Teasell, Robert W; Zwarenstein, Merrick; Mokry, Jennifer; Black, Sandra; Bayley, Mark T

2017-06-26

The Stroke Canada Optimization of Rehabilitation by Evidence Implementation Trial (SCORE-IT) was a cluster randomized controlled trial that evaluated two knowledge translation (KT) interventions for the promotion of the uptake of best practice recommendations for interventions targeting upper and lower extremity function, postural control, and mobility. Twenty rehabilitation centers across Canada were randomly assigned to either the facilitated or passive KT intervention. The objective of the current study was to understand the factors influencing the implementation of the recommended treatments and KT interventions from the perspective of nurses, occupational therapists and physical therapists, and clinical managers following completion of the trial. A qualitative descriptive approach involving focus groups was used. Thematic analysis was used to understand the factors influencing the implementation of the recommended treatments and KT interventions. The Clinical Practice Guidelines Framework for Improvement guided the analysis. Thirty-three participants were interviewed from 11 of the 20 study sites (6 sites from the facilitated KT arm and 5 sites from the passive KT arm). The following factors influencing the implementation of the recommended treatments and KT interventions emerged: facilitation, agreement with the intervention - practical, familiarity with the recommended treatments, and environmental factors, including time and resources. Each of these themes includes the sub-themes of facilitator and/or barrier. Improved team communication and interdisciplinary collaboration emerged as an unintended outcome of the trial across both arms in addition to a facilitator to the implementation of the treatment recommendations. Facilitation was identified as a facilitator to implementation of the KT interventions in the passive KT intervention arm despite the lack of formally instituted facilitators in this arm of the trial. This is one of the first studies to examine the factors influencing the implementation of stroke recommendations and associated KT interventions within the context of a trial. Findings highlight the important role of self-selected facilitators to implementation efforts. Future research should seek to better understand the specific characteristics of facilitators that are associated with successful implementation and clinical outcomes, especially within the context of stroke rehabilitation.

Video2vec Embeddings Recognize Events When Examples Are Scarce.

PubMed

Habibian, Amirhossein; Mensink, Thomas; Snoek, Cees G M

2017-10-01

This paper aims for event recognition when video examples are scarce or even completely absent. The key in such a challenging setting is a semantic video representation. Rather than building the representation from individual attribute detectors and their annotations, we propose to learn the entire representation from freely available web videos and their descriptions using an embedding between video features and term vectors. In our proposed embedding, which we call Video2vec, the correlations between the words are utilized to learn a more effective representation by optimizing a joint objective balancing descriptiveness and predictability. We show how learning the Video2vec embedding using a multimodal predictability loss, including appearance, motion and audio features, results in a better predictable representation. We also propose an event specific variant of Video2vec to learn a more accurate representation for the words, which are indicative of the event, by introducing a term sensitive descriptiveness loss. Our experiments on three challenging collections of web videos from the NIST TRECVID Multimedia Event Detection and Columbia Consumer Videos datasets demonstrate: i) the advantages of Video2vec over representations using attributes or alternative embeddings, ii) the benefit of fusing video modalities by an embedding over common strategies, iii) the complementarity of term sensitive descriptiveness and multimodal predictability for event recognition. By its ability to improve predictability of present day audio-visual video features, while at the same time maximizing their semantic descriptiveness, Video2vec leads to state-of-the-art accuracy for both few- and zero-example recognition of events in video.

A Study of relationship between frailty and physical performance in elderly women

PubMed Central

Jeoung, Bog Ja; Lee, Yang Chool

2015-01-01

Frailty is a disorder of multiple inter-related physiological systems. It is unclear whether the level of physical performance factors can serve as markers of frailty and a sign. The purpose of this study was to examine the relationship between frailty and physical performance in elderly women. One hundred fourteen elderly women participated in this study, their aged was from 65 to 80. We were measured 6-min walk test, grip-strength, 30-sec arm curl test, 30-sec chair stand test, 8 foot Up- and Go, Back scratch, chair sit and reach, unipedal stance, BMI, and the frailty with questionnaire. The collected data were analyzed by descriptive statistics, frequencies, correlation analysis, ANOVA, and simple liner regression using the IBM 21. SPSS program. In results, statistic tests showed that there were significant differences between frailty and 6-min walk test, 30-sec arm curl test, 30-sec chair stand test, grip-strength, Back scratch, and BMI. However, we did not find significant differences between frailty and 8 foot Up- and Go, unipedal stance. When the subjects were divided into five groups according to physical performance level, subjects with high 6-min walk, 30-sec arm curl test, chair sit and reach test, and high grip strength had low score frailty. Physical performance factors were strongly associated with decreased frailty, suggesting that physical performance improvements play an important role in preventing or reducing the frailty. PMID:26331137

Disorders of Upper Limb Movements in Ataxia-Telangiectasia

PubMed Central

Shaikh, Aasef G.; Zee, David S.; Mandir, Allen S.; Lederman, Howard M.; Crawford, Thomas O.

2013-01-01

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia. PMID:23826191

Estimation of true height: a study in population-specific methods among young South African adults.

PubMed

Lahner, Christen Renée; Kassier, Susanna Maria; Veldman, Frederick Johannes

2017-02-01

To investigate the accuracy of arm-associated height estimation methods in the calculation of true height compared with stretch stature in a sample of young South African adults. A cross-sectional descriptive design was employed. Pietermaritzburg, Westville and Durban, KwaZulu-Natal, South Africa, 2015. Convenience sample (N 900) aged 18-24 years, which included an equal number of participants from both genders (150 per gender) stratified across race (Caucasian, Black African and Indian). Continuous variables that were investigated included: (i) stretch stature; (ii) total armspan; (iii) half-armspan; (iv) half-armspan ×2; (v) demi-span; (vi) demi-span gender-specific equation; (vii) WHO equation; and (viii) WHO-adjusted equations; as well as categorization according to gender and race. Statistical analysis was conducted using IBM SPSS Statistics Version 21.0. Significant correlations were identified between gender and height estimation measurements, with males being anatomically larger than females (P<0·001). Significant differences were documented when study participants were stratified according to race and gender (P<0·001). Anatomical similarities were noted between Indians and Black Africans, whereas Caucasians were anatomically different from the other race groups. Arm-associated height estimation methods were able to estimate true height; however, each method was specific to each gender and race group. Height can be calculated by using arm-associated measurements. Although universal equations for estimating true height exist, for the enhancement of accuracy, the use of equations that are race-, gender- and population-specific should be considered.

Disorders of Upper Limb Movements in Ataxia-Telangiectasia.

PubMed

Shaikh, Aasef G; Zee, David S; Mandir, Allen S; Lederman, Howard M; Crawford, Thomas O

2013-01-01

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia.

Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease.

PubMed

Elahi, Fanny M; Marx, Gabe; Cobigo, Yann; Staffaroni, Adam M; Kornak, John; Tosun, Duygu; Boxer, Adam L; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J

2017-01-01

Degradation of white matter microstructure has been demonstrated in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). In preparation for clinical trials, ongoing studies are investigating the utility of longitudinal brain imaging for quantification of disease progression. To date only one study has examined sample size calculations based on longitudinal changes in white matter integrity in FTLD. To quantify longitudinal changes in white matter microstructural integrity in the three canonical subtypes of frontotemporal dementia (FTD) and AD using diffusion tensor imaging (DTI). 60 patients with clinical diagnoses of FTD, including 27 with behavioral variant frontotemporal dementia (bvFTD), 14 with non-fluent variant primary progressive aphasia (nfvPPA), and 19 with semantic variant PPA (svPPA), as well as 19 patients with AD and 69 healthy controls were studied. We used a voxel-wise approach to calculate annual rate of change in fractional anisotropy (FA) and mean diffusivity (MD) in each group using two time points approximately one year apart. Mean rates of change in FA and MD in 48 atlas-based regions-of-interest, as well as global measures of cognitive function were used to calculate sample sizes for clinical trials (80% power, alpha of 5%). All FTD groups showed statistically significant baseline and longitudinal white matter degeneration, with predominant involvement of frontal tracts in the bvFTD group, frontal and temporal tracts in the PPA groups and posterior tracts in the AD group. Longitudinal change in MD yielded a larger number of regions with sample sizes below 100 participants per therapeutic arm in comparison with FA. SvPPA had the smallest sample size based on change in MD in the fornix (n = 41 participants per study arm to detect a 40% effect of drug), and nfvPPA and AD had their smallest sample sizes based on rate of change in MD within the left superior longitudinal fasciculus (n = 49 for nfvPPA, and n = 23 for AD). BvFTD generally showed the largest sample size estimates (minimum n = 140 based on MD in the corpus callosum). The corpus callosum appeared to be the best region for a potential study that would include all FTD subtypes. Change in global measure of functional status (CDR box score) yielded the smallest sample size for bvFTD (n = 71), but clinical measures were inferior to white matter change for the other groups. All three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.

The behavioural/dysexecutive variant of Alzheimer’s disease: clinical, neuroimaging and pathological features

PubMed Central

Pijnenburg, Yolande A. L.; Perry, David C.; Cohn-Sheehy, Brendan I.; Scheltens, Nienke M. E.; Vogel, Jacob W.; Kramer, Joel H.; van der Vlies, Annelies E.; Joie, Renaud La; Rosen, Howard J.; van der Flier, Wiesje M.; Grinberg, Lea T.; Rozemuller, Annemieke J.; Huang, Eric J.; van Berckel, Bart N. M.; Miller, Bruce L.; Barkhof, Frederik; Jagust, William J.; Scheltens, Philip; Seeley, William W.; Rabinovici, Gil D.

2015-01-01

A ‘frontal variant of Alzheimer’s disease’ has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer’s disease pathology. The description of this rare Alzheimer’s disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer’s disease with a behavioural-predominant presentation (behavioural Alzheimer’s disease) and a neuropathological diagnosis of high-likelihood Alzheimer’s disease (n = 17) and/or biomarker evidence of Alzheimer’s disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer’s disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer’s disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer’s disease: 53%; dysexecutive Alzheimer’s disease: 83%) than behavioural (behavioural Alzheimer’s disease: 25%; dysexecutive Alzheimer’s disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer’s disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer’s disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer’s disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer’s disease (typical Alzheimer’s disease, n = 58), autopsy-confirmed/Alzheimer’s disease biomarker-negative behavioural variant frontotemporal dementia (n = 59), and controls (n = 61). Patients with behavioural Alzheimer’s disease showed worse memory scores than behavioural variant frontotemporal dementia and did not differ from typical Alzheimer’s disease, while executive function composite scores were lower compared to behavioural variant frontotemporal dementia and typical Alzheimer’s disease. Voxel-wise contrasts between behavioural and dysexecutive Alzheimer’s disease patients and controls revealed marked atrophy in bilateral temporoparietal regions and only limited atrophy in the frontal cortex. In direct comparison with behavioural and those with dysexecutive Alzheimer’s disease, patients with behavioural variant frontotemporal dementia showed more frontal atrophy and less posterior involvement, whereas patients with typical Alzheimer’s disease were slightly more affected posteriorly and showed less frontal atrophy (P < 0.001 uncorrected). Among 24 autopsied behavioural Alzheimer’s disease/dysexecutive Alzheimer’s disease patients, only two had primary co-morbid FTD-spectrum pathology (progressive supranuclear palsy). In conclusion, behavioural Alzheimer’s disease presentations are characterized by a milder and more restricted behavioural profile than in behavioural variant frontotemporal dementia, co-occurrence of memory dysfunction and high APOE ε4 prevalence. Dysexecutive Alzheimer’s disease presented as a primarily cognitive phenotype with minimal behavioural abnormalities and intermediate APOE ε4 prevalence. Both behavioural Alzheimer’s disease and dysexecutive Alzheimer’s disease presentations are distinguished by temporoparietal-predominant atrophy. Based on the relative sparing of frontal grey matter, we propose to redefine these clinical syndromes as ‘the behavioural/dysexecutive variant of Alzheimer’s disease’ rather than frontal variant Alzheimer’s disease. Further work is needed to determine whether behavioural and dysexecutive-predominant presentations of Alzheimer’s disease represent distinct phenotypes or a single continuum. PMID:26141491

New understandings of the genetic basis of isolated idiopathic central hypogonadism

PubMed Central

Bonomi, Marco; Vladimiro Libri, Domenico; Guizzardi, Fabiana; Guarducci, Elena; Maiolo, Elisabetta; Pignatti, Elisa; Asci, Roberta; Persani, Luca

2012-01-01

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary–gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network. PMID:22138902

New understandings of the genetic basis of isolated idiopathic central hypogonadism.

PubMed

Bonomi, Marco; Libri, Domenico Vladimiro; Guizzardi, Fabiana; Guarducci, Elena; Maiolo, Elisabetta; Pignatti, Elisa; Asci, Roberta; Persani, Luca

2012-01-01

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

Isomorphic semantic mapping of variant call format (VCF2RDF).

PubMed

Penha, Emanuel Diego S; Iriabho, Egiebade; Dussaq, Alex; de Oliveira, Diana Magalhães; Almeida, Jonas S

2017-02-15

The move of computational genomics workflows to Cloud Computing platforms is associated with a new level of integration and interoperability that challenges existing data representation formats. The Variant Calling Format (VCF) is in a particularly sensitive position in that regard, with both clinical and consumer-facing analysis tools relying on this self-contained description of genomic variation in Next Generation Sequencing (NGS) results. In this report we identify an isomorphic map between VCF and the reference Resource Description Framework. RDF is advanced by the World Wide Web Consortium (W3C) to enable representations of linked data that are both distributed and discoverable. The resulting ability to decompose VCF reports of genomic variation without loss of context addresses the need to modularize and govern NGS pipelines for Precision Medicine. Specifically, it provides the flexibility (i.e. the indexing) needed to support the wide variety of clinical scenarios and patient-facing governance where only part of the VCF data is fitting. Software libraries with a claim to be both domain-facing and consumer-facing have to pass the test of portability across the variety of devices that those consumers in fact adopt. That is, ideally the implementation should itself take place within the space defined by web technologies. Consequently, the isomorphic mapping function was implemented in JavaScript, and was tested in a variety of environments and devices, client and server side alike. These range from web browsers in mobile phones to the most popular micro service platform, NodeJS. The code is publicly available at https://github.com/ibl/VCFr , with a live deployment at: http://ibl.github.io/VCFr/ . jonas.almeida@stonybrookmedicine.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Ensembl variation resources

PubMed Central

2010-01-01

Background The maturing field of genomics is rapidly increasing the number of sequenced genomes and producing more information from those previously sequenced. Much of this additional information is variation data derived from sampling multiple individuals of a given species with the goal of discovering new variants and characterising the population frequencies of the variants that are already known. These data have immense value for many studies, including those designed to understand evolution and connect genotype to phenotype. Maximising the utility of the data requires that it be stored in an accessible manner that facilitates the integration of variation data with other genome resources such as gene annotation and comparative genomics. Description The Ensembl project provides comprehensive and integrated variation resources for a wide variety of chordate genomes. This paper provides a detailed description of the sources of data and the methods for creating the Ensembl variation databases. It also explores the utility of the information by explaining the range of query options available, from using interactive web displays, to online data mining tools and connecting directly to the data servers programmatically. It gives a good overview of the variation resources and future plans for expanding the variation data within Ensembl. Conclusions Variation data is an important key to understanding the functional and phenotypic differences between individuals. The development of new sequencing and genotyping technologies is greatly increasing the amount of variation data known for almost all genomes. The Ensembl variation resources are integrated into the Ensembl genome browser and provide a comprehensive way to access this data in the context of a widely used genome bioinformatics system. All Ensembl data is freely available at http://www.ensembl.org and from the public MySQL database server at ensembldb.ensembl.org. PMID:20459805

Translating natural genetic variation to gene expression in a computational model of the Drosophila gap gene regulatory network

PubMed Central

Kozlov, Konstantin N.; Kulakovskiy, Ivan V.; Zubair, Asif; Marjoram, Paul; Lawrie, David S.; Nuzhdin, Sergey V.; Samsonova, Maria G.

2017-01-01

Annotating the genotype-phenotype relationship, and developing a proper quantitative description of the relationship, requires understanding the impact of natural genomic variation on gene expression. We apply a sequence-level model of gap gene expression in the early development of Drosophila to analyze single nucleotide polymorphisms (SNPs) in a panel of natural sequenced D. melanogaster lines. Using a thermodynamic modeling framework, we provide both analytical and computational descriptions of how single-nucleotide variants affect gene expression. The analysis reveals that the sequence variants increase (decrease) gene expression if located within binding sites of repressors (activators). We show that the sign of SNP influence (activation or repression) may change in time and space and elucidate the origin of this change in specific examples. The thermodynamic modeling approach predicts non-local and non-linear effects arising from SNPs, and combinations of SNPs, in individual fly genotypes. Simulation of individual fly genotypes using our model reveals that this non-linearity reduces to almost additive inputs from multiple SNPs. Further, we see signatures of the action of purifying selection in the gap gene regulatory regions. To infer the specific targets of purifying selection, we analyze the patterns of polymorphism in the data at two phenotypic levels: the strengths of binding and expression. We find that combinations of SNPs show evidence of being under selective pressure, while individual SNPs do not. The model predicts that SNPs appear to accumulate in the genotypes of the natural population in a way biased towards small increases in activating action on the expression pattern. Taken together, these results provide a systems-level view of how genetic variation translates to the level of gene regulatory networks via combinatorial SNP effects. PMID:28898266

Shower PUVA: a novel variant of photochemotherapy. Distribution of photosensitivity and accumulation of trioxsalen in the skin.

PubMed

Sánchez Ruderisch, H; Aryee-Boi, J; Schwarz, C; Radenhausen, M; Tebbe, B

2004-01-01

Shower PUVA is a new variant of photochemotherapy suitable for therapy of various skin disorders. Psoralen, e.g. trioxsalen-containing water recirculates in a closed shower system and wets the skin continuously. After showering, whole-body UVA irradiation (320-400 nm) is performed. In order to prove the equal distribution of photosensitivity in vivo minimal phototoxic dose (MPD) was determined in different skin areas of healthy individuals. Additionally, we investigated the accumulation of trioxsalen in psoriasis lesions under the conditions described by quantifying psoralen in scales collected after showering. In a randomized study 20 healthy volunteers (skin type I-III) took showers for 5 and 10 min in trioxsalen (0.27 mg/l)-containing water at 37 degrees C. Immediately afterwards, MPD was tested on the inside of the upper arms and on the buttocks by using a polychromator light source (315-400 nm). The applied UVA doses were 0.06-0.75 J/cm(2) with steps of 0.125 J/cm(2). MPD was evaluated after 72 h. Equal distribution of photosensitivity was defined as equal MPD on the insides of the upper arm and the buttocks (+/-0.125 J/cm(2)). Skin scales of 21 patients with psoriasis were collected by scratching after showering with trioxsalen-containing water (0.27 mg/l) for 5 min. For quantification of trioxsalen in the scales HPLC was performed. An equal distribution of photosensitivity was achieved in 70% (14/20) cases after 10-min showering in trioxsalen-containing water. Showering for 5 min only revealed a 30% (6/20) rate of equal distributed photosensitivity. After 10-min shower time MPD was 0.325 J/cm(2) (median; range: 0.06-0.625 J/cm(2)). The average amount of trioxsalen found in the scales was 2.03 ng/mg scales (range: 0.38-7.2 ng/mg). For shower PUVA using trioxsalen, 10 min shower time is recommended to achieve sufficient distribution of photosensitivity on the skin. Clinical efficacy of shower PUVA can be explained by skin accumulation of trioxsalen which enters from the aqueous phase into the upper skin layers in detectable amounts. This is the first report demonstrating the efficacy of shower PUVA which in short shower time allows an uptake of psoralen by the skin. Copyright 2004 S. Karger AG, Basel

RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

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

Li, Donghui, E-mail: dli@mdanderson.org; Moughan, Jennifer; Crane, Christopher

Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival wasmore » analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.« less

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

PubMed

Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

2018-01-01

Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

Association of N-acetyltransferase-2 and glutathione S-transferase polymorphisms with idiopathic male infertility in Vietnam male subjects.

PubMed

Trang, Nguyen Thi; Huyen, Vu Thi; Tuan, Nguyen Thanh; Phan, Tran Duc

2018-04-25

N-acetyltransferase-2 (NAT2) and Glutathione S-transferases (GSTs) are phase-II xenobiotic metabolizing enzymes participating in detoxification of toxic arylamines, aromatic amines, hydrazines and reactive oxygen species (ROS), which are produced under oxidative and electrophile stresses. The purpose of this research was to investigate whether two common single-nucleotide polymorphisms (SNP) of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) associated with susceptibility to idiopathic male infertility. A total 300 DNA samples (150 infertile patients and 150 healthy control) were genotyped for the polymorphisms by ARMS - PCR. We revealed a significant association between the NAT2 variant genotypes (CT + TT (rs1799929), (OR: 3.74; p < 0.001)) and (GA + AA (rs1799930), (OR: 3.75; p < 0.001)) or GSTP1 variant genotypes (GA + AA (rs1695), (OR: 5.11; p < 0,001)) and (CT + TT (rs1138272), (OR: 7.42; p < 0,001) with idiopathic infertility risk. Our findings rate the effect of single-nucleotide polymorphisms of GSTP1 and/or NAT2 in modulation of the risk of male infertility in subjects from Vietnam. This pilot study is the first (as far as we know) to reveal that polymorphisms of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) are some novel genetic markers for susceptibility to idiopathic male infertility. Copyright © 2018 Elsevier B.V. All rights reserved.

TCF7L2 polymorphism, weight loss and proinsulin:insulin ratio in the diabetes prevention program.

PubMed

McCaffery, Jeanne M; Jablonski, Kathleen A; Franks, Paul W; Dagogo-Jack, Sam; Wing, Rena R; Knowler, William C; Delahanty, Linda; Dabelea, Dana; Hamman, Richard; Shuldiner, Alan R; Florez, Jose C

2011-01-01

TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P<0.001), higher baseline proinsulin:insulin ratio (p<0.0001) and increased proinsulin:insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin:insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.

Update on the role of genetics in the onset of age-related macular degeneration

PubMed Central

Francis, Peter James; Klein, Michael L

2011-01-01

Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century. PMID:21887094

[Prediction of the nutritional status by anthropometrical variables and food safety at homes of pregnant women from Caracas, Venezuela].

PubMed

Pérez Guillén, A; Bernal Rivas, J

2006-01-01

The objective of this research is to analyze the nutritional status and household food security of a sample of healthy pregnant women who attend to external medicine service at Concepcion Palacios Maternity located in Caracas, Venezuela, and identify variables, which could predict the nutritional status of the evaluated group. This cross sectional, descriptive, comparative study evaluates a sample of 89 pregnant women, between 14 and 44 years of age. Economical, social, demographic and alimentary consumption variables and nutritional conditions were studied. On the way, anthropometrics like weight, height, and middle-arm circumference and Household food security scale were obtained. In order to perform the descriptive statistic, bivariate, and multiple linear regression analysis required during the investigation, the software SPSS, version 12, was used. The predictive variables considered for the evaluation of the actual nutritional status in pregnant women were: right middle-arm circumference, household food security level and the supplementation with vitamins and/or minerals. These variables explain 78.2% of the actual nutritional status variation in this sample. Therefore, this investigation highlights the importance of the research on simple variables, as a good prediction of the actual nutritional status in pregnant women, with acceptable precision values and without requiring high-trained personnel to perform it. Under these findings, is very important the study of more predictive variables to evaluate the nutritional and alimentary conditions, with practical and easy mechanisms that can be applied by non-technical personnel. It is recommended to go deep into the study of methods, which evaluate the nutrition in an easy and practical way, applied by non-technical personnel, besides continuing the validation process of the variable combinations determined as predictive of the nutritional status.

Web-Based Just-in-Time Information and Feedback on Antibiotic Use for Village Doctors in Rural Anhui, China: Randomized Controlled Trial

PubMed Central

Shen, XingRong; Lu, Manman; Feng, Rui; Cheng, Jing; Chai, Jing; Xie, Maomao; Dong, Xuemeng; Jiang, Tao

2018-01-01

Background Excessive use of antibiotics is very common worldwide, especially in rural China; various measures that have been used in curbing the problem have shown only marginal effects. Objective The objective of this study was to test an innovative intervention that provided just-in-time information and feedback (JITIF) to village doctors on care of common infectious diseases. Methods The information component of JITIF consisted of a set of theory or evidence-based ingredients, including operation guideline, public commitment, and takeaway information, whereas the feedback component tells each participating doctor about his or her performance scores and percentages of antibiotic prescriptions. These ingredients were incorporated together in a synergetic way via a Web-based aid. Evaluation of JITIF adopted a randomized controlled trial design involving 24 village clinics randomized into equal control and intervention arms. Measures used included changes between baseline and endpoint (1 year after baseline) in terms of: percentages of patients with symptomatic respiratory or gastrointestinal tract infections (RTIs or GTIs) being prescribed antibiotics, delivery of essential service procedures, and patients’ beliefs and knowledge about antibiotics and infection prevention. Two researchers worked as a group in collecting the data at each site clinic. One performed nonparticipative observation of the service process, while the other performed structured exit interviews about patients’ beliefs and knowledge. Data analysis comprised mainly of: (1) descriptive estimations of beliefs or knowledge, practice of indicative procedures, and use of antibiotics at baseline and endpoint for intervention and control groups and (2) chi-square tests for the differences between these groups. Results A total of 1048 patients completed the evaluation, including 532 at baseline (intervention=269, control=263) and 516 at endpoint (intervention=262, control=254). Patients diagnosed with RTIs and GTIs accounted for 76.5% (407/532) and 23.5% (125/352), respectively, at baseline and 80.8% (417/532) and 19.2% (99/532) at endpoint. JITIF resulted in substantial improvement in delivery of essential service procedures (2.6%-24.8% at baseline on both arms and at endpoint on the control arm vs 88.5%-95.0% at endpoint on the intervention arm, P<.001), beliefs favoring rational antibiotics use (11.5%-39.8% at baseline on both arms and at endpoint on the control arm vs 19.8%-62.6% at endpoint on the intervention arm, P<.001) and knowledge about side effects of antibiotics (35.7% on the control arm vs 73.7% on the intervention arm, P<.001), measures for managing or preventing RTIs (39.1% vs 66.7%, P=.02), and measures for managing or preventing GTIs (46.8% vs 69.2%, P<.001). It also reduced antibiotics prescription (from 88.8%-62.3%, P<.001), and this decrease was consistent for RTIs (87.1% vs 64.3%, P<.001) and GTIs (94.7% vs 52.4%, P<.001). Conclusions JITIF is effective in controlling antibiotics prescription at least in the short term and may provide a low-cost and sustainable solution to the widespread excessive use of antibiotics in rural China. PMID:29444768

Localized diabatization applied to excitons in molecular crystals

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

Jin, Zuxin; Subotnik, Joseph E.

Traditional ab initio electronic structure calculations of periodic systems yield delocalized eigenstates that should be understood as adiabatic states. For example, excitons are bands of extended states which superimpose localized excitations on every lattice site. However, in general, in order to study the effects of nuclear motion on exciton transport, it is standard to work with a localized description of excitons, especially in a hopping regime; even in a band regime, a localized description can be helpful. To extract localized excitons from a band requires essentially a diabatization procedure. In this paper, three distinct methods are proposed for such localizedmore » diabatization: (i) a simple projection method, (ii) a more general Pipek-Mezey localization scheme, and (iii) a variant of Boys diabatization. Approaches (i) and (ii) require localized, single-particle Wannier orbitals, while approach (iii) has no such dependence. Lastly, these methods should be very useful for studying energy transfer through solids with ab initio calculations.« less

An Extended Petri-Net Based Approach for Supply Chain Process Enactment in Resource-Centric Web Service Environment

NASA Astrophysics Data System (ADS)

Wang, Xiaodong; Zhang, Xiaoyu; Cai, Hongming; Xu, Boyi

Enacting a supply-chain process involves variant partners and different IT systems. REST receives increasing attention for distributed systems with loosely coupled resources. Nevertheless, resource model incompatibilities and conflicts prevent effective process modeling and deployment in resource-centric Web service environment. In this paper, a Petri-net based framework for supply-chain process integration is proposed. A resource meta-model is constructed to represent the basic information of resources. Then based on resource meta-model, XML schemas and documents are derived, which represent resources and their states in Petri-net. Thereafter, XML-net, a high level Petri-net, is employed for modeling control and data flow of process. From process model in XML-net, RESTful services and choreography descriptions are deduced. Therefore, unified resource representation and RESTful services description are proposed for cross-system integration in a more effective way. A case study is given to illustrate the approach and the desirable features of the approach are discussed.

Localized diabatization applied to excitons in molecular crystals

DOE PAGES

Jin, Zuxin; Subotnik, Joseph E.

2017-06-28

Traditional ab initio electronic structure calculations of periodic systems yield delocalized eigenstates that should be understood as adiabatic states. For example, excitons are bands of extended states which superimpose localized excitations on every lattice site. However, in general, in order to study the effects of nuclear motion on exciton transport, it is standard to work with a localized description of excitons, especially in a hopping regime; even in a band regime, a localized description can be helpful. To extract localized excitons from a band requires essentially a diabatization procedure. In this paper, three distinct methods are proposed for such localizedmore » diabatization: (i) a simple projection method, (ii) a more general Pipek-Mezey localization scheme, and (iii) a variant of Boys diabatization. Approaches (i) and (ii) require localized, single-particle Wannier orbitals, while approach (iii) has no such dependence. Lastly, these methods should be very useful for studying energy transfer through solids with ab initio calculations.« less

Accurate adiabatic singlet-triplet gaps in atoms and molecules employing the third-order spin-flip algebraic diagrammatic construction scheme for the polarization propagator

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

Lefrancois, Daniel; Dreuw, Andreas, E-mail: dreuw@uni-heidelberg.de; Rehn, Dirk R.

For the calculation of adiabatic singlet-triplet gaps (STG) in diradicaloid systems the spin-flip (SF) variant of the algebraic diagrammatic construction (ADC) scheme for the polarization propagator in third order perturbation theory (SF-ADC(3)) has been applied. Due to the methodology of the SF approach the singlet and triplet states are treated on an equal footing since they are part of the same determinant subspace. This leads to a systematically more accurate description of, e.g., diradicaloid systems than with the corresponding non-SF single-reference methods. Furthermore, using analytical excited state gradients at ADC(3) level, geometry optimizations of the singlet and triplet states weremore » performed leading to a fully consistent description of the systems, leading to only small errors in the calculated STGs ranging between 0.6 and 2.4 kcal/mol with respect to experimental references.« less

Pediatric restless legs syndrome: analysis of symptom descriptions and drawings.

PubMed

Picchietti, Daniel L; Arbuckle, Robert A; Abetz, Linda; Durmer, Jeffrey S; Ivanenko, Anna; Owens, Judith A; Croenlein, Jens; Allen, Richard P; Walters, Arthur S

2011-11-01

The specific aims of this study were to collect and analyze detailed symptom descriptions from patients with pediatric restless legs syndrome, ages 6 to 17 years, as well as assess symptom impact and the usefulness of drawings. Trained qualitative interviewers conducted face-to-face audio-recorded interviews of children and adolescents who met criteria for definite restless legs syndrome. Thirty-three patients in 3 age groups used 16 different categories of descriptors for restless legs sensations, with a mean of 3 or more categories used per patient in each age group. "Need to move/kick," "pain/hurts," "uncomfortable/cannot get comfortable," and "like bugs or ants/crawling" were the most common descriptors. Two-thirds reported daytime sensations, and nearly half had arm involvement. They described impact on sleep, cognitive function, and affect. Drawings provided useful diagnostic information. These detailed empirical data will be useful in clinical practice, as well as in the development of formal diagnostic tools and severity measures.

Population differences in platinum toxicity as a means to identify novel genetic susceptibility variants

PubMed Central

O'Donnell, Peter H.; Gamazon, Eric; Zhang, Wei; Stark, Amy L.; Kistner-Griffin, Emily O.; Huang, R. Stephanie; Dolan, M. Eileen

2010-01-01

Objectives Clinical studies show that Asians (ASN) are more susceptible to toxicities associated with platinum-containing regimens. We hypothesized that studying ASN as an `enriched phenotype' population could enable the discovery of novel genetic determinants of platinum susceptibility. Methods Using well-genotyped lymphoblastoid cell lines from the HapMap, we determined cisplatin and carboplatin cytotoxicity phenotypes (IC50s) for ASN, Caucasians (CEU), and Africans (YRI). IC50s were used in genome-wide association studies. Results ASN were most sensitive to platinums, corroborating clinical findings. ASN genome-wide association studies produced 479 single-nucleotide polymorphisms (SNPs) associating with cisplatin susceptibility and 199 with carboplatin susceptibility (P<10−4). Considering only the most significant variants (P< 9.99 × 10−6), backwards elimination was then used to identify reduced-model SNPs, which robustly described the drug phenotypes within ASN. These SNPs comprised highly descriptive genetic signatures of susceptibility, with 12 SNPs explaining more than 95% of the susceptibility phenotype variation for cisplatin, and eight SNPs approximately 75% for carboplatin. To determine the possible function of these variants in ASN, the SNPs were tested for association with differential expression of target genes. SNPs were highly associated with the expression of multiple target genes, and notably, the histone H3 family was implicated for both drugs, suggesting a platinum-class mechanism. Histone H3 has repeatedly been described as regulating the formation of platinum-DNA adducts, but this is the first evidence that specific genetic variants might mediate these interactions in a pharmacogenetic manner. Finally, to determine whether any ASN-identified SNPs might also be important in other human populations, we interrogated all 479/199 SNPs for association with platinum susceptibility in an independent combined CEU/YRI population. Three unique SNPs for cisplatin and 10 for carboplatin replicated in CEU/YRI. Conclusion Enriched `platinum susceptible' populations can be used to discover novel genetic determinants governing interindividual platinum chemotherapy susceptibility. PMID:20393316

In search of causal variants: refining disease association signals using cross-population contrasts.

PubMed

Saccone, Nancy L; Saccone, Scott F; Goate, Alison M; Grucza, Richard A; Hinrichs, Anthony L; Rice, John P; Bierut, Laura J

2008-08-29

Genome-wide association (GWA) using large numbers of single nucleotide polymorphisms (SNPs) is now a powerful, state-of-the-art approach to mapping human disease genes. When a GWA study detects association between a SNP and the disease, this signal usually represents association with a set of several highly correlated SNPs in strong linkage disequilibrium. The challenge we address is to distinguish among these correlated loci to highlight potential functional variants and prioritize them for follow-up. We implemented a systematic method for testing association across diverse population samples having differing histories and LD patterns, using a logistic regression framework. The hypothesis is that important underlying biological mechanisms are shared across human populations, and we can filter correlated variants by testing for heterogeneity of genetic effects in different population samples. This approach formalizes the descriptive comparison of p-values that has typified similar cross-population fine-mapping studies to date. We applied this method to correlated SNPs in the cholinergic nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-American samples. Of the 10 SNPs genotyped in the r2 > or = 0.8 bin for rs16969968, three demonstrated significant cross-population heterogeneity and are filtered from priority follow-up; the remaining SNPs include rs16969968 (heterogeneity p = 0.75). Though the power to filter out rs16969968 is reduced due to the difference in allele frequency in the two groups, the results nevertheless focus attention on a smaller group of SNPs that includes the non-synonymous SNP rs16969968, which retains a similar effect size (odds ratio) across both population samples. Filtering out SNPs that demonstrate cross-population heterogeneity enriches for variants more likely to be important and causative. Our approach provides an important and effective tool to help interpret results from the many GWA studies now underway.

A new Cernosvitoviella species (Clitellata: Enchytraeidae) and its comparison with other Cernosvitoviella species from Sphagnum mires in Hungary.

PubMed

Dózsa-Farkas, Klára; Csitári, Bianka; Felföldi, Tamás

2017-04-18

Results of a comparative investigation on five Cernosvitoviella species from Hungarian Sphagnum mires including their distribution and the description of a new species, Cernosvitoviella farkasi sp. n., are presented in this paper. Cernosvitoviella atrata, C. aggtelekiensis, C. crassoductus and C. farkasi sp. n. could be easily distinguished from each other based on both morphological and molecular taxonomic analyses. However, C. minor seems to be a species complex on the basis of these investigations, so it was referred as C. minor sensu lato. The status of the C. minor variants requires further studies.

ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1

PubMed Central

de Castro, Fernando; Seal, Ruth

2017-01-01

Abstract It is accepted that confusion regarding the description of genetic variants occurs when researchers do not use standard nomenclature. The Human Genome Organization Gene Nomenclature Committee contacted a panel of consultants, all working on the KAL1 gene, to propose an update of the nomenclature of the gene, as there was a convention in the literature of using the ‘KAL1’ symbol, when referring to the gene, but using the name ‘anosmin-1’ when referring to the protein. The new name, ANOS1, reflects protein name and is more transferrable across species. PMID:27899353