Thermal and flow analysis subroutines for the SINDA-version 9 computer routine

NASA Technical Reports Server (NTRS)

Oren, J. A.; Williams, D. R.

1973-01-01

Fluid flow analysis, special thermal analysis and input/output capabilities of the MOTAR routine were incorporated into the SINDA routine. All the capabilities were added in the form of user subroutines so that they may be added to different versions of SINDA with a minimum of programmer effort. Two modifications were made to the existing subroutines of SINDA/8 to incorporate the above subroutines. These were: (1) A modification to the preprocessor to permit actual values of array numbers, conductor numbers, node numbers or constant numbers supplied as array data to be converted to relative numbers. (2) Modifications to execution subroutine CNFAST to make it compatible with the radiant interchange user subroutine, RADIR. This modified version of SINDA has been designated SINDA/version 9. A detailed discussion of the methods used for the capabilities added is presented. The modifications for the SINDA subroutines are described, as well as user subroutines. All subroutines added or modified are listed.

Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome.

PubMed

Hernández-Ortega, Karina; Garcia-Esparcia, Paula; Gil, Laura; Lucas, José J; Ferrer, Isidre

2016-09-01

Ribosomes and protein synthesis have been reported to be altered in the cerebral cortex at advanced stages of Alzheimer's disease (AD). Modifications in the hippocampus with disease progression have not been assessed. Sixty-seven cases including middle-aged (MA) and AD stages I-VI were analyzed. Nucleolar chaperones nucleolin, nucleophosmin and nucleoplasmin 3, and upstream binding transcription factor RNA polymerase I gene (UBTF) mRNAs are abnormally regulated and their protein levels reduced in AD. Histone modifications dimethylated histone H3K9 (H3K9me2) and acetylated histone H3K12 (H3K12ac) are decreased in CA1. Nuclear tau declines in CA1 and dentate gyrus (DG), and practically disappears in neurons with neurofibrillary tangles. Subunit 28 ribosomal RNA (28S rRNA) expression is altered in CA1 and DG in AD. Several genes encoding ribosomal proteins are abnormally regulated and protein levels of translation initiation factors eIF2α, eIF3η and eIF5, and elongation factor eEF2, are altered in the CA1 region in AD. These findings show alterations in the protein synthesis machinery in AD involving the nucleolus, nucleus and ribosomes in the hippocampus in AD some of them starting at first stages (I-II) preceding neuron loss. These changes may lie behind reduced numbers of dendritic branches and reduced synapses of CA1 and DG neurons which cause hippocampal atrophy. © 2015 International Society of Neuropathology.

78 FR 69322 - Modification of Regulations Regarding Time Limits for Submission of Information Pertaining to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-19

... Pertaining to Requests for Sampling in Antidumping Duty Administrative Reviews AGENCY: International Trade... sampling, and comments on sampling in antidumping (AD) administrative reviews. The modifications to the time limits, if adopted, will more clearly prescribe the time for filing requests for sampling in AD...

78 FR 65185 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... airplane reaching its limit of validity (LOV) of the engineering data that support the established structural maintenance program. This AD requires, for certain airplanes, a modification of the web of the... cracks in the web, and repair or modification as applicable. We are issuing this AD to prevent cracking...

78 FR 10564 - Proposed Modification of Class B Airspace; Minneapolis, MN

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-14

... about the proposed design. The Ad Hoc Committee was chaired by the Minnesota Soaring Club representative... Minnesota Soaring Club and Stanton Sport Aviation operations. The Ad Hoc Committee's report provided to the... indicate the proposed modifications would impact the Minnesota Soaring Club and Stanton Sport Aviation...

A simulation study of spine biofidelity in the hybrid-III 6-year-old ATD.

PubMed

Wu, Jun; Cao, Libo; Reed, Matthew P; Hu, Jingwen

2013-01-01

Because of the lack of pediatric biomechanical data, Hybrid-III (HIII) child anthropomorphic test devices (ATDs) are essentially scaled from the mid-size male ATD based on the geometric considerations. These ATDs inherit a rigid thoracic spine from the adult HIII ATDs, which has been criticized as unrealistic. Therefore, the objective of this study was to explore possible design modifications for improving the spine biofidelity of the HIII 6-year-old ATD. A previously developed and validated HIII 6-year-old MADYMO ATD model was used as the baseline model to investigate the effects of design modifications on the spine biofidelity of the current ATD. Several sets of child volunteer and cadaver test data were considered as the design targets, including child volunteer low-speed crash test data, pediatric cadaver cervical spine tensile test data, and child cadaver crash test data. ATD design modifications include adding an additional joint to the thoracic spine region and changing the joint characteristics at the cervical and lumbar spine regions. Optimization techniques were used to match simulation results to each set of test results. The results indicate that the translational characteristics of the cervical and lumbar spine in the current child ATD need to be reduced to achieve realistic spine flexibility. Adding an additional joint at the thoracic spine region with degree of freedom in both flexion/extension and tension would significantly improve the ATD biofidelity in terms of predicting the overall spine curvature and head excursion in frontal crashes. Future ATD spine modification should focus on reducing the neck and lumbar tension stiffness and adding additional flexibility both in flexion/extension and tension at the thoracic spine region. The child ATD model developed in this study can be used as an important tool to improve child ATD biofidelity and child restraint system design in motor vehicle crashes.

78 FR 77614 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

.... Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking... Turbomeca S.A. Arriel 2B1 turboshaft engines that do not have modification TU157 incorporated. AD 2007-19... the compliance interval; and include the power turbine (C2) cycle consumption rate when determining...

Catalytic modification of fats and oils to value-added biobased products

USDA-ARS?s Scientific Manuscript database

Biobased materials derived from fats and oils can be relatively benign to the environment because they tend to have good biodegradability. Oils are used in a myriad of applications, including foods, cosmetics, paints, biodegradable lubricants and polymers, biodiesel, and more. For many of these ap...

Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: implications in cytotoxicity and amyloid-β peptide aggregation.

PubMed

Ramos-Fernández, Eva; Tajes, Marta; Palomer, Ernest; Ill-Raga, Gerard; Bosch-Morató, Mònica; Guivernau, Biuse; Román-Dégano, Irene; Eraso-Pichot, Abel; Alcolea, Daniel; Fortea, Juan; Nuñez, Laura; Paez, Antonio; Alameda, Francesc; Fernández-Busquets, Xavier; Lleó, Alberto; Elosúa, Roberto; Boada, Mercé; Valverde, Miguel A; Muñoz, Francisco J

2014-01-01

Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties. Since both modifications are increased in Alzheimer's disease (AD) due to amyloid-β peptide (Aβ) accumulation, we have studied their effect on albumin, the most abundant protein in cerebrospinal fluid and blood. Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin. Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. Finally, of particular relevance to AD, these modified albumins were significantly less effective in avoiding Aβ aggregation than native albumin. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD.

KSC-98pc1164

NASA Image and Video Library

1998-09-28

The orbiter Atlantis is towed away from the Shuttle Landing Facility after returning home from California atop its Shuttle Carrier Aircraft. The orbiter spent 10 months in Palmdale undergoing extensive inspections and modifications in the orbiter processing facility there. The modifications included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

GSK-3 mediates the okadaic acid-induced modification of collapsin response mediator protein-2 in human SK-N-SH neuroblastoma cells.

PubMed

Ni, Mei-Hui; Wu, Chih-Ching; Chan, Wen-Hsiung; Chien, Kun-Yi; Yu, Jau-Song

2008-04-15

Collapsin response mediator protein-2 (CRMP-2), a phosphoprotein involved in axonal outgrowth and microtubule dynamics, is aberrantly phosphorylated in Alzheimer's disease (AD) brain. Alteration of glycogen synthase kinase-3 (GSK-3) activity is associated with the pathogenesis of AD. Here, we show that CRMP-2 is one of the major substrates for GSK-3 in pig brain extracts. Both GSK-3alpha and 3beta phosphorylate purified pig brain CRMP-2 and significantly alter its mobility in SDS-gels, resembling the CRMP-2 modification observed in AD brain. Interestingly, this modification can be detected in SK-N-SH neuroblastoma cells treated with a phosphatase inhibitor, okadaic acid (OA), and GSK-3 inhibitors completely block this OA-induced event. Knockdown of both GSK-3alpha and 3beta, but not either kinase alone, impairs OA-induced modification of CRMP-2. Mutation of Ser-518 or Ser-522 of CRMP-2, which are highly phosphorylated in AD brain, to Ala blocks the OA-induced modification of CRMP-2 in SK-N-SH cells. Ser-522 prephosphorylated by Cdk5 is required for subsequent GSK-3alpha-mediated phosphorylation of CRMP-2 in vitro. Collectively, our results demonstrate for the first time that OA can induce phosphorylation of CRMP-2 in SK-N-SH cells at sites aberrantly phosphorylated in AD brain, and both GSK-3alpha and 3beta and Ser-522 kinase(s) are involved in this process.

77 FR 65506 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-29

...We propose to supersede an existing airworthiness directive (AD) that applies to certain The Boeing Company Model 757-200 and - 200PF series airplanes. The existing AD currently requires modification of the nacelle strut and wing structure, and repair of any damage found during the modification. Since we issued that AD, a compliance time error involving the optional threshold formula was discovered, which could allow an airplane to exceed the acceptable compliance time for addressing the unsafe condition. This proposed AD would specify a maximum compliance time limit that overrides the optional threshold formula results. We are proposing this AD to prevent fatigue cracking in primary strut structure and consequent reduced structural integrity of the strut.

Variations on holography from modifications of gravity in anti-de sitter

NASA Astrophysics Data System (ADS)

Apolo Velez, Luis Alberto

In this thesis we study aspects of the AdS/CFT correspondence that result from modifications of gravity in the bulk and lead to novel features in the dual theories at the boundary. The variations on the holographic theme studied in this thesis are model-independent since we have not assumed a particular UV-completion of gravity. Our results can be applied to a wide class of models that include higher-spin theories and compactifications of string theory on AdS backgrounds. The modifications of the bulk physics studied in this thesis include massive gravitons, higher-derivative terms in the Einstein-Hilbert action, and new boundary conditions for gravity. We begin by showing that it is possible to construct duals with a massive graviton in the bulk by deforming the dual theory at the boundary. This procedure does not break the translation invariance of the dual theory and might be useful in the study of certain condensed matter systems. We then construct the most general class of parity-even tricritical gravities in three and four dimensions. These higher-derivative theories are not unitary and characterized by the logarithmic fall-off of their linearized perturbations. They are conjectured to be dual to rank-3 logarithmic conformal field theories. We will show that, at linear order in the equations of motion, it is possible to truncate the theory to a unitary subsector. We also show that tricritical gravities in three and four dimensions suffer from a linearization instability that forbids unitary truncations beyond linear order. Finally we consider the role of boundary conditions in the AdS3/CFT2 correspondence. We show that free boundary conditions that lead to enhanced asymptotic symmetry groups are dual to 2D theories of quantum gravity in either the conformal or lightcone gauges. In particular we match the generators of symmetries in the bulk and boundary theories and show that a proper identification of the generator of Virasoro transformations in the bulk leads to a vanishing total central charge. We also show that this identification is consistent with the constraint equations of 2D gravity.

78 FR 78703 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... fatigue damage (WFD). This AD requires modifying the aft pressure bulkhead. The modification includes... fatigue cracking of the aft pressure bulkhead, which could result in reduced structural integrity of the... No. FAA-2013- 0706; or in person at the Docket Management Facility between 9 a.m. and 5 p.m., Monday...

Improvements to the FATOLA computer program including nosewheel steering: Supplemental instruction manual

NASA Technical Reports Server (NTRS)

Carden, H. D.; Mcgehee, J. R.

1978-01-01

Modifications to a multidegree of freedom flexible aircraft take-off and landing analysis (FATOLA) computer program, which improved its simulation capabilities, are discussed, and supplemental instructions for use of the program are included. Sample analytical results which illustrate the capabilities of an added nosewheel steering option indicate consistent behavior of the airplane tracking, attitude, motions, and loads for the landing cases and steering situations which were investigated.

Core outcome measures for interventions to prevent or slow the progress of dementia for people living with mild to moderate dementia: Systematic review and consensus recommendations

PubMed Central

Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O’Brien, John T.; Mountain, Gail; Woods, Bob; Perneczky, Robert; McCleery, Jenny; Pickett, James; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Jones, Roy; Schneider, Justine; Shepperd, Sasha; Thompson-Coon, Jo; Ballard, Clive; Burns, Alistair; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Robinson, Louise

2017-01-01

Background There are no disease-modifying treatments for dementia. There is also no consensus on disease modifying outcomes. We aimed to produce the first evidence-based consensus on core outcome measures for trials of disease modification in mild-to-moderate dementia. Methods and findings We defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer’s disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer’s society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification. Limitations Most trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties. Interpretation This is the first review to identify the 81 outcome measures the research community uses for disease-modifying trials in mild-to-moderate dementia. Our recommendations will facilitate designing, comparing and meta-analysing disease modification trials in mild-to-moderate dementia, increasing their value. Trial registration PROSPERO no. CRD42015027346. PMID:28662127

KSC-98pc1165

NASA Image and Video Library

1998-09-28

The orbiter Atlantis, being towed from the Shuttle Landing Facility, is reflected in waters from the Banana Creek next to the towway. The orbiter spent 10 months in Palmdale, CA, undergoing extensive inspections and modifications in the orbiter processing facility there. The modifications included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies

PubMed Central

Kontaxi, Christiana; Piccardo, Pedro; Gill, Andrew C.

2017-01-01

Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an “unfolded” conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation. We are only beginning to define the site-specific impact of each type of lysine modification on tau biology as well as the possible interplay between them, but, like phosphorylation, these modifications are likely to play critical roles in tau's normal and pathobiology. This review summarizes the latest findings focusing on lysine post-translational modifications that occur at both endogenous tau protein and pathological tau forms in AD and other tauopathies. In addition, it highlights the significance of a site-dependent approach of studying tau post-translational modifications under normal and pathological conditions. PMID:28848737

Overcoming translational barriers impeding development of Alzheimer's disease modifying therapies.

PubMed

Golde, Todd E

2016-10-01

It has now been ~ 30 years since the Alzheimer's disease (AD) research entered what may be termed the 'molecular era' that began with the identification of the amyloid β protein (Aβ) as the primary component of amyloid within senile plaques and cerebrovascular amyloid and the microtubule-associated protein tau as the primary component of neurofibrillary tangles in the AD brain. These pivotal discoveries and the subsequent genetic, pathological, and modeling studies supporting pivotal roles for tau and Aβ aggregation and accumulation have provided firm rationale for a new generation of AD therapies designed not to just provide symptomatic benefit, but as disease modifying agents that would slow or even reverse the disease course. Indeed, over the last 20 years numerous therapeutic strategies for disease modification have emerged, been preclinically validated, and advanced through various stages of clinical testing. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome barriers that are not major foci of current research efforts. Seminal discoveries made over the past 25 years have provided firm rationale for a new generation of Alzheimer's disease (AD) therapies designed as disease modifying agents that would slow or even reverse the disease course. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful AD disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome these barriers. This article is part of the 60th Anniversary special issue. © 2016 International Society for Neurochemistry.

Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer’s Disease

PubMed Central

Kassaar, Omar; Pereira Morais, Marta; Xu, Suying; Adam, Emily L.; Chamberlain, Rosemary C.; Jenkins, Bryony; James, Tony; Francis, Paul T.; Ward, Stephen; Williams, Robert J.; van den Elsen, Jean

2017-01-01

Glucose and glucose metabolites are able to adversely modify proteins through a non-enzymatic reaction called glycation, which is associated with the pathology of Alzheimer’s Disease (AD) and is a characteristic of the hyperglycaemia induced by diabetes. However, the precise protein glycation profile that characterises AD is poorly defined and the molecular link between hyperglycaemia and AD is unknown. In this study, we define an early glycation profile of human brain using fluorescent phenylboronate gel electrophoresis and identify early glycation and oxidation of macrophage migration inhibitory factor (MIF) in AD brain. This modification inhibits MIF enzyme activity and ability to stimulate glial cells. MIF is involved in immune response and insulin regulation, hyperglycaemia, oxidative stress and glycation are all implicated in AD. Our study indicates that glucose modified and oxidised MIF could be a molecular link between hyperglycaemia and the dysregulation of the innate immune system in AD. PMID:28230058

78 FR 79333 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

...We propose to supersede airworthiness directive (AD) 2000-12- 12, for certain Airbus Model A300, A300-600, and A310 series airplanes. AD 2000-12-12 currently requires inspecting to detect cracks in the lower spar axis of the nacelle pylon between ribs 9 and 10, and repair if necessary. AD 2000-12-12 also provides for optional modification of the pylon, which terminates the inspections for Model A300 series airplanes. Since we issued AD 2000-12-12, we have received reports of cracking of the lower pylon spar after accomplishing the existing modification and have determined that shorter initial and repetitive inspection compliance times are necessary to address the identified unsafe condition. This proposed AD would reduce the initial and repetitive inspection compliance times. We are proposing this AD to detect and correct fatigue cracking, which could result in reduced structural integrity of the lower spar of the nacelle pylon.

A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer’s disease and loss of memory in women: design and baseline characteristics

PubMed Central

Sano, Mary; Jacobs, Diane; Andrews, Howard; Bell, Karen; Graff-Radford, Neill; Lucas, John; Rabins, Peter; Bolla, Karen; Tsai, Wei-Yan; Cross, Peter; Andrews, Karen; Costa, Rosann; Luo, Xiaodong

2012-01-01

Background Observational studies and small clinical trials suggested that hormone replacement therapy (HRT) decreases risk of cognitive loss and Alzheimer’s disease (AD) in postmenopausal women and may have value in primary prevention. Purpose A clinical trial was designed to determine if HRT delays AD or memory loss. This report describes the rationale and original design of the trial and details extensive modifications that were required to respond to unanticipated findings that emerged from other studies during the course of the trial. Methods The trial was designed as a multi-center, placebo-controlled primary prevention trial for women 65 years of age or older with a family history of dementia. Recruitment from local sites was supplemented by centralized efforts to use names of Medicare beneficiaries. Inclusion criteria included good general health and intact memory functioning. Participants were randomized to HRT or placebo in a 1:1 ratio. Assignment was stratified by hysterectomy status and site. The primary outcomes were incident AD and memory decline on neuropsychological testing. Results Enrollment began in March 1998. In response to the Women’s Health Initiative (WHI) May 2002 report of increased incidence of heart disease, stroke, pulmonary embolism, and breast cancer among women randomized to HRT, participants were re-consented with a revised consent form. Procedural modifications, including discontinuation of study medication and a modification of the planned primary outcome based on a final enrollment below the target enrollment (N = 477), were enacted in response to the subsequent WHI Memory Study report of increased risk of dementia and poorer cognitive function with HRT. The mean length of treatment exposure prior to discontinuation was 2.14 years. Participants’ mean age at baseline was 72.8; mean education was 14.2 years. Minority participation was 19% and 34% had a hysterectomy. The study continues to follow these participants for a total of 5 years blind to the original medication assignment. Limitations Results reported from the WHI during the course of this study mandated extensive procedural modifications, including discontinuing recruitment before completion and halting study medication. Alternative strategies for study redesign that were considered are discussed. PMID:18827045

Immirzi parameter and Noether charges in first order gravity

NASA Astrophysics Data System (ADS)

Durka, Remigiusz

2012-02-01

The framework of SO(3,2) constrained BF theory applied to gravity makes it possible to generalize formulas for gravitational diffeomorphic Noether charges (mass, angular momentum, and entropy). It extends Wald's approach to the case of first order gravity with a negative cosmological constant, the Holst modification and the topological terms (Nieh-Yan, Euler, and Pontryagin). Topological invariants play essential role contributing to the boundary terms in the regularization scheme for the asymptotically AdS spacetimes, so that the differentiability of the action is automatically secured. Intriguingly, it turns out that the black hole thermodynamics does not depend on the Immirzi parameter for the AdS-Schwarzschild, AdS-Kerr, and topological black holes, whereas a nontrivial modification appears for the AdS-Taub-NUT spacetime, where it impacts not only the entropy, but also the total mass.

A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

PubMed

Fonseca, Jairo Andres; Cabrera-Mora, Monica; Kashentseva, Elena A; Villegas, John Paul; Fernandez, Alejandra; Van Pelt, Amelia; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

2016-01-01

A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR) of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity and protective efficacy of adenoviral based malaria vaccines.

78 FR 21230 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... Failed Post-Modification Operational Test After accomplishment of the modification specified in paragraph... of the GFI or deactivation of the associated fuel pump following failure of any post-modification operational test of the GFI. We are issuing this AD to prevent the potential of ignition sources inside fuel...

Imaging epigenetics in Alzheimer's disease.

PubMed

Lista, Simone; Garaci, Francesco G; Toschi, Nicola; Hampel, Harald

2013-01-01

Sporadic Alzheimer's disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and behavioral decline. This decline includes reductions in the activities of daily living, quality of life, independence, and life expectancy. Evolving lines of research suggest that epigenetic mechanisms may play a crucial role during AD development and progression. Epigenetics designates molecular mechanisms that alter gene expression without modifications of the genetic code. This topic includes modifications on DNA and histone proteins, the primary elements of chromatin structure. Accumulating evidence has revealed the relevant processes that mediate epigenetic modifications and has begun to elucidate how these processes are apparently dysregulated in AD. This evidence has led to the clarification of the roles of specific classes of therapeutic compounds that affect epigenetic pathways and characteristics of the epigenome. This insight is accompanied by the development of new methods for studying the global patterns of DNA methylation and chromatin alterations. In particular, high-throughput sequencing approaches, such as next-generation DNA sequencing techniques, are beginning to drive the field into the next stage of development. In parallel, genetic imaging is beginning to answer additional questions through its ability to uncover genetic variants, with or without genome-wide significance, that are related to brain structure, function and metabolism, which impact disease risk and fundamental network-based cognitive processes. Neuroimaging measures can further be used to define AD systems and endophenotypes. The integration of genetic neuroimaging methods with epigenetic markers in humans appears promising. This evolving development may lead to a new research discipline - imaging epigenetics - that will provide deeper insight into the causative pathogenetic and pathophysiological pathways through which genes and environment interrelate during life and impact human brain development, physiology, aging and disease. This knowledge may open doors for the development of novel biomarkers and preventive and disease-modifying treatments.

Epigenetics Mechanisms in Alzheimer’s disease

PubMed Central

Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul D.; Rogers, Joseph

2011-01-01

Epigenetic modifications help orchestrate sweeping developmental, aging, and disease-causing changes in phenotype by altering transcriptional activity in multiple genes spanning multiple biologic pathways. Although previous epigenetic research has focused primarily on dividing cells, particularly in cancer, recent studies have shown rapid, dynamic, and persistent epigenetic modifications in neurons that have significant neuroendocrine, neurophysiologic, and neurodegenerative consequences. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and Alzheimer’s disease (AD). Because of their reach across the genome, epigenetic mechanisms may provide a unique integrative framework for the pathologic diversity and complexity of AD. PMID:21482442

KSC-98pc1166

NASA Image and Video Library

1998-09-28

The orbiter Atlantis, being towed from the Shuttle Landing Facility toward the Vehicle Assembly Building (VAB) , intersects the morning sun's rays. In the background, to the right of the VAB, are the Orbiter Processing Facility 1 and 2. Atlantis spent 10 months in Palmdale, CA, undergoing extensive inspections and modifications in the orbiter processing facility there. The modifications included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. Atlantis will undergo preparations at KSC in Orbiter Processing Facility 2 for its planned flight in June 1999

Enhanced capabilities and modified users manual for axial-flow compressor conceptual design code CSPAN

NASA Technical Reports Server (NTRS)

Glassman, Arthur J.; Lavelle, Thomas M.

1995-01-01

Modifications made to the axial-flow compressor conceptual design code CSPAN are documented in this report. Endwall blockage and stall margin predictions were added. The loss-coefficient model was upgraded. Default correlations for rotor and stator solidity and aspect-ratio inputs and for stator-exit tangential velocity inputs were included in the code along with defaults for aerodynamic design limits. A complete description of input and output along with sample cases are included.

78 FR 3367 - Modification of Regulation Regarding the Extension of Time Limits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

...-2747-01] RIN 0625-AA94 Modification of Regulation Regarding the Extension of Time Limits AGENCY: Import... the extension of time limits for submissions in antidumping (AD) and countervailing duty (CVD) proceedings. The modification, if adopted, will clarify that parties may request an extension of time limits...

Versatile and Rapid Postfunctionalization from Cyclodextrin Modified Host Polymeric Membrane Substrate.

PubMed

Deng, Jie; Liu, Xinyue; Zhang, Shuqing; Cheng, Chong; Nie, Chuanxiong; Zhao, Changsheng

2015-09-08

Surface modification has long been of great interest to impart desired functionalities to the bioimplants. However, due to the limitations of recent technologies in surface modification, it is highly desirable to explore novel protocols, which can advantageously and efficiently endow the inert material surfaces with versatile biofunctionalities. Herein, to achieve versatile and rapid postfunctionalization of polymeric membrane, we demonstrate a new strategy for the fabrication of β-cyclodextrin (β-CD) modified host membrane substrate that can recognize a series of well-designed guest macromolecules. The surface assembly procedure was driven by the host-guest interaction between adamantane (Ad) and β-CD. β-CD immobilized host membrane was fabricated via two steps: (1) epoxy groups enriched poly(ether sulfone) (PES) membrane was first prepared via in situ cross-linking polymerization and subsequently phase separation; (2) mono-6-deoxy-6-ethylenediamine-β-CD (EDA-β-CD) was then anchored onto the surface of the epoxy functionalized PES membrane to obtain PES-CD. Subsequently, three types of Ad-terminated polymers, including Ad-poly(styrenesulfonate-co-sodium acrylate) (Ad-PSA), Ad-methoxypoly(ethylene glycol) (Ad-PEG), and Ad-poly(methyl chloride-quaternized 2-(dimethylamino)ethyl methacrylate (Ad-PMT), were separately assembled onto the β-CD immobilized surfaces to endow the membranes with anticoagulant, antifouling, and antibacterial capability, respectively. Activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) measurements were carried out to explore the anticoagulant activity. The antifouling capability was evaluated via protein adsorption and platelet adhesion measurements. Moreover, Staphyllococcous aureus (S. aureus) was selected as model bacteria to evaluate the antibacterial ability of the functionalized membranes. The results indicated that well-regulated blood compatibility, antifouling capability, and bactericidal activity could be achieved by the proposed rapid postfunctionalization on polymeric membranes. This approach of versatile and rapid postfunctionalization is promising for the preparation of multifunctional polymeric membrane materials to meet with various demands for the further applications.

Recall of health warnings in smokeless tobacco ads

PubMed Central

Truitt, L; Hamilton, W; Johnston, P; Bacani, C; Crawford, S; Hozik, L; Celebucki, C

2002-01-01

Design: Subjects examined two distracter ads and one of nine randomly assigned smokeless tobacco ads varying in health warning presence, size (8 to 18 point font), and contrast (low versus high)—including no health warning. They were then interviewed about ad content using recall and recognition questions. Subjects: A convenience sample of 895 English speaking males aged 16–24 years old who were intercepted at seven shopping malls throughout Massachusetts during May 2000. Main outcome measures: Proven aided recall, or recall of a health warning and correct recognition of the warning message among distracters, and false recall. Results: Controlling for covariates such as education, employment/student status, and Hispanic background, proven aided recall increased significantly with font size; doubling size from 10 to 20 point font would increase recall from 63% to 76%. Although not statistically significant, recall was somewhat better for high contrast warnings. Ten per cent of the sample mistakenly recalled the warning where none existed. Conclusions: As demonstrated by substantially greater recall among ads that included health warnings over ads that had none, health warnings retained their value to consumers despite years of exposure (that can produce false recall). Larger health warnings would enhance recall, and the proposed model can be used to estimate potential recall that affects communication, perceived health risk, and behaviour modification. PMID:12034984

Epigenetics: A novel therapeutic approach for the treatment of Alzheimer’s disease

PubMed Central

Adwan, Lina; Zawia, Nasser H.

2013-01-01

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field. PMID:23562602

Aptamer modification improves the adenoviral transduction of malignant glioma cells.

PubMed

Chen, Hao; Zheng, Xiaojing; Di, BingYan; Wang, Dongyang; Zhang, Yaling; Xia, Haibin; Mao, Qinwen

2013-12-01

Adenovirus has shown increasing promise in the gene-viral therapy for glioblastoma, a treatment strategy that relies on the delivery of viruses or transgenes into tumor cells. However, targeting of adenovirus to human glioblastoma remains a challenge due to the low expression level of coxsackie and adenovirus receptor (CAR) in glioma cells. Aptamers are small and highly structured single-stranded oligonucleotides that bind at high affinity to a target molecule, and are good candidates for targeted imaging and therapy. In this study, to construct an aptamer-modified Ad5, we first genetically modified the HVR5 of Ad hexon by biotin acceptor peptide (BAP), which would be metabolically biotinylated during production in HEK293 cells, and then attached the biotin labeled aptamer to the modified Ad through avidin–biotin binding. The aptamers used in this study includes AS1411 and GBI-10. The former is a DNA aptamer that can bind to nucleolin, a nuclear matrix protein found on the surface of cancer cells. The latter is a DNA aptamer that can recognize the extracellular matrix protein tenascin-C on the surface of human glioblastoma cells. To examine if aptamer-modification of the hexon protein could improve the adenoviral transduction efficiency, a glioblastoma cell line, U251, was transduced with aptamer-modified Ads. The transduction efficiency of AS1411- or GBI-10-modified Ad was approximately 4.1-fold or 5.2-fold higher than that of the control. The data indicated that aptamer modified adenovirus would be a useful tool for cancer gene therapy. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Medical foods for Alzheimer's disease.

PubMed

Shah, Raj C

2011-06-01

Alzheimer's disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary foodstuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better understanding of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65 years and supplemented by other articles known to meet the inclusion criteria, revealed that only two medical foods, AC-1202 and Souvenaid® with Fortasyn Connect™, have clinical trial results available for discussion. As medical food development for AD is a relatively new endeavour, a window of opportunity exists for all stakeholders to develop a comprehensive framework for assuring that medical food interventions for AD achieve the highest possible scientific and ethical standards to warrant commercialization.

Recall of health warnings in smokeless tobacco ads.

PubMed

Truitt, Linda; Hamilton, William L; Johnston, P R; Bacani, C P; Crawford, S O; Hozik, L; Celebucki, Carolyn

2002-06-01

To determine the effects of health warning characteristics in smokeless tobacco magazine print ads on warning recall, and the implications for current US Federal regulations. Subjects examined two distracter ads and one of nine randomly assigned smokeless tobacco ads varying in health warning presence, size (8 to 18 point font), and contrast (low versus high)-including no health warning. They were then interviewed about ad content using recall and recognition questions. A convenience sample of 895 English speaking males aged 16-24 years old who were intercepted at seven shopping malls throughout Massachusetts during May 2000. Proven aided recall, or recall of a health warning and correct recognition of the warning message among distracters, and false recall. Controlling for covariates such as education, employment/student status, and Hispanic background, proven aided recall increased significantly with font size; doubling size from 10 to 20 point font would increase recall from 63% to 76%. Although not statistically significant, recall was somewhat better for high contrast warnings. Ten per cent of the sample mistakenly recalled the warning where none existed. As demonstrated by substantially greater recall among ads that included health warnings over ads that had none, health warnings retained their value to consumers despite years of exposure (that can produce false recall). Larger health warnings would enhance recall, and the proposed model can be used to estimate potential recall that affects communication, perceived health risk, and behaviour modification.

76 FR 81889 - Airworthiness Directives; Saab AB, Saab Aerosystems Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... Aerosystems Model SAAB 2000 airplanes. This proposed AD was prompted by reports of hydraulic accumulator failure. This proposed AD would require replacing certain hydraulic accumulators with stainless steel hydraulic accumulators, and structural modifications in the nose landing gear bay. We are proposing this AD...

77 FR 43545 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... Bombardier, Inc. Model DHC-8-400 series airplanes. The existing AD currently requires a modification to trim... the MLG tires, Bombardier Aerospace has developed a modification to trim the edge of the bumper plate...

Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.

PubMed

Wang, Sheng; Yang, Feng; Petyuk, Vladislav A; Shukla, Anil K; Monroe, Matthew E; Gritsenko, Marina A; Rodland, Karin D; Smith, Richard D; Qian, Wei-Jun; Gong, Cheng-Xin; Liu, Tao

2017-09-01

Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature. Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry. A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain. One hundred and thirty-one O-GlcNAc peptides covering 81 proteins were altered in AD brains as compared with controls (q < 0.05). Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes. The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins. These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

77 FR 47273 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

... the autopilot electrical wiring conduit and the wing bottom skin. This AD requires modifying the wiring installation on the right-hand wing. We are issuing this AD to prevent sparking due to electrical... above, this [EASA] AD requires modification of the wiring installation to improve the routing and the...

Flight performance summary for three NASA Terrier-Malemute II sounding rockets

NASA Technical Reports Server (NTRS)

Patterson, R. A.

1982-01-01

The subject of this paper is the presentation of flight data for three Terrier-Malemute II sounding rocket vehicles. The Malemute motor was modified by adding insulation and using a propellant that produced less Al2O3 agglomerate in the chamber. This modification, designated Malemute II, reduced the sensitivity of the motor to the roll rate induced motor case burnthrough experienced on some earlier Malemute flights. Two flight tests, including a single stage Malemute II and a Terrier-Malemute II, were made by Sandia to qualify this modification. The three NASA operational flights that are the subject of this paper were made using the modified Malemute II motors.

KSC-98pc1167

NASA Image and Video Library

1998-09-28

Seen from behind, the orbiter Atlantis approaches the entrance of Orbiter Processing Facility 2 (OPF-2) where it will undergo preparations for its planned flight in June 1999. Atlantis spent 10 months in Palmdale, CA, undergoing extensive inspections and modifications in the orbiter processing facility there. The modifications included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. OPF-2 consists of a 2,700-square-meter (29,000 square ft.) high bay. The building measures 29 meters (95 ft). high, 121 meters (397 ft.) long and 71 meters (233 ft.) wide

KSC-98pc1168

NASA Image and Video Library

1998-09-28

Seen from behind, the orbiter Atlantis moves into the Orbiter Processing Facility 2 (OPF-2) where it will undergo preparations for its planned flight in June 1999. Atlantis spent 10 months in Palmdale, CA, undergoing extensive inspections and modifications in the orbiter processing facility there. The modifications included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. OPF-2 consists of two 2,700-square-meter (29,000 square feet) high bays. It measures 29 meters (95 ft). high, 121 meters (397 ft) long and 71 meters (233 ft) wide

Tracking techniques for space shuttle rendezvous

NASA Technical Reports Server (NTRS)

1975-01-01

The space shuttle rendezvous radar has a requirement to track cooperative and non-cooperative targets. For this reason the Lunar Module (LM) Rendezvous Radar was modified to incorporate the capability of tracking a non-cooperative target. The modifications are discussed. All modifications except those relating to frequency diversity were completed, and system tests were performed to confirm proper performance in the non-cooperative mode. Frequency diversity was added to the radar and to the special test equipment, and then system tests were performed. This last set of tests included re-running the tests of the non-cooperative mode without frequency diversity, followed by tests with frequency diversity and tests of operation in the original cooperative mode.

Modification of chemical reactivity of enzymatic hydrolysis lignin by ultrasound treatment in dilute alkaline solutions.

PubMed

Ma, Zhuoming; Li, Shujun; Fang, Guizhen; Patil, Nikhil; Yan, Ning

2016-12-01

In this study, we have explored various ultrasound treatment conditions for structural modification of enzymatic hydrolysis lignin (EHL) for enhanced chemical reactivity. The key structural modifications were characterized by using a combination of analytical methods, including, Fourier Transform-Infrared spectroscopy (FTIR), Proton Nuclear Magnetic Resonance ( 1 H NMR), Gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS), and Folin-Ciocalteu (F-C) method. Chemical reactivity of the modified EHL samples was determined by both 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and their reactivity towards formaldehyde. It was observed that the modified EHL had a higher phenolic hydroxyl group content, a lower molecular weight, a higher reactivity towards formaldehyde, and a greater antioxidant property. The higher reactivity demonstrated by the samples after treatment suggesting that ultrasound is a promising method for modifying enzymatic hydrolysis lignin for value-added applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Phase space effects on fast ion distribution function modeling in tokamaks

NASA Astrophysics Data System (ADS)

Podestà, M.; Gorelenkova, M.; Fredrickson, E. D.; Gorelenkov, N. N.; White, R. B.

2016-05-01

Integrated simulations of tokamak discharges typically rely on classical physics to model energetic particle (EP) dynamics. However, there are numerous cases in which energetic particles can suffer additional transport that is not classical in nature. Examples include transport by applied 3D magnetic perturbations and, more notably, by plasma instabilities. Focusing on the effects of instabilities, ad-hoc models can empirically reproduce increased transport, but the choice of transport coefficients is usually somehow arbitrary. New approaches based on physics-based reduced models are being developed to address those issues in a simplified way, while retaining a more correct treatment of resonant wave-particle interactions. The kick model implemented in the tokamak transport code TRANSP is an example of such reduced models. It includes modifications of the EP distribution by instabilities in real and velocity space, retaining correlations between transport in energy and space typical of resonant EP transport. The relevance of EP phase space modifications by instabilities is first discussed in terms of predicted fast ion distribution. Results are compared with those from a simple, ad-hoc diffusive model. It is then shown that the phase-space resolved model can also provide additional insight into important issues such as internal consistency of the simulations and mode stability through the analysis of the power exchanged between energetic particles and the instabilities.

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

Podesta, M.; Gorelenkova, M.; Fredrickson, E. D.

Here, integrated simulations of tokamak discharges typically rely on classical physics to model energetic particle (EP) dynamics. However, there are numerous cases in which energetic particles can suffer additional transport that is not classical in nature. Examples include transport by applied 3D magnetic perturbations and, more notably, by plasma instabilities. Focusing on the effects of instabilities,ad-hocmodels can empirically reproduce increased transport, but the choice of transport coefficients is usually somehow arbitrary. New approaches based on physics-based reduced models are being developed to address those issues in a simplified way, while retaining a more correct treatment of resonant wave-particle interactions. Themore » kick model implemented in the tokamaktransport code TRANSP is an example of such reduced models. It includes modifications of the EP distribution by instabilities in real and velocity space, retaining correlations between transport in energy and space typical of resonant EP transport. The relevance of EP phase space modifications by instabilities is first discussed in terms of predicted fast ion distribution. Results are compared with those from a simple, ad-hoc diffusive model. It is then shown that the phase-space resolved model can also provide additional insight into important issues such as internal consistency of the simulations and mode stability through the analysis of the power exchanged between energetic particles and the instabilities.« less

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

Podestà, M., E-mail: mpodesta@pppl.gov; Gorelenkova, M.; Fredrickson, E. D.

Integrated simulations of tokamak discharges typically rely on classical physics to model energetic particle (EP) dynamics. However, there are numerous cases in which energetic particles can suffer additional transport that is not classical in nature. Examples include transport by applied 3D magnetic perturbations and, more notably, by plasma instabilities. Focusing on the effects of instabilities, ad-hoc models can empirically reproduce increased transport, but the choice of transport coefficients is usually somehow arbitrary. New approaches based on physics-based reduced models are being developed to address those issues in a simplified way, while retaining a more correct treatment of resonant wave-particle interactions.more » The kick model implemented in the tokamak transport code TRANSP is an example of such reduced models. It includes modifications of the EP distribution by instabilities in real and velocity space, retaining correlations between transport in energy and space typical of resonant EP transport. The relevance of EP phase space modifications by instabilities is first discussed in terms of predicted fast ion distribution. Results are compared with those from a simple, ad-hoc diffusive model. It is then shown that the phase-space resolved model can also provide additional insight into important issues such as internal consistency of the simulations and mode stability through the analysis of the power exchanged between energetic particles and the instabilities.« less

Phase space effects on fast ion distribution function modeling in tokamaks

DOE Data Explorer

White, R. B. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Podesta, M. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Gorelenkova, M. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Fredrickson, E. D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Gorelenkov, N. N. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)

2016-06-01

Integrated simulations of tokamak discharges typically rely on classical physics to model energetic particle (EP) dynamics. However, there are numerous cases in which energetic particles can suffer additional transport that is not classical in nature. Examples include transport by applied 3D magnetic perturbations and, more notably, by plasma instabilities. Focusing on the effects of instabilities, ad-hoc models can empirically reproduce increased transport, but the choice of transport coefficients is usually somehow arbitrary. New approaches based on physics-based reduced models are being developed to address those issues in a simplified way, while retaining a more correct treatment of resonant wave-particle interactions. The kick model implemented in the tokamak transport code TRANSP is an example of such reduced models. It includes modifications of the EP distribution by instabilities in real and velocity space, retaining correlations between transport in energy and space typical of resonant EP transport. The relevance of EP phase space modifications by instabilities is first discussed in terms of predicted fast ion distribution. Results are compared with those from a simple, ad-hoc diffusive model. It is then shown that the phase-space resolved model can also provide additional insight into important issues such as internal consistency of the simulations and mode stability through the analysis of the power exchanged between energetic particles and the instabilities.

Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones.

PubMed

Fosso, Marina Y; LeVine, Harry; Green, Keith D; Tsodikov, Oleg V; Garneau-Tsodikova, Sylvie

2015-09-28

As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu(2+)/Zn(2+), while others were effective at inhibiting the action of AChE.

77 FR 76516 - Notice of Availability of the Record of Decision for the Federal Coal Lease Modifications COC...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

...] Notice of Availability of the Record of Decision for the Federal Coal Lease Modifications COC-1362 and... INFORMATION: The ROD covered by this Notice of Availability (NOA) is for modification Federal coal leases in..., to modify Mountain Coal Company's existing Federal coal lease COC-1362 by adding 921 acres and the...

The evolution of adenoviral vectors through genetic and chemical surface modifications.

PubMed

Capasso, Cristian; Garofalo, Mariangela; Hirvinen, Mari; Cerullo, Vincenzo

2014-02-17

A long time has passed since the first clinical trial with adenoviral (Ad) vectors. Despite being very promising, Ad vectors soon revealed their limitations in human clinical trials. The pre-existing immunity, the marked liver tropism and the high toxicity of first generation Ad (FG-Ad) vectors have been the main challenges for the development of new approaches. Significant effort toward the development of genetically and chemically modified adenoviral vectors has enabled researchers to create more sophisticated vectors for gene therapy, with an improved safety profile and a higher transduction ability of different tissues. In this review, we will describe the latest findings in the high-speed, evolving field of genetic and chemical modifications of adenoviral vectors, a field in which different disciplines, such as biomaterial research, virology and immunology, co-operate synergistically to create better gene therapy tools for modern challenges.

The impact of teachers’ modifications of an evidenced-based HIV prevention intervention on program outcomes

PubMed Central

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2015-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade six students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers’ modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25% or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers’ level of implementation. We conclude that poorer student outcomes were associated with heavy modifications. PMID:26297497

The Impact of Teachers' Modifications of an Evidenced-Based HIV Prevention Intervention on Program Outcomes.

PubMed

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2016-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade 6 students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers' modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25 % or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, and shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers' level of implementation. We conclude that poorer student outcomes were associated with heavy modifications.

Genetic Techniques for Manipulation of the Phytosterol Biotransformation Strain Mycobacterium neoaurum NRRL B-3805.

PubMed

Loraine, Jessica K; Smith, Margaret C M

2017-01-01

Mycobacterium neoaurum is a saprophytic, soil-dwelling bacterium. The strain NRRL B-3805 converts phytosterols to androst-4-ene-3,17-dione (androstenedione; AD), a precursor of multiple C19 steroids of importance to industry. NRRL B-3805 itself is able to convert AD to other steroid products, including testosterone (Ts) and androst-1,4-diene-3,17-dione (androstadienedione; ADD). However to improve this strain for industrial use, genetic modification is a priority. In this chapter, we describe a range of genetic techniques that can be used for M. neoaurum NRRL B-3805. Methods for transformation, expression, and gene knockouts are presented as well as plasmid maintenance and stability.

The RNA polymerase II CTD coordinates transcription and RNA processing

PubMed Central

Hsin, Jing-Ping; Manley, James L.

2012-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit consists of multiple heptad repeats (consensus Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7), varying in number from 26 in yeast to 52 in vertebrates. The CTD functions to help couple transcription and processing of the nascent RNA and also plays roles in transcription elongation and termination. The CTD is subject to extensive post-translational modification, most notably phosphorylation, during the transcription cycle, which modulates its activities in the above processes. Therefore, understanding the nature of CTD modifications, including how they function and how they are regulated, is essential to understanding the mechanisms that control gene expression. While the significance of phosphorylation of Ser2 and Ser5 residues has been studied and appreciated for some time, several additional modifications have more recently been added to the CTD repertoire, and insight into their function has begun to emerge. Here, we review findings regarding modification and function of the CTD, highlighting the important role this unique domain plays in coordinating gene activity. PMID:23028141

77 FR 731 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-06

... mechanism of the horizontal stabilizer trim actuator (HSTA). This AD requires repetitive inspections... trim actuator of the horizontal stabilizer; various modification(s); and corrective actions if... the ball nut and ballscrew and attachment (Gimbal) fittings for the trim actuator of the horizontal...

Empirical Examinations of Modifications and Adaptations to Evidence-Based Psychotherapies: Methodologies, Impact, and Future Directions.

PubMed

Stirman, Shannon Wiltsey; Gamarra, Jennifer; Bartlett, Brooke; Calloway, Amber; Gutner, Cassidy

2017-12-01

This review describes methods used to examine the modifications and adaptations to evidence-based psychological treatments (EBPTs), assesses what is known about the impact of modifications and adaptations to EBPTs, and makes recommendations for future research and clinical care. One hundred eight primary studies and three meta-analyses were identified. All studies examined planned adaptations, and many simultaneously investigated multiple types of adaptations. With the exception of studies on adding or removing specific EBPT elements, few studies compared adapted EBPTs to the original protocols. There was little evidence that adaptations in the studies were detrimental, but there was also limited consistent evidence that adapted protocols outperformed the original protocols, with the exception of adding components to EBPTs. Implications for EBPT delivery and future research are discussed.

77 FR 58002 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... Airworthiness Directives; Turbomeca S.A. Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT... Turbomeca S.A. Arriel 2B and 2B1 turboshaft engines. That AD currently requires accomplishment of the TU166 modification. This new AD requires adding the Arriel 2S2 and 2C2 engines to the applicability of engines...

Investigate optimum way of adding wideband capability and recommend a design for modification of one government furnished AM baseband demultiplexer, phase 1

NASA Technical Reports Server (NTRS)

1972-01-01

The effort to analyze and test the Teledyne/Adcom model G-146 demultiplexer to determine the feasibility and optimum method(s) for modifying the unit for broadband operation is described. The desired bandwidths under consideration included 2, 4, and 8 kHz for double sideband and quadrature double sideband, and 4, 8, and 16 kHz for single sideband.

Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease.

PubMed

Di Domenico, Fabio; Pupo, Gilda; Tramutola, Antonella; Giorgi, Alessandra; Schininà, Maria Eugenia; Coccia, Raffaella; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

2014-06-01

Down syndrome (DS) is the most common genetic cause of intellectual disability, due to partial or complete triplication of chromosome 21. DS subjects are characterized by a number of abnormalities including premature aging and development of Alzheimer disease (AD) neuropathology after approximately 40 years of age. Several studies show that oxidative stress plays a crucial role in the development of neurodegeneration in the DS population. Increased lipid peroxidation is one of the main events causing redox imbalance within cells through the formation of toxic aldehydes that easily react with DNA, lipids, and proteins. In this study we used a redox proteomics approach to identify specific targets of 4-hydroxynonenal modifications in the frontal cortex from DS cases with and without AD pathology. We suggest that a group of identified proteins followed a specific pattern of oxidation in DS vs young controls, probably indicating characteristic features of the DS phenotype; a second group of identified proteins showed increased oxidation in DS/AD vs DS, thus possibly playing a role in the development of AD. The third group of comparison, DS/AD vs old controls, identified proteins that may be considered specific markers of AD pathology. All the identified proteins are involved in important biological functions including intracellular quality control systems, cytoskeleton network, energy metabolism, and antioxidant response. Our results demonstrate that oxidative damage is an early event in DS, as well as dysfunctions of protein-degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to oxidative damage accumulation that might contribute to AD development. Further, considering that the majority of proteins have been already demonstrated to be oxidized in AD brain, our results strongly support similarities with AD in DS. Copyright © 2014 Elsevier Inc. All rights reserved.

Disclosing Pleiotropic Effects during Genetic Risk Assessment for Alzheimer’s Disease: A Randomized, Controlled Trial

PubMed Central

Christensen, Kurt D.; Roberts, J. Scott; Whitehouse, Peter J.; Royal, Charmaine D. M.; Obisesan, Thomas O.; Cupples, L. Adrienne; Vernarelli, Jacqueline A.; Bhatt, Deepak L.; Linnenbringer, Erin; Butson, Melissa B.; Fasaye, Grace-Ann; Uhlmann, Wendy R.; Hiraki, Susan; Wang, Na; Cook-Deegan, Robert; Green, Robert C.

2016-01-01

Background Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective To determine the safety and behavioral impact of disclosing modest associations between APOE genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer’s disease (AD). Design Randomized, multicenter equivalence clinical trial Setting Four teaching hospitals Participants 257 asymptomatic adults enrolled, 69% with one AD-affected first degree relative Intervention Disclosing AD and CAD genetic risk information (AD+CAD) versus disclosing only AD genetic risk (AD-only) Measurements Co-primary outcomes were Beck Anxiety Index (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes included test-related distress at 12 months, all measures at 6 weeks and 6 months, and health behavior changes at 12 months. Results 12 months after disclosure, mean BAI scores were 3.5 and 3.5 in AD-only and AD+CAD arms (Δ=0.0, 95%CI: −1.0 to 1.0), and mean CES-D scores were 6.4 and 7.1 in AD-only and AD+CAD arms (Δ=0.7, 95%CI: −1.0 to 2.4). Both confidence bounds fell within the equivalence margin of +/−5 points. Among ε4-positive participants, distress was lower in AD+CAD arms than AD-only arms (Δ=−4.8, 95%CI: −8.6 to −1.0) (p=0.031 for disclosure arm x APOE genotype). AD+CAD participants also reported more health behavior changes, regardless of APOE genotype. Limitations Outcomes were self-reported from volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomized participants. Conclusion Disclosing pleiotropic information did not increase anxiety or depression, and may have decreased distress among those at increased risk for two conditions. Providing risk modification information regarding CAD improved health behaviors. Findings highlight potential benefits of secondary genetic findings disclosure when options exist for decreasing risk. PMID:26810768

Possible modification of Alzheimer's disease by statins in midlife: interactions with genetic and non-genetic risk factors.

PubMed

Shinohara, Mitsuru; Sato, Naoyuki; Shimamura, Munehisa; Kurinami, Hitomi; Hamasaki, Toshimitsu; Chatterjee, Amarnath; Rakugi, Hiromi; Morishita, Ryuichi

2014-01-01

The benefits of statins, commonly prescribed for hypercholesterolemia, in treating Alzheimer's disease (AD) have not yet been fully established. A recent randomized clinical trial did not show any therapeutic effects of two statins on cognitive function in AD. Interestingly, however, the results of the Rotterdam study, one of the largest prospective cohort studies, showed reduced risk of AD in statin users. Based on the current understanding of statin actions and AD pathogenesis, it is still worth exploring whether statins can prevent AD when administered decades before the onset of AD or from midlife. This review discusses the possible beneficial effects of statins, drawn from previous clinical observations, pathogenic mechanisms, which include β-amyloid (Aβ) and tau metabolism, genetic and non-genetic risk factors (apolipoprotein E, cholesterol, sex, hypertension, and diabetes), and other clinical features (vascular dysfunction and oxidative and inflammatory stress) of AD. These findings suggest that administration of statins in midlife might prevent AD in late life by modifying genetic and non-genetic risk factors for AD. It should be clarified whether statins inhibit Aβ accumulation, tau pathological features, and brain atrophy in humans. To answer this question, a randomized controlled study using amyloid positron emission tomography (PET), tau-PET, and magnetic resonance imaging would be useful. This clinical evaluation could help us to overcome this devastating disease.

Characteristic profiles of DNA epigenetic modifications in colon cancer and its predisposing conditions-benign adenomas and inflammatory bowel disease.

PubMed

Dziaman, Tomasz; Gackowski, Daniel; Guz, Jolanta; Linowiecka, Kinga; Bodnar, Magdalena; Starczak, Marta; Zarakowska, Ewelina; Modrzejewska, Martyna; Szpila, Anna; Szpotan, Justyna; Gawronski, Maciej; Labejszo, Anna; Liebert, Ariel; Banaszkiewicz, Zbigniew; Klopocka, Maria; Foksinski, Marek; Marszalek, Andrzej; Olinski, Ryszard

2018-01-01

Active demethylation of 5-methyl-2'-deoxycytidine (5-mdC) in DNA occurs by oxidation to 5-(hydroxymethyl)-2'-deoxycytidine (5-hmdC) and further oxidation to 5-formyl-2'-deoxycytidine (5-fdC) and 5-carboxy-2'-deoxycytidine (5-cadC), and is carried out by enzymes of the ten-eleven translocation family (TETs 1, 2, 3). Decreased level of epigenetic DNA modifications in cancer tissue may be a consequence of reduced activity/expression of TET proteins. To determine the role of epigenetic DNA modifications in colon cancer development, we analyzed their levels in normal colon and various colonic pathologies. Moreover, we determined the expressions of TETs at mRNA and protein level.The study included material from patients with inflammatory bowel disease (IBD), benign polyps (AD), and colorectal cancer (CRC). The levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in examined tissues were determined by means of isotope-dilution automated online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS). The expressions of TET mRNA were measured with RT-qPCR, and the expressions of TET proteins were determined immunohistochemically. IBD was characterized by the highest level of 8-oxodG among all analyzed tissues, as well as by a decrease in 5-hmdC and 5-mdC levels (at a midrange between normal colon and CRC). AD had the lowest levels of 5-hmdC and 5-mdC of all examined tissues and showed an increase in 8-oxodG and 5-(hydroxymethyl)-2'-deoxyuridine (5-hmdU) levels. CRC was characterized by lower levels of 5-hmdC and 5-mdC, the lowest level of 5-fdC among all analyzed tissues, and relatively high content of 5-cadC. The expression of TET1 mRNA in CRC and AD was significantly weaker than in IBD and normal colon. Furthermore, CRC and AD showed significantly lower levels of TET2 and AID mRNA than normal colonic tissue. Our findings suggest that a complex relationship between aberrant pattern of DNA epigenetic modification and cancer development does not depend solely on the transcriptional status of TET proteins, but also on the characteristics of premalignant/malignant cells. This study showed for the first time that the examined colonic pathologies had their unique epigenetic marks, distinguishing them from each other, as well as from normal colonic tissue. A decrease in 5-fdC level may be a characteristic feature of largely undifferentiated cancer cells.

Mild cognitive impairment: searching for the prodrome of Alzheimer's disease.

PubMed

Rosenberg, Paul B; Lyketsos, Constantine

2008-01-01

The concept of mild cognitive impairment (MCI) identifies persons who are neither cognitively normal nor demented. There is increasing evidence that MCI defines a group of persons who are at near-term risk of developing dementia and particularly Alzheimer's disease (AD). MCI thus constitutes an attractive target population for preventive treatments of AD. MCI is associated with aging and is more prevalent than dementia. There are several clinical and biological markers that are predictive of MCI prognosis, including depressive symptoms, cognitive deficits, brain imaging and neurochemical findings. The clinician needs to be especially alert to depressive and other mood symptoms which are common in MCI and potentially treatable. Trials of current medications for prevention of MCI progression to dementia have been largely negative. There are observational data suggesting that lifestyle modifications including exercise, leisure activities, cognitive stimulation, and social activities may be effective for prevention of MCI progression. There are many novel therapies currently in trials for early AD, and if effective they may prove to be helpful in prevention of MCI progression as well.

48 CFR 204.7106 - Contract modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 204.7106 Contract modifications. (a) If new items are added, assign new contract line or subline item... those item numbers. (2) If the contracting officer decides to assign new identifications to existing contract or exhibit line items, the following rules apply— (i) Definitized and undefinitized items. (A) The...

40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... modifications to the existing transportation network which the transportation plan envisions to be operational in the horizon years. Additions and modifications to the highway network shall be sufficiently... effect on route options between transportation analysis zones. Each added or modified highway segment...

77 FR 61539 - Airworthiness Directives; DASSAULT AVIATION Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-10

... the area of the wheel well. We are proposing this AD to prevent fuel spillage in the event of a MLG... modification of the wing fuel tanks in the area of the wheel well which introduces a dry bay by adding a sealed...

Optimizing cardiovascular gene therapy: increased vascular gene transfer with modified adenoviral vectors.

PubMed

Kibbe, M R; Murdock, A; Wickham, T; Lizonova, A; Kovesdi, I; Nie, S; Shears, L; Billiar, T R; Tzeng, E

2000-02-01

Adenovirus is widely used as a vector for gene transfer to the vasculature. However, the efficiency of these vectors can be limited by ineffective viral-target cell interactions. Viral attachment, which largely determines adenoviral tropism, is mediated through binding of the adenoviral fiber coat protein to the Coxsackievirus and adenovirus receptor, while internalization follows binding of the adenoviral RGD motif to alpha(v)-integrin receptors. Modifications of the fiber coat protein sequence have been successful for targeting the adenovirus to more prevalent receptors in the vasculature, including heparan sulfate-containing receptors and alpha(v)-integrin receptors. Modified adenoviral vectors targeted to receptors more prevalent in the vasculature result in an increased transfer efficiency of the virus in vitro and in vivo even in the presence of clinically relevant doses of heparin. We tested 2 modified E1- and E3-deleted Ad5 type adenoviral vectors containing the beta-galactosidase gene. AdZ.F(pK7) contains multiple positively charged lysines in the fiber coat protein that target the adenovirus to heparan sulfate receptors, while AdZ.F(RGD) contains an RGD integrin-binding sequence in the fiber coat protein that allows binding to alpha(v)-integrin receptors. The gene transfer efficiency of these modified viruses was compared in rat aortic smooth muscle cells in vitro and in an in vivo porcine model of balloon-induced arterial injury. Because of the use of heparin during most vascular surgical procedures and the concern that heparin might interfere with the binding of AdZ.F(pK7) to heparan sulfate receptors, the effect of heparin on the in vitro and in vivo transfer efficiency of these 2 modified adenoviruses was evaluated. In vitro infection of rat aortic smooth muscle cells with AdZ.F(pK7) and AdZ.F(RGD) resulted in significantly higher levels of beta-galactosidase expression compared with the unmodified adenovirus (mean +/- SEM, 1766.3 +/- 89.1 and 44.8 +/- 3.4 vs 10.1 +/- 0.7 mU per milligram of protein; P<.001). Following heparin administration, the gene transfer efficiency achieved with AdZ.F(pK7) diminished slightly in a concentration-dependent manner. However, the transfer efficiency was still greater than with the unmodified virus (mean +/- SEM, 1342.3 +/- 101.8 vs 4.8 +/- 0.4 mU per milligram of protein; P<.001). In vivo, following injury to the pig iliac artery with a 4F Fogarty balloon catheter, we found that AdZ.F(pK7) transduced the artery approximately 35-fold more efficiently than AdZ.F and 3-fold more efficiently than AdZ.F(RGD) following the administration of intravenous heparin, 100 U/kg body weight, and heparinized saline irrigation. Modifications of the adenovirus that lead to receptor targeting resulted in significantly improved gene transfer efficiencies. These improvements in transfer efficiencies observed with the modified vectors decreased slightly in the presence of heparin. However, AdZ.F(pK7) was still superior to AdZ.F(RGD) and AdZ.F despite heparin administration. These data demonstrate that modifications of adenoviral vectors that enhance binding to heparan sulfate receptors significantly improve gene transfer efficiency even in the presence of heparin and suggest an approach to optimize gene transfer into blood vessels.

Small black holes and near-extremal CFTs

DOE PAGES

Benjamin, Nathan; Dyer, Ethan; Fitzpatrick, A. Liam; ...

2016-08-02

Pure theories of AdS 3 quantum gravity are conjectured to be dual to CFTs with sparse spectra of light primary operators. The sparsest possible spectrum consistent with modular invariance includes only black hole states above the vacuum. Witten conjectured the existence of a family of extremal CFTs, which realize this spectrum for all admissible values of the central charge. We consider the quantum corrections to the classical spectrum, and propose a specific modification of Witten’s conjecture which takes into account the existence of “small” black hole states. These have zero classical horizon area, with a calculable entropy attributed solely tomore » loop effects. Lastly, our conjecture passes various consistency checks, especially when generalized to include theories with supersymmetry. In theories with N = 2 supersymmetry, this “near-extremal CFT” proposal precisely evades the no-go results of Gaberdiel et al.« less

Phase space effects on fast ion distribution function modeling in tokamaks

DOE PAGES

Podesta, M.; Gorelenkova, M.; Fredrickson, E. D.; ...

2016-04-14

Here, integrated simulations of tokamak discharges typically rely on classical physics to model energetic particle (EP) dynamics. However, there are numerous cases in which energetic particles can suffer additional transport that is not classical in nature. Examples include transport by applied 3D magnetic perturbations and, more notably, by plasma instabilities. Focusing on the effects of instabilities,ad-hocmodels can empirically reproduce increased transport, but the choice of transport coefficients is usually somehow arbitrary. New approaches based on physics-based reduced models are being developed to address those issues in a simplified way, while retaining a more correct treatment of resonant wave-particle interactions. Themore » kick model implemented in the tokamaktransport code TRANSP is an example of such reduced models. It includes modifications of the EP distribution by instabilities in real and velocity space, retaining correlations between transport in energy and space typical of resonant EP transport. The relevance of EP phase space modifications by instabilities is first discussed in terms of predicted fast ion distribution. Results are compared with those from a simple, ad-hoc diffusive model. It is then shown that the phase-space resolved model can also provide additional insight into important issues such as internal consistency of the simulations and mode stability through the analysis of the power exchanged between energetic particles and the instabilities.« less

Low emissions diesel fuel

DOEpatents

Compere, Alicia L.; Griffith, William L.; Dorsey, George F.; West, Brian H.

1998-01-01

A method and matter of composition for controlling NO.sub.x emissions from existing diesel engines. The method is achieved by adding a small amount of material to the diesel fuel to decrease the amount of NO.sub.x produced during combustion. Specifically, small amounts, less than about 1%, of urea or a triazine compound (methylol melamines) are added to diesel fuel. Because urea and triazine compounds are generally insoluble in diesel fuel, microemulsion technology is used to suspend or dissolve the urea or triazine compound in the diesel fuel. A typical fuel formulation includes 5% t-butyl alcohol, 4.5% water, 0.5% urea or triazine compound, 9% oleic acid, and 1% ethanolamine. The subject invention provides improved emissions in heavy diesel engines without the need for major modifications.

Low emissions diesel fuel

DOEpatents

Compere, A.L.; Griffith, W.L.; Dorsey, G.F.; West, B.H.

1998-05-05

A method and matter of composition for controlling NO{sub x} emissions from existing diesel engines. The method is achieved by adding a small amount of material to the diesel fuel to decrease the amount of NO{sub x} produced during combustion. Specifically, small amounts, less than about 1%, of urea or a triazine compound (methylol melamines) are added to diesel fuel. Because urea and triazine compounds are generally insoluble in diesel fuel, microemulsion technology is used to suspend or dissolve the urea or triazine compound in the diesel fuel. A typical fuel formulation includes 5% t-butyl alcohol, 4.5% water, 0.5% urea or triazine compound, 9% oleic acid, and 1% ethanolamine. The subject invention provides improved emissions in heavy diesel engines without the need for major modifications.

Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease.

PubMed

Aliev, Gjumrakch; Ashraf, Ghulam Md; Kaminsky, Yury G; Sheikh, Ishfaq Ahmed; Sudakov, Sergey K; Yakhno, Nikolay N; Benberin, Valery V; Bachurin, Sergey O

2013-11-01

It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.

77 FR 64765 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... failure of any post- modification operational test of the GFI. You may obtain further information by... GFI or deactivation of the associated fuel pump following failure of any post-modification operational test of the GFI. We are proposing this AD to prevent the potential of ignition sources inside fuel...

78 FR 42720 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-17

... airplane reaching its limit of validity (LOV) of the engineering data that support the established structural maintenance program. For certain airplanes, this proposed AD would require modification of the web... would require an inspection for cracks in the web, and repair or modification as applicable. We are...

76 FR 38961 - Tobacco Products, Exemptions From Substantial Equivalence Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

..., tobacco products that are modified by adding or deleting a tobacco additive, or by increasing or decreasing the quantity of an existing tobacco additive, if FDA determines that: (1) The modification would... modifications to additives that meet the statutory criteria. Many of the comments provided us with detailed...

21 CFR 640.17 - Modifications for specific products.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.17 Modifications for specific products. Red Blood Cells Frozen: A cryophylactic substance may be added to the Red... safety, purity, and potency for Red Blood Cells, and that the frozen product will maintain those...

21 CFR 640.17 - Modifications for specific products.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.17 Modifications for specific products. Red Blood Cells Frozen: A cryophylactic substance may be added to the Red... safety, purity, and potency for Red Blood Cells, and that the frozen product will maintain those...

21 CFR 640.17 - Modifications for specific products.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.17 Modifications for specific products. Red Blood Cells Frozen: A cryophylactic substance may be added to the Red... safety, purity, and potency for Red Blood Cells, and that the frozen product will maintain those...

21 CFR 640.17 - Modifications for specific products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.17 Modifications for specific products. Red Blood Cells Frozen: A cryophylactic substance may be added to the Red Blood Cells for extended manufacturers' storage at −65° C or colder, provided the manufacturer submits...

Evaluation of Floodplain Modifications to Reduce the Effect of Floods Using a Two-Dimensional Hydrodynamic Model of the Flint River at Albany, Georgia

USGS Publications Warehouse

Musser, Jonathan W.

2008-01-01

Potential flow characteristics of future flooding along a 4.8-mile reach of the Flint River in Albany, Georgia, were simulated using recent digital-elevation-model data and the U.S. Geological Survey finite-element surface-water modeling system for two-dimensional flow in the horizontal plane (FESWMS-2DH). The model was run at four water-surface altitudes at the Flint River at Albany streamgage (02352500): 181.5-foot (ft) altitude with a flow of 61,100 cubic feet per second (ft3/s), 184.5-ft altitude with a flow of 75,400 ft3/s, 187.5-ft altitude with a flow of 91,700 ft3/s, and 192.5-ft altitude with a flow of 123,000 ft3/s. The model was run to measure changes in inundated areas and water-surface altitudes for eight scenarios of possible modifications to the 4.8-mile reach on the Flint River. The eight scenarios include removing a human-made peninsula located downstream from Oglethorpe Boulevard, increasing the opening under the Oakridge Drive bridge, adding culverts to the east Oakridge Drive bridge approach, adding culverts to the east and west Oakridge Drive bridge approaches, adding an overflow across the oxbow north of Oakridge Drive, making the overflow into a channel, removing the Oakridge Drive bridge, and adding a combination of an oxbow overflow and culverts on both Oakridge Drive bridge approaches. The modeled inundation and water-surface altitude changes were mapped for use in evaluating the river modifications. The most effective scenario at reducing inundated area was the combination scenario. At the 187.5-ft altitude, the inundated area decreased from 4.24 square miles to 4.00 square miles. The remove-peninsula scenario was the least effective with a reduction in inundated area of less than 0.01 square miles. In all scenarios, the inundated area reduction increased with water-surface altitude, peaking at the 187.5-ft altitude. The inundated area reduction then decreased at the gage altitude of 192.5 ft.

RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF

PubMed Central

Krause, A; Whu, W Z; Qiu, J; Wafadari, D; Hackett, N R; Sharma, A; Crystal, R G; Worgall, S

2013-01-01

Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine–glycine–aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity. PMID:23607394

One-step fabrication of nickel nanocones by electrodeposition using CaCl2·2H2O as capping reagent

NASA Astrophysics Data System (ADS)

Lee, Jae Min; Jung, Kyung Kuk; Lee, Sung Ho; Ko, Jong Soo

2016-04-01

In this research, a method for the fabrication of nickel nanocones through the addition of CaCl2·2H2O to an electrodeposition solution was proposed. When electrodeposition was performed after CaCl2·2H2O addition, precipitation of the Ni ions onto the (2 0 0) crystal face was suppressed and anisotropic growth of the nickel electrodeposited structures was promoted. Sharper nanocones were produced with increasing concentration of CaCl2·2H2O added to the solution. Moreover, when temperature of the electrodeposition solutions approached 60 °C, the apex angle of the nanostructures decreased. In addition, the nanocones produced were applied to superhydrophobic surface modification using a plasma-polymerized fluorocarbon (PPFC) coating. When the solution temperature was maintained at 60 °C and the concentration of the added CaCl2·2H2O was 1.2 M or higher, the fabricated samples showed superhydrophobic surface properties. The proposed nickel nanocone formation method can be applied to various industrial fields that require metal nanocones, including superhydrophobic surface modification.

Oxidative modification of lipoic acid by HNE in Alzheimer disease brain.

PubMed

Hardas, Sarita S; Sultana, Rukhsana; Clark, Amy M; Beckett, Tina L; Szweda, Luke I; Murphy, M Paul; Butterfield, D Allan

2013-01-01

Alzheimer disease (AD) is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP) and intracellular neurofibrillary tangles (NFTs). The major component of SP is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE). HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH) were measured in AD and control brains. Additionally, LADH activities were measured after in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidative dysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.

77 FR 26158 - Airworthiness Directives; Saab AB, Saab Aerosystems Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

... of hydraulic accumulator failure. This AD requires replacing certain hydraulic accumulators with stainless steel hydraulic accumulators, and structural modifications in the nose landing gear bay. We are issuing this AD to prevent failure of hydraulic accumulators, which may result in damage to the airplane...

75 FR 55455 - Airworthiness Directives; The Boeing Company Model 737-700 (IGW) Series Airplanes Equipped With...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... modification of PATS Aircraft, LLC, auxiliary fuel tanks. This AD results from fuel system reviews conducted by... Aircraft Systems, 21652 Nanticoke Avenue, Georgetown, Delaware 19947; telephone 302-253-6157; fax 302-855... proposed to require deactivation or modification of PATS Aircraft, LLC, auxiliary fuel tanks. Comments We...

Epigenetic drug discovery for Alzheimer's disease.

PubMed

Cacabelos, Ramón; Torrellas, Clara

2014-09-01

It is assumed that epigenetic modifications are reversible and could potentially be targeted by pharmacological and dietary interventions. Epigenetic drugs are gaining particular interest as potential candidates for the treatment of Alzheimer's disease (AD). This article covers relevant information from over 50 different epigenetic drugs including: DNA methyltransferase inhibitors; histone deacetylase inhibitors; histone acetyltransferase modulators; histone methyltransferase inhibitors; histone demethylase inhibitors; non-coding RNAs (microRNAs) and dietary regimes. The authors also review the pharmacoepigenomics and the pharmacogenomics of epigenetic drugs. The readers will gain insight into i) the classification of epigenetic drugs; ii) the mechanisms by which these drugs might be useful in AD; iii) the pharmacological properties of selected epigenetic drugs; iv) pharmacoepigenomics and the influence of epigenetic drugs on genes encoding CYP enzymes, transporters and nuclear receptors; and v) the genes associated with the pharmacogenomics of anti-dementia drugs. Epigenetic drugs reverse epigenetic changes in gene expression and might open future avenues in AD therapeutics. Unfortunately, clinical trials with this category of drugs are lacking in AD. The authors highlight the need for pharmacogenetic and pharmacoepigenetic studies to properly evaluate any efficacy and safety issues.

Impact of aging, Alzheimer's disease and Parkinson's disease on the blood-brain barrier transport of therapeutics.

PubMed

Pan, Yijun; Nicolazzo, Joseph A

2018-04-14

Older people are at a greater risk of medicine-induced toxicity resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

[Thyroid carcinoma--differentiated, poorly differentiated and anaplastic carcinoma].

PubMed

Kakudo, Kennichi; Bai, Yanhua; Li, Yaqiong; Wakasa, Tomoko; Mori, Ichiro

2007-11-01

The poorly differentiated carcinoma was first added as a new member in the lists of classification of thyroid carcinomas in the WHO 2004 edition. However its histological criteria include necrosis and increased mitoses in addition to the original definition by Sakamoto's proposal, solid, trabecular and schirrhous growth. This modification creates a significant change in the incidence and prognosis of this carcinoma. This carcinoma, defined by the new WHO classification, is about 1-5% of all thyroid malignancy and has more aggressive outcome than the previous definition.

Challenges and Issues with the Further Aging of U.S. Air Force Aircraft: Policy Options for Effective Life-Cycle Management of Resources

DTIC Science & Technology

2009-01-01

maintenance , and modifications. Value-adding products from this domain could include sufficiency review/analysis for satisfaction of sustainment...c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 This product is part of the RAND Corporation technical...Airplanes, Military—United States— Maintenance and repair. 3. United States. Air Force—Planning. 4. Airplanes—Airworthiness. I. Title. UG1243.G429

78 FR 60800 - Airworthiness Directives; Bombardier Inc., Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... from fuel system reviews conducted by the manufacturer. This proposed AD would require accomplishing modifications to the fuel system. We are proposing this AD to prevent the potential of ignition sources inside... regulations, and existing maintenance practices for fuel tank systems. As a result of those findings, we...

75 FR 12667 - Airworthiness Directives; Learjet Inc. Model 45 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... certain Model 45 airplanes. This AD requires a general visual inspection for cracked and missing ballscrew... sleeve or flap actuator for cracks, and replacement or modification of the flap actuator if necessary. This AD results from reports of cracked and missing ballscrew assembly sleeves of the flap actuators...

77 FR 73270 - Airworthiness Directives; Embraer S.A. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... Airworthiness Limitation Section (ALS) of the EMBRAER ERJ 190 Maintenance Review Board Report (MRBR). This new AD requires revising the maintenance program to incorporate modifications in the ALS of the EMBRAER... issuing this AD since failure to inspect these structural components according to the new ALS tasks...

75 FR 59060 - Airworthiness Directives; Turboméca S.A. ARRIEL 2B Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... Airworthiness Directives; Turbom[eacute]ca S.A. ARRIEL 2B Turboshaft Engines AGENCY: Federal Aviation... turboshaft engines. That AD currently requires initial and repetitive inspections, cleaning, lubrication, and... engines that incorporate modification TU 132. That AD also provides an optional terminating action for the...

78 FR 40057 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... A321 series airplanes. This proposed AD was prompted by reports of certain sliding windows that were... numbers of sliding windows and sliding window seals, and modification if necessary. This proposed AD also... could lead to the functional loss of the sliding window as an exit, possibly preventing the flightcrew...

77 FR 67256 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

.... This AD requires either incorporating a design change to the rudder control system and/ or other systems, or installing a stop rudder inputs warning (SRIW) modification. We are issuing this AD to prevent... a design change to the rudder control system and/or other systems to address the unsafe condition...

Generalized Procrustes analysis of an ontogenetic series of modified crania: Evaluating the technique of modification in the Migration Period of Europe (4th-7th century AD).

PubMed

Mayall, Peter; Pilbrow, Varsha

2018-05-01

The arrival of the Huns into Europe in the fourth century AD increased the occurrence of intentional cranial modification among European nomads. It has been postulated that the Huns used a two-bandage cranial binding technique to differentiate themselves from surrounding nomadic groups, including those from Georgia. This study examines this hypothesis by comparing Migration Period (4th to 7th century AD) juvenile crania, which retain strong impressions of bindings, with adult modified crania from Hungary and Georgia. Twelve surface landmarks and 251 semi-landmarks were used to study ontogenetic trajectories in 9 juvenile and 16 adult modified skulls from 8 Hungarian sites and 21 adult skulls from two Georgian sites. Generalized Procrustes analysis, linear regression of Procrutes distance on dental age and log centroid size, and warping the principal components (PCs) in shape space helped to identify cranial shape changes. The PCs provide significant separation of the juvenile and adult groups from Georgia and Hungary. Variation in modified cranial shape was limited in Hungary compared to Georgia. There was stronger correlation between juvenile and adult modified cranial shape in Hungary than in Georgia. Warping along the first axis reveals the trajectory from marked flattening of the frontal and occipital regions in juveniles to diminished flattening in the same regions in adult crania, corresponding with one binding. Another depression extending from the post-bregmatic region to the temporal region, similarly strong in juveniles but diminishing in adults, marks the second binding. Hungarian crania were modified with two bindings with limited shape variation, whereas the Georgian crania had greater variation in shape being also modified with antero-posterior bindings. The findings from this study alongside contemporary historical sources help to understand the role of intentional cranial modification as a mark of social identity among nomads in the Migration Period of Europe. © 2018 Wiley Periodicals, Inc.

Current opinion in Alzheimer's disease therapy by nanotechnology-based approaches.

PubMed

Ansari, Shakeel Ahmed; Satar, Rukhsana; Perveen, Asma; Ashraf, Ghulam Md

2017-03-01

Nanotechnology typically deals with the measuring and modeling of matter at nanometer scale by incorporating the fields of engineering and technology. The most prominent feature of these engineered materials involves their manipulation/modification for imparting new functional properties. The current review covers the most recent findings of Alzheimer's disease (AD) therapeutics based on nanoscience and technology. Current studies involve the application of nanotechnology in developing novel diagnostic and therapeutic tools for neurological disorders. Nanotechnology-based approaches can be exploited for limiting/reversing these diseases for promoting functional regeneration of damaged neurons. These strategies offer neuroprotection by facilitating the delivery of drugs and small molecules more effectively across the blood-brain barrier. Nanotechnology based approaches show promise in improving AD therapeutics. Further replication work on synthesis and surface modification of nanoparticles, longer-term clinical trials, and attempts to increase their impact in treating AD are required.

Around Marshall

NASA Image and Video Library

2002-10-01

This is a ground level view of Test Stand 300 at the east test area of the Marshall Space Flight Center. Test Stand 300 was constructed in 1964 as a gas generator and heat exchanger test facility to support the Saturn/Apollo Program. Deep-space simulation was provided by a 1960 modification that added a 20-ft thermal vacuum chamber and a 1981 modification that added a 12-ft vacuum chamber. The facility was again modified in 1989 when 3-ft and 15-ft diameter chambers were added to support Space Station and technology programs. This multiposition test stand is used to test a wide range of rocket engine components, systems, and subsystems. It has the capability to simulate launch thermal and pressure profiles. Test Stand 300 was designed for testing solid rocket booster (SRB) insulation panels and components, super-insulated tanks, external tank (ET) insulation panels and components, Space Shuttle components, solid rocket motor materials, and advanced solid rocket motor materials.

Emerging drug targets for Aβ and tau in Alzheimer’s disease: a systematic review

PubMed Central

West, Sophie; Bhugra, Praveen

2015-01-01

Aims Currently, treatment for Alzheimer’s disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD. Methods A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group 1. Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence. Results The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration. Conclusions There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition. PMID:25753046

Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’

PubMed Central

Kapoor, Utkarsh

2017-01-01

The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications. PMID:28566301

Modifications of the IBM personal computer synchronous communications support programs for use with the Multics

USGS Publications Warehouse

Kork, John O.

1983-01-01

Version 1.00 of the Asynchronous Communications Support supplied with the IBM Personal Computer must be modified to be used for communications with Multics. Version 2.00 can be used as supplied, but error checking and screen printing capabilities can be added by using modifications very similar to those required for Version 1.00. This paper describes and lists required programs on Multics and appropriate modifications to both Versions 1.00 and 2.00 of the programs supplied by IBM.

A facile method of hydrophobic surface modification for acrylonitrile-styrene-acrylate terpolymer based on the out-migration property of metallic soaps

NASA Astrophysics Data System (ADS)

Qi, Yanli; Chen, Tingting; Zhang, Jun

2018-03-01

Hydrophobic surface modification is conducted in this study by using additives with long alkyl chains. Several kinds of metallic soaps, such as calcium stearate (CaSt), zinc stearate (ZnSt), magnesium stearate (MgSt) and barium stearate (BaSt) were employed. Polymer matrix is acrylonitrile-styrene-acrylate (ASA) terpolymer due to its wonderful weather resistance property. The surface chemical characterization was studied by Fourier transformed infrared (FTIR) technology and X-ray photoelectron spectroscopy (XPS). Carboxylate (Osbnd Csbnd O-) indexes of composites in both transmittance and reflection modes were calculated according to FTIR results. As to the ratio of carboxylate index in reflection mode to that in transmittance mode, the sample added with 5 wt% ZnSt shows a higher value of 8.77, and a much higher value of 14.47 for the sample added with 10 wt% ZnSt. The corresponding Csbnd C/ Csbnd H /Cdbnd C peak areas of the samples added with 5 wt% or 10 wt% ZnSt are 75.4% and 77.3% respectively, much higher than other samples. This indicates ZnSt is much easier to out-migrate to material surface and therefore is more suitable for hydrophobic surface modification. In particular, the water contact angle of the ASA/ZnSt composite added with 10 wt% ZnSt significantly increased to 127o (40o increase in comparison with pure ASA), successfully converting the surface wettability from hydrophilic to hydrophobic.

Solar energy plant as a complement to a conventional heating system: Measurement of the storage and consumption of solar energy

NASA Astrophysics Data System (ADS)

Doering, E.; Lippe, W.

1982-08-01

The technical and economic performances of a complementary solar heating installation for a new swimming pool added to a two-floor dwelling were examined after measurements were taken over a period of 12 months and analyzed. In particular, the heat absorption and utilization were measured and modifications were carried out to improve pipe insulation and regulation of mixer valve motor running and volume flow. The collector system efficiency was evaluated at 15.4%, the proportion of solar energy of the total consumption being 6.1%. The solar plant and the measuring instruments are described and recommendations are made for improved design and performance, including enlargement of the collector surface area, further modification of the regulation system, utilization of temperature stratification in the storage tanks and avoiding mutual overshadowing of the collectors.

RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification: RAPID study protocol.

PubMed

Almeida, Osvaldo P; MacLeod, Colin; Flicker, Leon; Ford, Andrew; Grafton, Ben; Etherton-Beer, Christopher

2014-07-23

Depressive symptoms are common and undermine the quality of life of people with Alzheimer's disease (AD). Cholinesterase inhibitors and antidepressants have all but no effect on the mood of patients, and their use increases adverse events. Cognitive bias modification (CBM) targets attentional and interpretative biases associated with anxiety, dysphoria and depression and may be useful to treat depression in AD (DAD). This trial aims to determine the effect of CBM on depression scores and the quality of life of people with DAD. Randomised, double-blind, parallel, controlled trial of CBM (1:1 allocation ratio). Participants will be 80 adults with probable AD living in the Western Australian community who score 8 or more on the Cornell Scale for Depression in Dementia (CSDD). They will have mild to moderate dementia (Mini-Mental State Examination-MMSE score ≥15) and will be free of severe sensory impairment or suicidal intent. The intervention will consist of 10 40 min sessions of CBM delivered over 2 weeks using a high-resolution monitor using a local computer station at the Western Australian Centre for Health and Ageing. The primary outcomes of interest are the 2-week change, from baseline, in the severity of CSDD scores and the Quality of Life AD (QoL-AD) scores. Secondary outcomes include changes in the CSDD, QoL-AD after 12 weeks, and changes in MMSE scores, negative attentional and interpretative bias and the proportion of participants with CSDD <8 after 2 and 12 weeks. The study will comply with the principles of the Declaration of Helsinki and participants will provide written informed consent. The Ethics Committee of the Royal Perth Hospital will approve and oversee the study (REG14-036). The results of this trial will provide level 2 evidence of efficacy for CBM as a treatment of DAD. Australian and New Zealand Clinical Trials Registry number ACTRN12614000420640, date registered 06/04/2014. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

77 FR 29863 - Airworthiness Directives; Cessna Aircraft Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... the left and right wing lower main spar caps for cracks and either replacing cracked wing lower main... found free of cracks or incorporating an FAA-approved modification. This AD also requires reporting the results of the inspections to the FAA. This AD was prompted by reports of cracks found in the wing lower...

76 FR 66609 - Airworthiness Directives; Bell Helicopter Textron Canada (Bell) Model 407 and 427 Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

... surface. The AD also requires reidentifying the servo by metal-impression stamping or by vibro- etching... surface. The AD also requires reidentifying the servo by metal-impression stamping or by vibro-etching... metal-impression stamping or by vibro-etching ``67.01'' onto the modification plate. Before installing a...

76 FR 34918 - Airworthiness Directives; The Boeing Company Model 767 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

...We propose to adopt a new airworthiness directive (AD) for the products listed above. This proposed AD would require modification of the fluid drain path in the leading edge area of the wing. This proposed AD was prompted by a design review following a ground fire incident and reports of flammable fluid leaks from the wing leading edge area onto the engine exhaust area. We are proposing this AD to prevent flammable fluid from leaking onto the engine exhaust nozzle which could result in a fire.

Boundary conditions and unitarity in AdS/CFT

NASA Astrophysics Data System (ADS)

Andrade, Tomas

This thesis investigates various issues regarding unitarity in the context of Anti-de Sitter/Conformal Field theory (AdS/CFT) dualities. When the boundary duals are conformal, unitarity implies that there are lower bounds on the dimension of primary operators. Now, the AdS/CFT dictionary relates insertions of boundary operators to different choices of boundary conditions on the gravity side. Therefore, we expect the possible choices of boundary conditions in AdS to be restricted accordingly. Our first main goal will be to identify what are the pathologies that occur in the gravitational side of the duality when the boundary operators violate the pertinent unitarity bounds. In all the studied cases, we find that such bulk theories are ill-defined as expected, although unitarity is not nec- essarily violated. As our first example we consider a Klein-Gordon field in AdS, and extend the analysis to bosonic fields of spin 1 and 2 later on, with analogous results. Interestingly, it turns our that the bulk settings are pathological even in the absence of strict conformal invariance. Secondly, we argue that introducing a geometrical cut-off in spacetime along with the appropriate modifications of the boundary conditions yields the resulting (IR) theories well-defined. By study- ing in detail a Klein-Gordon field with boundary conditions that correspond to double-trace deformations, we are able to explicitly verify this claim. Finally, we discuss future research directions which include generalizations of AdS/CFT-like dualities and potential applications for condensed matter theory.

Brief communication: Artificial cranial modification in Kow Swamp and Cohuna.

PubMed

Durband, Arthur C

2014-09-01

The crania from Kow Swamp and Cohuna have been important for a number of debates in Australian paleoanthropology. These crania typically have long, flat foreheads that many workers have cited as evidence of genetic continuity with archaic Indonesian populations, particularly the Ngandong sample. Other scientists have alleged that at least some of the crania from Kow Swamp and the Cohuna skull have been altered through artificial modification, and that the flat foreheads possessed by these individuals are not phylogenetically informative. In this study, several Kow Swamp crania and Cohuna are compared to known modified and unmodified comparative samples. Canonical variates analyses and Mahalanobis distances are generated, and random expectation statistics are used to calculate statistical significance for these tests. The results of this study agree with prior work indicating that a portion of this sample shows evidence for artificial modification of the cranial vault. Many Kow Swamp crania and Cohuna display shape similarities with a population of known modified individuals from New Britain. Kow Swamp 1, 5, and Cohuna show the strongest evidence for modification, but other individuals from this sample also show evidence of culturally manipulated changes in cranial shape. This project provides added support for the argument that at least some Pleistocene Australian groups were practicing artificial cranial modification, and suggests that caution should be used when including these individuals in phylogenetic studies. Copyright © 2014 Wiley Periodicals, Inc.

F-100 and F-100A on ramp - comparison showing tail modifications that solved control problems during

NASA Technical Reports Server (NTRS)

1955-01-01

On the left is NACA High-Speed Flight Station's North American F-100A (52-5778) Super Sabre with a modified vertical fin. On the right is an Air Force's North American F-100A (52-5773) with the original vertical fin configuration. 1955. NACA added a larger vertical fin to the airplane in December 1954, adding 10 percent more surface area. Later North American installed an even larger fin, having 27 percent greater area, as well as wingtip extensions. The modifications solved the dangerous directional stability and roll coupling problems that the F-100 was experiencing. The F-100 series went on to a long and distinguished service life.

Efficacy of trap modifications for increasing capture rates of aquatic snakes in floating aquatic funnel traps

USGS Publications Warehouse

Halstead, Brian J.; Wylie, Glenn D.; Casazza, Michael L.

2013-01-01

Increasing detection and capture probabilities of rare or elusive herpetofauna of conservation concern is important to inform the scientific basis for their management and recovery. The Giant Gartersnake (Thamnophis gigas) is an example of a secretive, wary, and generally difficult-to-sample species about which little is known regarding its patterns of occurrence and demography. We therefore evaluated modifications to existing traps to increase the detection and capture probabilities of the Giant Gartersnake to improve the precision with which occurrence, abundance, survival, and other demographic parameters are estimated. We found that adding a one-way valve constructed of cable ties to the small funnel opening of traps and adding hardware cloth extensions to the wide end of funnels increased capture rates of the Giant Gartersnake by 5.55 times (95% credible interval = 2.45–10.51) relative to unmodified traps. The effectiveness of these modifications was insensitive to the aquatic habitat type in which they were deployed. The snout-vent length of the smallest and largest captured snakes did not vary among trap modifications. These trap modifications are expected to increase detection and capture probabilities of the Giant Gartersnake, and show promise for increasing the precision with which demographic parameters can be estimated for this species. We anticipate that the trap modifications found effective in this study will be applicable to a variety of aquatic and semi-aquatic reptiles and amphibians and improve conservation efforts for these species.

O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease

NASA Astrophysics Data System (ADS)

Marotta, Nicholas P.; Lin, Yu Hsuan; Lewis, Yuka E.; Ambroso, Mark R.; Zaro, Balyn W.; Roth, Maxwell T.; Arnold, Don B.; Langen, Ralf; Pratt, Matthew R.

2015-11-01

Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation.

Analysis of pre-service physics teacher skills designing simple physics experiments based technology

NASA Astrophysics Data System (ADS)

Susilawati; Huda, C.; Kurniawan, W.; Masturi; Khoiri, N.

2018-03-01

Pre-service physics teacher skill in designing simple experiment set is very important in adding understanding of student concept and practicing scientific skill in laboratory. This study describes the skills of physics students in designing simple experiments based technologicall. The experimental design stages include simple tool design and sensor modification. The research method used is descriptive method with the number of research samples 25 students and 5 variations of simple physics experimental design. Based on the results of interviews and observations obtained the results of pre-service physics teacher skill analysis in designing simple experimental physics charged technology is good. Based on observation result, pre-service physics teacher skill in designing simple experiment is good while modification and sensor application are still not good. This suggests that pre-service physics teacher still need a lot of practice and do experiments in designing physics experiments using sensor modifications. Based on the interview result, it is found that students have high enough motivation to perform laboratory activities actively and students have high curiosity to be skilled at making simple practicum tool for physics experiment.

Dual targeting of gene delivery by genetic modification of adenovirus serotype 5 fibers and cell-selective transcriptional control.

PubMed

Work, L M; Ritchie, N; Nicklin, S A; Reynolds, P N; Baker, A H

2004-08-01

Adenovirus (Ad)-mediated gene delivery is a promising approach for genetic manipulation of the vasculature and is being used in both preclinical models and clinical trials. However, safety concerns relating to infection of nontarget tissue and the poor infectivity of vascular cells compared to other cell types necessitates Ad vector refinement. Here, we combine a transductional targeting approach to improve vascular cell infectivity through RGD peptide insertion into adenovirus fibers, combined with transcriptional targeting to endothelial cells using a approximately 1 kb fragment of the fms-like tyrosine kinase receptor-1 (FLT-1) promoter. Single- and double-modified vectors were characterized in human cell lines that either support or have silenced FLT-1 expression. In rat hepatocytes and endothelial cells, the double modification substantially shifted transduction profiles toward vascular endothelial cells. Furthermore, in intact aortae derived from spontaneously hypertensive rats that display enhanced alphav integrin expression on dysfunctional endothelium, enhanced levels of transduction were observed using the double-modified vector but not in aortae derived from normotensive control rats. Our data indicate that Ad-mediated transduction can be beneficially modified in vitro and in vivo by combining fiber modification and a cell-selective promoter within a single-component vector system.

Facilitating progress in health behaviour theory development and modification: the reasoned action approach as a case study.

PubMed

Head, Katharine J; Noar, Seth M

2014-01-01

This paper explores the question: what are barriers to health behaviour theory development and modification, and what potential solutions can be proposed? Using the reasoned action approach (RAA) as a case study, four areas of theory development were examined: (1) the theoretical domain of a theory; (2) tension between generalisability and utility, (3) criteria for adding/removing variables in a theory, and (4) organisational tracking of theoretical developments and formal changes to theory. Based on a discussion of these four issues, recommendations for theory development are presented, including: (1) the theoretical domain for theories such as RAA should be clarified; (2) when there is tension between generalisability and utility, utility should be given preference given the applied nature of the health behaviour field; (3) variables should be formally removed/amended/added to a theory based on their performance across multiple studies and (4) organisations and researchers with a stake in particular health areas may be best suited for tracking the literature on behaviour-specific theories and making refinements to theory, based on a consensus approach. Overall, enhancing research in this area can provide important insights for more accurately understanding health behaviours and thus producing work that leads to more effective health behaviour change interventions.

Model polymer etching and surface modification by a time modulated RF plasma jet: role of atomic oxygen and water vapor

NASA Astrophysics Data System (ADS)

Luan, P.; Knoll, A. J.; Wang, H.; Kondeti, V. S. S. K.; Bruggeman, P. J.; Oehrlein, G. S.

2017-01-01

The surface interaction of a well-characterized time modulated radio frequency (RF) plasma jet with polystyrene, poly(methyl methacrylate) and poly(vinyl alcohol) as model polymers is investigated. The RF plasma jet shows fast polymer etching but mild chemical modification with a characteristic carbonate ester and NO formation on the etched surface. By varying the plasma treatment conditions including feed gas composition, environment gaseous composition, and treatment distance, we find that short lived species, especially atomic O for Ar/1% O2 and 1% air plasma and OH for Ar/1% H2O plasma, play an essential role for polymer etching. For O2 containing plasma, we find that atomic O initiates polymer etching and the etching depth mirrors the measured decay of O atoms in the gas phase as the nozzle-surface distance increases. The etching reaction probability of an O atom ranging from 10-4 to 10-3 is consistent with low pressure plasma research. We also find that adding O2 and H2O simultaneously into Ar feed gas quenches polymer etching compared to adding them separately which suggests the reduction of O and OH density in Ar/O2/H2O plasma.

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

PubMed

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

2017-12-01

Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

77 FR 1 - Airworthiness Directives; Saab AB, Saab Aerosystems Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

...;Federal Register / Vol. 77, No. 1 / Tuesday, January 3, 2012 / Rules and Regulations#0;#0; [[Page 1... unsafe condition, Swedish AD (SAD) 1-186 was issued to require an inspection and, depending on findings... modification (SAAB SB 340-32-128) was made mandatory by SAD 1- 189 [which corresponds to FAA AD 2004-12-03...

78 FR 34020 - Federal Acquisition Regulation; Uniform Procurement Identification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... paragraph (a) ``4.1601,'' and adding ``4.601 to 4.1603,'' in its place; and 0 b. Adding paragraph (e) to..., agencies shall comply with paragraph (a) of this section and use the requirements in 4.1602 and 4.1603 for... the requirements in 4.1602 and 4.1603 for all amendments to solicitations and modifications to awards...

77 FR 11421 - Airworthiness Directives; Pratt & Whitney Canada, Auxiliary Power Units

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... separation of the rear gas generator case and release of high energy debris. This proposed AD would require modifications of the rear gas generator case, exhaust duct support, and turbine exhaust duct flanges. We are proposing this AD to prevent separation of the rear gas generator case and release of high energy debris...

Controversies in Alzheimer's disease drug development.

PubMed

Cummings, Jeffrey L

2008-08-01

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.

Entry dynamics of space shuttle orbiter with longitudinal stability and control uncertainties at supersonic and hypersonic speeds

NASA Technical Reports Server (NTRS)

Stone, H. W.; Powell, R. W.

1977-01-01

A six-degree-of-freedom simulation analysis was conducted to examine the effects of longitudinal static aerodynamic stability and control uncertainties on the performance of the space shuttle orbiter automatic (no manual inputs) entry guidance and control systems. To establish the acceptable boundaries, the static aerodynamic characteristics were varied either by applying a multiplier to the aerodynamic parameter or by adding an increment. With either of two previously identified control system modifications included, the acceptable longitudinal aerodynamic boundaries were determined.

Preparation of transition metal nanoparticles and surfaces modified with (CO)polymers synthesized by RAFT

DOEpatents

McCormick, III., Charles L.; Lowe, Andrew B.; Sumerlin, Brent S.

2006-11-21

A new, facile, general one-phase method of generating thio-functionalized transition metal nanoparticles and surfaces modified by (co)polymers synthesized by the RAFT method is described. The method includes the stops of forming a (co)polymer in aqueous solution using the RAFT methodology, forming a colloidal transition metal precursor solution from an appropriate transition metal; adding the metal precursor solution or surface to the (co)polymer solution, adding a reducing agent into the solution to reduce the metal colloid in situ to produce the stabilized nanoparticles or surface, and isolating the stabilized nanoparticles or surface in a manner such that aggregation is minimized. The functionalized surfaces generated using these methods can further undergo planar surface modifications, such as functionalization with a variety of different chemical groups, expanding their utility and application.

Preparation of transition metal nanoparticles and surfaces modified with (co)polymers synthesized by RAFT

DOEpatents

McCormick, III, Charles L.; Lowe, Andrew B [Hattiesburg, MS; Sumerlin, Brent S [Pittsburgh, PA

2011-12-27

A new, facile, general one-phase method of generating thiol-functionalized transition metal nanoparticles and surfaces modified by (co)polymers synthesized by the RAFT method is described. The method includes the steps of forming a (co)polymer in aqueous solution using the RAFT methodology, forming a colloidal transition metal precursor solution from an appropriate transition metal; adding the metal precursor solution or surface to the (co)polymer solution, adding a reducing agent into the solution to reduce the metal colloid in situ to produce the stabilized nanoparticles or surface, and isolating the stabilized nanoparticles or surface in a manner such that aggregation is minimized. The functionalized surfaces generated using these methods can further undergo planar surface modifications, such as functionalization with a variety of different chemical groups, expanding their utility and application.

76 FR 34625 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-14

...We propose to adopt a new airworthiness directive (AD) for the products listed above. This proposed AD would require modification of the fluid drain path in the leading edge area of the wing. This proposed AD was prompted by a design review following a ground fire incident and reports of flammable fluid leaks from the wing leading edge area onto the engine exhaust area. We are proposing this AD to prevent flammable fluid from leaking onto the engine exhaust nozzle, which could result in a fire.

A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

DTIC Science & Technology

2005-11-01

biological properties. CAV-1 is known to cause allergic two knobs may in fact be distinct based on our uveitis, called the ’blue eye syndrome ’ and rarely...system - first steps towards gene therapy of Alport syndrome . Gene Ther 3(1), 2 1-7. Hemminki, A., and Alvarez, R. D. 2002. Adenoviruses in oncology: a...Ad-IX- Ad-IX-imRFPI or Ad-IX-tdimer2(12) (10000 viral particles/ tdimer2(12) with plX modifications, and wild-type El/E3 cell) were added to the

Space shuttle orbiter trimmed center-of-gravity extension study. Volume 5: Effects of configuration modifications on the aerodynamic characteristics of the 140A/B orbiter at Mach numbers of 2.5, 3.95 and 4.6

NASA Technical Reports Server (NTRS)

Phillips, W. P.; Fournier, R. H.

1979-01-01

Supersonic aerodynamic characteristics are presented for the 140A/B space shuttle orbiter configuration (0.010 scale) and for the configuration modified to incorporate geometry changes in the wing planform fillet region. The modifications designed to extend the orbiter's longitudinal trim capability to more forward center-of-gravity locations, included reshaping of the baseline wing planform fillet and adding canards. The investigation was made in the high Mach number test section of the Langley Unitary Plan Wind Tunnel at a Reynolds number of approximately 2.2 million based on fuselage reference length. The angle-of-attack range for the investigation extended from -1 deg to 31 deg. Data were obtained with the elevators and body flap deflected at appropriate negative and positive conditions to assess the trim limits.

Marginal Loss Calculations for the DCOPF

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

Eldridge, Brent; O'Neill, Richard P.; Castillo, Andrea R.

2016-12-05

The purpose of this paper is to explain some aspects of including a marginal line loss approximation in the DCOPF. The DCOPF optimizes electric generator dispatch using simplified power flow physics. Since the standard assumptions in the DCOPF include a lossless network, a number of modifications have to be added to the model. Calculating marginal losses allows the DCOPF to optimize the location of power generation, so that generators that are closer to demand centers are relatively cheaper than remote generation. The problem formulations discussed in this paper will simplify many aspects of practical electric dispatch implementations in use today,more » but will include sufficient detail to demonstrate a few points with regard to the handling of losses.« less

Biomarker and Clinical Trial Design Support for Disease-Modifying Therapies: Report of a Survey of the EU/US: Alzheimer's Disease Task Force.

PubMed

Cummings, J; Fox, N; Vellas, B; Aisen, P; Shan, G

2018-01-01

Disease-modifying therapies are urgently needed for the treatment of Alzheimer's disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. A survey of members of the EU/US Alzheimer's Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification. Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations. The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.

Lorentz invariance with an invariant energy scale.

PubMed

Magueijo, João; Smolin, Lee

2002-05-13

We propose a modification of special relativity in which a physical energy, which may be the Planck energy, joins the speed of light as an invariant, in spite of a complete relativity of inertial frames and agreement with Einstein's theory at low energies. This is accomplished by a nonlinear modification of the action of the Lorentz group on momentum space, generated by adding a dilatation to each boost in such a way that the Planck energy remains invariant. The associated algebra has unmodified structure constants. We also discuss the resulting modifications of field theory and suggest a modification of the equivalence principle which determines how the new theory is embedded in general relativity.

Osteoblastic differentiation of human and equine adult bone marrow-derived mesenchymal stem cells when BMP-2 or BMP-7 homodimer genetic modification is compared to BMP-2/7 heterodimer genetic modification in the presence and absence of dexamethasone.

PubMed

Carpenter, Ryan S; Goodrich, Laurie R; Frisbie, David D; Kisiday, John D; Carbone, Beth; McIlwraith, C Wayne; Centeno, Christopher J; Hidaka, Chisa

2010-10-01

Bone marrow-derived mesenchymal stem cells (BMDMSCs) have been targeted for use in enhancement of bone healing; and their osteogenic potential may be further augmented by genes encoding bone morphogenetic proteins (BMP's). The purpose of this study was to compare the effect of genetic modification of human and equine BMDMSCs with BMP-2 or -7 or BMP-2 and -7 on their osteoblastogenic differentiation in the presence or absence of dexamethasone. The BMDMSCs were harvested from the iliac crest of three human donors and tuber coxae of three equine donors. Monolayer cells were genetically modified using adenovirus vectors encoding BMP-2, -7 or both and cultured in the presence or absence of dexamethasone. Expression of BMPs was confirmed by enzyme linked immunosorbent assay (ELISA). To evaluate osteoblastic differentiation, cellular morphology was assessed every other day and expression and secretion of alkaline phosphatase (ALP), as well as expression levels of osteonectin (OSTN), osteocalcin (OCN), and runt-related transcription factor-2 (Runx2) were measured for up to 14 days. Human and equine BMDMSCs showed a capacity for osteogenic differentiation regardless of genetic modification or dexamethasone supplementation. Dexamethasone supplementation was more important for osteoblastogenic differentiation of equine BMDMSCs than human BMDMSCs. Genetic modification of BMDMSCs increased ALP secretion with AdBMP-2 homodimer having the greatest effect in both human and equine cells compared to AdBMP 7 or AdBMP 2/7. BMP protein elution rates reached their maximal concentration between day 4 and 8 and remained relatively stable thereafter, suggesting that genetically modified BMDMSCs could be useful for cell-based delivery of BMPs to a site of bone formation. Published by Wiley Periodicals, Inc. J Orthop Res 28:1330-1337, 2010.

Mechanisms for Teaching Typewriting to Special Students.

ERIC Educational Resources Information Center

Rosetti, Mary Ellen

1979-01-01

Gives examples of specialized typewriting instructional methods for students with disabilities, involving modifications to typewriters, using special keyboards, and adding sensory devices for different impairments. (MF)

Forward-backward scheme on the B/E grid modified to suppress lattice separation: the two versions, and any impact of the choice made?

NASA Astrophysics Data System (ADS)

Mesinger, Fedor; Popovic, Jelena

2010-09-01

Ever since its introduction to meteorology in the early 1970s, the forward-backward scheme has proven to be a very efficient method of treating gravity waves, with an added bonus of avoiding the time computational mode of the leapfrog scheme. It has been and it is used today in a number of models. When used on a square grid other than the Arakawa C grid, modification is or modifications are available to suppress the noise-generating separation of solutions on elementary C grids. Yet, in spite of a number of papers addressing the scheme and its modification, or modifications, issues remain that have either not been addressed or have been commented upon in a misleading or even in an incorrect way. Specifically, restricting ourselves to the B/E grid does it matter and if so how which of the two equations, momentum and the continuity equation, is integrated forward? Is there just one modification suppressing the separation of solutions, or have there been proposed two modification schemes? Questions made are addressed and a number of misleading statements made are recalled and commented upon. In particular, it is demonstrated that there is no added computational cost in integrating the momentum equation forward, and it is pointed out that this would seem advantageous given the height perturbations excited in the first step following a perturbation at a single height point. Yet, 48-h numerical experiments with a full-physics model show only a barely visible difference between the forecasts done using one and the other equation forward.

75 FR 81427 - Airworthiness Directives; The Boeing Company Model 747-200C, -200F, -400, -400D, and -400F Series...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

.... This AD results from a structural review of affected skin lap joints for widespread fatigue damage. We are issuing this AD to prevent fatigue cracking in certain lap joints, which could result in rapid... operation beyond 15,000 total flight cycles after doing the proposed modification. Boeing stated that...

Aging is associated with altered inflammatory, arachidonic acid cascade and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex

PubMed Central

Keleshian, Vasken L.; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated. PMID:23336521

Modification to the Capsid of the Adenovirus Vector That Enhances Dendritic Cell Infection and Transgene-Specific Cellular Immune Responses

PubMed Central

Worgall, Stefan; Busch, Annette; Rivara, Michael; Bonnyay, David; Leopold, Philip L.; Merritt, Robert; Hackett, Neil R.; Rovelink, Peter W.; Bruder, Joseph T.; Wickham, Thomas J.; Kovesdi, Imi; Crystal, Ronald G.

2004-01-01

Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing β-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the β-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing β-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to β-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-β-galactosidase antibody levels following vector administration. However, cellular responses to β-galactosidase were significantly enhanced, with the frequency of CD4+ as well as the CD8+ β-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing β-galactosidase: BALB/c mice implanted with the CT26 syngeneic β-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif to the Ad fiber knob increases the infectibility of DC and leads to enhanced cellular immune responses to the Ad-transferred transgene, suggesting that the RGD capsid modification may be useful in developing Ad-based vaccines. PMID:14963160

Baking a mass-spectrometry data PIE with McMC and simulated annealing: predicting protein post-translational modifications from integrated top-down and bottom-up data.

PubMed

Jefferys, Stuart R; Giddings, Morgan C

2011-03-15

Post-translational modifications are vital to the function of proteins, but are hard to study, especially since several modified isoforms of a protein may be present simultaneously. Mass spectrometers are a great tool for investigating modified proteins, but the data they provide is often incomplete, ambiguous and difficult to interpret. Combining data from multiple experimental techniques-especially bottom-up and top-down mass spectrometry-provides complementary information. When integrated with background knowledge this allows a human expert to interpret what modifications are present and where on a protein they are located. However, the process is arduous and for high-throughput applications needs to be automated. This article explores a data integration methodology based on Markov chain Monte Carlo and simulated annealing. Our software, the Protein Inference Engine (the PIE) applies these algorithms using a modular approach, allowing multiple types of data to be considered simultaneously and for new data types to be added as needed. Even for complicated data representing multiple modifications and several isoforms, the PIE generates accurate modification predictions, including location. When applied to experimental data collected on the L7/L12 ribosomal protein the PIE was able to make predictions consistent with manual interpretation for several different L7/L12 isoforms using a combination of bottom-up data with experimentally identified intact masses. Software, demo projects and source can be downloaded from http://pie.giddingslab.org/

Scale invariance of the η-deformed AdS5 × S5 superstring, T-duality and modified type II equations

NASA Astrophysics Data System (ADS)

Arutyunov, G.; Frolov, S.; Hoare, B.; Roiban, R.; Tseytlin, A. A.

2016-02-01

We consider the ABF background underlying the η-deformed AdS5 ×S5 sigma model. This background fails to satisfy the standard IIB supergravity equations which indicates that the corresponding sigma model is not Weyl invariant, i.e. does not define a critical string theory in the usual sense. We argue that the ABF background should still define a UV finite theory on a flat 2d world-sheet implying that the η-deformed model is scale invariant. This property follows from the formal relation via T-duality between the η-deformed model and the one defined by an exact type IIB supergravity solution that has 6 isometries albeit broken by a linear dilaton. We find that the ABF background satisfies candidate type IIB scale invariance conditions which for the R-R field strengths are of the second order in derivatives. Surprisingly, we also find that the ABF background obeys an interesting modification of the standard IIB supergravity equations that are first order in derivatives of R-R fields. These modified equations explicitly depend on Killing vectors of the ABF background and, although not universal, they imply the universal scale invariance conditions. Moreover, we show that it is precisely the non-isometric dilaton of the T-dual solution that leads, after T-duality, to modification of type II equations from their standard form. We conjecture that the modified equations should follow from κ-symmetry of the η-deformed model. All our observations apply also to η-deformations of AdS3 ×S3 ×T4and AdS2 ×S2 ×T6models.

Scale invariance of the η-deformed AdS 5 × S 5 superstring, T-duality and modified type II equations

DOE PAGES

Arutyunov, G.; Frolov, S.; Hoare, B.; ...

2015-12-23

We consider the ABF background underlying the η-deformed AdS 5 × S 5 sigma model. This background fails to satisfy the standard IIB supergravity equations which indicates that the corresponding sigma model is not Weyl invariant, i.e. does not define a critical string theory in the usual sense. We argue that the ABF background should still define a UV finite theory on a flat 2d world-sheet implying that the η-deformed model is scale invariant. This property follows from the formal relation via T-duality between the η-deformed model and the one defined by an exact type IIB supergravity solution that hasmore » 6 isometries albeit broken by a linear dilaton. We find that the ABF background satisfies candidate type IIB scale invariance conditions which for the R–R field strengths are of the second order in derivatives. Surprisingly, we also find that the ABF background obeys an interesting modification of the standard IIB supergravity equations that are first order in derivatives of R–R fields. These modified equations explicitly depend on Killing vectors of the ABF background and, although not universal, they imply the universal scale invariance conditions. Moreover, we show that it is precisely the non-isometric dilaton of the T-dual solution that leads, after T-duality, to modification of type II equations from their standard form. We conjecture that the modified equations should follow from κ-symmetry of the η-deformed model. All our observations apply also to η-deformations of AdS 3 × S 3 × T 4 and AdS 2 × S 2 × T 6 models.« less

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease

PubMed Central

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A.

2017-01-01

Abstract Aims: Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Results: Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APPSwe/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9–10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Innovation: Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. Conclusions: We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269–1280. PMID:28264587

A simplified immunoprecipitation method for quantitatively measuring antibody responses in clinical sera samples by using mammalian-produced Renilla luciferase-antigen fusion proteins.

PubMed

Burbelo, Peter D; Goldman, Radoslav; Mattson, Thomas L

2005-08-18

Assays detecting human antigen-specific antibodies are medically useful. However, the usefulness of existing simple immunoassay formats is limited by technical considerations such as sera antibodies to contaminants in insufficiently pure antigen, a problem likely exacerbated when antigen panels are screened to obtain clinically useful data. We developed a novel and simple immunoprecipitation technology for identifying clinical sera containing antigen-specific antibodies and for generating quantitative antibody response profiles. This method is based on fusing protein antigens to an enzyme reporter, Renilla luciferase (Ruc), and expressing these fusions in mammalian cells, where mammalian-specific post-translational modifications can be added. After mixing crude extracts, sera and protein A/G beads together and incubating, during which the Ruc-antigen fusion become immobilized on the A/G beads, antigen-specific antibody is quantitated by washing the beads and adding coelenterazine substrate and measuring light production. We have characterized this technology with sera from patients having three different types of cancers. We show that 20-85% of these sera contain significant titers of antibodies against at least one of five frequently mutated and/or overexpressed tumor-associated proteins. Five of six colon cancer sera tested gave responses that were statistically significantly greater than the average plus three standard deviations of 10 control sera. The results of competition experiments, preincubating positive sera with unmodified E. coli-produced antigens, varied dramatically. This technology has several advantages over current quantitative immunoassays including its relative simplicity, its avoidance of problems associated with E. coli-produced antigens and its use of antigens that can carry mammalian or disease-specific post-translational modifications. This assay should be generally useful for analyzing sera for antibodies recognizing any protein or its post-translational modifications.

A simplified immunoprecipitation method for quantitatively measuring antibody responses in clinical sera samples by using mammalian-produced Renilla luciferase-antigen fusion proteins

PubMed Central

Burbelo, Peter D; Goldman, Radoslav; Mattson, Thomas L

2005-01-01

Background Assays detecting human antigen-specific antibodies are medically useful. However, the usefulness of existing simple immunoassay formats is limited by technical considerations such as sera antibodies to contaminants in insufficiently pure antigen, a problem likely exacerbated when antigen panels are screened to obtain clinically useful data. Results We developed a novel and simple immunoprecipitation technology for identifying clinical sera containing antigen-specific antibodies and for generating quantitative antibody response profiles. This method is based on fusing protein antigens to an enzyme reporter, Renilla luciferase (Ruc), and expressing these fusions in mammalian cells, where mammalian-specific post-translational modifications can be added. After mixing crude extracts, sera and protein A/G beads together and incubating, during which the Ruc-antigen fusion become immobilized on the A/G beads, antigen-specific antibody is quantitated by washing the beads and adding coelenterazine substrate and measuring light production. We have characterized this technology with sera from patients having three different types of cancers. We show that 20–85% of these sera contain significant titers of antibodies against at least one of five frequently mutated and/or overexpressed tumor-associated proteins. Five of six colon cancer sera tested gave responses that were statistically significantly greater than the average plus three standard deviations of 10 control sera. The results of competition experiments, preincubating positive sera with unmodified E. coli-produced antigens, varied dramatically. Conclusion This technology has several advantages over current quantitative immunoassays including its relative simplicity, its avoidance of problems associated with E. coli-produced antigens and its use of antigens that can carry mammalian or disease-specific post-translational modifications. This assay should be generally useful for analyzing sera for antibodies recognizing any protein or its post-translational modifications. PMID:16109166

Brain local and regional neuroglial alterations in Alzheimer's Disease: cell types, responses and implications.

PubMed

Toledano, Adolfo; Álvarez, María-Isabel; Toledano-Díaz, Adolfo; Merino, José-Joaquín; Rodríguez, José Julio

2016-01-01

From birth to death, neurons are dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. Three families have been classically considered within the CNS: astroglia, oligodendroglia and microglia. Many types/subtypes (including NGR2+ cells), with a wide variety of physiological and pathological effects on neurons, have been described using morphological and immunocytochemical criteria. Glio-glial, glio-neuronal and neuro-glial cell signaling and gliotransmission are phenomena that are essential to support brain functions. Morphofunctional changes resulting from the plasticity of all the glial cell types parallel the plastic neuronal changes that optimize the functionality of neuronal circuits. Moreover, neuroglia possesses the ability to adopt a reactive status (gliosis) in which, generally, new functions arise to improve and restore if needed the neural functionality. All these features make neuroglial cells elements of paramount importance when attempting to explain any physiological or pathological processes in the CNS, because they are involved in both, neuroprotection/neurorepair and neurodegeneration. There exist diverse and profound, regional and local, neuroglial changes in all involutive processes (physiological and pathological aging; neurodegenerative disorders, including Alzheimer ´s disease -AD-), but today, the exact meaning of such modifications (the modifications of the different neuroglial types, in time and place), is not well understood. In this review we consider the different neuroglial cells and their responses in order to understand the possible role they fulfill in pathogenesis, diagnosis and treatment (preventive or palliative) of AD. The existence of differentiated and/or concurrent pathogenic and neuro-protective/neuro-restorative astroglial and microglial responses is highlighted.

KSC-98pc1160

NASA Image and Video Library

1998-09-27

KENNEDY SPACE CENTER, FLA. -- The Shuttle Carrier Aircraft with orbiter Atlantis on top touches down at the Shuttle Landing Facility. Atlantis returns home after a 10-month stay in the Palmdale, CA, orbiter processing facility undergoing extensive inspections and modifications. They included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. The flight from Palmdale included a fueling stop in Ft. Hood, TX, and overnight stay at Ft. Campbell, KY. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

KSC-98pc1161

NASA Image and Video Library

1998-09-27

KENNEDY SPACE CENTER, FLA. -- The Shuttle Carrier Aircraft gently lands its piggyback cargo orbiter Atlantis at the Shuttle Landing Facility. Atlantis returns home after a 10-month stay in the Palmdale, CA, orbiter processing facility undergoing extensive inspections and modifications. They included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. The flight from Palmdale included a fueling stop in Ft. Hood, TX, and overnight stay at Ft. Campbell, KY. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

KSC-98pc1159

NASA Image and Video Library

1998-09-27

KENNEDY SPACE CENTER, FLA. -- The Shuttle Carrier Aircraft with orbiter Atlantis on top arrives at the Shuttle Landing Facility. Atlantis returns home after a 10-month stay in the Palmdale, CA, orbiter processing facility undergoing extensive inspections and modifications. They included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. The flight from Palmdale included a fueling stop in Ft. Hood, TX, and overnight stay at Ft. Campbell, KY. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

A new proposal for randomized start design to investigate disease-modifying therapies for Alzheimer disease.

PubMed

Zhang, Richard Y; Leon, Andrew C; Chuang-Stein, Christy; Romano, Steven J

2011-02-01

The increasing prevalence of Alzheimer disease (AD) and lack of effective agents to attenuate progression have accelerated research and development of disease modifying (DM) therapies. The traditional parallel group design and single time point analysis used in the support of past AD drug approvals address symptomatic benefit over relatively short treatment durations. More recent trials investigating disease modification are by necessity longer in duration and require larger sample sizes. Nevertheless, trial design and analysis remain mostly unchanged and may not be adequate to meet the objective of demonstrating disease modification. Randomized start design (RSD) has been proposed as an option to study DM effects, but its application in AD trials may have been hampered by certain methodological challenges. To address the methodological issues that have impeded more extensive use of RSD in AD trial and to encourage other researchers to develop novel design and analysis methodologies to better ascertain DM effects for the next generation of AD therapies, we propose a stepwise testing procedure to evaluate potential DM effects of novel AD therapies. Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog) is used for illustration. We propose to test three hypotheses in a stepwise sequence. The three tests pertain to treatment difference at two separate time points and a difference in the rate of change. Estimation is facilitated by the Mixed-effects Model for Repeated Measures approach. The required sample size is estimated using Monte Carlo simulations and by modeling ADAS-cog data from prior longitudinal AD studies. The greatest advantage of the RSD proposed in this article is its ability to critically address the question on a DM effect. The AD trial using the new approach would be longer (12-month placebo period plus 12-month delay-start period; total 24-month duration) and require more subjects (about 1000 subjects per arm for the non-inferiority margin chosen in the illustration). It would also require additional evaluations to estimate the rate of ADAS-cog change toward the end of the trial. A regulatory claim of disease modification for any compound will likely require additional verification of a drug's effect on a validated biomarker of Alzheimer's pathology. Incorporation of the RSD in AD trials is feasible. With proper trial setup and statistical procedures, this design could support the detection of a disease-modifying effect. In our opinion, a two-phase RSD with a stepwise hypothesis testing procedure could be a reasonable option for future studies.

Model modifications for simulation of flow through stratified rocks in eastern Ohio

USGS Publications Warehouse

Helgesen, J.O.; Razem, A.C.; Larson, S.P.

1982-01-01

A quasi three-dimensional groundwater flow model is being used as part of a study to determine impacts of coal-strip mining on local hydrologic systems. Modifications to the model were necessary to simulate local hydrologic conditions properly. Perched water tables required that the method of calculating vertical flow rate be changed. A head-dependent spring-discharge function and a head-dependent stream aquifer-interchange function were added to the program. Modifications were also made to allow recharge from precipitation to any layer. The modified program, data deck instructions, and sample input and output are presented. (USGS)

Simulator study of the stall departure characteristics of a light general aviation airplane with and without a wing-leading-edge modification

NASA Technical Reports Server (NTRS)

Riley, D. R.

1985-01-01

A six-degree-of-freedom nonlinear simulation was developed for a two-place, single-engine, low-wing general aviation airplane for the stall and initial departure regions of flight. Two configurations, one with and one without an outboard wing-leading-edge modification, were modeled. The math models developed are presented simulation predictions and flight-test data for validation purposes and simulation results for the two configurations for various maneuvers and power settings are compared to show the beneficial influence of adding the wing-leading-edge modification.

Amyloid-β oligomer Aβ*56 induces specific alterations of tau phosphorylation and neuronal signaling

PubMed Central

Amar, Fatou; Sherman, Mathew A.; Rush, Travis; Larson, Megan; Boyle, Gabriel; Chang, Liu; Götz, Jürgen; Buisson, Alain; Lesné, Sylvain E.

2018-01-01

Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer’s disease (AD). Amyloid-β (Aβ) oligomers are implicated in pathological modification and aggregation of the microtubule-associated protein tau. To investigate the specific molecular pathways activated by different assemblies, we isolated various forms of Aβ from Tg2576 mice. We found that the Aβ*56, which is linked with preclinical AD, interacted with NMDA receptors (NMDARs) in primary cortical neurons, increased NMDAR-dependent Ca2+ influx and, consequently, increased intracellular calcium concentrations and the activation of Ca2+-dependent calmodulin kinase IIα (CaMKIIα). In neurons in mice and in culture, activated CaMKIIα induced increased phosphorylation and missorting of tau, which is associated with AD pathology. In contrast, exposure of cultured primary cortical neurons to other oligomeric Aβ forms (dimers and trimers) did not trigger these effects. Our results indicate that distinct Aβ assemblies activate neuronal signaling pathways in a selective manner, and that dissecting the molecular events caused by each may inform more effective therapeutic strategies. PMID:28487416

Worldsheet scattering in AdS3/CFT2

NASA Astrophysics Data System (ADS)

Sundin, Per; Wulff, Linus

2013-07-01

We confront the recently proposed exact S-matrices for AdS 3/ CFT 2 with direct worldsheet calculations. Utilizing the BMN and Near Flat Space (NFS) expansions for strings on AdS 3 × S 3 × S 3 × S 1 and AdS 3 × S 3 × T 4 we compute both tree-level and one-loop scattering amplitudes. Up to some minor issues we find nice agreement in the tree-level sector. At the one-loop level however we find that certain non-zero tree-level processes, which are not visible in the exact solution, contribute, via the optical theorem, and give an apparent mismatch for certain amplitudes. Furthermore we find that a proposed one-loop modification of the dressing phase correctly reproduces the worldsheet calculation while the standard Hernandez-Lopez phase does not. We also compute several massless to massless processes.

Melanoma cultures show different susceptibility towards E1A-, E1B-19 kDa- and fiber-modified replication-competent adenoviruses.

PubMed

Schmitz, M; Graf, C; Gut, T; Sirena, D; Peter, I; Dummer, R; Greber, U F; Hemmi, S

2006-06-01

Replicating adenovirus (Ad) vectors with tumour tissue specificity hold great promise for treatment of cancer. We have recently constructed a conditionally replicating Ad5 AdDeltaEP-TETP inducing tumour regression in a xenograft mouse model. For further improvement of this vector, we introduced four genetic modifications and analysed the viral cytotoxicity in a large panel of melanoma cell lines and patient-derived melanoma cells. (1) The antiapoptotic gene E1B-19 kDa (Delta19 mutant) was deleted increasing the cytolytic activity in 18 of 21 melanoma cells. (2) Introduction of the E1A 122-129 deletion (Delta24 mutant), suggested to attenuate viral replication in cell cycle-arrested cells, did not abrogate this activity and increased the cytolytic activity in two of 21 melanoma cells. (3) We inserted an RGD sequence into the fiber to extend viral tropism to alphav integrin-expressing cells, and (4) swapped the fiber with the Ad35 fiber (F35) enhancing the tropism to malignant melanoma cells expressing CD46. The RGD-fiber modification strongly increased cytolysis in all of the 11 CAR-low melanoma cells. The F35 fiber-chimeric vector boosted the cytotoxicity in nine of 11 cells. Our results show that rational engineering additively enhances the cytolytic potential of Ad vectors, a prerequisite for the development of patient-customized viral therapies.

Calcium Treatment for FeSi-killed Fe-13 Pct Cr Stainless Steel with Various Top Slag Compositions

NASA Astrophysics Data System (ADS)

Wang, Qi; Wang, Lijun; Zhai, Jun; Li, Jianmin; Chou, Kuochih

2018-02-01

Calcium treatment of Fe-13 pct Cr stainless steel, with inclusion modification as its main purpose, was evaluated on a laboratory scale. The stability diagram of Ca-Al was obtained using the FactSage software and could be divided into three parts based on the [Al] content: the ultra-low-Al region, the low-Al region, and the medium-high-Al region. Each of these regions required different amounts of calcium for inclusion modification. The ferrosilicon deoxidation product could be modified into low melting temperature inclusions by a CaO-SiO2 top slag in the ultra-low-Al region ([Al] content less than 40 ppm). Calcium treatment was necessary to modify the ferrosilicon deoxidation product into low melting temperature inclusions in the low-Al region ([Al] content from 40 to 100 ppm) for the CaO-SiO2-Al2O3 top slag. Calcium addition has a "liquid window" where adding calcium can accelerate inclusion modification. Adding calcium for 15 and 30 minutes resulted in complete modification times of 45 and 60 minutes, respectively, which indicates that early calcium treatment can produce plastic inclusions sooner. The relationship between the steel and inclusion content was determined by fitting the experimental data in the low-Al region. An appropriate range of T.Ca/T.O (total calcium content/total oxygen content) for inclusion modification is 0.99 to 1.44.

Ad-Hoc Networks and the Mobile Application Security System (MASS)

DTIC Science & Technology

2006-01-01

solution to this problem that addresses critical aspects of security in ad-hoc mobile application networks. This approach involves preventing unauthorized...modification of a mobile application , both by other applications and by hosts, and ensuring that mobile code is authentic and authorized. These...capabilities constitute the Mobile Application Security System (MASS). The MASS applies effective, robust security to mobile application -based systems

Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer’s disease

PubMed Central

Gredilla, Ricardo; Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A.; Stevnsner, Tinna

2010-01-01

Brain aging is associated with synaptic decline and cognitive impairment. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). In mitochondria, base excision repair (BER) is the main DNA repair pathway for base modifications such as deamination and oxidation, and constitutes an important mechanism to avoid accumulation of mtDNA mutations. Synaptic function is highly dependent on mitochondria, and in the current study we have investigated BER in synaptosomes of mouse brain during normal aging and in an AD model. Synaptosomes are isolated synapses in membranous structures produced by subcellular fractionation of brain tissue. They include the whole presynaptic terminal as well as portions of the postsynaptic terminal. Synaptosomes contain the molecular machinery necessary for uptake, storage, and release of neurotransmitters, including synaptic vesicles and mitochondria. BER activities were measured in synaptosomal fractions from young and old mice and from pre-symptomatic and symptomatic AD mice harboring mutated APP, Tau and PS1 (3xTgAD). During normal aging, a reduction in the BER capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of pre-symptomatic and symptomatic AD mice. Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed. PMID:20708822

Controversies in Alzheimer’s disease drug development

PubMed Central

Cummings, Jeffrey L.

2010-01-01

Understanding of the pathophysiological basis of Alzheimer’s disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer’s disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described. PMID:18925488

Post-polymerization functionalization of polyolefins.

PubMed

Boaen, Nicole K; Hillmyer, Marc A

2005-03-01

Polyolefins are macromolecular alkanes and include the most familiar and most commercially produced plastic, polyethylene. The low cost of these materials combined with their diverse and desirable property profiles drive such large-scale production. One property that renders polyolefins so attractive is their resistance to harsh chemical environments. However, this attribute becomes a severe limitation when attempting to chemically convert these plastics into value-added materials. Functionalization of polymers is a useful methodology for the generation of new materials with wide ranging applications, and this tutorial review describes both new and established methods for the post-polymerization modification of polyolefins.

Ionospheric tomography using Faraday rotation of Automatic Dependent Surveillance Broadcast (UHF) signals Ionospheric Measurement From ADS-B Signals

NASA Astrophysics Data System (ADS)

Cushley, Alex Clay

The proposed launch of a CubeSat carrying the first space-borne ADS-B receiver by RMCC will create a unique opportunity to study the modification of radio waves following propagation through the ionosphere as the signals propagate from the transmitting aircraft to the passive satellite receiver(s). Experimental work is described which successfully demonstrated that ADS-B data can be used to reconstruct two-dimensional electron density maps of the ionosphere using techniques from computerized tomography. Ray-tracing techniques are used to determine the characteristics of individual waves, including the wave path and the state of polarization at the satellite receiver. The modelled Faraday rotation is determined and converted to TEC along the ray-paths. The resulting TEC is used as input for CIT using ART. This study concentrated on meso-scale structures 100--1000 km in horizontal extent. The primary scientific interest of this thesis was to show the feasibility of a new method to image the ionosphere and obtain a better understanding of magneto-ionic wave propagation. Keywords: Automatic Dependent Surveillance-Broadcast (ADS-B), Faraday rotation, electromagnetic (EM) waves, radio frequency (RF) propagation, ionosphere (auroral, irregularities, instruments and techniques), electron density profile, total electron content (TEC), computer ionospheric tomography (CIT), algebraic reconstruction technique (ART).

Resistively Loaded Microstrip-Patch Antenna

NASA Technical Reports Server (NTRS)

Bailey, Marion C.

1993-01-01

Strips of thin resistive material added near two edges of conventional micro-strip-patch antenna. Bandwidth doubled by simple modification. Optimum bandwidth performance obtained by adjustment of shapes, resistances, and locations of resistive strips.

Recent Advances in the LEWICE Icing Model

NASA Technical Reports Server (NTRS)

Wright, William B.; Addy, Gene; Struk, Peter; Bartkus, Tadas

2015-01-01

This paper will describe two recent modifications to the Glenn ICE software. First, a capability for modeling ice crystals and mixed phase icing has been modified based on recent experimental data. Modifications have been made to the ice particle bouncing and erosion model. This capability has been added as part of a larger effort to model ice crystal ingestion in aircraft engines. Comparisons have been made to ice crystal ice accretions performed in the NRC Research Altitude Test Facility (RATFac). Second, modifications were made to the run back model based on data and observations from thermal scaling tests performed in the NRC Altitude Icing Tunnel.

78 FR 78705 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

..., and equipment to perform this type of modification, repair, and access. UAL also stated that certain... Association (ATA) of America Code 25, Equipment/ Furnishings; and Code 53, Fuselage. (e) Reason This AD was...

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor.

PubMed

Bussiere, Renaud; Lacampagne, Alain; Reiken, Steven; Liu, Xiaoping; Scheuerman, Valerie; Zalk, Ran; Martin, Cécile; Checler, Frederic; Marks, Andrew R; Chami, Mounia

2017-06-16

Alteration of ryanodine receptor (RyR)-mediated calcium (Ca 2+ ) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca 2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca 2+ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenergic signaling, and altered Ca 2+ signaling via leaky RyR2 channels. Thus, post-translational modifications of RyR occur downstream of Aβ through a β2-adrenergic signaling cascade that activates PKA. RyR2 remodeling in turn enhances βAPP processing. Importantly, pharmacological stabilization of the binding of calstabin2 to RyR2 channels, which prevents Ca 2+ leakage, or blocking the β2-adrenergic signaling cascade reduced βAPP processing and the production of Aβ in APPswe-expressing SH-SY5Y cells. We conclude that targeting RyR-mediated Ca 2+ leakage may be a therapeutic approach to treat AD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

KSC-98pc1162

NASA Image and Video Library

1998-09-27

KENNEDY SPACE CENTER, FLA. -- The Shuttle Carrier Aircraft rolls to a stop with its piggyback cargo orbiter Atlantis at the Shuttle Landing Facility. In the background is the Vehicle Assembly Building. Atlantis returns home after a 10-month stay in the Palmdale, CA, orbiter processing facility undergoing extensive inspections and modifications. They included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. The flight from Palmdale included a fueling stop in Ft. Hood, TX, and overnight stay at Ft. Campbell, KY. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

KSC-98pc1163

NASA Image and Video Library

1998-09-27

KENNEDY SPACE CENTER, FLA. -- Stairs are rolled to the forward opening of the Shuttle Carrier Aircraft with its piggyback cargo, the orbiter Atlantis after it rolls to a stop at the Shuttle Landing Facility. Atlantis returns home after a 10-month stay in the Palmdale, CA, orbiter processing facility undergoing extensive inspections and modifications. They included several upgrades enabling it to support International Space Station missions, such as adding an external airlock for ISS docking missions and installing thinner, lighter thermal protection blankets for weight reduction which will allow it to haul heavier cargo. The flight from Palmdale included a fueling stop in Ft. Hood, TX, and overnight stay at Ft. Campbell, KY. Atlantis will undergo preparations in the Orbiter Processing Facility at KSC for its planned flight in June 1999

Disparity modifications and the emotional effects of stereoscopic images

NASA Astrophysics Data System (ADS)

Kawai, Takashi; Atsuta, Daiki; Tomiyama, Yuya; Kim, Sanghyun; Morikawa, Hiroyuki; Mitsuya, Reiko; Häkkinen, Jukka

2014-03-01

This paper describes a study that focuses on disparity changes in emotional scenes of stereoscopic (3D) images, in which an examination of the effects on pleasant and arousal was carried out by adding binocular disparity to 2D images that evoke specific emotions, and applying disparity modification based on the disparity analysis of famous 3D movies. From the results of the experiment, for pleasant, a significant difference was found only for the main effect of the emotions. On the other hand, for arousal, there was a trend of increasing the evaluation values in the order 2D condition, 3D condition and 3D condition applied the disparity modification for happiness, surprise, and fear. This suggests the possibility that binocular disparity and the modification affect arousal.

Computer program documentation modified version of the JA70 aerodynamic heating computer program H800 (MINIVER with a DISSPLA plot package

NASA Technical Reports Server (NTRS)

Olmedo, L.

1980-01-01

The changes, modifications, and inclusions which were adapted to the current version of the MINIVER program are discussed. Extensive modifications were made to various subroutines, and a new plot package added. This plot package is the Johnson Space Center DISSPLA Graphics System currently driven under an 1110 EXEC 8 configuration. User instructions on executing the MINIVER program are provided and the plot package is described.

SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters.

PubMed

Oh, Chun-do; Lu, Yue; Liang, Shoudan; Mori-Akiyama, Yuko; Chen, Di; de Crombrugghe, Benoit; Yasuda, Hideyo

2014-01-01

The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes.

Does a medical history of hypertension influence disclosing genetic testing results of the risk for salt-sensitive hypertension, in primary care?

PubMed

Okayama, Masanobu; Takeshima, Taro; Harada, Masanori; Ae, Ryusuke; Kajii, Eiji

2016-01-01

Disclosing genetic testing results may contribute to the prevention and management of many common diseases. However, whether the presence of a disease influences these effects is unclear. This study aimed to clarify the difference in the effects of disclosing genetic testing results of the risk for developing salt-sensitive hypertension on the behavioral modifications with respect to salt intake in hypertensive and nonhypertensive patients. A cross-sectional study using a self-administered questionnaire was conducted for outpatients aged >20 years (N=2,237) at six primary care clinics and hospitals in Japan. The main factors assessed were medical histories of hypertension, salt preferences, reduced salt intakes, and behavior modifications for reducing salt intake. Behavioral modifications of participants were assessed using their behavior stages before and after disclosure of the hypothetical genetic testing results. Of the 2,237 participants, 1,644 (73.5%) responded to the survey. Of these respondents, 558 (33.9%) patients were hypertensive and 1,086 (66.1%) were nonhypertensive. After being notified of the result "If with genetic risk", the nonhypertensive participants were more likely to make positive behavioral modifications compared to the hypertensive patients among all participants and in those aged <65 years (adjusted relative ratio [ad-RR], 1.76; 95% confidence interval, 1.12-2.76 and ad-RR, 1.99; 1.11-3.57, respectively). In contrast, no difference in negative behavioral modifications between hypertensive and nonhypertensive patients was detected after being notified of the result "If without genetic risk" (ad-RR, 1.05; 95% confidence interval, 0.70-1.57). The behavior of modifying salt intake after disclosure of the genetic testing results differed between hypertensive and nonhypertensive patients. Disclosing a genetic risk for salt-sensitive hypertension was likely to cause nonhypertensive patients, especially those aged <65 years, to improve their behavior regarding salt intake. We conclude that disclosing genetic testing results could help prevent hypertension, and that the doctor should communicate the genetic testing results to those patients with a medical history of hypertension, or those who are at risk of developing hypertension.

Incorporation of Methionine Analogues Into Bombyx mori Silk Fibroin for Click Modifications.

PubMed

Teramoto, Hidetoshi; Kojima, Katsura

2015-05-01

Bombyx mori silk fibroin incorporating three methionine (Met) analogues-homopropargylglycine (Hpg), azidohomoalanine (Aha), and homoallylglycine (Hag)-can be produced simply by adding them to the diet of B. mori larvae. The Met analogues are recognized by methionyl-tRNA synthetase, bound to tRNA(Met), and used for the translation of adenine-uracil-guanine (AUG) codons competitively with Met. In the presence of the standard amount of Met in the diet, incorporation of these analogues remains low. Lowering the amount of Met in the diet drastically improves incorporation efficiencies. Alkyne and azide groups in Hpg and Aha incorporated into silk fibroin can be selectively modified with Cu-catalyzed azide-alkyne cycloaddition reactions (click chemistry). Since Met residues exist only at the N-terminal domain of the fibroin heavy chain and in the fibroin light chain, good access to the reactive sites is expected and domain-selective modifications are possible without perturbing other major domains, including repetitive domains. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of X-31 Flight and Ground-Based Yawing Moment Asymmetries at High Angles of Attack

NASA Technical Reports Server (NTRS)

Cobleigh, Brent R.; Croom, Mark A.

2001-01-01

Significant yawing moment asymmetries were encountered during the high-angle-of-attack envelope expansion of the two X-31 aircraft. These asymmetries caused position saturations of the thrust-vectoring vanes and trailing-edge flaps during some stability-axis rolling maneuvers at high angles of attack. The two test aircraft had different asymmetry characteristics, and ship two has asymmetries that vary as a function of Reynolds number. Several aerodynamic modifications have been made to the X-31 forebody with the goal of minimizing the asymmetry. These modifications include adding transition strips on the forebody and noseboom, using two different length strakes, and increasing nose bluntness. Ultimately, a combination of forebody strakes, nose blunting, and noseboom transition strips reduced the yawing moment asymmetry enough to fully expand the high-angle-of-attack envelope. Analysis of the X-31 flight data is reviewed and compared to wind-tunnel and water-tunnel measurements. Several lessons learned are outlined regarding high-angle-of-attack configuration design and ground testing.

Diarrhea in the International Traveler.

PubMed

Duchini; Rodgers

1999-06-01

International travelers to developing countries have a 40% risk of developing a diarrheal illness, usually acute and occasionally chronic. Preventive measures, including diet and lifestyle modifications, are highly recommended but may not be sufficient. Prophylaxis with bismuth subsalicylate or an antimicrobial should be considered in travelers with immunodeficiencies, co-morbid conditions, achlorhydria, or those who cannot afford a loss of time. Oral rehydration is the primary goal of therapy. Bismuth-subsalicylate is a first-line agent for treatment of milder cases with less than three watery bowel movements per day and prominent nausea. Use of an antibiotic is indicated for more severe cases or in the presence of fever, dysentery, or severe dehydration. A short course of a quinolone is highly effective, safe and well tolerated. Antimicrobial resistance among enteropathogens is growing and appropriate therapeutic modifications should be considered according to specific geographic areas. Metronidazole may be empirically added in those cases that do not respond to quinolones. Specific guidelines for particular pathogens are highlighted.

Modifications to holographic entanglement entropy in warped CFT

NASA Astrophysics Data System (ADS)

Song, Wei; Wen, Qiang; Xu, Jianfei

2017-02-01

In [1] it was observed that asymptotic boundary conditions play an important role in the study of holographic entanglement beyond AdS/CFT. In particular, the Ryu-Takayanagi proposal must be modified for warped AdS3 (WAdS3) with Dirichlet boundary conditions. In this paper, we consider AdS3 and WAdS3 with Dirichlet-Neumann boundary conditions. The conjectured holographic duals are warped conformal field theories (WCFTs), featuring a Virasoro-Kac-Moody algebra. We provide a holographic calculation of the entanglement entropy and Rényi entropy using AdS3/WCFT and WAdS3/WCFT dualities. Our bulk results are consistent with the WCFT results derived by Castro-Hofman-Iqbal using the Rindler method. Comparing with [1], we explicitly show that the holographic entanglement entropy is indeed affected by boundary conditions. Both results differ from the Ryu-Takayanagi proposal, indicating new relations between spacetime geometry and quantum entanglement for holographic dualities beyond AdS/CFT.

The Effect of Decision Training on Career Decision-Making Competence

DTIC Science & Technology

1980-08-01

Campbell and Stanley (1966) as one of the three " true " experi- mental designs. Several modifications were made: (a) a stratified rather than a simple...information from conversations with friends. Horoscope : information from horoscopes written daily for an astrological sign. Newspaper ad: information from...handbook, a friend, horoscope , newspaper ad, and personal ex- perience) the information is written on 3" x 5" index cards. The cards are contained in

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2012 CFR

2012-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2014 CFR

2014-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2013 CFR

2013-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

Major food sources of calories, added sugars, and saturated fat and their contribution to essential nutrient intakes in the U.S. diet: data from the National Health and Nutrition Examination Survey (2003-2006).

PubMed

Huth, Peter J; Fulgoni, Victor L; Keast, Debra R; Park, Keigan; Auestad, Nancy

2013-08-08

The risk of chronic disease cannot be predicted simply by the content of a single nutrient in a food or food group in the diet. The contribution of food sources of calories, added sugars and saturated fat (SFA) to intakes of dietary fiber and micronutrients of public health importance is also relevant to understanding the overall dietary impact of these foods. Identify the top food sources of calories, added sugars and SFA in the U.S. diet and quantify their contribution to fiber and micronutrient intakes. Single 24-hour dietary recalls (Day 1) collected from participants ≥2 years (n = 16,822) of the What We Eat in America, National Health and Nutrition Examination Survey (WWEIA/NHANES 2003-2006) were analyzed. All analyses included sample weights to account for the survey design. Calorie and nutrient intakes from foods included contributions from disaggregated food mixtures and tabulated by rank order. No one food category contributes more than 7.2% of calories to the overall U.S. diet, but half of the top 10 contribute 10% or more of total dietary fiber and micronutrients. Three of the top 10 sources of calories and SFA (beef, milk and cheese) contribute 46.3% of the calcium, 49.5% of the vitamin D, 42.3% of the vitamin B12 as well as other essential nutrients to the American diet. On the other hand, foods categorized as desserts, snacks, or beverages, contribute 13.6% of total calories, 83% of added sugar intake, and provide little or no nutritional value. Including food components of disaggregated recipes more accurately estimated the contribution of foods like beef, milk or cheese to overall nutrient intake compared to "as consumed" food categorizations. Some food sources of calories, added sugars and SFA make major contributions to American dietary fiber and micronutrient intakes. Dietary modifications targeting reductions in calories, added sugar, or SFA need to take these key micronutrient sources into account so as not to have the unintended consequence of lowering overall dietary quality.

Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

PubMed Central

Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

2014-01-01

High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only APP and Aβ. The purpose of this review, therefore, is to examine the above-mentioned issues and discuss the pros and cons of the cholesterol-AD hypothesis, and the involvement of other lipids in the mevalonate pathway, such as isoprenoids and oxysterols, in AD. PMID:24329875

Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43.

PubMed

Belousova, Natalya; Mikheeva, Galina; Xiong, Chiyi; Stagg, Loren J; Gagea, Mihai; Fox, Patricia S; Bassett, Roland L; Ladbury, John E; Braun, Michael B; Stehle, Thilo; Li, Chun; Krasnykh, Victor

2016-08-16

Unique molecular properties of species D adenoviruses (Ads)-the most diverse yet underexplored group of Ads-have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies.

Performance of the AOAC use-dilution method with targeted modifications: collaborative study.

PubMed

Tomasino, Stephen F; Parker, Albert E; Hamilton, Martin A; Hamilton, Gordon C

2012-01-01

The U.S. Environmental Protection Agency (EPA), in collaboration with an industry work group, spearheaded a collaborative study designed to further enhance the AOAC use-dilution method (UDM). Based on feedback from laboratories that routinely conduct the UDM, improvements to the test culture preparation steps were prioritized. A set of modifications, largely based on culturing the test microbes on agar as specified in the AOAC hard surface carrier test method, were evaluated in a five-laboratory trial. The modifications targeted the preparation of the Pseudomonas aeruginosa test culture due to the difficulty in separating the pellicle from the broth in the current UDM. The proposed modifications (i.e., the modified UDM) were compared to the current UDM methodology for P. aeruginosa and Staphylococcus aureus. Salmonella choleraesuis was not included in the study. The goal was to determine if the modifications reduced method variability. Three efficacy response variables were statistically analyzed: the number of positive carriers, the log reduction, and the pass/fail outcome. The scope of the collaborative study was limited to testing one liquid disinfectant (an EPA-registered quaternary ammonium product) at two levels of presumed product efficacies, high and low. Test conditions included use of 400 ppm hard water as the product diluent and a 5% organic soil load (horse serum) added to the inoculum. Unfortunately, the study failed to support the adoption of the major modification (use of an agar-based approach to grow the test cultures) based on an analysis of method's variability. The repeatability and reproducibility standard deviations for the modified method were equal to or greater than those for the current method across the various test variables. However, the authors propose retaining the frozen stock preparation step of the modified method, and based on the statistical equivalency of the control log densities, support its adoption as a procedural change to the current UDM. The current UDM displayed acceptable responsiveness to changes in product efficacy; acceptable repeatability across multiple tests in each laboratory for the control counts and log reductions; and acceptable reproducibility across multiple laboratories for the control log density values and log reductions. Although the data do not support the adoption of all modifications, the UDM collaborative study data are valuable for assessing sources of method variability and a reassessment of the performance standard for the UDM.

Ionospheric modification at twice the electron cyclotron frequency.

PubMed

Djuth, F T; Pedersen, T R; Gerken, E A; Bernhardt, P A; Selcher, C A; Bristow, W A; Kosch, M J

2005-04-01

In 2004, a new transmission band was added to the HAARP high-frequency ionospheric modification facility that encompasses the second electron cyclotron harmonic at altitudes between approximately 220 and 330 km. Initial observations indicate that greatly enhanced airglow occurs whenever the transmission frequency approximately matches the second electron cyclotron harmonic at the height of the upper hybrid resonance. This is the reverse of what happens at higher electron cyclotron harmonics. The measured optical emissions confirm the presence of accelerated electrons in the plasma.

High spectral resolution lidar at the university of wisconsin-madison

NASA Astrophysics Data System (ADS)

Razenkov, Ilya I.; Eloranta, Edwin W.

2018-04-01

This paper describes the modifications done on the University of Wisconsin-Madison High Spectral Resolution Lidar (HSRL) that improved the instrument's performance. The University of Wisconsin HSRL lidars designed by our group at the Space Science and Engineering Center were deployed in numerous field campaigns in various locations around the world. Over the years the instruments have undergone multiple modifications that improved the performance and added new measurement capabilities such as atmospheric temperature profile and extinction cross-section measurements.

Aerodynamic Investigation of C-141 Leading Edge Modifications for Cruise Drag Reduction--Test 2.

DTIC Science & Technology

1981-04-01

82171.6 1 ((1 I III 11 1 - MI( RO( )FY R~ I IN II I (I 041PI AD A099 6 6 2 _ AFWAL-TR-81-3032 AERODYNAMIC INVESTIGATION OF C-141 LEADING EDGE MODIFICATIONS...FOR CRUISE DRAG REDUCTION -- TEST 2 Robert A. Large, Captain, USAF Aerodynamics & Airframe Branch Aeromechanics Division Flight Dynamics Laboratory...KEMloUA Ch, Aerodynamics & Airframe Br Aeromechanics Division FOR THE COMMANDER hie" Aeromechanics Division "If your address has changed, if you wish to

Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43

PubMed Central

Belousova, Natalya; Mikheeva, Galina; Xiong, Chiyi; Stagg, Loren J.; Gagea, Mihai; Fox, Patricia S.; Bassett, Roland L.; Ladbury, John E.; Braun, Michael B.; Stehle, Thilo; Li, Chun; Krasnykh, Victor

2016-01-01

Unique molecular properties of species D adenoviruses (Ads)—the most diverse yet underexplored group of Ads—have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies. PMID:27462785

76 FR 58722 - Airworthiness Directives; the Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-22

...- 200B, 747-200C, 747-200F, 747-400F, 747SR, and 747SP series airplanes, without a stretched upper deck or stretched upper deck modification. The existing AD currently requires repetitive inspections for...

76 FR 69123 - Airworthiness Directives; Cessna Aircraft Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

..., and the attachment hardware with a new rudder stop modification kit for certain Cessna Models 150F... with the portion of the AD per compliance with 14 CFR 43.9. * * * * * Issued in Kansas City, Missouri...

Space Station Furnace Facility Management Information System (SSFF-MIS) Development

NASA Technical Reports Server (NTRS)

Meade, Robert M.

1996-01-01

This report summarizes the chronology, results, and lessons learned from the development of the SSFF-MIS. This system has been nearly two years in development and has yielded some valuable insights into specialized MIS development. General: In December of 1994, the Camber Corporation and Science Applications International Corporation (SAIC) were contracted to design, develop, and implement a MIS for Marshall Space Flight Center's Space Station Furnace Facility Project. The system was to be accessible from both EBM-Compatible PC and Macintosh platforms. The system was required to contain data manually entered into the MIS as well as data imported from other MSFC sources. Electronic interfaces were established for each data source and retrieval was to be performed at prescribed time intervals. The SOW requirement that predominantly drove the development software selection was the dual-platform (IBM-PC and Macintosh) requirement. The requirement that the system would be maintained by Government personnel influenced the selection of Commercial Off-the-shelf software because of its inherent stability and readily available documentation and support. Microsoft FoxPro Professional 2.6 for Windows and Macintosh was selected as the development tool. This is a software development tool that has been in use for many years. It is stable and powerful. Microsoft has since released the replacement for this product, Microsoft Visual FoxPro, but at the time of this development, it was only available on the Windows platform. The initial contract included included the requirement for capabilities relating to the Work- and Organizational Breakdown Structures, cost (plan and actuals), workforce (plan and actuals), critical path scheduling, trend analysis, procurements and contracts, interface to manufacturing, Safety and Mission Assurance, risk analysis, and technical performance indicators. It also required full documentation of the system and training of users. During the course of the contract, the requirements for Safety and Mission Assurance interface, risk analysis, and technical performance indicators were deleted. Additional capabilities were added as reflected in the Contract Chronology below. Modification 4 added the requirement for Support Contractor manpower data, the ability to manually input data not imported from non-nal sources, a general 'health' indicator screen, and remote usage. Mod 6 included the ability to change the level of planning of Civil Service Manpower at any time and the ability to manually enter Op Codes in the manufacturing data where such codes were not provided by the EMPACS database. Modification 9 included a number of changes to report contents and formats. Modification 11 required the preparation of a detailed System Design Document.

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

Audette, L.G.

As originally conceived, the project called for modification of existing, commercially available stoker components. We experienced substantial delays in procurement, caused by supply backlogs and a major fire at the plant which ultimately provided the main stoker frame. Added to the problems was the bankruptcy of the L.W. Gay Stoveworks, where the project was to be located. Ultimately, parts were assembled and a combustion chamber was constructed at the Leyden Energy Corporation of Shelburne Falls, Massachusetts. A firing chamber with provision for measuring various physical and combustion parameters was constructed. The stoker, with appropriate modifications, was installed. Combustion analysis equipmentmore » was procured, and coal and wood pellets were stoked in order to test the effectiveness of the modifications. This report describes the configuration of the demonstration stoker and its modifications, as well as the testing exercise performed over the course of the project. 10 figs.« less

When gene medication is also genetic modification--regulating DNA treatment.

PubMed

Foss, Grethe S; Rogne, Sissel

2007-07-26

The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

Surfactant replacement therapy: development of criteria for appropriate use. Ohio State University Hospitals.

PubMed

Gardner, D K

1992-08-01

At The Ohio State University (OSU) Hospitals, DUE criteria were established when colfosceril palmitate, a synthetic surfactant, was added to the formulary in January 1991. The DUE criteria were designed to assure appropriate drug use, educate physicians, and establish an effective way to monitor drug use and patient outcome (ie, response rate and complications). The criteria include a mechanism for evaluation and modification of the guidelines, as necessary. In addition, a review process will be used to determine the therapy's cost effectiveness and to serve as a guideline for making recommendations on other surfactant formulations as they become available.

Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions

NASA Astrophysics Data System (ADS)

Rood, Mark T. M.; Spa, Silvia J.; Welling, Mick M.; Ten Hove, Jan Bart; van Willigen, Danny M.; Buckle, Tessa; Velders, Aldrik H.; van Leeuwen, Fijs W. B.

2017-01-01

The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.

Renewable synthetic diesel fuel from triglycerides and organic waste materials

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

Hillard, J.C.; Strassburger, R.S.

1986-03-01

A renewable, synthetic diesel fuel has been developed that employs ethanol and organic waste materials. These organic materials, such as soybean oil or animal fats, are hydrolized to yield a mixture of solid soap like materials and glycerol. These soaps, now soluble in ethanol, are blended with ethanol; the glycerol is nitrated and added as well as castor oil when necessary. The synthetic fuel is tailored to match petroleum diesel fuel in viscosity, lubricity and cetane quality and, therefore, does not require any engine modifications. Testing in a laboratory engine and in a production Oldsmobile Cutlass has revealed that thismore » synthetic fuel is superior to petroleum diesel fuel in vehicle efficiency, cetane quality, combustion noise, cold start characteristics, exhaust odor and emissions. Performance characteristics are indistinguishable from those of petroleum diesel fuel. These soaps are added to improve the calorific value, lubricity and cetane quality of the ethanol. The glycerol from the hydrolysis process is nitrated and added to the ethanol as an additional cetane quality improver. Caster oil is added to the fuel when necessary to match the viscosity and lubricity of petroleum diesel fuel as well as to act as a corrosion inhibitor, thereby, precluding any engine modifications. The cetane quality of the synthetic fuel is better than that of petroleum diesel as the fuel carries its own oxygen. The synthetic fuel is also completely miscible with petroleum diesel.« less

The Adenovirus Genome Contributes to the Structural Stability of the Virion

PubMed Central

Saha, Bratati; Wong, Carmen M.; Parks, Robin J.

2014-01-01

Adenovirus (Ad) vectors are currently the most commonly used platform for therapeutic gene delivery in human gene therapy clinical trials. Although these vectors are effective, many researchers seek to further improve the safety and efficacy of Ad-based vectors through detailed characterization of basic Ad biology relevant to its function as a vector system. Most Ad vectors are deleted of key, or all, viral protein coding sequences, which functions to not only prevent virus replication but also increase the cloning capacity of the vector for foreign DNA. However, radical modifications to the genome size significantly decreases virion stability, suggesting that the virus genome plays a role in maintaining the physical stability of the Ad virion. Indeed, a similar relationship between genome size and virion stability has been noted for many viruses. This review discusses the impact of the genome size on Ad virion stability and emphasizes the need to consider this aspect of virus biology in Ad-based vector design. PMID:25254384

Studies on human fetal lens crystallins under oxidative stress and protective effects of tea polyphenols.

PubMed

Xiang, H; Pan, S; Li, S

1998-09-01

To investigate the oxidative modification of water-soluble crystallins of human fetal lens with H2O2 and fourteen metal ions with or without EDTA. Tea-polyphenols (TP) was added to above solutions in order to testing their antioxidative abilities. The experiments were performed at 37 degrees C with final concentration of 2.5 mg/ml protein, 0.1 mM metal ions, 0.3 mM EDTA and 1.0 mM H2O2. Then the TP was added to the solution with CuSO4 and H2O2, after 5 or 24 hours, the crystallins were analysed with SDS-PAGE and IEF. There were marked oxidative modifications of lens protein in H2O2 and copper without EDTA. In SDS-PAGE patterns, we found an increase in those species above of bands higher than 30 kD and some diffuse bands from 30 to 17 kD after 5 hours. In IEF patterns, there were a general increase on acidity with loss of the more basic species. When the TP was added, there was not any difference with control group. The results indicate that exposure of water-soluble protein to H2O2 and copper leads to covalent crosslinking and cleavage of polypeptides. After 24 hours, the development of the oxidative modifications of crystallins continues, comparison with the catalytic strength, copper ions stronger than the iron ions. On other hand, this work reported that the anti-oxidative action of TP is strong.

Modification of CuI based Hole Transport Material for Solid State DSSC Application

NASA Astrophysics Data System (ADS)

Hanif, Q. A.; Ramelan, A. H.; Saputri, L. N. M. Z.; Wahyuningsih, S.

2018-03-01

Modification of Hole Transport Material (HTM) with addition of tetramethylethylenediamine (TMED) and ammonium thiocyanate (NH4SCN) have been conducted. Copper Iodide (CuI) were used as the main component of HTM. Several volume variations of TMED (0.1; 0.2; and 0.4 mL) was added into 0.05 M CuI solutions. While TMED: NH4SCN ratio were 1:1,1:2,2:1 also introduced to the dissolved CuI. Optical properties of these materials showed the band gap energy value ranging from 2.38 to 3.79 eV. The conductivity of HTM has been measured and showed the maximum value in CuI added with 0.4 mL TMED = 0.29 S m-1, and ratio of TMED: NH4SCN=2:1 added into CuI = 0.39 S m-1, these value were increased compared to the CuI conductivity itself (0.26 S m-1). The effect of this modification towards SS DSSC efficiency also has been monitored. The SS DSSC construction consists of TiO2 nanorods sensitized by N3, HTM, and platinum as a counter electrode. The performance of SS DSSC showed rising efficiency as follows TiO2|N3|CuI

Epigenetic Contribution of the Myosin Light Chain Kinase Gene to the Risk for Acute Respiratory Distress Syndrome

PubMed Central

Szilágyi, Keely L.; Liu, Cong; Zhang, Xu; Wang, Ting; Fortman, Jeffrey D.; Zhang, Wei; Garcia, Joe G.N.

2016-01-01

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (~30-40%). Health disparities exist with African descent subjects (ADs) exhibiting greater mortality than European descent individuals (EDs). Myosin light chain kinase (MLCK) is encoded by MYLK whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, i.e. cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK CpGs between ARDS patients and ICU controls overall and by ethnicity in a nested case control study of 39 ARDS cases and 75 non-ARDS intensive care unit controls. Two MYLK CpG sites (cg03892735, cg23344121) were differentially modified between ARDS subjects and controls (p<0.05; q<0.25) in a logistic regression model, where no effect modification from ethnicity or age was found. One CpG site was associated with ARDS in patients less than 58 years old, cg19611163 (intron 19,20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2,3) and CpG (cg16212219, intron 31,32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting mQTL (modified cytosine quantitative trait loci) were identified using linear regression between local genetic variants and modification levels for two ARDS-associated CpGs (cg23344121, cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL, suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS. PMID:27543902

Nanoscale patterning of a self-assembled monolayer by modification of the molecule-substrate bond.

PubMed

Shen, Cai; Buck, Manfred

2014-01-01

The intercalation of Cu at the interface of a self-assembled monolayer (SAM) and a Au(111)/mica substrate by underpotential deposition (UPD) is studied as a means of high resolution patterning. A SAM of 2-(4'-methylbiphenyl-4-yl)ethanethiol (BP2) prepared in a structural phase that renders the Au substrate completely passive against Cu-UPD, is patterned by modification with the tip of a scanning tunneling microscope. The tip-induced defects act as nucleation sites for Cu-UPD. The lateral diffusion of the metal at the SAM-substrate interface and, thus, the pattern dimensions are controlled by the deposition time. Patterning down to the sub-20 nm range is demonstrated. The difference in strength between the S-Au and S-Cu bond is harnessed to develop the latent Cu-UPD image into a patterned binary SAM. Demonstrated by the exchange of BP2 by adamantanethiol (AdSH) this is accomplished by a sequence of reductive desorption of BP2 in Cu free areas followed by adsorption of AdSH. The appearance of Au adatom islands upon the thiol exchange suggests that the interfacial structures of BP2 and AdSH SAMs are different.

Potential for Sonic Boom Reduction of the Boeing HSCT

NASA Technical Reports Server (NTRS)

Haglund, George T.

1999-01-01

The HSR sonic boom technology program includes a goal of reducing the objectionable aspects of sonic boom. Earlier HSCT sonic boom studies considered achieving significant sonic boom reduction by the use of arrow-wing planforms and detailed shaping of the airplane to produce shaped waveforms (non N-waves) at the ground. While these design efforts were largely successful, the added risk and cost of the airplanes were judged to be unacceptable. The objective of the current work is to explore smaller configuration refinements that could lead to reduced sonic boom impact, within design and operational constraints. A somewhat modest target of 10% reduction in sonic boom maximum overpressure was selected to minimize the effect on the configuration performance. This work was a joint NASA/Industry effort, utilizing the respective strengths of team members at Boeing, NASA Langley, and NASA Ames. The approach used was to first explore a wide range of modifications and airplane characteristics for their effects on sonic boom and drag, using classical Modified Linear Theory (MLT) methods. CFD methods were then used to verify promising, modifications and to analyze modifications for which the MLT methods were not appropriate. The tea m produced a list of configuration changes with their effects on sonic boom and, in some cases, an estimate of the drag penalty. The most promising modifications were applied to produce a boom-softened derivative of the baseline Boeing High Speed Civil Transport (HSCT) configuration. This boom-softened configuration was analyzed in detail for the reduce sonic boom impact and also for the effect of the configuration modifications on drag, weight, and overall performance relative to the baseline.

DataSpread: Unifying Databases and Spreadsheets.

PubMed

Bendre, Mangesh; Sun, Bofan; Zhang, Ding; Zhou, Xinyan; Chang, Kevin ChenChuan; Parameswaran, Aditya

2015-08-01

Spreadsheet software is often the tool of choice for ad-hoc tabular data management, processing, and visualization, especially on tiny data sets. On the other hand, relational database systems offer significant power, expressivity, and efficiency over spreadsheet software for data management, while lacking in the ease of use and ad-hoc analysis capabilities. We demonstrate DataSpread, a data exploration tool that holistically unifies databases and spreadsheets. It continues to offer a Microsoft Excel-based spreadsheet front-end, while in parallel managing all the data in a back-end database, specifically, PostgreSQL. DataSpread retains all the advantages of spreadsheets, including ease of use, ad-hoc analysis and visualization capabilities, and a schema-free nature, while also adding the advantages of traditional relational databases, such as scalability and the ability to use arbitrary SQL to import, filter, or join external or internal tables and have the results appear in the spreadsheet. DataSpread needs to reason about and reconcile differences in the notions of schema, addressing of cells and tuples, and the current "pane" (which exists in spreadsheets but not in traditional databases), and support data modifications at both the front-end and the back-end. Our demonstration will center on our first and early prototype of the DataSpread, and will give the attendees a sense for the enormous data exploration capabilities offered by unifying spreadsheets and databases.

DataSpread: Unifying Databases and Spreadsheets

PubMed Central

Bendre, Mangesh; Sun, Bofan; Zhang, Ding; Zhou, Xinyan; Chang, Kevin ChenChuan; Parameswaran, Aditya

2015-01-01

Spreadsheet software is often the tool of choice for ad-hoc tabular data management, processing, and visualization, especially on tiny data sets. On the other hand, relational database systems offer significant power, expressivity, and efficiency over spreadsheet software for data management, while lacking in the ease of use and ad-hoc analysis capabilities. We demonstrate DataSpread, a data exploration tool that holistically unifies databases and spreadsheets. It continues to offer a Microsoft Excel-based spreadsheet front-end, while in parallel managing all the data in a back-end database, specifically, PostgreSQL. DataSpread retains all the advantages of spreadsheets, including ease of use, ad-hoc analysis and visualization capabilities, and a schema-free nature, while also adding the advantages of traditional relational databases, such as scalability and the ability to use arbitrary SQL to import, filter, or join external or internal tables and have the results appear in the spreadsheet. DataSpread needs to reason about and reconcile differences in the notions of schema, addressing of cells and tuples, and the current “pane” (which exists in spreadsheets but not in traditional databases), and support data modifications at both the front-end and the back-end. Our demonstration will center on our first and early prototype of the DataSpread, and will give the attendees a sense for the enormous data exploration capabilities offered by unifying spreadsheets and databases. PMID:26900487

Composition and location of simulated lake-shore redds influence incubation success in kokanee, Oncorhynchus nerka

USGS Publications Warehouse

Fincel, M.J.; Chipps, S.R.; Bennett, D.H.

2009-01-01

Methods for improving spawning habitat for lakeshore spawning kokanee, Oncorhynchus nerka (Walbaum), were explored by quantifying incubation success of embryos exposed to three substrate treatments in Lake Pend Oreille, Idaho, USA. Substrate treatments included no modification that used existing gravels in the lake (EXISTING), a cleaned substrate treatment where existing gravels were sifted in the water column to remove silt (CLEANED) and the addition of new, silt-free gravel (ADDED). Incubation success was evaluated using Whitlock-Vibert incubation boxes buried within each substrate treatment that contained recently fertilised embryos. Upon retrieval, live and dead sac fry and eyed eggs were enumerated to determine incubation success (sac fry and eyed eggs ?? 100/number of fertilised embryos). Incubation success varied significantly among locations and redd treatments. In general, incubation success among ADDED redds (0.0-13.0%) was significantly lower than that for EXISTING (1.4-61.0%) and CLEANED (0.4-62.5%) redds. Adding new gravel to spawning areas changed the morphometry of the gravel-water interface and probably exposed embryos to disturbance from wave action and reduced embryo survival. Moreover, efforts to improve spawning habitat for lakeshore spawning kokanee should consider water depth and location (e.g. protected shorelines) as important variables. Adding clean gravel to existing spawning areas may provide little benefit if water depth or lake-bottom morphometry are altered. ?? 2009 Blackwell Publishing Ltd.

Administrative Responses to AD/HD.

ERIC Educational Resources Information Center

Beyda, Sandra D.; Zentall, Sydney S.

1998-01-01

States that teacher resistance to making classroom modifications for students with Attention Deficit/Hyperactivity Disorder is partially due to a lack of administrative support. Offers numerous ways that administrators can offer support to teachers. Also gives information on alternative discipline policies. (MKA)

75 FR 42339 - List of Approved Spent Fuel Storage Casks: NAC-MPC System, Revision 6

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

...; minor design modifications to the Vertical Concrete Cask (VCC) incorporating design features from the... (ALARA) principles; an increase in the concrete pad compression strength from 4000 psi to 6000 psi; added...

The Role of Biomarkers in Clinical Trials for Alzheimer Disease

PubMed Central

Thal, Leon J.; Kantarci, Kejal; Reiman, Eric M.; Klunk, William E.; Weiner, Michael W.; Zetterberg, Henrik; Galasko, Douglas; Praticò, Domenico; Griffin, Sue; Schenk, Dale; Siemers, Eric

2007-01-01

Biomarkers are likely to be important in the study of Alzheimer disease (AD) for a variety of reasons. A clinical diagnosis of Alzheimer disease is inaccurate even among experienced investigators in about 10% to 15% of cases, and biomarkers might improve the accuracy of diagnosis. Importantly for the development of putative disease-modifying drugs for Alzheimer disease, biomarkers might also serve as indirect measures of disease severity. When used in this way, sample sizes of clinical trials might be reduced, and a change in biomarker could be considered supporting evidence of disease modification. This review summarizes a meeting of the Alzheimer’s Association’s Research Roundtable, during which existing and emerging biomarkers for AD were evaluated. Imaging biomarkers including volumetric magnetic resonance imaging and positron emission tomography assessing either glucose utilization or ligands binding to amyloid plaque are discussed. Additionally, biochemical biomarkers in blood or cerebrospinal fluid are assessed. Currently appropriate uses of biomarkers in the study of Alzheimer disease, and areas where additional work is needed, are discussed. PMID:16493230

77 FR 15638 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

...We are revising an earlier proposed airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -700C, -800, - 900 and -900ER series airplanes. That NPRM proposed to require modifying the fluid drain path in the wing leading edge area, forward of the wing front spar, and doing all applicable related investigative and corrective actions. That NPRM was prompted by a report of leaking fuel from the wing leading edge area at the inboard end of the number 5 leading edge slat. This action revises that NPRM by including installing new seal disks on the latches in the fuel shutoff valve access door as part of the modification and by specifying that certain inspections are detailed inspections. This action also revises the applicability to include additional airplanes. We are proposing this AD to prevent flammable fluids from accumulating in the wing leading edge, and draining inboard and onto the engine exhaust nozzle, which could result in a fire. Since these actions impose an additional burden over that proposed in the NPRM, we are reopening the comment period to allow the public the chance to comment on these proposed changes.

Adaptive Flight Control Design with Optimal Control Modification on an F-18 Aircraft Model

NASA Technical Reports Server (NTRS)

Burken, John J.; Nguyen, Nhan T.; Griffin, Brian J.

2010-01-01

In the presence of large uncertainties, a control system needs to be able to adapt rapidly to regain performance. Fast adaptation is referred to as the implementation of adaptive control with a large adaptive gain to reduce the tracking error rapidly; however, a large adaptive gain can lead to high-frequency oscillations which can adversely affect the robustness of an adaptive control law. A new adaptive control modification is presented that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. The modification is based on the minimization of the Y2 norm of the tracking error, which is formulated as an optimal control problem. The optimality condition is used to derive the modification using the gradient method. The optimal control modification results in a stable adaptation and allows a large adaptive gain to be used for better tracking while providing sufficient robustness. A damping term (v) is added in the modification to increase damping as needed. Simulations were conducted on a damaged F-18 aircraft (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) with both the standard baseline dynamic inversion controller and the adaptive optimal control modification technique. The results demonstrate the effectiveness of the proposed modification in tracking a reference model.

Shooting string holography of jet quenching at RHIC and LHC

DOE PAGES

Ficnar, Andrej; Gubser, Steven S.; Gyulassy, Miklos

2014-10-13

We derive a new formula for jet energy loss using finite endpoint momentum shooting strings initial conditions in SYM plasmas to overcome the difficulties of previous falling string holographic scenarios. We apply the new formula to compute the nuclear modification factor R AA and the elliptic flow parameter v 2 of light hadrons at RHIC and LHC. We show furthermore that Gauss–Bonnet quadratic curvature corrections to the AdS 5 geometry improve the agreement with the recent data.

Shooting string holography of jet quenching at RHIC and LHC

NASA Astrophysics Data System (ADS)

Ficnar, Andrej; Gubser, Steven S.; Gyulassy, Miklos

2014-11-01

We derive a new formula for jet energy loss using finite endpoint momentum shooting strings initial conditions in SYM plasmas to overcome the difficulties of previous falling string holographic scenarios. We apply the new formula to compute the nuclear modification factor RAA and the elliptic flow parameter v2 of light hadrons at RHIC and LHC. We show furthermore that Gauss-Bonnet quadratic curvature corrections to the AdS5 geometry improve the agreement with the recent data.

Starch: chemistry, microstructure, processing and enzymatic degradation

USDA-ARS?s Scientific Manuscript database

Starch is recognized as one of the most abundant and important commodities containing value added attributes for a vast number of industrial applications. Its chemistry, structure, property and susceptibility to various chemical, physical and enzymatic modifications offer a high technological value ...

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

PubMed

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

Passive Solar still: Recent advancement in design and related Performance.

PubMed

Awasthi, Anuradha; Kumari, Kanchan; Panchal, Hitesh; Sathyamurthy, Ravishankar

2018-05-31

Present review paper mainly focuses on different varieties of solar stills and highlights mostly the passive solar still with advanced modifications in the design and development of material, single and multi-effect solar still with augmentation of different materials, energy absorbing, insulators, mechanisms of heat and mass transfer to improve the loss of heat and enhance the productivity of solar still. The cost-benefit analysis along with the progressive advancement for solar stills is the major highlights of this review. To increase the output of solar still nowadays, applications of advance modifications is one of the promising tools, and it is anticipated that shortly more vigor will be added in this area with the modifications in designs of solar stills.

Detecting Precontact Anthropogenic Microtopographic Features in a Forested Landscape with Lidar: A Case Study from the Upper Great Lakes Region, AD 1000-1600

PubMed Central

Howey, Meghan C. L.; Sullivan, Franklin B.; Tallant, Jason; Kopple, Robert Vande; Palace, Michael W.

2016-01-01

Forested settings present challenges for understanding the full extent of past human landscape modifications. Field-based archaeological reconnaissance in forests is low-efficiency and most remote sensing techniques are of limited utility, and together, this means many past sites and features in forests are unknown. Archaeologists have increasingly used light detection and ranging (lidar), a remote sensing tool that uses pulses of light to measure reflecting surfaces at high spatial resolution, to address these limitations. Archaeology studies using lidar have made significant progress identifying permanent structures built by large-scale complex agriculturalist societies. Largely unaccounted for, however, are numerous small and more practical modifications of landscapes by smaller-scale societies. Here we show these may also be detectable with lidar by identifying remnants of food storage pits (cache pits) created by mobile hunter-gatherers in the upper Great Lakes during Late Precontact (ca. AD 1000–1600) that now only exist as subtle microtopographic features. Years of intensive field survey identified 69 cache pit groups between two inland lakes in northern Michigan, almost all of which were located within ~500 m of a lakeshore. Applying a novel series of image processing techniques and statistical analyses to a high spatial resolution DTM we created from commercial-grade lidar, our detection routine identified 139 high potential cache pit clusters. These included most of the previously known clusters as well as several unknown clusters located >1500 m from either lakeshore, much further from lakeshores than all previously identified cultural sites. Food storage is understood to have emerged regionally as a risk-buffering strategy after AD 1000 but our results indicate the current record of hunter-gatherer cache pit food storage is markedly incomplete and this practice and its associated impact on the landscape may be greater than anticipated. Our study also demonstrates the potential of harnessing commercial-grade lidar for other fine-grained archaeology applications. PMID:27584031

Detecting Precontact Anthropogenic Microtopographic Features in a Forested Landscape with Lidar: A Case Study from the Upper Great Lakes Region, AD 1000-1600.

PubMed

Howey, Meghan C L; Sullivan, Franklin B; Tallant, Jason; Kopple, Robert Vande; Palace, Michael W

2016-01-01

Forested settings present challenges for understanding the full extent of past human landscape modifications. Field-based archaeological reconnaissance in forests is low-efficiency and most remote sensing techniques are of limited utility, and together, this means many past sites and features in forests are unknown. Archaeologists have increasingly used light detection and ranging (lidar), a remote sensing tool that uses pulses of light to measure reflecting surfaces at high spatial resolution, to address these limitations. Archaeology studies using lidar have made significant progress identifying permanent structures built by large-scale complex agriculturalist societies. Largely unaccounted for, however, are numerous small and more practical modifications of landscapes by smaller-scale societies. Here we show these may also be detectable with lidar by identifying remnants of food storage pits (cache pits) created by mobile hunter-gatherers in the upper Great Lakes during Late Precontact (ca. AD 1000-1600) that now only exist as subtle microtopographic features. Years of intensive field survey identified 69 cache pit groups between two inland lakes in northern Michigan, almost all of which were located within ~500 m of a lakeshore. Applying a novel series of image processing techniques and statistical analyses to a high spatial resolution DTM we created from commercial-grade lidar, our detection routine identified 139 high potential cache pit clusters. These included most of the previously known clusters as well as several unknown clusters located >1500 m from either lakeshore, much further from lakeshores than all previously identified cultural sites. Food storage is understood to have emerged regionally as a risk-buffering strategy after AD 1000 but our results indicate the current record of hunter-gatherer cache pit food storage is markedly incomplete and this practice and its associated impact on the landscape may be greater than anticipated. Our study also demonstrates the potential of harnessing commercial-grade lidar for other fine-grained archaeology applications.

Modifications to ELIM-COMPLIP and MOSLS for Mobilization Strength Planning and Management for Enlisted Personnel.

DTIC Science & Technology

1982-05-01

AD-AllA 143 GENERAL RESEARCH CORP MCLEAN VA MANAGEMENT SYSTEMS DIV F/G 5/9 MoD IFI CATI ONS TO ELIM-COMPL.IP AND MOSLS FOR MOBILIZATION STRENG--ETC...111111____22 I Report 1257-02-CR I Modifications I To ELIM-COMPLIP and MOSLS for I ’ Mobilization Strength Planning and Management -~ For Enlisted...Personnel By: I K.D. Midlamn, Project Manage W.E. Bartlett E. Bergs B.W. Holz M.J. Maloney I May 1982 MANAGEMENT SYSTEMS DIVISIONI GENERAL ( RESEARCH

Improving 6061-Al Grain Growth and Penetration across HIP-Bonded Clad Interfaces in Monolithic Fuel Plates: Initial Studies

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

Hackenberg, Robert E.; McCabe, Rodney J.; Montalvo, Joel D.

2013-05-06

Grain penetration across aluminum-aluminum cladding interfaces in research reactor fuel plates is desirable and was obtained by a legacy roll-bonding process, which attained 20-80% grain penetration. Significant grain penetration in monolithic fuel plates produced by Hot Isostatic Press (HIP) fabrication processing is equally desirable but has yet to be attained. The goal of this study was to modify the 6061-Al in such a way as to promote a much greater extent of crossinterface grain penetration in monolithic fuel plates fabricated by the HIP process. This study documents the outcomes of several strategies attempted to attain this goal. The grain responsemore » was characterized using light optical microscopy (LOM) electron backscatter diffraction (EBSD) as a function of these prospective process modifications done to the aluminum prior to the HIP cycle. The strategies included (1) adding macroscopic gaps in the sandwiches to enhance Al flow, (2) adding engineering asperities to enhance Al flow, (3) adding stored energy (cold work), and (4) alternative cleaning and coating. Additionally, two aqueous cleaning methods were compared as baseline control conditions. The results of the preliminary scoping studies in all the categories are presented. In general, none of these approaches were able to obtain >10% grain penetration. Recommended future work includes further development of macroscopic grooving, transferred-arc cleaning, and combinations of these with one another and with other processes.« less

Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer.

PubMed

Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q; Schmidt, Christoph Q Andreas; Wortmann, Andreas; Bachem, Max G; Simmet, Thomas; Kochanek, Stefan

2015-01-01

Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety.

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

PubMed Central

Reyes, Juan F.; Fu, Yifan; Vana, Laurel; Kanaan, Nicholas M.; Binder, Lester I.

2011-01-01

A substantial body of evidence suggests that nitrative injury contributes to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. Previously, we showed in vitro that within the tau protein the N-terminal tyrosine residues (Y18 and Y29) are more susceptible to nitrative modifications than other tyrosine sites (Y197 and Y394). Using site-specific antibodies to nitrated tau at Y18 and Y29, we identified tau nitrated in both glial (Y18) and neuronal (Y29) tau pathologies. In this study, we report the characterization of two novel monoclonal antibodies, Tau-nY197 and Tau-nY394, recognizing tau nitrated at Y197 and Y394, respectively. By Western blot analysis, Tau-nY197 labeled soluble tau and insoluble paired helical filament proteins (PHF-tau) nitrated at Y197 from control and AD brain samples. Tau-nY394 failed to label soluble tau isolated from control or severe AD samples, but labeled insoluble PHF-tau to a limited extent. Immunohistochemical analysis using Tau-nY197 revealed the hallmark tau pathology associated with AD; Tau-nY394 did not detect any pathological lesions characteristic of the disorder. These data suggest that a subset of the hallmark pathological inclusions of AD contain tau nitrated at Y197. However, nitration at Y197 was also identified in soluble tau from all control samples, including those at Braak stage 0, suggesting that nitration at this site in the proline-rich region of tau may have normal biological functions in the human brain. PMID:21514440

Hydra 1 data display system

NASA Technical Reports Server (NTRS)

Hodgkins, R. L.; Osgood, D. R.

1968-01-01

System, named Hydra, generates charts, graphs, and printed matter on slides or conventional negatives and positives, and combines these media with a capability of storage on magnetic tape for future updating to accommodate engineering changes or contract modifications to be readily added to basic data.

Adenovirus Type 5 Viral Particles Pseudotyped with Mutagenized Fiber Proteins Show Diminished Infectivity of Coxsackie B-Adenovirus Receptor-Bearing Cells

PubMed Central

Jakubczak, John L.; Rollence, Michele L.; Stewart, David A.; Jafari, Jonathon D.; Von Seggern, Dan J.; Nemerow, Glen R.; Stevenson, Susan C.; Hallenbeck, Paul L.

2001-01-01

A major limitation of adenovirus type 5 (Ad5)-based gene therapy, the inability to target therapeutic genes to selected cell types, is attributable to the natural tropism of the virus for the widely expressed coxsackievirus-adenovirus receptor (CAR) protein. Modifications of the Ad5 fiber knob domain have been shown to alter the tropism of the virus. We have developed a novel system to rapidly evaluate the function of modified fiber proteins in their most relevant context, the adenoviral capsid. This transient transfection/infection system combines transfection of cells with plasmids that express high levels of the modified fiber protein and infection with Ad5.βgal.ΔF, an E1-, E3-, and fiber-deleted adenoviral vector encoding β-galactosidase. We have used this system to test the adenoviral transduction efficiency mediated by a panel of fiber protein mutants that were proposed to influence CAR interaction. A series of amino acid modifications were incorporated via mutagenesis into the fiber expression plasmid, and the resulting fiber proteins were subsequently incorporated onto adenoviral particles. Mutations located in the fiber knob AB and CD loops demonstrated the greatest reduction in fiber-mediated gene transfer in HeLa cells. We also observed effects on transduction efficiency with mutations in the FG loop, indicating that the binding site may extend to the adjacent monomer in the fiber trimer and in the HI loop. These studies support the concept that modification of the fiber knob domain to diminish or ablate CAR interaction should result in a detargeted adenoviral vector that can be combined simultaneously with novel ligands for the development of a systemically administered, targeted adenoviral vector. PMID:11222722

International Space Station United States Laboratory Module Water Recovery Management Subsystem Verification from Flight 5A to Stage ULF2

NASA Technical Reports Server (NTRS)

Williams, David E.; Labuda, Laura

2009-01-01

The International Space Station (ISS) Environmental Control and Life Support (ECLS) system comprises of seven subsystems: Atmosphere Control and Supply (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), Vacuum System (VS), Water Recovery and Management (WRM), and Waste Management (WM). This paper provides a summary of the nominal operation of the United States (U.S.) Laboratory Module WRM design and detailed element methodologies utilized during the Qualification phase of the U.S. Laboratory Module prior to launch and the Qualification of all of the modification kits added to it from Flight 5A up and including Stage ULF2.

An Overview of Modifications Applied to a Turbulence Response Analysis Method for Flexible Aircraft Configurations

NASA Technical Reports Server (NTRS)

Funk, Christie J.

2013-01-01

A software program and associated methodology to study gust loading on aircraft exists for a classification of geometrically simplified flexible configurations. This program consists of a simple aircraft response model with two rigid and three flexible symmetric degrees of freedom and allows for the calculation of various airplane responses due to a discrete one-minus-cosine gust as well as continuous turbulence. Simplifications, assumptions, and opportunities for potential improvements pertaining to the existing software program are first identified, then a revised version of the original software tool is developed with improved methodology to include more complex geometries, additional excitation cases, and output data so as to provide a more useful and accurate tool for gust load analysis. Revisions are made in the categories of aircraft geometry, computation of aerodynamic forces and moments, and implementation of horizontal tail mode shapes. In order to improve the original software program to enhance usefulness, a wing control surface and horizontal tail control surface is added, an extended application of the discrete one-minus-cosine gust input is employed, a supplemental continuous turbulence spectrum is implemented, and a capability to animate the total vehicle deformation response to gust inputs in included. These revisions and enhancements are implemented and an analysis of the results is used to validate the modifications.

Supportive intervention using a mobile phone in behavior modification.

PubMed

Hareva, David H; Okada, Hiroki; Kitawaki, Tomoki; Oka, Hisao

2009-04-01

The authors previously developed a mobile ecological momentary assessment (EMA) system as a real-time data collection device using a mobile phone. In this study, a real-time advice function and real-time reporting function were added to the previous system as a supportive intervention. The improved system was found to work effectively and was applied to several clinical cases, including patients with depressive disorder, dizziness, smoking habit, and bronchial asthma. The average patient compliance rate was high (89%) without the real-time advice and higher (93%) with the advice. The trends in clinical data for patients using a mobile EMA with/without the new function were analyzed for up to several months. In the case of dizziness, an improving trend in its clinical data was observed after applying the real-time advice, and in the case of depressive disorder, a stabilizing trend was observed. The mobile EMA system with the real-time advice function could be useful as a supportive intervention in behavior modification and for motivating patients in self-management of their disease.

Holographic Jet Quenching

NASA Astrophysics Data System (ADS)

Ficnar, Andrej

In this dissertation we study the phenomenon of jet quenching in quark-gluon plasma using the AdS/CFT correspondence. We start with a weakly coupled, perturbative QCD approach to energy loss, and present a Monte Carlo code for computation of the DGLV radiative energy loss of quarks and gluons at an arbitrary order in opacity. We use the code to compute the radiated gluon distribution up to n=9 order in opacity, and compare it to the thin plasma (n=1) and the multiple soft scattering (n=infinity) approximations. We furthermore show that the gluon distribution at finite opacity depends in detail on the screening mass mu and the mean free path lambda. In the next part, we turn to the studies of how heavy quarks, represented as "trailing strings" in AdS/CFT, lose energy in a strongly coupled plasma. We study how the heavy quark energy loss gets modified in a "bottom-up" non-conformal holographic model, constructed to reproduce some properties of QCD at finite temperature and constrained by fitting the lattice gauge theory results. The energy loss of heavy quarks is found to be strongly sensitive to the medium properties. We use this model to compute the nuclear modification factor RAA of charm and bottom quarks in an expanding plasma with Glauber initial conditions, and comment on the range of validity of the model. The central part of this thesis is the energy loss of light quarks in a strongly coupled plasma. Using the standard model of "falling strings", we present an analytic derivation of the stopping distance of light quarks, previously available only through numerical simulations, and also apply it to the case of Gauss-Bonnet higher derivative gravity. We then present a general formula for computing the instantaneous energy loss in non-stationary string configurations. Application of this formula to the case of falling strings reveals interesting phenomenology, including a modified Bragg-like peak at late times and an approximately linear path dependence. Based on these results, we develop a phenomenological model of light quark energy loss and use it compute the nuclear modification factor RAA of light quarks in an expanding plasma. Comparison with the LHC pion suppression data shows that, although RAA has the right qualitative structure, the overall magnitude is too low, indicating that the predicted jet quenching is too strong. In the last part of the thesis we consider a novel idea of introducing finite momentum at endpoints of classical (bosonic and supersymmetric) strings, and the phenomenological consequences of this proposal on the energy loss of light quarks. We show that in a general curved background, finite momentum endpoints must propagate along null geodesics and that the distance they travel in an AdS5-Schwarzschild background is greater than in the previous treatments of falling strings. We also argue that this leads to a more realistic description of energetic quarks, allowing for an unambiguous way of distinguishing between the energy in the dual hard probe and the energy in the color fields surrounding it. This proposal also naturally allows for a clear and simple definition of the instantaneous energy loss. Using this definition and the "shooting string" initial conditions, we develope a new formula for light quark energy loss. Finally, we apply this formula to compute the nuclear modification factor RAA of light hadrons at RHIC and LHC, which, after the inclusion of the Gauss-Bonnet quadratic curvature corrections to the AdS5 geometry, shows a reasonably good agreement with the recent data.

Method modification of the Legipid® Legionella fast detection test kit.

PubMed

Albalat, Guillermo Rodríguez; Broch, Begoña Bedrina; Bono, Marisa Jiménez

2014-01-01

Legipid(®) Legionella Fast Detection is a test based on combined magnetic immunocapture and enzyme-immunoassay (CEIA) for the detection of Legionella in water. The test is based on the use of anti-Legionella antibodies immobilized on magnetic microspheres. Target microorganism is preconcentrated by filtration. Immunomagnetic analysis is applied on these preconcentrated water samples in a final test portion of 9 mL. The test kit was certified by the AOAC Research Institute as Performance Tested Method(SM) (PTM) No. 111101 in a PTM validation which certifies the performance claims of the test method in comparison to the ISO reference method 11731-1998 and the revision 11731-2004 "Water Quality: Detection and Enumeration of Legionella pneumophila" in potable water, industrial water, and waste water. The modification of this test kit has been approved. The modification includes increasing the target analyte from L. pneumophila to Legionella species and adding an optical reader to the test method. In this study, 71 strains of Legionella spp. other than L. pneumophila were tested to determine its reactivity with the kit based on CEIA. All the strains of Legionella spp. tested by the CEIA test were confirmed positive by reference standard method ISO 11731. This test (PTM 111101) has been modified to include a final optical reading. A methods comparison study was conducted to demonstrate the equivalence of this modification to the reference culture method. Two water matrixes were analyzed. Results show no statistically detectable difference between the test method and the reference culture method for the enumeration of Legionella spp. The relative level of detection was 93 CFU/volume examined (LOD50). For optical reading, the LOD was 40 CFU/volume examined and the LOQ was 60 CFU/volume examined. Results showed that the test Legipid Legionella Fast Detection is equivalent to the reference culture method for the enumeration of Legionella spp.

Major food sources of calories, added sugars, and saturated fat and their contribution to essential nutrient intakes in the U.S. diet: data from the national health and nutrition examination survey (2003–2006)

PubMed Central

2013-01-01

Background The risk of chronic disease cannot be predicted simply by the content of a single nutrient in a food or food group in the diet. The contribution of food sources of calories, added sugars and saturated fat (SFA) to intakes of dietary fiber and micronutrients of public health importance is also relevant to understanding the overall dietary impact of these foods. Objective Identify the top food sources of calories, added sugars and SFA in the U.S. diet and quantify their contribution to fiber and micronutrient intakes. Methods Single 24-hour dietary recalls (Day 1) collected from participants ≥2 years (n = 16,822) of the What We Eat in America, National Health and Nutrition Examination Survey (WWEIA/NHANES 2003–2006) were analyzed. All analyses included sample weights to account for the survey design. Calorie and nutrient intakes from foods included contributions from disaggregated food mixtures and tabulated by rank order. Results No one food category contributes more than 7.2% of calories to the overall U.S. diet, but half of the top 10 contribute 10% or more of total dietary fiber and micronutrients. Three of the top 10 sources of calories and SFA (beef, milk and cheese) contribute 46.3% of the calcium, 49.5% of the vitamin D, 42.3% of the vitamin B12 as well as other essential nutrients to the American diet. On the other hand, foods categorized as desserts, snacks, or beverages, contribute 13.6% of total calories, 83% of added sugar intake, and provide little or no nutritional value. Including food components of disaggregated recipes more accurately estimated the contribution of foods like beef, milk or cheese to overall nutrient intake compared to “as consumed” food categorizations. Conclusions Some food sources of calories, added sugars and SFA make major contributions to American dietary fiber and micronutrient intakes. Dietary modifications targeting reductions in calories, added sugar, or SFA need to take these key micronutrient sources into account so as not to have the unintended consequence of lowering overall dietary quality. PMID:23927718

Exploring Elements of Fun to Motivate Youth to Do Cognitive Bias Modification.

PubMed

Boendermaker, Wouter J; Boffo, Marilisa; Wiers, Reinout W

2015-12-01

Heavy drinking among young adults poses severe health risks, including development of later addiction problems. Cognitive retraining of automatic appetitive processes related to alcohol (so-called cognitive bias modification [CBM]) may help to prevent escalation of use. Although effective as a treatment in clinical patients, the use of CBM in youth proves more difficult, as motivation in this group is typically low, and the paradigms used are often viewed as boring and tedious. This article presents two separate studies that focused on three approaches that may enhance user experience and motivation to train: a serious game, a serious game in a social networking context, and a mobile application. In the Game Study, 77 participants performed a regular CBM training, aimed at response matching, a gamified version, or a placebo version of that training. The gamified version was presented as a stand-alone game or in the context of a social network. In the Mobile Study, 64 participants completed a different CBM training, aimed at approach bias, either on a computer or on their mobile device. Although no training effects were found in the Game Study, adding (social) game elements did increase aspects of the user experience and motivation to train. The mobile training appeared to increase motivation to train in terms how often participants trained, but this effect disappeared after controlling for baseline motivation to train. Adding (social) game elements can increase motivation to train, and mobile training did not underperform compared with the regular training in this sample, which warrants more research into motivational elements for CBM training in younger audiences.

Benefits of a 4th Ice Class in the Simulated Radar Reflectivities of Convective Systems Using a Bulk Microphysics Scheme

NASA Technical Reports Server (NTRS)

Lang, Stephen E.; Tao, Wei-Kuo; Chern, Jiun-Dar; Wu, Di; Li, Xiaowen

2015-01-01

Numerous cloud microphysical schemes designed for cloud and mesoscale models are currently in use, ranging from simple bulk to multi-moment, multi-class to explicit bin schemes. This study details the benefits of adding a 4th ice class (hail) to an already improved 3-class ice bulk microphysics scheme developed for the Goddard Cumulus Ensemble model based on Rutledge and Hobbs (1983,1984). Besides the addition and modification of several hail processes from Lin et al. (1983), further modifications were made to the 3-ice processes, including allowing greater ice super saturation and mitigating spurious evaporationsublimation in the saturation adjustment scheme, allowing graupelhail to become snow via vapor growth and hail to become graupel via riming, and the inclusion of a rain evaporation correction and vapor diffusivity factor. The improved 3-ice snowgraupel size-mapping schemes were adjusted to be more stable at higher mixing rations and to increase the aggregation effect for snow. A snow density mapping was also added. The new scheme was applied to an intense continental squall line and a weaker, loosely-organized continental case using three different hail intercepts. Peak simulated reflectivities agree well with radar for both the intense and weaker case and were better than earlier 3-ice versions when using a moderate and large intercept for hail, respectively. Simulated reflectivity distributions versus height were also improved versus radar in both cases compared to earlier 3-ice versions. The bin-based rain evaporation correction affected the squall line case more but did not change the overall agreement in reflectivity distributions.

Reducing drag of a commuter train, using engine exhaust momentum

NASA Astrophysics Data System (ADS)

Ha, Dong Keun

The objective of this thesis was to perform numerical investigations of two different methods of injecting fluid momentum into the air flow above a commuter train to reduce its drag. Based on previous aerodynamic modifications of heavy duty trucks in improving fuel efficiency, two structural modifications were designed and applied to a Metrolink Services commuter train in the Los Angeles (LA) County area to reduce its drag and subsequently improve fuel efficiency. The first modification was an L-shaped channel, added to the exhaust cooling fan above the locomotive roof to divert and align the exhaust gases in the axial direction. The second modification was adding an airfoil shaped lid over the L-shape channel, to minimize the drag of the perturbed structure, and thus reduce the overall drag. The computational fluid dynamic (CFD) software CCM+ from CD-Adapco with the ?-? turbulence model was used for the simulations. A single train set which consists of three vehicles: one locomotive, one trailer car and one cab car were used. All the vehicles were modeled based on the standard Metrolink fleet train size. The wind speed was at 90 miles per hour (mph), which is the maximum speed for the Orange County Metrolink line. Air was used as the exhaust gas in the simulation. The temperature of the exhausting air emitting out of the cooling fan on the roof was 150 F and the average fan speed was 120 mph. Results showed that with the addition of the lid, momentum injection results in reduced flow separation and pressure recovery behind the locomotive, which reduces the overall drag by at least 30%.

Chemical modification of uniform soils and soils with high/low plasticity index.

DOT National Transportation Integrated Search

2016-08-01

The addition of chemicals into the subgrade has been widely used during construction to improve the soil properties. The chemicals, often Lime Kiln Dust (LKD) and Portland cement, are added to the soil to improve its workability, compactability and e...

77 FR 9211 - South Atlantic Fishery Management Council; Public Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... Panel; Ad Hoc Data Collection Committee; Law Enforcement Committee; Spiny Lobster Committee; Ecosystem... Amendment 20B (wreckfish Individual Transferable Quota (ITQ) program modifications); Spiny Lobster Amendment... report from the Law Enforcement AP and discuss other issues as appropriate. 4. Spiny Lobster Committee...

GTAP model and database modification to better handle cropping changes on the intensive margin.

DOT National Transportation Integrated Search

2017-07-25

Previously, induced land use change estimates considered only the extensive margin; that is, adding to harvested area by converting forest or pasture to cropland. However, recent data suggests that some of the increase in global harvested area comes ...

HNE-modified proteins in Down syndrome: Involvement in development of Alzheimer disease neuropathology.

PubMed

Barone, Eugenio; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

2017-10-01

Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylationg in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as in AD, thus generating a vicious cycle that amplifies OS-induced intracellular changes. The present review describes the current literature that demonstrates the accumulation of oxidative damage in DS with a focus on the lipid peroxidation by-product, 4-hydroxy-2-nonenal (HNE). HNE reacts with proteins and can irreversibly impair their functions. We suggest that among different post-translational modifications, HNE-adducts on proteins accumulate in DS brain and play a crucial role in causing the impairment of glucose metabolism, neuronal trafficking, protein quality control and antioxidant response. We hypothesize that dysfunction of these specific pathways contribute to accelerated neurodegeneration associated with AD neuropathology. Copyright © 2017 Elsevier Inc. All rights reserved.

Trepanation in South-Central Peru during the early late intermediate period (ca. AD 1000-1250).

PubMed

Kurin, Danielle S

2013-12-01

This study evaluates trepanations from five well-contextualized prehistoric sites in the south-central highlands of Andahuaylas, Peru. The emergence of trepanation in this region coincides with the collapse of the Wari Empire, ca. ad 1000. Thirty-two individuals from Andahuaylas, AMS radiocarbon dated to the early Late Intermediate Period (ca. ad 1000-1250), were found to have 45 total trepanations. Various surgical techniques were being employed concurrently throughout the region. Scraping trepanations evinced the highest survival rate; circular grooving, drilling and boring, and linear cutting were far less successful. Evidence of perioperative procedures like hair shaving, poultice application, and possible cranioplasty use aimed to ensure the survival of a trepanation recipient. Postmortem trepanations, also present in Andahuaylas, were likely executed on corpses as a means of better understanding cranial anatomy and improving techniques. Similarities in trepanation patterns throughout the region attest to common motivations to engage in surgery. Although moderate physical head trauma seems to be the impetus for intervention in many cases of trepanation, other motivations included physiological and possibly psychosomatic factors. Nevertheless, treatment was not for everyone. In Andahuaylas, trepanations were withheld from subadults, females, and those individuals who practiced cranial modification. Copyright © 2013 Wiley Periodicals, Inc.

Adaptation of commercial microscopes for advanced imaging applications

NASA Astrophysics Data System (ADS)

Brideau, Craig; Poon, Kelvin; Stys, Peter

2015-03-01

Today's commercially available microscopes offer a wide array of options to accommodate common imaging experiments. Occasionally, an experimental goal will require an unusual light source, filter, or even irregular sample that is not compatible with existing equipment. In these situations the ability to modify an existing microscopy platform with custom accessories can greatly extend its utility and allow for experiments not possible with stock equipment. Light source conditioning/manipulation such as polarization, beam diameter or even custom source filtering can easily be added with bulk components. Custom and after-market detectors can be added to external ports using optical construction hardware and adapters. This paper will present various examples of modifications carried out on commercial microscopes to address both atypical imaging modalities and research needs. Violet and near-ultraviolet source adaptation, custom detection filtering, and laser beam conditioning and control modifications will be demonstrated. The availability of basic `building block' parts will be discussed with respect to user safety, construction strategies, and ease of use.

Low-Speed Aerodynamic Data for an 0.18-Scale Model of an F-16XL with Various Leading-Edge Modifications

NASA Technical Reports Server (NTRS)

Hahne, Daniel E.

1999-01-01

Using the F-16XL as a test-bed, two strategies for improving the low-speed flying characteristics that had minimal impact on high-speed performance were evaluated. In addition to the basic F-16XL configuration several modifications to the baseline configuration were tested in the Langley 30- X 60-Foot Tunnel: 1) the notched area at the wing leading edge and fuselage juncture was removed resulting in a continuous 70 deg leading-edge sweep on the inboard portion of the wing; 2) an integral attached-flow leading-edge flap concept was added to the continuous leading edge; and 3) a deployable vortex flap concept was added to the continuous leading edge. The purpose of this report is simply to document the test configurations, test conditions, and data obtained in this investigation for future reference and analysis. No analysis is presented herein and the data only appear in tabulated format.

Oxbow Fish Hatchery Snake River Sockeye Salmon Smolt Program, 2008 Annual Report.

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

Banks, Duane D.

2009-11-14

This contract proposal is in response to the Federal Columbia River Power System Biological Opinion Implementation Plan/Update Proposed Action (UPA) associated with increasing the number of Snake River sockeye smolts by 150,000. To accomplish this proposal the cooperation and efforts of three government entities has been planned (e.g., Idaho Department of Fish and Game (IDFG), Oregon Department of Fish and Wildlife (ODFW), and the National Marine Fisheries Service (NMFS)). Improvements at the IDFG Eagle Fish Hatchery and NMFS Burley Creek Hatchery will focus on increasing sockeye salmon captive broodstock and egg production. Improvements at the ODFW Oxbow Fish Hatchery willmore » be made to accommodate the incubation, hatching and rearing of 150,000 sockeye salmon smolts for release into Idaho's Sawtooth Valley, Upper Salmon River near IDFG's Sawtooth Fish Hatchery and/or Redfish Lake Creek 1.4 km downstream of Redfish Lake. Modifications to Oxbow Fish Hatchery (ODFW) will include retro-fit existing pond drains so pond cleaning effluent water can be routed to the pollution abatement pond, and modifications to the abatement pond. Also included in this project as an added phase, was the rerouting of the hatchery building effluent water to meet state DEQ guidelines for the use of formalin to treat salmonid eggs. Some additional funding for the described Oxbow Hatchery modifications will come from Mitchell Act Funding. All personnel costs associated with this project will come from Mitchell Act funding. Due to heavy work load issues, being under staffed, and two emergency projects in the spring and summer of 2006, ODFW engineers were not able to complete all plans and get them out for bid in 2006. As a result of these circumstances retro-fitting pond drains and modifications to the abatement pond was carried over into fiscal year 2007-2008. A no cost time extension to the contract was approved by BPA. The format for this report will follow the standard format for Statement of Work Report (SOW), which includes sub-categories Work Element (WE), and within the WE the Milestone Titles.« less

The clinical and economic burden of newly diagnosed Alzheimer's disease in a medicare advantage population.

PubMed

Suehs, Brandon T; Davis, Cralen D; Alvir, Jose; van Amerongen, Derek; Pharmd, Nick C Patel; Joshi, Ashish V; Faison, Warachal E; Shah, Sonali N

2013-06-01

Alzheimer's disease (AD) represents a serious public health issue affecting approximately 5.4 million individuals in the United States and is projected to affect up to 16 million by 2050. This study examined health care resource utilization (HCRU), costs, and comorbidity burden immediately preceding new diagnosis of AD and 2 years after diagnosis. This study utilized a claims-based, retrospective cohort design. Medicare Advantage members newly diagnosed with AD (n = 3374) were compared to matched non-AD controls (n = 6748). All patients with AD were required to have 12 months of continuous enrollment prior to AD diagnosis (International Classification of Diseases, Clinical Modification [ICD-9] 331.0), during which time no diagnosis of AD, a related dementia, or an AD medication was observed. Non-AD controls demonstrated no diagnosis of AD, a related dementia, or a prescription claim for an AD medication treatment during their health plan enrollment. Medical and pharmacy claims data were used to measure HCRU, costs, and comorbidity burden over a period of 36 months (12 months pre-diagnosis and 24 months post-diagnosis). The HCRU and costs were greater for AD members during the year prior to diagnosis and during postdiagnosis years 1 and 2 compared to controls. The AD members also displayed greater comorbidity than their non-AD counterparts during postdiagnosis years 1 and 2, as measured by 2 different comorbidity indices. Members newly diagnosed with AD demonstrated greater HCRU, health care costs, and comorbidity burden compared to matched non-AD controls.

Phonetic Modification of Vowel Space in Storybook Speech to Infants up to 2 Years of Age

PubMed Central

Burnham, Evamarie B.; Wieland, Elizabeth A.; Kondaurova, Maria V.; McAuley, J. Devin; Bergeson, Tonya R.

2015-01-01

Purpose A large body of literature has indicated vowel space area expansion in infant-directed (ID) speech compared with adult-directed (AD) speech, which may promote language acquisition. The current study tested whether this expansion occurs in storybook speech read to infants at various points during their first 2 years of life. Method In 2 studies, mothers read a storybook containing target vowels in ID and AD speech conditions. Study 1 was longitudinal, with 11 mothers recorded when their infants were 3, 6, and 9 months old. Study 2 was cross-sectional, with 48 mothers recorded when their infants were 3, 9, 13, or 20 months old (n = 12 per group). The 1st and 2nd formants of vowels /i/, /ɑ/, and /u/ were measured, and vowel space area and dispersion were calculated. Results Across both studies, 1st and/or 2nd formant frequencies shifted systematically for /i/ and /u/ vowels in ID compared with AD speech. No difference in vowel space area or dispersion was found. Conclusions The results suggest that a variety of communication and situational factors may affect phonetic modifications in ID speech, but that vowel space characteristics in speech to infants stay consistent across the first 2 years of life. PMID:25659121

Facile Modification of Reverse Osmosis Membranes by Surfactant-Assisted Acrylate Grafting for Enhanced Selectivity.

PubMed

Baransi-Karkaby, Katie; Bass, Maria; Levchenko, Stanislav; Eitan, Shahar; Freger, Viatcheslav

2017-02-21

The top polyamide layer of composite reverse osmosis (RO) membranes has a fascinatingly complex structure, yet nanoscale nonuniformities inherently present in polyamide layer may reduce selectivity, e.g., for boron rejection. This study examines improving selectivity by in situ "caulking" such nonuniformities using concentration polarization-enhanced graft-polymerization with a surfactant added to the reactive solution. The surfactant appears to enhance both polarization (via monomer solubilization in surfactant micelles) and adherence of graft-polymer to the membrane surface, which facilitates grafting and reduces monomer consumption. The effect of surfactant was particularly notable for a hydrophobic monomer glycidyl methacrylate combined with a nonionic surfactant Triton X-100. With Triton added at an optimal level, close to critical micellization concentration (CMC), monomer gets solubilized and highly concentrated within micelles, which results in a significantly increased degree of grafting and uniformity of the coating compared to a procedure with no surfactant added. Notably, no improvement was obtained for an anionic surfactant SDS or the cationic surfactant DTAB, in which cases the high CMC of surfactant precludes high monomer concentration within micelles. The modification procedure was also up-scalable to membranes elements and resulted in elements with permeability comparable to commercial brackish water RO elements with superior boric acid rejection.

Thyroid function, Alzheimer's disease and postoperative cognitive dysfunction: a tale of dangerous liaisons?

PubMed

Mafrica, Federica; Fodale, Vincenzo

2008-05-01

Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. Moreover, thyroid hormones negatively regulate expression of the amyloid-beta protein precursor (AbetaPP), which plays a key role in the development of AD. A condition, the so called euthyroid sick syndrome (ESS), characterized by reduced serum T_{3} and T_{4} concentrations without increased serum thyroid stimulation hormone secretion, occurs within hours after major surgery. After surgery, elderly patients often exhibit a transient, reversible state of cognitive alterations. Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.

The X-43 Fin Actuation System Problem - Reliability in Shades of Gray

NASA Technical Reports Server (NTRS)

Peebles, Curtis

2006-01-01

Following the loss of the first X-43 during launch, the mishap investigation board indicated the Fin Actuator System (FAS) needed to have a larger torque margin. To supply this added torque, a second actuator was added. The consequences of what seemed to be a simple modification would trouble the X-43 program. Because of the second actuator, a new computer board was required. This proved to be subject to electronic noise. This resulted in the actuator latch up in ground tests of the FAS for the second launch. Such a latch up would cause the Pegasus booster to fail, as the FAS was a single string system. The problem was corrected and the second flight was successful. The same modifications were added to the FAS for flight three. When the FAS underwent ground tests, it also latched up. The failure indicated that each computer board had a different tolerance to electronic noise. The problem with the FAS was corrected. Subsequently, another failure occurred, raising questions about the design, and the probability of failure for the X-43 Mach 10 flight. This was not simply a technical issue, but illuminated the difficulties facing both managers and engineers in assessing risk, design requirements, and probabilities in cutting edge aerospace projects.

Effect of surface modification on photoluminescence properties of Y3Al5O12:Ce3+, Gd3+ nano-phosphors.

PubMed

Li, Jie; Zhao, Junfu; Zhou, Hefeng; Liang, Jian; Liu, Xuguang; Xu, Bingshe

2011-04-01

In this study, a series of Y(3)Al(5)O(12):Ce(3+), Gd(3+) nano-phosphors were prepared using a simply wet chemical process with polyvinyl pyrrolidone as a modifier. The crystal and bonding structures of Y(3)Al(5)O(12):Ce(3+), Gd(3+) nano-phosphors prepared with different weight percentages of polyvinyl pyrrolidone were characterized by X-ray diffractometry and infrared spectrometry. The decomposition process of dried precursor gel with adding 1.37 wt% polyvinyl pyrrolidone was investigated by differential thermal and thermogravimetric analysis. The effect of surface modification on photoluminescence properties for the samples was studied. The results show that the steric hindrance effect of polyvinyl pyrrolidone leads to high dispersion and good crystallinity of Y(3)Al(5)O(12):Ce(3+), Gd(3+) nano-phosphors prepared with adding a proper weight percentages of polyvinyl pyrrolidone. Adding polyvinyl pyrrolidone is beneficial for the photoluminescence enhancement of the samples, which is attributed to the promotion of the incorporation of Ce(3+) and Gd(3+) into the Y(3)Al(5)O(12) nanocrystal and the surface passivation of the nano-particles by the polyvinyl pyrrolidone molecules. Copyright © 2011 Elsevier B.V. All rights reserved.

A Comparative Study of Polymer and Biomolecule Surface Modifications by an Atmospheric Pressure Plasma Jet and Surface Microdischarge in Controlled Environments

NASA Astrophysics Data System (ADS)

Bartis, Elliot; Knoll, Andrew; Luan, Pingshan; Hart, Connor; Seog, Joonil; Oehrlein, Gottlieb; Graves, David; Lempert, Walter

2014-10-01

In this work, polymer- and lipopolysaccharide-coated Si substrates were exposed to a surface microdischarge (SMD) and an atmospheric pressure plasma jet (APPJ) in controlled ambients. We seek to understand how plasma-ambient interactions impact biodeactivation and surface modifications by regulating the ambient gas chemistry and the proximity of the plasma to the ambient. A key difference between the SMD and APPJ is that the APPJ needs an Ar feed gas and the SMD does not. By adding small N2/O2 admixtures to Ar, we find that the O2 admixture in the APPJ is a key factor for both deactivation and surface modification. After plasma treatments, we detected a new chemical species on a variety of surfaces that was identified as NO3. We find that NO3 forms even with no N2 in the feed gas, demonstrating that this species forms due to interactions with ambient N2. Despite a very different discharge mechanism, the SMD modifies surfaces similarly to the APPJ, including NO3 formation. The SMD generates large O3 concentrations, which do not correlate with NO3, suggesting that O3 alone is not involved in the NO3 formation mechanism. The authors gratefully acknowledge financial support by the US Department of Energy (DE-SC0005105 and DE-SC0001939) and National Science Foundation (PHY-1004256).

Modification of the fault logic circuit of a high-energy linear accelerator to accommodate selectively coded, large-field wedges.

PubMed

Miller, R W; van de Geijn, J

1987-01-01

A modification to the fault logic circuit that controls the collimator (COLL) fault is described. This modification permits the use of large-field wedges by adding an additional input into the reference voltage that determines the fault condition. The resistor controlling the amount of additional voltage is carried on board each wedge, within the wedge plug. This allows each wedge to determine its own, individual field size limit. Additionally, if no coding resistor is provided, the factory-supplied reference voltage is used, which sets the maximum allowable field size to 15 cm. This permits the use of factory-supplied wedges in conjunction with selected, large-field wedges, allowing proper sensing of the field size maximum in all conditions.

Code Development in Coupled PARCS/RELAP5 for Supercritical Water Reactor

DOE PAGES

Hu, Po; Wilson, Paul

2014-01-01

The new capability is added to the existing coupled code package PARCS/RELAP5, in order to analyze SCWR design under supercritical pressure with the separated water coolant and moderator channels. This expansion is carried out on both codes. In PARCS, modification is focused on extending the water property tables to supercritical pressure, modifying the variable mapping input file and related code module for processing thermal-hydraulic information from separated coolant/moderator channels, and modifying neutronics feedback module to deal with the separated coolant/moderator channels. In RELAP5, modification is focused on incorporating more accurate water properties near SCWR operation/transient pressure and temperature in themore » code. Confirming tests of the modifications is presented and the major analyzing results from the extended codes package are summarized.« less

Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction.

PubMed

Pandey, Anjali; Bani, Sarang; Dutt, Prabhu; Kumar Satti, Naresh; Avtar Suri, Krishan; Nabi Qazi, Ghulam

2018-02-01

Alzheimer's disease (AD) is a chronic disorder that slowly worsens and impairs the person's memory, learning, reasoning, judgment, communication and familiar tasks with loss of orientation. AD is characterized clinically by cognitive deficit and pathologically by the deposition of β amyloid plaques, neurofibrillary tangles, associated with degeneration of the cholinergic forebrain. Withanone (WS-2), a compound isolated from root extract of Withania somnifera at doses administered orally/day to wistar rats for duration of 21 days showed significant improvement in the cognitive skill by inhibiting amyloid β-42 and attenuated the elevated levels of pro-inflammatory cytokines like TNF alpha, IL-1 beta, IL-6, MCP-1, Nitric oxide, lipid peroxidation and both β- and γ- secretase enzymatic activity. Administration of WS-2 also significantly reversed the decline in acetyl choline and Glutathione (GSH) activity. None of the treatments that are available today alter the underlying causes of this terminal disease. Few preliminary clinical treatments have demonstrated that some plant medicines do ameliorate and improve memory and learning in patients with mild-to-moderate AD. WS-2 showed promise in AD treatment because of cognitive benefits and more importantly, mechanisms of action with respect to the fundamental pathophysiology of the disease, not limited to the inhibition of AChE, but also include the modification of Aβ processing, protection against oxidative stress and anti-inflammatory effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathological reorganization of NMDA receptors subunits and postsynaptic protein PSD-95 distribution in Alzheimer's disease.

PubMed

Leuba, Genevieve; Vernay, Andre; Kraftsik, Rudolf; Tardif, Eric; Riederer, Beat Michel; Savioz, Armand

2014-01-01

In Alzheimer's disease (AD), synaptic alterations play a major role and are often correlated with cognitive changes. In order to better understand synaptic modifications, we compared alterations in NMDA receptors and postsynaptic protein PSD-95 expression in the entorhinal cortex (EC) and frontal cortex (FC; area 9) of AD and control brains. We combined immunohistochemical and image analysis methods to quantify on consecutive sections the distribution of PSD-95 and NMDA receptors GluN1, GluN2A and GluN2B in EC and FC from 25 AD and control cases. The density of stained receptors was analyzed using multivariate statistical methods to assess the effect of neurodegeneration. In both regions, the number of neuronal profiles immunostained for GluN1 receptors subunit and PSD-95 protein was significantly increased in AD compared to controls (3-6 fold), while the number of neuronal profiles stained for GluN2A and GluN2B receptors subunits was on the contrary decreased (3-4 fold). The increase in marked neuronal profiles was more prominent in a cortical band corresponding to layers 3 to 5 with large pyramidal cells. Neurons positive for GluN1 or PSD-95 staining were often found in the same localization on consecutive sections and they were also reactive for the anti-tau antibody AD2, indicating a neurodegenerative process. Differences in the density of immunoreactive puncta representing neuropile were not statistically significant. Altogether these data indicate that GluN1 and PSD-95 accumulate in the neuronal perikarya, but this is not the case for GluN2A and GluN2B, while the neuropile compartment is less subject to modifications. Thus, important variations in the pattern of distribution of the NMDA receptors subunits and PSD-95 represent a marker in AD and by impairing the neuronal network, contribute to functional deterioration.

Unique Structural Modifications Are Present in the Lipopolysaccharide from Colistin-Resistant Strains of Acinetobacter baumannii

DTIC Science & Technology

2013-10-01

13). Freeze-dried bacteria were resuspended in endotoxin -free water at a concentration of 10 mg/ml. A 12.5-ml volume of 90% phenol was added, and the...temperature for 30 min. The aqueous phase was collected, and an equal volume of endotoxin -free water was added to the organic phase. The sample was...The resultant pel- let was resuspended at a concentration of 10 mg/ml in endotoxin -free water, treated with DNase (Sigma, St. Louis, MO) at 100 g/ml

Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer's Disease.

PubMed

Winick-Ng, Warren; Rylett, R Jane

2018-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons. Dysregulation of epigenetic processes have been observed in the aging brain and in patients with AD, though there is not yet agreement on the impact of these changes on transcription. New evidence shows that proteins involved in genome organization have altered expression and localization in the AD brain, suggesting that the genomic landscape may play a critical role in the development of AD. This review discusses the role of the chromatin organizers and epigenetic modifiers in post-mitotic cells, the aging brain, and in the development and progression of AD. How these new insights can be used to help determine disease risk and inform treatment strategies will also be discussed.

Genetic Targeting of an Adenovirus Vector via Replacement of the Fiber Protein with the Phage T4 Fibritin

PubMed Central

Krasnykh, Victor; Belousova, Natalya; Korokhov, Nikolay; Mikheeva, Galina; Curiel, David T.

2001-01-01

The utility of adenovirus (Ad) vectors for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural conflicts between the fiber and the targeting ligand. Here we present a strategy to derive an Ad vector with enhanced targeting potential by a radical replacement of the fiber protein in the Ad capsid with a chimeric molecule containing a heterologous trimerization motif and a receptor-binding ligand. Our approach, which capitalized upon the overall structural similarity between the human Ad type 5 (Ad5) fiber and bacteriophage T4 fibritin proteins, has resulted in the generation of a genetically modified Ad5 incorporating chimeric fiber-fibritin proteins targeted to artificial receptor molecules. Gene transfer studies employing this novel viral vector have demonstrated its capacity to efficiently deliver a transgene payload to the target cells in a receptor-specific manner. PMID:11287567

Q ‑ Φ criticality and microstructure of charged AdS black holes in f(R) gravity

NASA Astrophysics Data System (ADS)

Deng, Gao-Ming; Huang, Yong-Chang

2017-12-01

The phase transition and critical behaviors of charged AdS black holes in f(R) gravity with a conformally invariant Maxwell (CIM) source and constant curvature are further investigated. As a highlight, this research is carried out by employing new state parameters (T,Q, Φ) and contributes to deeper understanding of the thermodynamics and phase structure of black holes. Our analyses manifest that the charged f(R)-CIM AdS black hole undergoes a first-order small-large black hole phase transition, and the critical behaviors qualitatively behave like a Van der Waals liquid-vapor system. However, differing from the case in Einstein’s gravity, phase structures of the black holes in f(R) theory exhibit an interesting dependence on gravity modification parameters. Moreover, we adopt the thermodynamic geometry to probe the black hole microscopic properties. The results show that, on the one hand, both the Ruppeiner curvature and heat capacity diverge exactly at the critical point, on the other hand, the f(R)-CIM AdS black hole possesses the property as ideal Fermi gases. Of special interest, we discover a microscopic similarity between the black holes and a Van der Waals liquid-vapor system.

29 CFR 801.71 - Filing and service.

Code of Federal Regulations, 2011 CFR

2011-07-01

... EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 Administrative Proceedings Modification Or Vacation of Decision... of time for delivery by mail. Documents are not deemed filed with the Secretary until actually... Secretary either on or before the due date. No additional time shall be added where service of a document...

29 CFR 801.71 - Filing and service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 Administrative Proceedings Modification Or Vacation of Decision... of time for delivery by mail. Documents are not deemed filed with the Secretary until actually... Secretary either on or before the due date. No additional time shall be added where service of a document...

39 CFR 3020.50 - General.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Product Lists Described Within the Mail Classification Schedule § 3020.50 General. Users of the... product list or the competitive product list appearing in the Mail Classification Schedule. For purposes of this part, modification shall be defined as adding a product to a list, removing a product from a...

39 CFR 3020.30 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Product Lists Described Within the Mail Classification Schedule § 3020.30 General. The Postal... product list or the competitive product list appearing in the Mail Classification Schedule. For purposes of this part, modification shall be defined as adding a product to a list, removing a product from a...

39 CFR 3020.30 - General.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Product Lists Described Within the Mail Classification Schedule § 3020.30 General. The Postal... product list or the competitive product list appearing in the Mail Classification Schedule. For purposes of this part, modification shall be defined as adding a product to a list, removing a product from a...

39 CFR 3020.50 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Product Lists Described Within the Mail Classification Schedule § 3020.50 General. Users of the... product list or the competitive product list appearing in the Mail Classification Schedule. For purposes of this part, modification shall be defined as adding a product to a list, removing a product from a...

78 FR 24673 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... involving lithium ion battery failures that resulted in release of flammable electrolytes, heat damage, and... prompted by recent incidents involving lithium ion battery failures that resulted in release of flammable... modification of the battery system, or other actions. That AD resulted from recent incidents involving lithium...

10 CFR 50.34 - Contents of applications; technical information.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., and a program to ensure that the results of these studies are factored into the final design of the... assessment study to determine the optimum automatic depressurization system (ADS) design modifications that... capability for containment purging/venting designed to minimize the purging time consistent with ALARA...

10 CFR 50.34 - Contents of applications; technical information.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., and a program to ensure that the results of these studies are factored into the final design of the... assessment study to determine the optimum automatic depressurization system (ADS) design modifications that... capability for containment purging/venting designed to minimize the purging time consistent with ALARA...

A Database of Reaction Monitoring Mass Spectrometry Assays for Elucidating Therapeutic Response in Cancer

PubMed Central

Remily-Wood, Elizabeth R.; Liu, Richard Z.; Xiang, Yun; Chen, Yi; Thomas, C. Eric; Rajyaguru, Neal; Kaufman, Laura M.; Ochoa, Joana E.; Hazlehurst, Lori; Pinilla-Ibarz, Javier; Lancet, Jeffrey; Zhang, Guolin; Haura, Eric; Shibata, David; Yeatman, Timothy; Smalley, Keiran S.M.; Dalton, William S.; Huang, Emina; Scott, Ed; Bloom, Gregory C.; Eschrich, Steven A.; Koomen, John M.

2012-01-01

Purpose The Quantitative Assay Database (QuAD), http://proteome.moffitt.org/QUAD/, facilitates widespread implementation of quantitative mass spectrometry in cancer biology and clinical research through sharing of methods and reagents for monitoring protein expression and modification. Experimental Design Liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM) assays are developed using SDS-PAGE fractionated lysates from cancer cell lines. Pathway maps created using GeneGO Metacore provide the biological relationships between proteins and illustrate concepts for multiplexed analysis; each protein can be selected to examine assay development at the protein and peptide level. Results The coupling of SDS-PAGE and LC-MRM screening has been used to detect 876 peptides from 218 cancer-related proteins in model systems including colon, lung, melanoma, leukemias, and myeloma, which has led to the development of 95 quantitative assays including stable-isotope labeled peptide standards. Methods are published online and peptide standards are made available to the research community. Protein expression measurements for heat shock proteins, including a comparison with ELISA and monitoring response to the HSP90 inhibitor, 17-DMAG, are used to illustrate the components of the QuAD and its potential utility. Conclusions and Clinical Relevance This resource enables quantitative assessment of protein components of signaling pathways and biological processes and holds promise for systematic investigation of treatment responses in cancer. PMID:21656910

A randomized trial testing the efficacy of modifications to the nutrition facts table on comprehension and use of nutrition information by adolescents and young adults in Canada.

PubMed

Hobin, E; Sacco, J; Vanderlee, L; White, C M; Zuo, F; Sheeshka, J; McVey, G; Fodor O'Brien, M; Hammond, D

2015-12-01

Given the proposed changes to nutrition labelling in Canada and the dearth of research examining comprehension and use of nutrition facts tables (NFts) by adolescents and young adults, our objective was to experimentally test the efficacy of modifications to NFts on young Canadians' ability to interpret, compare and mathematically manipulate nutrition information in NFts on prepackaged food. An online survey was conducted among 2010 Canadians aged 16 to 24 years drawn from a consumer sample. Participants were randomized to view two NFts according to one of six experimental conditions, using a between-groups 2 x 3 factorial design: serving size (current NFt vs. standardized serving-sizes across similar products) x percent daily value (% DV) (current NFt vs. "low/med/high" descriptors vs. colour coding). The survey included seven performance tasks requiring participants to interpret, compare and mathematically manipulate nutrition information on NFts. Separate modified Poisson regression models were conducted for each of the three outcomes. The ability to compare two similar products was significantly enhanced in NFt conditions that included standardized serving-sizes (p ≤ .001 for all). Adding descriptors or colour coding of % DV next to calories and nutrients on NFts significantly improved participants' ability to correctly interpret % DV information (p ≤ .001 for all). Providing both standardized serving-sizes and descriptors of % DV had a modest effect on participants' ability to mathematically manipulate nutrition information to calculate the nutrient content of multiple servings of a product (relative ratio = 1.19; 95% confidence limit: 1.04-1.37). Standardizing serving-sizes and adding interpretive % DV information on NFts improved young Canadians' comprehension and use of nutrition information. Some caution should be exercised in generalizing these findings to all Canadian youth due to the sampling issues associated with the study population. Further research is needed to replicate this study in a more heterogeneous sample in Canada and across a range of food products and categories.

Reducing the oxygen concentration of gases delivered from anaesthetic machines unadapted for medical air

PubMed Central

Clutton, R. E.; Schoeffmann, G.; Chesnil, M.; Gregson, R.; Reed, F.; Lawson, H.; Eddleston, M.

2014-01-01

High fractional concentrations of inspired oxygen (FiO2) delivered over prolonged periods produce characteristic histological changes in the lungs and airway of exposed animals. Modern medical anaesthetic machines are adapted to deliver medical air (FiO2=0.21) for the purpose of reducing FiO2; anaesthetic machines designed for the veterinary market have not been so adapted. Two inexpensive modifications that allow medical air to be added to the gas flow from veterinary anaesthetic machines are described. The advantages and disadvantages of each modification are discussed. PMID:21862470

Entry dynamics of space shuttle orbiter with lateral-directional stability and control uncertainties at supersonic and hypersonic speeds

NASA Technical Reports Server (NTRS)

Stone, H. W.; Powell, R. W.

1977-01-01

A six-degree-of-freedom simulation analysis was conducted to examine the effects of the lateral-directional static aerodynamic stability and control uncertainties on the performance of the automatic (no manual inputs) entry-guidance and control systems of the space shuttle orbiter. To establish the acceptable boundaries of the uncertainties, the static aerodynamic characteristics were varied either by applying a multiplier to the aerodynamic parameter or by adding an increment. Control-system modifications were identified that decrease the sensitivity to off-nominal aerodynamics. With these modifications, the acceptable aerodynamic boundaries were determined.

Disparity modification in stereoscopic images for emotional enhancement

NASA Astrophysics Data System (ADS)

Kawai, Takashi; Atsuta, Daiki; Kim, Sanghyun; Häkkinen, Jukka

2015-03-01

This paper describes an experiment that focuses on disparity changes in emotional scenes of stereoscopic (3D) images, in which an examination of the effects on pleasant and arousal was carried out by adding binocular disparity to 2D images that evoke specific emotions, and applying disparity modification based on the disparity analysis of prominent 3D movies. From the results of the experiment, it was found that pleasant and arousal was increased by expanding 3D space to a certain level. In addition, pleasant gradually decreased and arousal gradually increased by expansion of 3D space above a certain level.

Air flow testing on aerodynamic truck

NASA Technical Reports Server (NTRS)

1975-01-01

After leasing a cab-over tractor-trailer from a Southern California firm, Dryden researchers added sheet metal modifications like those shown here. They rounded the front corners and edges, and placed a smooth fairing on the cab's roofs and sides extending back to the trailer. During the investigation of truck aerodynamics, the techniques honed in flight research proved highly applicable. By closing the gap between the cab and the trailer, for example, researchers discovered a significant reduction in aerodynamic drag, one resulting in 20 to 25 percent less fuel consumption than the standard design. Many truck manufacturers subsequently incorporated similar modifications on their products.

Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome.

PubMed

Szilágyi, Keely L; Liu, Cong; Zhang, Xu; Wang, Ting; Fortman, Jeffrey D; Zhang, Wei; Garcia, Joe G N

2017-02-01

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (∼30%-40%). Health disparities exist with African descent (AD) subjects exhibiting greater mortality than European descent (ED) individuals. Myosin light chain kinase is encoded by MYLK, whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, that is, cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK cytosine-guanine dinucleotides (CpGs) between ARDS patients and intensive care unit (ICU) controls overall and by ethnicity in a nested case-control study of 39 ARDS cases and 75 non-ARDS ICU controls. Two MYLK CpG sites (cg03892735 and cg23344121) were differentially modified between ARDS subjects and controls (P < 0.05; q < 0.25) in a logistic regression model, where no effect modification by ethnicity or age was found. One CpG site was associated with ARDS in patients aged <58 years, cg19611163 (intron 19, 20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2, 3) and CpG (cg16212219, intron 31, 32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting modified cytosine quantitative trait loci (mQTL) were identified using linear regression between local genetic variants and modification levels for 2 ARDS-associated CpGs (cg23344121 and cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing the functionality of cotton fabric by physical and chemical pre-treatments: A comparative study.

PubMed

Gargoubi, Sondes; Tolouei, Ranna; Chevallier, Pascale; Levesque, Lucie; Ladhari, Neji; Boudokhane, Chedly; Mantovani, Diego

2016-08-20

Recently, antimicrobial and decontaminating textiles, such as cotton a natural carbohydrate polymer, are generating more attention. Plant materials used for natural dyes are expected to impart biofunctional properties and high added valued functional textiles. In the current study, surface modification of cotton to maximize the dye amount on the surface has been investigated. Physical modification using nitrogen-hydrogen plasma, chemical modification using chitosan and chemical modification using dopamine as biopolymers imparting amino groups were explored. Furthermore, dye exhaustion of curcumin, as a natural functional dye has been studied. Dye stability tests were also performed after fabric washing using hospital washing protocol to predict the durability of the functionalizations. The results demonstrated that cotton surfaces treated with dopamine exhibit a high level of dye uptake (78%) and a good washing fastness. The use of non-toxic and natural additives during cotton finishing process could give the opportunity of cradle to cradle design for antimicrobial textile industries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients

PubMed Central

Corlier, F; Rivals, I; Lagarde, J; Hamelin, L; Corne, H; Dauphinot, L; Ando, K; Cossec, J-C; Fontaine, G; Dorothée, G; Malaplate-Armand, C; Olivier, J-L; Dubois, B; Bottlaender, M; Duyckaerts, C; Sarazin, M; Potier, M-C; Alnajjar-Carpentier, Dr Amer; Logak, Dr Michel; Leder, Dr Sara; Marchal, Dr Dominique; Pitti-Ferandi, Dr Hélène; Brugeilles, Dr Hélene; Roualdes, Dr Brigitte; Michon, Dr Agnes

2015-01-01

Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C11]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker. PMID:26151923

The Value of 18F-FDG PET/CT in Diagnosis and During Follow-up in 273 Patients with Chronic Q Fever.

PubMed

Kouijzer, Ilse J E; Kampschreur, Linda M; Wever, Peter C; Hoekstra, Corneline; van Kasteren, Marjo E E; de Jager-Leclercq, Monique G L; Nabuurs-Franssen, Marrigje H; Wegdam-Blans, Marjolijn C A; Ammerlaan, Heidi S M; Buijs, Jacqueline; Geus-Oei, Lioe-Fee de; Oyen, Wim J G; Bleeker-Rovers, Chantal P

2018-01-01

In 1%-5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the diagnostic value of 18 F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up. Methods: All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one 18 F-FDG PET/CT scan was obtained. Clinical data and results from 18 F-FDG PET/CT at diagnosis and during follow-up were collected. 18 F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system. Results: In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all 18 F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever-related mortality rate in patients with and without vascular infection based on 18 F-FDG PET/CT was 23.8% and 2.1%, respectively ( P = 0.001). When 18 F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of 18 F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of 18 F-FDG PET/CT scans resulted in treatment modification. Conclusion: 18 F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

77 FR 63270 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... missing fastener between certain stringers of the fuselage frame which connects the frame to a tee. This proposed AD would require a rototest inspection and modification or repair of the fuselage frame at the... Portal: Go to http://www.regulations.gov . Follow the instructions for submitting comments. Fax: (202...

77 FR 75827 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P. O. Box 3707, MC 2H-65..., per Part 1 of the Work Instructions of Boeing Special Attention Service Bulletin 757- 53-0089, dated... the repair specified in paragraph (i) or (l) of this AD, or doing the preventive modification...

76 FR 74665 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... Certificate (STC) ST00753NY (Transport Canada Civil Aviation (TCCA) STC SA97-106) installed. This AD results... unsafe condition as: It has been determined that modifications by DECA Aviation Engineering Limited on... INFORMATION: Discussion The Transport Canada Civil Aviation (TCCA), which is the aviation authority for Canada...

77 FR 58330 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... requires repetitive inspections of the aft attach lugs of the elevator tab control mechanisms, and replacement of any discrepant elevator tab control mechanism. Since we issued that AD, Boeing has developed a modification of the aft attach lugs of the elevator tab control mechanisms, which will adequately address the...

77 FR 15291 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

... wiring conduit and the wing bottom skin. This proposed AD would require modifying the wiring installation... modification of the wiring installation to improve the routing and the protection of the harnesses in the zone... wiring conduit and the wing bottom skin. This condition, in the scope of published FAA SFAR88 [Special...

Oxidative stress, protein modification and Alzheimer disease.

PubMed

Tramutola, A; Lanzillotta, C; Perluigi, M; Butterfield, D Allan

2017-07-01

Alzheimer disease (AD) is a progressive neurodegenerative disease that affects the elderly population with complex etiology. Many hypotheses have been proposed to explain different causes of AD, but the exact mechanisms remain unclear. In this review, we focus attention on the oxidative-stress hypothesis of neurodegeneration and we discuss redox proteomics approaches to analyze post-mortem human brain from AD brain. Collectively, these studies have provided valuable insights into the molecular mechanisms involved both in the pathogenesis and progression of AD, demonstrating the impairment of numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and degradative systems. Each of these cellular functions normally contributes to maintain healthy neuronal homeostasis, so the deregulation of one or more of these functions could contribute to the pathology and clinical presentation of AD. In particular, we discuss the evidence demonstrating the oxidation/dysfunction of a number of enzymes specifically involved in energy metabolism that support the view that reduced glucose metabolism and loss of ATP are crucial events triggering neurodegeneration and progression of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Symptoms of depression and anxiety after the disclosure of the diagnosis of Alzheimer disease.

PubMed

Mormont, Eric; Jamart, Jacques; Jacques, Denis

2014-12-01

Many people fear that the disclosure of the diagnosis of Alzheimer disease (AD) to patients will prompt depressive symptoms or catastrophic reactions. We aimed to prospectively evaluate the modification of anxiety and depressive symptoms 3 months after the disclosure of the diagnosis of AD. A total of 100 consecutive newly diagnosed patients with AD (mild or moderate stage) and their caregivers were included. The evolution of symptoms of depression and anxiety was assessed with the Zung Self-Rating Depression Scale (Zung SDS) and the depression item of the Neuropsychiatric Inventory (NPI-d) and the anxiety item of the Neuropsychiatric Inventory (NPI-a). After 3 months, the caregivers were asked their opinions on the global effect of the disclosure using a Likert-type scale. At 3 months, there was no significant change in the mean NPI-d (P = .87) and Zung SDS (P = .18) and a significant reduction in the NPI-a (P = .05). The NPI-d worsened in 22% of patients, improved in 22%, and remained unchanged in 56%. The NPI-a worsened in 12% of patients, improved in 33%, and remained unchanged in 54%. The caregivers rated the global effect of the disclosure as negative in 8%, neutral in 71%, and positive in 21% of patients. None of the patients or their proxies reported suicide attempts or catastrophic reactions. The disclosure of AD is safe in most cases and may improve anxiety. Symptoms of depression and anxiety worsen only in a minority of patients. The fear of depression or catastrophic reaction should not prevent clinicians to disclose the diagnosis of AD. © The Author(s) 2014.

Hypochlorite modification of sphingomyelin generates chlorinated lipid species that induce apoptosis and proteome alterations in dopaminergic PC12 neurons in vitro

PubMed Central

Nusshold, Christoph; Kollroser, Manfred; Köfeler, Harald; Rechberger, Gerald; Reicher, Helga; Üllen, Andreas; Bernhart, Eva; Waltl, Sabine; Kratzer, Ingrid; Hermetter, Albin; Hackl, Hubert; Trajanoski, Zlatko; Hrzenjak, Andelko; Malle, Ernst; Sattler, Wolfgang

2014-01-01

Recent observations link myeloperoxidase (MPO) activation to neurodegeneration. In multiple sclerosis MPO is present in areas of active demyelination where the potent oxidant hypochlorous acid (HOCl), formed by MPO from H2O2 and chloride ions, could oxidatively damage myelin-associated lipids. The purpose of this study was (i) to characterize reaction products of sphingomyelin (SM) formed in response to modification by HOCl, (ii) to define the impact of exogenously added SM and HOCl-modified SM (HOCl-SM) on viability parameters of a neuronal cell line (PC12), and (iii) to study alterations in the PC12 cell proteome in response to SM and HOCl-SM. MALDI-TOF-MS analyses revealed that HOCl, added as reagent or generated enzymatically, transforms SM into chlorinated species. On the cellular level HOCl-SM but not SM induced the formation of reactive oxygen species. HOCl-SM induced severely impaired cell viability, dissipation of the mitochondrial membrane potential, and activation of caspase-3 and DNA damage. Proteome analyses identified differential expression of specific subsets of proteins in response to SM and HOCl-SM. Our results demonstrate that HOCl modification of SM results in the generation of chlorinated lipid species with potent neurotoxic properties. Given the emerging connections between the MPO–H2O2–chloride axis and neurodegeneration, this chlorinating pathway might be implicated in neuropathogenesis. PMID:20226853

Epigenetic modification: possible approach to reduce Salmonella enterica serovar enteritidis susceptibility under stress conditions.

PubMed

Soleimani, A F; Zulkifli, I; Hair-Bejo, M; Ebrahimi, M; Jazayeri, S D; Hashemi, S R; Meimandipour, A; Goh, Y M

2012-01-01

Stressors may influence chicken susceptibility to pathogens such as Salmonella enterica. Feed withdrawal stress can cause changes in normal intestinal epithelial structure and may lead to increased attachment and colonization of Salmonella. This study aimed to investigate modulatory effects of epigenetic modification by feed restriction on S. enterica serovar Enteritidis colonization in broiler chickens subjected to feed withdrawal stress. Chicks were divided into four groups: ad libitum feeding; ad libitum feeding with 24-h feed withdrawal on day 42; 60% feed restriction on days 4, 5, and 6; and 60% feed restriction on days 4, 5, and 6 with 24-h feed withdrawal on day 42. Attachment of S. Enteritidis to ileal tissue was determined using an ex vivo ileal loop assay, and heat shock protein 70 (Hsp70) expression was evaluated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting. Feed withdrawal stress increased S. Enteritidis attachment to ileal tissue. However, following feed withdrawal the epigenetically modified chickens had significantly lower attachment of S. Enteritidis than their control counterparts. A similar trend with a very positive correlation was observed for Hsp70 expression. It appears that epigenetic modification can enhance resistance to S. Enteritidis colonization later in life in chickens under stress conditions. The underlying mechanism could be associated with the lower Hsp70 expression in the epigenetically modified chickens.

Treatment Sequencing for Childhood ADHD: A Multiple-Randomization Study of Adaptive Medication and Behavioral Interventions.

PubMed

Pelham, William E; Fabiano, Gregory A; Waxmonsky, James G; Greiner, Andrew R; Gnagy, Elizabeth M; Pelham, William E; Coxe, Stefany; Verley, Jessica; Bhatia, Ira; Hart, Katie; Karch, Kathryn; Konijnendijk, Evelien; Tresco, Katy; Nahum-Shani, Inbal; Murphy, Susan A

2016-01-01

Behavioral and pharmacological treatments for children with attention deficit/hyperactivity disorder (ADHD) were evaluated to address whether endpoint outcomes are better depending on which treatment is initiated first and, in case of insufficient response to initial treatment, whether increasing dose of initial treatment or adding the other treatment modality is superior. Children with ADHD (ages 5-12, N = 146, 76% male) were treated for 1 school year. Children were randomized to initiate treatment with low doses of either (a) behavioral parent training (8 group sessions) and brief teacher consultation to establish a Daily Report Card or (b) extended-release methylphenidate (equivalent to .15 mg/kg/dose bid). After 8 weeks or at later monthly intervals as necessary, insufficient responders were rerandomized to secondary interventions that either increased the dose/intensity of the initial treatment or added the other treatment modality, with adaptive adjustments monthly as needed to these secondary treatments. The group beginning with behavioral treatment displayed significantly lower rates of observed classroom rule violations (the primary outcome) at study endpoint and tended to have fewer out-of-class disciplinary events. Further, adding medication secondary to initial behavior modification resulted in better outcomes on the primary outcomes and parent/teacher ratings of oppositional behavior than adding behavior modification to initial medication. Normalization rates on teacher and parent ratings were generally high. Parents who began treatment with behavioral parent training had substantially better attendance than those assigned to receive training following medication. Beginning treatment with behavioral intervention produced better outcomes overall than beginning treatment with medication.

snpAD: An ancient DNA genotype caller.

PubMed

Prüfer, Kay

2018-06-21

The study of ancient genomes can elucidate the evolutionary past. However, analyses are complicated by base-modifications in ancient DNA molecules that result in errors in DNA sequences. These errors are particularly common near the ends of sequences and pose a challenge for genotype calling. I describe an iterative method that estimates genotype frequencies and errors along sequences to allow for accurate genotype calling from ancient sequences. The implementation of this method, called snpAD, performs well on high-coverage ancient data, as shown by simulations and by subsampling the data of a high-coverage Neandertal genome. Although estimates for low-coverage genomes are less accurate, I am able to derive approximate estimates of heterozygosity from several low-coverage Neandertals. These estimates show that low heterozygosity, compared to modern humans, was common among Neandertals. The C ++ code of snpAD is freely available at http://bioinf.eva.mpg.de/snpAD/. Supplementary data are available at Bioinformatics online.

Thermodynamic studies of different black holes with modifications of entropy

NASA Astrophysics Data System (ADS)

Haldar, Amritendu; Biswas, Ritabrata

2018-02-01

In recent years, the thermodynamic properties of black holes are topics of interests. We investigate the thermodynamic properties like surface gravity and Hawking temperature on event horizon of regular black holes viz. Hayward Class and asymptotically AdS (Anti-de Sitter) black holes. We also analyze the thermodynamic volume and naive geometric volume of asymptotically AdS black holes and show that the entropy of these black holes is simply the ratio of the naive geometric volume to thermodynamic volume. We plot the different graphs and interpret them physically. We derive the `cosmic-Censorship-Inequality' for both type of black holes. Moreover, we calculate the thermal heat capacity of aforesaid black holes and study their stabilities in different regimes. Finally, we compute the logarithmic correction to the entropy for both the black holes considering the quantum fluctuations around the thermal equilibrium and study the corresponding thermodynamics.

LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Modification of biological objects in water media by CO2-laser radiation

NASA Astrophysics Data System (ADS)

Baranov, G. A.; Belyaev, A. A.; Onikienko, S. B.; Smirnov, S. A.; Khukharev, V. V.

2005-09-01

The modification of biological objects (polysaccharides and cells) by CO2-laser radiation in water added drop by drop into the interaction region is studied theoretically and experimentally. Calculations are performed by using the models describing gas-dynamic and heterogeneous processes caused by absorption of laser radiation by water drops. It is found experimentally that the laser modification of polysaccharides leads to the formation of low-molecular derivatives with immunostimulating properties. A dose of the product of laser activation of the yeast culture Saccharamyces cerevisiae prevented the development of a toxic emphysema in mice and protected them against lethal grippe and also prevented a decrease of survival rate, increased the average life, and prevented the development of metabolic and immune disorders in mice exposed to sublethal gamma-radiation doses.

KSC-07pd1774

NASA Image and Video Library

2007-07-03

KENNEDY SPACE CENTER, FLA. -- The main engines on the orbiter Endeavour (upper right) are seen as Endeavour is lowered into high bay 1 of the Vehicle Assembly Building for stacking with the external tank (seen at left) and solid rocket boosters on the mobile launcher platform. Endeavour will be launched on mission STS-118, its first flight in more than four years. The shuttle has undergone extensive modifications, including the addition of safety upgrades already added to shuttles Discovery and Atlantis. Endeavour also features new hardware, such as the Station-to-Shuttle Power Transfer System that will allow the docked shuttle to draw electrical power from the station and extend its visits to the orbiting lab. Endeavour is targeted for launch on Aug. 7. Photo credit: NASA/Troy Cryder

Analysis of Automated Aircraft Conflict Resolution and Weather Avoidance

NASA Technical Reports Server (NTRS)

Love, John F.; Chan, William N.; Lee, Chu Han

2009-01-01

This paper describes an analysis of using trajectory-based automation to resolve both aircraft and weather constraints for near-term air traffic management decision making. The auto resolution algorithm developed and tested at NASA-Ames to resolve aircraft to aircraft conflicts has been modified to mitigate convective weather constraints. Modifications include adding information about the size of a gap between weather constraints to the routing solution. Routes that traverse gaps that are smaller than a specific size are not used. An evaluation of the performance of the modified autoresolver to resolve both conflicts with aircraft and weather was performed. Integration with the Center-TRACON Traffic Management System was completed to evaluate the effect of weather routing on schedule delays.

Not of African Descent: Dental Modification among Indigenous Caribbean People from Canímar Abajo, Cuba

PubMed Central

Roksandic, Mirjana; Alarie, Kaitlynn; Rodríguez Suárez, Roberto; Huebner, Erwin; Roksandic, Ivan

2016-01-01

Dental modifications in the Caribbean are considered to be an African practice introduced to the Caribbean archipelago by the influx of enslaved Africans during colonial times. Skeletal remains which exhibited dental modifications are by default considered to be Africans, African descendants, or post-contact indigenous people influenced by an African practice. Individual E-105 from the site of Canímar Abajo (Cuba), with a direct 14C AMS date of 990–800 cal BC, provides the first unequivocal evidence of dental modifications in the Antilles prior to contact with Europeans in AD 1492. Central incisors showing evidence of significant crown reduction (loss of crown volume regardless of its etiology) were examined macroscopically and with a scanning electron microscope (SEM) to determine if the observed alterations were due to deliberate modification or other (unintentional) factors considered: postmortem breakage, violent accidental breakage, non-dietary use of teeth, and wear caused by habitual or repeated actions. The pattern of crown reduction is consistent with deliberate dental modification of the type commonly encountered among African and African descendent communities in post-contact Caribbean archaeological assemblages. Six additional individuals show similar pattern of crown reduction of maxillary incisors with no analogous wear in corresponding mandibular dentition. PMID:27071012

Not of African Descent: Dental Modification among Indigenous Caribbean People from Canímar Abajo, Cuba.

PubMed

Roksandic, Mirjana; Alarie, Kaitlynn; Rodríguez Suárez, Roberto; Huebner, Erwin; Roksandic, Ivan

2016-01-01

Dental modifications in the Caribbean are considered to be an African practice introduced to the Caribbean archipelago by the influx of enslaved Africans during colonial times. Skeletal remains which exhibited dental modifications are by default considered to be Africans, African descendants, or post-contact indigenous people influenced by an African practice. Individual E-105 from the site of Canímar Abajo (Cuba), with a direct 14C AMS date of 990-800 cal BC, provides the first unequivocal evidence of dental modifications in the Antilles prior to contact with Europeans in AD 1492. Central incisors showing evidence of significant crown reduction (loss of crown volume regardless of its etiology) were examined macroscopically and with a scanning electron microscope (SEM) to determine if the observed alterations were due to deliberate modification or other (unintentional) factors considered: postmortem breakage, violent accidental breakage, non-dietary use of teeth, and wear caused by habitual or repeated actions. The pattern of crown reduction is consistent with deliberate dental modification of the type commonly encountered among African and African descendent communities in post-contact Caribbean archaeological assemblages. Six additional individuals show similar pattern of crown reduction of maxillary incisors with no analogous wear in corresponding mandibular dentition.

Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer’s Disease

PubMed Central

Winick-Ng, Warren; Rylett, R. Jane

2018-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons. Dysregulation of epigenetic processes have been observed in the aging brain and in patients with AD, though there is not yet agreement on the impact of these changes on transcription. New evidence shows that proteins involved in genome organization have altered expression and localization in the AD brain, suggesting that the genomic landscape may play a critical role in the development of AD. This review discusses the role of the chromatin organizers and epigenetic modifiers in post-mitotic cells, the aging brain, and in the development and progression of AD. How these new insights can be used to help determine disease risk and inform treatment strategies will also be discussed. PMID:29541020

Developing a Sealing Material: Effect of Epoxy Modification on Specific Physical and Mechanical Properties

PubMed Central

Schoberleitner, Christoph; Archodoulaki, Vasiliki-Maria; Koch, Thomas; Lüftl, Sigrid; Werderitsch, Markus; Kuschnig, Gerhard

2013-01-01

To develop a matched sealing material for socket rehabilitation of grey cast iron pipes, an epoxy resin is modified by the addition of different components to improve the flexibility. Three different modifications are made by adding ethylene-propylene diene monomer (EPDM) rubber powder, reactive liquid polymer (ATBN) and epoxidized modifier. In this paper the effect of the modification method as well as the influence of absorption of water on the mechanical and physical properties are analyzed in terms of: tensile strength, modulus of elasticity, adhesion performance, pressure resistance, glass transition temperature and water content. A comparison with neat epoxy shows for all materials that the modulus of elasticity and strength decrease. Unlike other tested modification methods, the modification with rubber powder did not enhance the flexibility. All materials absorb water and a plasticization effect arises with further changes of mechanical and physical properties. The application of the sealant on the grey cast iron leads to a reduction of the strain at break (in comparison to the common tensile test of the pure materials) and has to be evaluated. The main requirement of pressure resistance up to 1 MPa was tested on two chosen materials. Both materials fulfill this requirement. PMID:28788404

Developing a Sealing Material: Effect of Epoxy Modification on Specific Physical and Mechanical Properties.

PubMed

Schoberleitner, Christoph; Archodoulaki, Vasiliki-Maria; Koch, Thomas; Lüftl, Sigrid; Werderitsch, Markus; Kuschnig, Gerhard

2013-11-27

To develop a matched sealing material for socket rehabilitation of grey cast iron pipes, an epoxy resin is modified by the addition of different components to improve the flexibility. Three different modifications are made by adding ethylene-propylene diene monomer (EPDM) rubber powder, reactive liquid polymer (ATBN) and epoxidized modifier. In this paper the effect of the modification method as well as the influence of absorption of water on the mechanical and physical properties are analyzed in terms of: tensile strength, modulus of elasticity, adhesion performance, pressure resistance, glass transition temperature and water content. A comparison with neat epoxy shows for all materials that the modulus of elasticity and strength decrease. Unlike other tested modification methods, the modification with rubber powder did not enhance the flexibility. All materials absorb water and a plasticization effect arises with further changes of mechanical and physical properties. The application of the sealant on the grey cast iron leads to a reduction of the strain at break (in comparison to the common tensile test of the pure materials) and has to be evaluated. The main requirement of pressure resistance up to 1 MPa was tested on two chosen materials. Both materials fulfill this requirement.

Spine interbody implants: material selection and modification, functionalization and bioactivation of surfaces to improve osseointegration.

PubMed

Rao, Prashanth J; Pelletier, Matthew H; Walsh, William R; Mobbs, Ralph J

2014-05-01

The clinical outcome of lumbar spinal fusion is correlated with achievement of bony fusion. Improving interbody implant bone on-growth and in-growth may enhance fusion, limiting pseudoarthrosis, stress shielding, subsidence and implant failure. Polyetheretherketone (PEEK) and titanium (Ti) are commonly selected for interbody spacer construction. Although these materials have desirable biocompatibility and mechanical properties, they require further modification to support osseointegration. Reports of extensive research on this topic are available in biomaterial-centric published reports; however, there are few clinical studies concerning surface modification of interbody spinal implants. The current article focuses on surface modifications aimed at fostering osseointegration from a clinician's point of view. Surface modification of Ti by creating rougher surfaces, modifying its surface topography (macro and nano), physical and chemical treatment and creating a porous material with high interconnectivity can improve its osseointegrative potential and bioactivity. Coating the surface with osteoconductive materials like hydroxyapatite (HA) can improve osseointegration. Because PEEK spacers are relatively inert, creating a composite by adding Ti or osteoconductive materials like HA can improve osseointegration. In addition, PEEK may be coated with Ti, effectively bio-activating the coating. © 2014 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

The RCSB protein data bank: integrative view of protein, gene and 3D structural information

PubMed Central

Rose, Peter W.; Prlić, Andreas; Altunkaya, Ali; Bi, Chunxiao; Bradley, Anthony R.; Christie, Cole H.; Costanzo, Luigi Di; Duarte, Jose M.; Dutta, Shuchismita; Feng, Zukang; Green, Rachel Kramer; Goodsell, David S.; Hudson, Brian; Kalro, Tara; Lowe, Robert; Peisach, Ezra; Randle, Christopher; Rose, Alexander S.; Shao, Chenghua; Tao, Yi-Ping; Valasatava, Yana; Voigt, Maria; Westbrook, John D.; Woo, Jesse; Yang, Huangwang; Young, Jasmine Y.; Zardecki, Christine; Berman, Helen M.; Burley, Stephen K.

2017-01-01

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, http://rcsb.org), the US data center for the global PDB archive, makes PDB data freely available to all users, from structural biologists to computational biologists and beyond. New tools and resources have been added to the RCSB PDB web portal in support of a ‘Structural View of Biology.’ Recent developments have improved the User experience, including the high-speed NGL Viewer that provides 3D molecular visualization in any web browser, improved support for data file download and enhanced organization of website pages for query, reporting and individual structure exploration. Structure validation information is now visible for all archival entries. PDB data have been integrated with external biological resources, including chromosomal position within the human genome; protein modifications; and metabolic pathways. PDB-101 educational materials have been reorganized into a searchable website and expanded to include new features such as the Geis Digital Archive. PMID:27794042

Reality of Dental Implant Surface Modification: A Short Literature Review

PubMed Central

Yeo, In-Sung

2014-01-01

Screw-shaped endosseous implants that have a turned surface of commercially pure titanium have a disadvantage of requiring a long time for osseointegration while those implants have shown long-term clinical success in single and multiple restorations. Titanium implant surfaces have been modified in various ways to improve biocompatibility and accelerate osseointegration, which results in a shorter edentulous period for a patient. This article reviewed some important modified titanium surfaces, exploring the in vitro, in vivo and clinical results that numerous comparison studies reported. Several methods are widely used to modify the topography or chemistry of titanium surface, including blasting, acid etching, anodic oxidation, fluoride treatment, and calcium phosphate coating. Such modified surfaces demonstrate faster and stronger osseointegration than the turned commercially pure titanium surface. However, there have been many studies finding no significant differences in in vivo bone responses among the modified surfaces. Considering those in vivo results, physical properties like roughening by sandblasting and acid etching may be major contributors to favorable bone response in biological environments over chemical properties obtained from various modifications including fluoride treatment and calcium phosphate application. Recently, hydrophilic properties added to the roughened surfaces or some osteogenic peptides coated on the surfaces have shown higher biocompatibility and have induced faster osseointegration, compared to the existing modified surfaces. However, the long-term clinical studies about those innovative surfaces are still lacking. PMID:25400716

75 FR 6865 - Airworthiness Directives; The Boeing Company Model 737-700 (IGW) Series Airplanes Equipped With...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-12

... deactivation or modification of PATS Aircraft, LLC, auxiliary fuel tanks. This proposed AD results from fuel... for fuel tank systems. As a result of those findings, we issued a regulation titled ``Transport Airplane Fuel Tank System Design Review, Flammability Reduction and Maintenance and Inspection Requirements...

Alternative Computer Access for Young Handicapped Children: A Systematic Selection Procedure.

ERIC Educational Resources Information Center

Morris, Karen J.

The paper describes the type of computer access products appropriate for use by handicapped children and presents a systematic procedure for selection of such input and output devices. Modification of computer input is accomplished by three strategies: modifying the keyboard, adding alternative keyboards, and attaching switches to the keyboard.…

Transforming PC Power Supplies into Smart Car Battery Conditioners

ERIC Educational Resources Information Center

Rodriguez-Ascariz, J. M.; Boquete-Vazquez, L.

2011-01-01

This paper describes a laboratory project consisting of a PC power supply modification into an intelligent car-battery conditioner with both wireless and wired networking capabilities. Adding a microcontroller to an average PC power supply transforms it into a flexible, intelligent device that can be configured and that is suitable to keep car…

Modification of ruminal fermentation and methane production by adding legumes containing condensed tannins to an orchardgrass diet in continuous culture systems

USDA-ARS?s Scientific Manuscript database

Condensed tannins (CT) can alter ruminal fermentation and enteric methane (CH4) production in ruminants; however, research is lacking on how increased CT levels affect nutrient digestibility, volatile fatty acid (VFA) production, bacterial protein synthesis, fatty acid (FA) profiles, protozoal popul...

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

Martin-Aranda, Maria; Rementeria, Rosalia; Hackenberg, Robert Errol

Here, the goal of this paper is to analyse the effect of adding Al on the non-steady pearlite growth occurring in a Fe–C–Mn system. The results are discussed in terms of the partitioning of elements across the austenite/ferrite and austenite/cementite interfaces, and the modification of the pearlite driving force related to the change in carbon activity in austenite.

Lignin Degradation and Modification by the Soil-Inhabiting Fungus Fusarium proliferatum

PubMed Central

Regalado, V.; Rodriguez, A.; Perestelo, F.; Carnicero, A.; De La Fuente, G.; Falcon, M. A.

1997-01-01

A soil-inhabiting Fusarium proliferatum strain was capable of transforming or degrading nonlabeled and (sup14)C-labeled industrial, natural, and synthetic lignin. The mineralization rate per day (expressed as the percentage of added radioactivity recovered as to (sup14)CO(inf2)) was maximal during primary metabolism. PMID:16535700

75 FR 60010 - Airworthiness Directives; Airbus Model A330-200 and -300 Series Airplanes and Model A340-200...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

... hydraulic pump electrical motor connector internal arcing, resulting in: --Either false hydraulic system... uncontrolled fire. In order to protect the hydraulic pump electrical motor connectors against fluid ingress... hydraulic pump electrical motor malfunction, this AD requires modification of the three hydraulic pump...

76 FR 10230 - Airworthiness Directives; Airbus Model A330-200 and -300 Series Airplanes and Model A340-200...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-24

... hydraulic pump electrical motor connector internal arcing, resulting in: --Either false hydraulic system... uncontrolled fire. In order to protect the hydraulic pump electrical motor connectors against fluid ingress... hydraulic pump electrical motor malfunction, this AD requires modification of the three hydraulic pump...

A comparison of protein and phenolic compounds in seed from GMO and non-GMO soybean

USDA-ARS?s Scientific Manuscript database

Soybean protein is a valuable and important component in human and animal diets. Approximately 94% of the soybean planted in the US is genetically modified (GM) to enhance quality and productivity. Since value-added traits are continuously being developed by genetic modification, it is important t...

77 FR 43547 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... stringers S-22 and S-23, left and right sides; and corrective actions and preventive modification if... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590...

Ambient response of a unique performance-based design building with dynamic response modification features

USGS Publications Warehouse

Çelebi, Mehmet; Huang, Moh; Shakal, Antony; Hooper, John; Klemencic, Ron

2012-01-01

A 64-story, performance-based design building with reinforced concrete core shear-walls and unique dynamic response modification features (tuned liquid sloshing dampers and buckling-restrained braces) has been instrumented with a monitoring array of 72 channels of accelerometers. Ambient vibration data recorded are analyzed to identify modes and associated frequencies and damping. The low-amplitude dynamic characteristics are considerably different than those computed from design analyses, but serve as a baseline against which to compare with future strong shaking responses. Such studies help to improve our understanding of the effectiveness of the added features to the building and help improve designs in the future.

Research flight-control system development for the F-18 high alpha research vehicle

NASA Technical Reports Server (NTRS)

Pahle, Joseph W.; Powers, Bruce; Regenie, Victoria; Chacon, Vince; Degroote, Steve; Murnyak, Steven

1991-01-01

The F-18 high alpha research vehicle was recently modified by adding a thrust vectoring control system. A key element in the modification was the development of a research flight control system integrated with the basic F-18 flight control system. Discussed here are design requirements, system development, and research utility of the resulting configuration as an embedded system for flight research in the high angle of attack regime. Particular emphasis is given to control system modifications and control law features required for high angle of attack flight. Simulation results are used to illustrate some of the thrust vectoring control system capabilities and predicted maneuvering improvements.

Vent modification of large ribbon parachutes to enhance cluster performance

NASA Technical Reports Server (NTRS)

Kolega, D. J.; Woodis, W. R.; Reuter, J. D.

1986-01-01

Due to uneven load sharing and lagging inflation rates, the design of the Large Main Parachute (LMP) cluster, used to recover the Space Shuttle steel case Solid Rocket Boosters, had to be modified. The cause of the problem was excessive variation in effective porosity in the crown area of the LMP during first stage inflation. The design modification consisted of adding horizontal ribbons above the existing vent band to reduce the vent porosity and better control the position and attitude of the vent lines. Performance of modified LMP's since introduction indicates that the load sharing between the clustered chutes has been significantly improved.

TFTR neutral beam control and monitoring for DT operations

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

O`Connor, T.; Kamperschroer, J.; Chu, J.

1995-12-31

Record fusion power output has recently been obtained in TFTR with the injection of deuterium and tritium neutral beams. This significant achievement was due in part to the controls, software, and data processing capabilities added to the neutral beam system for DT operations. Chief among these improvements was the addition of SUN workstations and large dynamic data storage to the existing Central Instrumentation Control and Data Acquisition (CICADA) system. Essentially instantaneous look back over the recent shot history has been provided for most beam waveforms and analysis results. Gas regulation controls allowing remote switchover between deuterium and tritium were alsomore » added. With these tools, comparison of the waveforms and data of deuterium and tritium for four test conditioning pulses quickly produced reliable tritium setpoints. Thereafter, all beam conditioning was performed with deuterium, thus saving the tritium supply for the important DT injection shots. The lookback capability also led to modifications of the gas system to improve reliability and to control ceramic valve leakage by backbiasing. Other features added to improve the reliability and availability of DT neutral beam operations included master beamline controls and displays, a beamline thermocouple interlock system, a peak thermocouple display, automatic gas inventory and cryo panel gas loading monitoring, beam notching controls, a display of beam/plasma interlocks, and a feedback system to control beam power based on plasma conditions.« less

ND3, ND1 and 39 kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I

PubMed Central

Babot, Marion; Labarbuta, Paola; Birch, Amanda; Kee, Sara; Fuszard, Matthew; Botting, Catherine H.; Wittig, Ilka; Heide, Heinrich; Galkin, Alexander

2014-01-01

An intriguing feature of mitochondrial complex I from several species is the so-called A/D transition, whereby the idle enzyme spontaneously converts from the active (A) form to the de-active (D) form. The A/D transition plays an important role in tissue response to the lack of oxygen and hypoxic deactivation of the enzyme is one of the key regulatory events that occur in mitochondria during ischaemia. We demonstrate for the first time that the A/D conformational change of complex I does not affect the macromolecular organisation of supercomplexes in vitro as revealed by two types of native electrophoresis. Cysteine 39 of the mitochondrially-encoded ND3 subunit is known to become exposed upon de-activation. Here we show that even if complex I is a constituent of the I + III2 + IV (S1) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39 kDa (NDUFA9). These results clearly show that structural rearrangements during de-activation of complex I include several subunits located at the junction between hydrophilic and hydrophobic domains, in the region of the quinone binding site. De-activation of mitochondrial complex I results in concerted structural rearrangement of membrane subunits which leads to the disruption of the sealed quinone chamber required for catalytic turnover. PMID:24560811

Modified Allergens for Immunotherapy.

PubMed

Satitsuksanoa, Pattraporn; Głobińska, Anna; Jansen, Kirstin; van de Veen, Willem; Akdis, Mübeccel

2018-02-16

During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

Optical Autocovariance Wind Lidar (OAWL): aircraft test-flight history and current plans

NASA Astrophysics Data System (ADS)

Tucker, Sara C.; Weimer, Carl; Adkins, Mike; Delker, Tom; Gleeson, David; Kaptchen, Paul; Good, Bill; Kaplan, Mike; Applegate, Jeff; Taudien, Glenn

2015-09-01

To address mission risk and cost limitations the US has faced in putting a much needed Doppler wind lidar into space, Ball Aerospace and Technologies Corp, with support from NASA's Earth Science Technology Office (ESTO), has developed the Optical Autocovariance Wind Lidar (OAWL), designed to measure winds from aerosol backscatter at the 355 nm or 532 nm wavelengths. Preliminary proof of concept hardware efforts started at Ball back in 2004. From 2008 to 2012, under an ESTO-funded Instrument Incubator Program, Ball incorporated the Optical Autocovariance (OA) interferometer receiver into a prototype breadboard lidar system by adding a laser, telescope, and COTS-based data system for operation at the 355 nm wavelength. In 2011, the prototype system underwent ground-based validation testing, and three months later, after hardware and software modifications to ensure autonomous operation and aircraft safety, it was flown on the NASA WB-57 aircraft. The history of the 2011 test flights are reviewed, including efforts to get the system qualified for aircraft flights, modifications made during the flight test period, and the final flight data results. We also present lessons learned and plans for the new, robust, two-wavelength, aircraft system with flight demonstrations planned for Spring 2016.

Neuroaging through the Lens of the Resting State Networks

PubMed Central

2018-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) allows studying spontaneous brain activity in absence of task, recording changes of Blood Oxygenation Level Dependent (BOLD) signal. rs-fMRI enables identification of brain networks also called Resting State Networks (RSNs) including the most studied Default Mode Network (DMN). The simplicity and speed of execution make rs-fMRI applicable in a variety of normal and pathological conditions. Since it does not require any task, rs-fMRI is particularly useful for protocols on patients, children, and elders, increasing participant's compliance and reducing intersubjective variability due to the task performance. rs-fMRI has shown high sensitivity in identification of RSNs modifications in several diseases also in absence of structural modifications. In this narrative review, we provide the state of the art of rs-fMRI studies about physiological and pathological aging processes. First, we introduce the background of resting state; then we review clinical findings provided by rs-fMRI in physiological aging, Mild Cognitive Impairment (MCI), Alzheimer Dementia (AD), and Late Life Depression (LLD). Finally, we suggest future directions in this field of research and its potential clinical applications. PMID:29568755

Knowledge Provenance in Semantic Wikis

NASA Astrophysics Data System (ADS)

Ding, L.; Bao, J.; McGuinness, D. L.

2008-12-01

Collaborative online environments with a technical Wiki infrastructure are becoming more widespread. One of the strengths of a Wiki environment is that it is relatively easy for numerous users to contribute original content and modify existing content (potentially originally generated by others). As more users begin to depend on informational content that is evolving by Wiki communities, it becomes more important to track the provenance of the information. Semantic Wikis expand upon traditional Wiki environments by adding some computationally understandable encodings of some of the terms and relationships in Wikis. We have developed a semantic Wiki environment that expands a semantic Wiki with provenance markup. Provenance of original contributions as well as modifications is encoded using the provenance markup component of the Proof Markup Language. The Wiki environment provides the provenance markup automatically, thus users are not required to make specific encodings of author, contribution date, and modification trail. Further, our Wiki environment includes a search component that understands the provenance primitives and thus can be used to provide a provenance-aware search facility. We will describe the knowledge provenance infrastructure of our Semantic Wiki and show how it is being used as the foundation of our group web site as well as a number of project web sites.

Enhancement of mechanical properties of epoxy/graphene nanocomposite

NASA Astrophysics Data System (ADS)

Berhanuddin, N. I. C.; Zaman, I.; Rozlan, S. A. M.; Karim, M. A. A.; Manshoor, B.; Khalid, A.; Chan, S. W.; Meng, Q.

2017-10-01

Graphene is a novel class of nanofillers possessing outstanding characteristics including most compatible with most polymers, high absolute strength, high aspect ratio and cost effectiveness. In this study, graphene was used to reinforce epoxy as a matrix, to enhance its mechanical properties. Two types of epoxy composite were developed which are epoxy/graphene nanocomposite and epoxy/modified graphene nanocomposite. The fabrication of graphene was going through thermal expansion and sonication process. Chemical modification was only done for modified graphene where 4,4’-Methylene diphenyl diisocyanate (MDI) is used. The mechanical properties of both nanocomposite, such as Young’s modulus and maximum stress were investigated. Three weight percentage were used for this study which are 0.5 wt%, 1.0 wt% and 1.5 wt%. At 0.5 wt%, modified and unmodified shows the highest value compared to neat epoxy, where the value were 8 GPa, 6 GPa and 0.675 GPa, respectively. For maximum stress, neat epoxy showed the best result compared to both nanocomposite due to the changes of material properties when adding the filler into the matrix. Therefore, both nanocomposite increase the mechanical properties of the epoxy, however modification surface of graphene gives better improvement.

Role of the Adenovirus DNA-Binding Protein in In Vitro Adeno-Associated Virus DNA Replication

PubMed Central

Ward, Peter; Dean, Frank B.; O’Donnell, Michael E.; Berns, Kenneth I.

1998-01-01

A basic question in adeno-associated virus (AAV) biology has been whether adenovirus (Ad) infection provided any function which directly promoted replication of AAV DNA. Previously in vitro assays for AAV DNA replication, using linear duplex AAV DNA as the template, uninfected or Ad-infected HeLa cell extracts, and exogenous AAV Rep protein, demonstrated that Ad infection provides a direct helper effect for AAV DNA replication. It was shown that the nature of this helper effect was to increase the processivity of AAV DNA replication. Left unanswered was the question of whether this effect was the result of cellular factors whose activity was enhanced by Ad infection or was the result of direct participation of Ad proteins in AAV DNA replication. In this report, we show that in the in vitro assay, enhancement of processivity occurs with the addition of either the Ad DNA-binding protein (Ad-DBP) or the human single-stranded DNA-binding protein (replication protein A [RPA]). Clearly Ad-DBP is present after Ad infection but not before, whereas the cellular level of RPA is not apparently affected by Ad infection. However, we have not measured possible modifications of RPA which might occur after Ad infection and affect AAV DNA replication. When the substrate for replication was an AAV genome inserted into a plasmid vector, RPA was not an effective substitute for Ad-DBP. Extracts supplemented with Ad-DBP preferentially replicated AAV sequences rather than adjacent vector sequences; in contrast, extracts supplemented with RPA preferentially replicated vector sequences. PMID:9420241

[Angiotensin converting enzyme: the antigenic properties of the domain, role in Alzheimer's disease and tumor progression].

PubMed

Kugaevskaya, E V; Timoshenko, O S; Solovyeva, N I

2015-01-01

Angiotensin converting enzyme (ACE, EC 3.4.15.1) was discovered and characterized in the Laboratory of biochemistry and chemical pathology of proteins under the direction of academician V.N. Orekhovich, where its physiological function, associated with a key role in the regulation of the renin-angiotensin (RAS) and the kallikrein-kinin systems that control blood flow in the body and homeostasis was first deciphered. We carried out a search for structural differences between the two highly homologous domains (N- and C-domains) of somatic ACE (sACE); it was based on a comparative analysis of antigenic determinants (or B-epitopes) of both domains. The revealed epitopes were classified with variable and conserved regions and functionally important sites of the molecule ACE. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. These data indicate the existence of structural differences between the domains of sACE. We studied the role of the domains of ACE in the metabolism of human amyloid beta peptide (Ab) - the main component of senile plaques, found in the brains of patients with Alzheimer's disease (AD). Our results demonstrated that only N-domain ACE cleaved the Ab between residues R5-H6, while, the C-domain of ACE failed to hydrolyze this region. In addition, the effect of post-translational modifications of Ab on its hydrolysis by the ACE was investigated. We show that isomerization of residue D7, a common non-enzymatic age-related modification found in AD-associated species, does not reduce the affinity of the peptide to the N-domain of ACE, and conversely, it increases. According to our data, the role of ACE in the metabolism of Ab becomes more significant in the development of AD. RAS is involved in malignant transformation and tumor progression. RAS components, including ACE and angiotensin II receptors type 1 (AT1R) are expressed in various human tumors. We found a significant increase in the level of ACE activity in the tumor tissue of squamous cell carcinoma of the cervix. In our viewpoint, the increase in ACE activity may be a marker of poor clinical prognosis.

Effect of Bronchodilation and Exercise Training with Behavior Modification on Exercise Tolerance and Downstream Effects on Symptoms and Physical Activity in COPD.

PubMed

Troosters, Thierry; Maltais, François; Leidy, Nancy; Lavoie, Kim L; Sedeno, Maria; Janssens, Wim; Garcia-Aymerich, Judith; Erzen, Damijan; De Sousa, Dorothy; Korducki, Lawrence; Hamilton, Alan; Bourbeau, Jean

2018-04-17

Bronchodilation and exercise training (ExT) improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD); however, behavior modification is required to impact on daily physical activity (PA). To assess whether tiotropium/olodaterol, ±ExT, would improve exercise endurance time (EET) and PA compared with placebo in patients participating in a self-management behavior-modification (SMBM) program. A 12-week, randomized, partially double-blind, placebo-controlled, parallel-group trial in patients with COPD (PHYSACTO®; NCT02085161). All patients were enrolled into SMBM and randomized 1:1:1:1 to once-daily placebo, tiotropium 5 µg, tiotropium/olodaterol 5/5 µg, or tiotropium/olodaterol 5/5 µg plus 8 weeks ExT. EET, measured by endurance shuttle walk test after 8 weeks, was the primary endpoint. Additional endpoints assessed downstream effects on PA (measured via accelerometry), and activity-related dyspnea and difficulty (using validated patient-reported questionnaires). SMBM + tiotropium/olodaterol, ±ExT, significantly improved EET at Week 8 versus SMBM + placebo (treatment ratio versus placebo: with ExT 1.46 [95% CI: 1.20, 1.78]; P=0.0002; without ExT 1.29 [1.06, 1.57]; P=0.0109). No significant increases in steps per day from baseline were observed over SMBM + placebo at Week 12 (increase of 1,098) when other therapies were added. Adding tiotropium/olodaterol, ±ExT, to SMBM reduced activity-related dyspnea versus placebo, while adding tiotropium/olodaterol + ExT reduced activity-related difficulty. Tiotropium/olodaterol, ±ExT, improved EET in patients with COPD taking part in an SMBM program. Combination bronchodilation, ±ExT, did not provide additional increases in objective PA compared with SMBM alone, but did reduce physical activity-related dyspnea and difficulty. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02085161.

Minimum area rig concept update: H and P 101 modifications and first infield move

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

Sigurdson, S.R.

1987-03-01

The minimum area rig concept (MARC) is a cost-effective alternative to the typical self-contained platform rig (SCPR). Helmerich and Payne (HandP) built the first MARC rig, HandP 101, to drill and to work over wells up to 16,000 ft (4877 m) measured depth. This rig began operation in May 1983 in the Gulf of Mexico at Arco Oil and Gas Co.'s South Pass Block 61 field and has undergone one infield move. Since the rig's initial mobilization, several rig modifications have been added to increase storage area, to promote safety, to provide a more efficient drilling/workover rig, and to reducemore » overall move time. This paper describes the modifications and recaps the rig's first move. This provides further insight into the MARC rig and show the benefits of the MARC design in relation to a move.« less

Modification Site Localization in Peptides.

PubMed

Chalkley, Robert J

2016-01-01

There are a large number of search engines designed to take mass spectrometry fragmentation spectra and match them to peptides from proteins in a database. These peptides could be unmodified, but they could also bear modifications that were added biologically or during sample preparation. As a measure of reliability for the peptide identification, software normally calculates how likely a given quality of match could have been achieved at random, most commonly through the use of target-decoy database searching (Elias and Gygi, Nat Methods 4(3): 207-214, 2007). Matching the correct peptide but with the wrong modification localization is not a random match, so results with this error will normally still be assessed as reliable identifications by the search engine. Hence, an extra step is required to determine site localization reliability, and the software approaches to measure this are the subject of this part of the chapter.

Revisions to the original extent of the Devonian Shale-Middle and Upper Paleozoic Total Petroleum System

USGS Publications Warehouse

Enomoto, Catherine B.; Rouse, William A.; Trippi, Michael H.; Higley, Debra K.

2016-04-11

Technically recoverable undiscovered hydrocarbon resources in continuous accumulations are present in Upper Devonian and Lower Mississippian strata in the Appalachian Basin Petroleum Province. The province includes parts of New York, Pennsylvania, Ohio, Maryland, West Virginia, Virginia, Kentucky, Tennessee, Georgia, and Alabama. The Upper Devonian and Lower Mississippian strata are part of the previously defined Devonian Shale-Middle and Upper Paleozoic Total Petroleum System (TPS) that extends from New York to Tennessee. This publication presents a revision to the extent of the Devonian Shale-Middle and Upper Paleozoic TPS. The most significant modification to the maximum extent of the Devonian Shale-Middle and Upper Paleozoic TPS is to the south and southwest, adding areas in Tennessee, Georgia, Alabama, and Mississippi where Devonian strata, including potential petroleum source rocks, are present in the subsurface up to the outcrop. The Middle to Upper Devonian Chattanooga Shale extends from southeastern Kentucky to Alabama and eastern Mississippi. Production from Devonian shale has been established in the Appalachian fold and thrust belt of northeastern Alabama. Exploratory drilling has encountered Middle to Upper Devonian strata containing organic-rich shale in west-central Alabama. The areas added to the TPS are located in the Valley and Ridge, Interior Low Plateaus, and Appalachian Plateaus physiographic provinces, including the portion of the Appalachian fold and thrust belt buried beneath Cretaceous and younger sediments that were deposited on the U.S. Gulf Coastal Plain.

Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model.

PubMed

Goodrich, L R; Hidaka, C; Robbins, P D; Evans, C H; Nixon, A J

2007-05-01

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral joint received 2 x 10(7) naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model. The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.

Decreasing phosphorus runoff losses from land-applied poultry litter with dietary modifications and alum addition.

PubMed

Smith, Douglas R; Moore, P A; Miles, D M; Haggard, B E; Daniel, T C

2004-01-01

Phosphorus (P) losses from pastures fertilized with poultry litter contribute to the degradation of surface water quality in the United States. Dietary modification and manure amendments may reduce potential P runoff losses from pastures. In the current study, broilers were fed a normal diet, phytase diet, high available phosphorus (HAP) corn diet, or HAP corn + phytase diet. Litter treatments were untreated control and alum added at 10% by weight between flocks. Phytase and HAP corn diets reduced litter dissolved P content in poultry litter by 10 and 35%, respectively, compared with the normal diet (789 mg P kg(-1)). Alum treatment of poultry litter reduced the amount of dissolved P by 47%, while a 74% reduction was noted after alum treatment of litter from the HAP corn + phytase diet. The P concentrations in runoff water were highest from plots receiving poultry litter from the normal diet, whereas plots receiving poultry litter from phytase and HAP corn diets had reduced P concentrations. The addition of alum to the various poultry litters reduced P runoff by 52 to 69%; the greatest reduction occurred when alum was used in conjunction with HAP corn and phytase. This study demonstrates the potential added benefits of using dietary modification in conjunction with manure amendments in poultry operations. Integrators and producers should consider the use of phytase, HAP corn, and alum to reduce potential P losses associated with poultry litter application to pastures.

Facile modification of nanodiamonds with hyperbranched polymers based on supramolecular chemistry and their potential for drug delivery.

PubMed

Huang, Hongye; Liu, Meiying; Jiang, Ruming; Chen, Junyu; Mao, Liucheng; Wen, Yuanqing; Tian, Jianwen; Zhou, Naigen; Zhang, Xiaoyong; Wei, Yen

2018-03-01

Due to their excellent chemical stability and remarkable biocompatibility, nanodiamonds (NDs) have received widespread research attention by the biomedical field. The excellent water dispersibility of NDs has significant importance for biomedical applications. Therefore, surface modification of NDs with hydrophilic polymers has been extensively investigated over the past few decades. In this study, we synthesize β-CD containing hyperbranched polymer functionalized ND (ND-β-CD-HPG) composites with high water dispersibility via supramolecular chemistry based on the host-guest interactions between β-Cyclodextrin (β-CD) and adamantine (Ad). The hydroxyl groups of NDs first reacted with 1, 1-adamantanecarbonyl chloride to obtain ND-Ad, which was further functionalized with β-CD containing hyperbranched polymers to form the final ND-β-CD-HPG composites. The successful preparation of ND-β-CD-HPG composites was confirmed by several characterization techniques. Furthermore, the loading and release of the anticancer agent doxorubicin hydrochloride (DOX) on ND-β-CD-HPG composites was also examined to explore its potential in drug delivery. When compared with traditional methods of surface modification of NDs, this method was convenient, fast and efficient. We demonstrated that ND-β-CD-HPG composites have great water dispersibility, low toxicity, high drug-loading capacity and controlled drug-release behavior. Based on these characteristics, ND-β-CD-HPG composites are expected to have high potential for biomedical applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Levels of retinal IAPP are altered in Alzheimer's disease patients and correlate with vascular changes and hippocampal IAPP levels.

PubMed

Schultz, Nina; Byman, Elin; Wennström, Malin

2018-06-01

Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer's disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD patients and nondemented controls were analyzed using ELISA. Number of pericytes and vessel length were determined by analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fractions contained increased levels of the same. Total IAPP levels and pericyte numbers in retina mirrored corresponding variables in the hippocampus. Moreover, levels of total unmodified IAPP correlated negatively with the vessel length both in retina and hippocampus across the group and positively with pericyte numbers in retina in AD patients. Our studies indicate that changes in brain IAPP are reflected by corresponding levels in the retina. Our results also suggest modification of IAPP as an important event implicated in vascular changes associated with AD. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures.

PubMed

Mueller, Jakob C; Riemenschneider, Matthias; Schoepfer-Wendels, Andreas; Gohlke, Henning; Konta, Lidija; Friedrich, Patricia; Illig, Thomas; Laws, Simon M; Förstl, Hans; Kurz, Alexander

2007-05-01

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.

Utilization of air conditioner condenser as water heater in an effort to energy conservation

NASA Astrophysics Data System (ADS)

Sonawan, Hery; Saputro, Panji; Kurniawan, Iden Muhtar

2018-04-01

This paper presents an experimental study of utilization of air conditioner condenser as water heater. Modification of existing air conditioner system is an effort to harvest waste heat energy from condenser. Modification is conducted in order to test the system into two mode tests, first mode with one condenser and second mode with two condensers. Harvesting the waste heat from condenser needs a theoretical and practice study to see how much the AC performance changes if modifications are made. It should also be considered how the technique of harvesting waste heat for water heating purposes. From the problem, this paper presents a comparison between AC performance before and after modification. From the experiment, an increase in compressor power consumption is 4.3% after adding a new condenser. The hot water temperature is attained to 69 °C and ready for warm bath. The increase in power consumption is not too significant compared to the attainable hot water temperature. Also seen that the value of condenser Performance Factor increase from 5.8 to 6.25 or by 7.8%.

Swelling and tensile properties of starch glycerol system with various crosslinking agents

NASA Astrophysics Data System (ADS)

Mohamed, R.; Mohd, N.; Nurazzi, N.; Siti Aisyah, M. I.; Fauzi, F. Mohd

2017-07-01

Brittle properties of starch had been overcome by the modification process. In this work, sago starch is being modified with variable amount of plasticiser, namely glycerol at 20 and 40% and crosslinking agent had been added to the system. The film of the modification and characterizations of the starch glycerol system with various crosslinking systems were produced by casting method. The film properties of the starch glycerol system were then characterized by tensile strength (mechanical properties) and swelling (physical properties). The modification of the starch glycerol had improved that system by increasing the tensile strength, modulus however lowering its elongation. The increasing in percentage of the water absorption and also swelling are due to the intrinsic hydroxyl groups presence from the starch and glycerol itself that can attract more water to the system. Upon crosslinking, films casted with chemicals namely, glyoxal, malonic acid, borax, PEG were characterised. It was found that, all the film of sago starch crosslinked and undergoing easy film formation. From this modification, borax and malonic acid crosslinking agent had been determined as the best crosslinking agent to the starch glycerol system.

[Absorption of Uranium with Tea Oil Tree Sawdust Modified by Succinic Acid].

PubMed

Zhang, Xiao-feng; Chen, Di-yun; Peng, Yan; Liu, Yong-sheng; Xiong, Xue-ying

2015-05-01

In order to explore how the modification of succinic acid improves the adsorption of tea oil tree sawdust for uranium, the tea oil tree sawdust was modified by succinic acid, after the pretreatments of crushing, screening, alkalization and acidification. Infrared analysis indicated carboxylic acid groups and ester groups were added to the sawdust after modification, and scanning electron microscope demonstrated after modification the appearance of tea oil tree sawdust was transferred from the structure like compact and straight stripped into the structure like loose and wrinkled leaves, which meant modification increased its inner pores. By the static experiments, effects of reaction time between adsorbent and solvent, dosage of adsorbent, temperature, pH value and initial concentration of uranium were investigated. The results showed that after the modification by succinic acid, the absorption rate of tea oil tree sawdust for uranium increased significantly by about 20% in 12.5 mg · L(-1) initial concentration uranium solution. Adsorption equilibrium was achieved within 180 min, and the kinetic data can be well described by the pseudo-second-order kinetic model. The experimental adsorption isotherm followed the Langmuir and Freundlich models. In addition, the maximum adsorption amounts of tea oil tree sawdust after modification calculated from Langmuir equation raised from 21.413 3 to 31.545 7 mg · g(-1) at 35°C and pH 4.0.

CSF N-glycoproteomics for early diagnosis in Alzheimer's disease.

PubMed

Palmigiano, Angelo; Barone, Rita; Sturiale, Luisa; Sanfilippo, Cristina; Bua, Rosaria Ornella; Romeo, Donata Agata; Messina, Angela; Capuana, Maria Luisa; Maci, Tiziana; Le Pira, Francesco; Zappia, Mario; Garozzo, Domenico

2016-01-10

This work aims at exploring the human CSF (Cerebrospinal fluid) N-glycome by MALDI MS techniques, in order to assess specific glycosylation pattern(s) in patients with Alzheimer's disease (n:24) and in subjects with mild cognitive impairment (MCI) (n:11), these last as potential AD patients at a pre-dementia stage. For comparison, 21 healthy controls were studied. We identified a group of AD and MCI subjects (about 40-50% of the studied sample) showing significant alteration of CSF N-glycome profiling, consisting of a decrease in the overall sialylation degree and an increase in species bearing bisecting GlcNAc. Noteworthy, all the MCI patients that converted to AD within the clinical follow-up, had an abnormal CSF glycosylation profile. Based on the studied cohort, CSF glycosylation changes may occur before an AD clinical onset. Previous studies specifically focused on the key role of glycosyltransferase GnT-III on AD-pathogenesis, addressing the patho-mechanism to specific sugar modification of BACE-1 glycoprotein with bisecting GlcNAc. Our patients addressed protein N-glycosylation changes at an early phase of the whole biomolecular misregulation on AD, pointing to CSF N-glycome analyses as promising tool to enhance early detection of AD and also suggesting alternative therapeutics target molecules, such as specific glyco-enzymes. Copyright © 2015 Elsevier B.V. All rights reserved.

Apathy and emotion-based decision-making in amnesic mild cognitive impairment and Alzheimer's disease.

PubMed

Bayard, Sophie; Jacus, Jean-Pierre; Raffard, Stéphane; Gely-Nargeot, Marie-Christine

2014-01-01

Apathy and reduced emotion-based decision-making are two behavioral modifications independently described in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). The aims of this study were to investigate decision-making based on emotional feedback processing in AD and aMCI and to study the impact of reduced decision-making performances on apathy. We recruited 20 patients with AD, 20 participants with aMCI, and 20 healthy controls. All participants completed the Lille apathy rating scale (LARS) and the Iowa gambling task (IGT). Both aMCI and AD participants had reduced performances on the IGT and were more apathetic compared to controls without any difference between aMCI and AD groups. For the entire sample, LARS initiation dimension was related to IGT disadvantageous decision-making profile. We provide the first study showing that both aMCI and AD individuals make less profitable decisions than controls, whereas aMCI and AD did not differ. Disadvantageous decision-making profile on the IGT was associated with higher level of apathy on the action initiation dimension. The role of an abnormal IGT performance as a risk factor for the development of apathy needs to be investigated in other clinical populations and in normal aging.

Personal cooling air filtering device

DOEpatents

Klett, James [Knoxville, TN; Conway, Bret [Denver, NC

2002-08-13

A temperature modification system for modifying the temperature of fluids includes at least one thermally conductive carbon foam element, the carbon foam element having at least one flow channel for the passage of fluids. At least one temperature modification device is provided, the temperature modification device thermally connected to the carbon foam element and adapted to modify the temperature of the carbon foam to modify the temperature of fluids flowing through the flow channels. Thermoelectric and/or thermoionic elements can preferably be used as the temperature modification device. A method for the reversible temperature modification of fluids includes the steps of providing a temperature modification system including at least one thermally conductive carbon foam element having flow channels and at least one temperature modification device, and flowing a fluid through the flow channels.

Fractal Geometry in Physics

DTIC Science & Technology

1993-09-30

AD-A273 271 OFFICE OF NAVAL RESEARCH 3-0 1993 CONTRACT NUMBER: N00014-90-J- 1 30 MODIFICATION NO: P00005 19 R&T PROJECT: 4123041-10 & 11 A S.O. CODE...investigated. Indirectly related to these topics is a papaer by D. Stauffer, A. Aharony and B. Man- delbrot in Phy•sica A 196, 1993, 1-5. It evaluates

78 FR 22180 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... 972B-84, RB211-Trent 977-84, RB211-Trent 977B-84, and RB211-Trent 980-84 turbofan engines. This AD... 977B-84, and RB211-Trent 980-84 turbofan engines that incorporate RR production Modification 72-G585 or...

77 FR 50407 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... requires repetitive inspections to detect cracking of the lower corners of the door frame and cross beam of... modification of the outboard radius of the lower corners of the door frame and reinforcement of the cross beam... the lower frames and in the lower number 5 cross beam of the forward cargo door. This proposed AD...

75 FR 42292 - List of Approved Spent Fuel Storage Casks: NAC-MPC System, Revision 6

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... modifications to the Vertical Concrete Cask (VCC) incorporating design features from the MAGNASTOR system for...; an increase in the concrete pad compression strength from 4,000 psi to 6,000 psi; added justification... system while adhering to ALARA principles; (5) an increase in the concrete pad compression strength from...

The Scholarly Activity Predictor Model among Counseling Psychology Doctoral Students: A Modification and Extension

ERIC Educational Resources Information Center

Huber, Daniel M.

2010-01-01

The purpose of the current study was to help understand scholarly activity better among counseling psychology doctoral students. Two new variables were added to the previously created predictor model of scholarly activity: advisory working alliance and research competence. Three path analytic models were designed in the current study: (1) a…

RHIC BPM SYSTEM MODIFICATIONS AND PERFORMANCE.

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

SATOGATA, T.; CALAGA, R.; CAMERON, P.

2005-05-16

The RHIC beam position monitor (BPM) system provides independent average orbit and turn-by-turn (TBT) position measurements. In each ring, there are 162 measurement locations per plane (horizontal and vertical) for a total of 648 BPM planes in the RHIC machine. During 2003 and 2004 shutdowns, BPM processing electronics were moved from the RHIC tunnel to controls alcoves to reduce radiation impact, and the analog signal paths of several dozen modules were modified to eliminate gain-switching relays and improve signal stability. This paper presents results of improved system performance, including stability for interaction region beam-based alignment efforts. We also summarize performancemore » of recently-added DSP profile scan capability, and improved million-turn TBT acquisition channels for 10 Hz triplet vibration, nonlinear dynamics, and echo studies.« less

Treatment of Cancer in the Older Aged Person.

PubMed Central

Balducci, Lodovico

2010-01-01

Cancer is a disease of aging.1 Currently 50% of all malignancies occur in individuals 65 and over1 and by the year 2030 older individuals will account for 70% of all neoplasms. With the aging of the population the management of cancer in the older person with chemotherapy is beoming increasingly common. This treatment may be safe and effective if some appropriate measures are taken, including, an assessment of the physiologic age of each patient, modification of doses according to the renal function, use of meyelopoietic growth factors prophylactically in presence of moderately toxic chemotherapy, and provision of an adequate caregiver. Cure, prolongation of survival, and symptom palliation are universal goals of medical treatment. Prolongation of active life expectancy should be added to the treatment goal of the older aged person. PMID:21415975

Adding the Fourth "R": A Systems Approach to Solving the Hacker's Arms Race

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

Endicott-Popovsky, Barbara E.; Frincke, Deborah A.

2006-01-01

In this paper, the authors propose a modification of CERT's 3 R model to include a 4 th R, the discipline of Redress, identified as a necessary step to end the hacker arms race. Redress will require implementation of computer forensic investigation methods, tools and techniques that will permit evidence gathered to be admissible in a court of law, a standard not often understood or followed by many who are responsible for securing networks today. This leads the authors to conclude that there is a need for future work that will involve re-examination of the mechanisms and procedures used tomore » collect evidence of network intrusions in order to ensure that the Rules of Evidence requirements are considered.« less

Bioreactors for plant cells: hardware configuration and internal environment optimization as tools for wider commercialization.

PubMed

Georgiev, Milen I; Weber, Jost

2014-07-01

Mass production of value-added molecules (including native and heterologous therapeutic proteins and enzymes) by plant cell culture has been demonstrated as an efficient alternative to classical technologies [i.e. natural harvest and chemical (semi)synthesis]. Numerous proof-of-concept studies have demonstrated the feasibility of scaling up plant cell culture-based processes (most notably to produce paclitaxel) and several commercial processes have been established so far. The choice of a suitable bioreactor design (or modification of an existing commercially available reactor) and the optimization of its internal environment have been proven as powerful tools toward successful mass production of desired molecules. This review highlights recent progress (mostly in the last 5 years) in hardware configuration and optimization of bioreactor culture conditions for suspended plant cells.

A modification of the finite-difference model for simulation of two dimensional ground-water flow to include surface-ground water relationships

USGS Publications Warehouse

Ozbilgin, M.M.; Dickerman, D.C.

1984-01-01

The two-dimensional finite-difference model for simulation of groundwater flow was modified to enable simulation of surface-water/groundwater interactions during periods of low streamflow. Changes were made to the program code in order to calculate surface-water heads for, and flow either to or from, contiguous surface-water bodies; and to allow for more convenient data input. Methods of data input and output were modified and entries (RSORT and HDRIVER) were added to the COEF and CHECKI subroutines to calculate surface-water heads. A new subroutine CALC was added to the program which initiates surface-water calculations. If CALC is not specified as a simulation option, the program runs the original version. The subroutines which solve the ground-water flow equations were not changed. Recharge, evapotranspiration, surface-water inflow, number of wells, pumping rate, and pumping duration can be varied for any time period. The Manning formula was used to relate stream depth and discharge in surface-water streams. Interactions between surface water and ground water are represented by the leakage term in the ground-water flow and surface-water mass balance equations. Documentation includes a flow chart, data deck instructions, input data, output summary, and program listing. Numerical results from the modified program are in good agreement with published analytical results. (USGS)

The importance of indirect costs in primary cardiovascular disease prevention: can we save lives and money with statins?

PubMed

Grover, Steven A; Ho, Vivian; Lavoie, Frédéric; Coupal, Louis; Zowall, Hanna; Pilote, Louise

2003-02-10

The losses in productivity due to cardiovascular disease (CVD) are substantial but rarely considered in health economic analyses. We compared the cost-effectiveness of lipid level modification in the primary prevention of CVD with and without these indirect costs. We used the Cardiovascular Life Expectancy Model to estimate the long-term benefits and cost-effectiveness of lipid level modification with atorvastatin calcium, including 28% and 38% reductions in total cholesterol and low-density lipoprotein cholesterol levels, respectively, and a 5.5% increase in high-density lipoprotein cholesterol level. The direct costs included all medical care costs associated with CVD. The indirect costs represented the loss of employment income and the decreased value of housekeeping services after different manifestations of CVD. All costs were expressed in 2000 Canadian dollars. When only direct medical care costs were considered, the incremental cost-effectiveness ratios for lifelong therapy with atorvastatin calcium, 10 mg/d, were generally positive, ranging from a few thousand to nearly $20 000 per year of life saved. When the societal point of view was adopted and indirect costs were included, the total costs were generally negative, representing substantial cost savings (up to $50 000) and increased life expectancy for most groups of individuals. Lipid therapy with statins can reduce CVD morbidity and mortality as demonstrated in a number of clinical trials. Adding the indirect CVD costs associated with productivity losses at work and home can result in forecasted cost savings to society as a whole such that lipid therapy could potentially save lives and money.

78 FR 21246 - Definition of Factual Information and Time Limits for Submission of Factual Information

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

...The Department of Commerce (the Department) is modifying its regulations, which define ``factual information'' and establish time limits for the submission of factual information in antidumping (AD) and countervailing duty (CVD) proceedings. The modifications to the definition of factual information more clearly describe the types of information that can be submitted by a person or placed on the record by the Department in a segment of the proceeding. The modifications to the time limits enable the Department to efficiently determine the type of information being submitted and whether it is timely filed; they also ensure that the Department has sufficient opportunity to review submissions of factual information.

Fine Tuning Gene Expression: The Epigenome

PubMed Central

Mohtat, Davoud; Susztak, Katalin

2011-01-01

An epigenetic trait is a stably inherited phenotype resulting from changes in a chromosome without alterations in the DNA sequence. Epigenetic modifications, such as; DNA methylation, together with covalent modification of histones, are thought to alter chromatin density and accessibility of the DNA to cellular machinery, thereby modulating the transcriptional potential of the underlying DNA sequence. As epigenetic marks under environmental influence, epigenetics provides an added layer of variation that might mediate the relationship between genotype and internal and external environmental factors. Integration of our knowledge in genetics, epigenomics and genomics with the use of systems biology tools may present investigators with new powerful tools to study many complex human diseases such as kidney disease. PMID:21044758

Starch--value addition by modification.

PubMed

Tharanathan, Rudrapatnam N

2005-01-01

Starch is one of the most important but flexible food ingredients possessing value added attributes for innumerable industrial applications. Its various chemically modified derivatives offer a great scope of high technological value in both food and non-food industries. Modified starches are designed to overcome one or more of the shortcomings, such as loss of viscosity and thickening power upon cooking and storage, particularly at low pH, retrogradation characteristics, syneresis, etc., of native starches. Oxidation, esterification, hydroxyalkylation, dextrinization, and cross-linking are some of the modifications commonly employed to prepare starch derivatives. In a way, starch modification provides desirable functional attributes as well as offering economic alternative to other hydrocolloid ingredients, such as gums and mucilages, which are unreliable in quality and availability. Resistant starch, a highly retrograded starch fractionformed upon food processing, is another useful starch derivative. It exhibits the beneficial physiological effects of therapeutic and nutritional values akin to dietary fiber. There awaits considerable opportunity for future developments, especially for tailor-made starch derivatives with multiple modifications and with the desired functional and nutritional properties, although the problem of obtaining legislative approval for the use of novel starch derivatives in processed food formulations is still under debate. Nevertheless, it can be predicted that new ventures in starch modifications and their diverse applications will continue to be of great interest in applied research.

Acrosin activity in turkey spermatozoa: assay by clinical method and effect of zinc and benzamidine on the activity.

PubMed

Glogowski, J; Jankowski, J; Faruga, A; Ottobre, J S; Ciereszko, A

2001-09-15

We optimized a clinical assay developed for measuring total acrosin activity for mammalian and fish semen for use in turkey spermatozoa. The main modifications included dilution of semen to a final concentration of 25 to 1000 x 10(3) spermatozoa, an increase of Triton X-100 concentration to 0.05% and 1 hr preincubation without substrate, Acrosin activity in turkey spermatozoa was much higher than in human spermatozoa (about 100-times) but similar to that of boar sperm. To optimize this assay for turkey spermatozoa, it was necessary to use higher Triton X-100 concentrations in the reaction mixture. There was a better catalytic efficiency at higher temperatures and a special requirement for a preincubation period for proacrosin activation. We observed high inhibition of acrosin activity by zinc added during preincubation (90% at 0.01 mM of zinc chloride). Benzamidine also inhibited turkey acrosin, and the extent of inhibition was similar for the incubation or preincubation period. When zinc ions were added during incubation, this inhibition was lower (24%). The results suggest that zinc influences proacrosin activation of turkey spermatozoa. This influence may be important for successful long-term storage of spermatozoa in the hen's oviduct.

A cost-analysis of complex workplace nutrition education and environmental dietary modification interventions.

PubMed

Fitzgerald, Sarah; Kirby, Ann; Murphy, Aileen; Geaney, Fiona; Perry, Ivan J

2017-01-09

The workplace has been identified as a priority setting to positively influence individuals' dietary behaviours. However, a dearth of evidence exists regarding the costs of implementing and delivering workplace dietary interventions. This study aimed to conduct a cost-analysis of workplace nutrition education and environmental dietary modification interventions from an employer's perspective. Cost data were obtained from a workplace dietary intervention trial, the Food Choice at Work Study. Micro-costing methods estimated costs associated with implementing and delivering the interventions for 1 year in four multinational manufacturing workplaces in Cork, Ireland. The workplaces were allocated to one of the following groups: control, nutrition education alone, environmental dietary modification alone and nutrition education and environmental dietary modification combined. A total of 850 employees were recruited across the four workplaces. For comparison purposes, total costs were standardised for 500 employees per workplace. The combined intervention reported the highest total costs of €31,108. The nutrition education intervention reported total costs of €28,529. Total costs for the environmental dietary modification intervention were €3689. Total costs for the control workplace were zero. The average annual cost per employee was; combined intervention: €62, nutrition education: €57, environmental modification: €7 and control: €0. Nutritionist's time was the main cost contributor across all interventions, (ranging from 53 to 75% of total costs). Within multi-component interventions, the relative cost of implementing and delivering nutrition education elements is high compared to environmental modification strategies. A workplace environmental modification strategy added marginal additional cost, relative to the control. Findings will inform employers and public health policy-makers regarding the economic feasibility of implementing and scaling dietary interventions. Current Controlled Trials: ISRCTN35108237 . Date of registration: The trial was retrospectively registered on 02/07/2013.

DESIGN OF COMPREHENSIVE ALZHEIMER’S DISEASE CENTERS TO ADDRESS UNMET NATIONAL NEEDS

PubMed Central

Trojanowski, John Q.; Arnold, Steven E.; Karlawish, Jason H.; Brunden, Kurt; Cary, Mark; Davatzikos, Christos; Detre, John; Gaulton, Glen; Grossman, Murray; Hurtig, Howard; Jedrziewski, Kathryn; McCluskey, Leo; Naylor, Mary; Polsky, Daniel; Schellenberg, Gerard D.; Siderowf, Andrew; Shaw, Leslie M.; Van Deerlin, Vivianna; Wang, Li-San; Werner, Rachel; Xie, Sharon X.; Lee, Virginia M.-Y.

2010-01-01

The problem of Alzheimer’s disease (AD) exemplifies the challenges of dealing with a broad range of aging related chronic disorders that require long-term, labor-intensive and expensive care. As the “baby-boom” generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD with special focus on prevention. The “Prevent Alzheimer’s Disease 2020” (PAD 2020) initiative aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging related memory and motor impairments. PAD 2020 is developing an implementation plan to justify: a) increasing the federal budget for research; b) developing novel national resources to discover new interventions for memory and motor disorders; c) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978, the National Institute on Aging (NIA/NIH) established an extensive national network of AD research facilities at academic institutions including: AD Centers (ADCs), Consortium to Establish a Registry for AD (CERAD), AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer’s Coordinating Center (NACC), National Cell Repository for AD (NCRAD), and AD Neuroimaging Initiative (ADNI). However, despite the success of these program and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive AD Centers (CADCs) to support not only research, but also by being demonstration projects on care/ treatment, clinical trials, and education as well as by seamlessly integrating multi-site collaborative studies (ADCS, ADNI, Patient Registries, Clinical Data Banks, etc.) into a cohesive structure that further enhances the original mission of the NIA ADCs. Regional CADCs offer greater efficiency and cost savings while serving as coordinating hubs of existing ADCs thereby offering greater economies of scale and programmatic integration. The CADCs also broaden the scope of ADC activities to include research on interventions, diagnosis, imaging, prevention trials, and other longitudinal studies that require long-term support. Thus, CADCs can address the urgent need to identify subjects at high risk of AD for prevention trials and very early in the course of AD for clinical trials of disease modification. The enhanced CADCs will allow more flexibility among ADCs by supporting collaborative linkages with other institutions, and drawing upon a wider expertise from different locations. This perspective paper describes the University of Pennsylvania (Penn) CADC Model as an illustrative example of how an existing ADC can be converted into a CADC by better utilization of Penn academic resources to address the wide range of problems concerning AD. The intent of this position paper is to stimulate thinking and foster the development of other or alternative models for a systems approach to the study of dementia and movement disorders. PMID:20298979

Design of comprehensive Alzheimer's disease centers to address unmet national needs.

PubMed

Trojanowski, John Q; Arnold, Steven E; Karlawish, Jason H; Brunden, Kurt; Cary, Mark; Davatzikos, Christos; Detre, John; Gaulton, Glen; Grossman, Murray; Hurtig, Howard; Jedrziewski, Kathryn; McCluskey, Leo; Naylor, Mary; Polsky, Daniel; Schellenberg, Gerard D; Siderowf, Andrew; Shaw, Leslie M; Van Deerlin, Vivianna; Wang, Li-San; Werner, Rachel; Xie, Sharon X; Lee, Virginia M-Y

2010-03-01

The problem of Alzheimer's disease (AD) exemplifies the challenges of dealing with a broad range of aging-related chronic disorders that require long-term, labor-intensive, and expensive care. As the baby boom generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD, with special focus on prevention. The Campaign to Prevent Alzheimer's Disease by 2020 (PAD2020) aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging-related memory and motor impairments. PAD 2020 is developing an implementation plan to justify (1) increasing the federal budget for research, (2) developing novel national resources to discover new interventions for memory and motor disorders, and (3) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978 the National Institute on Aging or National Institute of Health (NIH) established an extensive national network of AD research facilities at academic institutions including AD Centers (ADCs), Consortium to Establish a Registry for AD, AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer's Coordinating Center, National Cell Repository for AD, and AD Neuroimaging Initiative. However, despite the success of these programs and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD 2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive Alzheimer's Disease Centers (CADCs) to support not only research, but also by being demonstration projects on care/treatment, clinical trials, and education as well as by seamlessly integrating multisite collaborative studies (ADCS, AD Neuroimaging Initiative, Patient Registries, Clinical Data Banks, etc) into a cohesive structure that further enhances the original mission of the National Institute on Aging ADCs. Regional CADCs offer greater efficiency and cost savings while serving as coordinating hubs of existing ADCs, thereby offering greater economies of scale and programmatic integration. The CADCs also broaden the scope of ADC activities to include research on interventions, diagnosis, imaging, prevention trials, and other longitudinal studies that require long-term support. Thus, CADCs can address the urgent need to identify subjects at high risk of AD for prevention trials and very early in the course of AD for clinical trials of disease modification. The enhanced CADCs will allow more flexibility among ADCs by supporting collaborative linkages with other institutions and drawing on a wider expertise from different locations. This perspective article describes the University of Pennsylvania (Penn) CADC Model as an illustrative example of how an existing ADC can be converted into a CADC by better utilization of Penn academic resources to address the wide range of problems concerning AD. The intent of this position paper is to stimulate thinking and foster the development of other or alternative models for a systematic approach to the study of dementia and movement disorders. 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease.

PubMed

Geijselaers, Stefan L C; Aalten, Pauline; Ramakers, Inez H G B; De Deyn, Peter Paul; Heijboer, Annemieke C; Koek, Huiberdina L; OldeRikkert, Marcel G M; Papma, Janne M; Reesink, Fransje E; Smits, Lieke L; Stehouwer, Coen D A; Teunissen, Charlotte E; Verhey, Frans R J; van der Flier, Wiesje M; Biessels, Geert Jan

2018-01-01

Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD). To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype. From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65.2% male) diagnosed with subjective cognitive impairment (n = 45), amnestic mild cognitive impairment (n = 44), or AD (n = 49), who completed a neuropsychological assessment, including tests of global cognition and memory performance, and who underwent lumbar puncture. We measured CSF levels of insulin, amyloid-β1-42, total (t-)Tau, and phosphorylated (p-)Tau. CSF insulin levels did not differ between the diagnostic groups (p = 0.136). Across the whole study population, CSF insulin was unrelated to cognitive performance and CSF biomarkers of AD, after adjustment for age, sex, body mass index, diabetes status, and clinic site (all p≥0.131). Importantly, however, we observed effect modification by sex and APOE ɛ4 genotype. Specifically, among women, higher insulin levels in the CSF were associated with worse global cognition (standardized regression coefficient -0.483; p = 0.008) and higher p-Tau levels (0.353; p = 0.040). Among non-carriers of the APOE ɛ4 allele, higher CSF insulin was associated with higher t-Tau (0.287; p = 0.008) and p-Tau (0.246; p = 0.029). Our findings provide further evidence for a relationship between brain insulin signaling and AD pathology. It also highlights the need to consider sex and APOE ɛ4 genotype when assessing the role of insulin.

No added diagnostic value of non-phosphorylated tau fraction (p-taurel) in CSF as a biomarker for differential dementia diagnosis.

PubMed

Goossens, Joery; Bjerke, Maria; Struyfs, Hanne; Niemantsverdriet, Ellis; Somers, Charisse; Van den Bossche, Tobi; Van Mossevelde, Sara; De Vil, Bart; Sieben, Anne; Martin, Jean-Jacques; Cras, Patrick; Goeman, Johan; De Deyn, Peter Paul; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan

2017-07-14

The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls. The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

Clinical comparison of human and canine atopic dermatitis using human diagnostic criteria (Japanese Dermatological Association, 2009): proposal of provisional diagnostic criteria for canine atopic dermatitis.

PubMed

Terada, Yuri; Nagata, Masahiko; Murayama, Nobuo; Nanko, Hiroko; Furue, Masutaka

2011-08-01

Atopic dermatitis (AD) is a common skin disease encountered in both humans and dogs. Canine AD can be used in the analysis of naturally occurring AD; however, details of clinical comparison have been lacking. The purpose of this study is to compare those clinical features using the human diagnostic criteria (Japanese Dermatological Association, 2009). Fifty-one dogs with canine AD were evaluated by the human criteria. Prior to this study, canine AD was basically diagnosed by the fulfillment of two authentic canine AD criteria and a positive reaction against Dermatophagoides farinae in serum immunoglobulin E levels and/or in intradermal tests. Among the human AD criteria items, behavior corresponding to pruritus was observed in all 51 dogs. Skin lesions corresponding to eczematous dermatitis were seen in 50 dogs, and symmetrical distribution of skin lesions was noted in all 51 dogs. A chronic or chronically relapsing course was observed in 50 dogs. Based on these results, the concordance rate for the criteria was 96% (49/51). Differential diagnoses of AD were also investigated in the same manner. The concordance rate for the criteria was 0% (0/69) in scabies, 2% (1/50) in pyoderma, 0% (0/50) in demodicosis, 0% (0/9) in cutaneous lymphoma, 0% (0/2) in ichthyosis, 25% (2/7) in flea allergy, 48% (24/50) in seborrheic dermatitis and 75% (3/4) in food allergy. Canine AD is thus indicated as a valuable counterpart to human AD in clinical aspects. In addition, the human AD criteria could be applicable, with some modification, as provisional diagnostic criteria for canine AD. © 2011 Japanese Dermatological Association.

75 FR 9814 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model ERJ 190-100 STD...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-04

... airplane Airworthiness Limitation Items (ALI), to include new inspections tasks or modification of existing... (ALI), to include new inspections tasks or modification of existing ones and its respective thresholds... resulted in modifications on the airplane Airworthiness Limitation Items (ALI), to include new inspections...

75 FR 30277 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model ERJ 190-100 STD...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

... cracks resulted in modifications on the airplane Airworthiness Limitation Items (ALI), to include new... Limitation Items (ALI), to include new inspections tasks or modification of existing ones and its respective... modifications on the airplane Airworthiness Limitation Items (ALI), to include new inspections tasks or...

75 FR 2067 - Airworthiness Directives; Turbomeca S.A. Model Arriel 1B, 1D, and 1D1 Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... originated at the pinion teeth root due to increased vibratory stresses. This increase in vibratory stresses... reduce the level of vibratory stresses and improve tooth resistance, Turbom[eacute]ca modification... estimate that it would take about 6 work-hours per product to comply with this AD. The average labor rate...

76 FR 12972 - Joint Meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

.../phone line to learn about possible modifications before coming to the meeting. Agenda: On May 17 and 18... children less than 2 years of age. In addition, the committees will consider adding a weight-based dosing regimen to the existing age-based dosing regimen for children 2 to 12 years of age. Dosing for children 12...

Design, Development, and Testing of Advanced Bridge Structures

DTIC Science & Technology

1993-12-23

experiment used a reduced EEW resin (215) with Hycar CTBN 1872 being added with the curing agent, rather than the resin . The result was a very... resins are mainly phenolics , carbon monoxide and water. Thermal decomposition products should therefore be treated as potentially hazardous substances...26 2.3.5 Chemical Surface Modification ............................................. 26 2.3.5.1 Resin Impregnation of a Swelled

Laptops to Go: A Student Assessment of a Library Laptop Lending Service

ERIC Educational Resources Information Center

Summey, Terri; Gutierrez, Art

2012-01-01

Approximately five years ago, the library at Emporia State University started a laptop lending service to provide laptops for use in the library. The program has been highly successful. In the last few years, some modifications were made to the program, and netbooks were added. In this article, the authors will explore laptop programs in a variety…

Self-Cleaning Tubular-Membrane Module

NASA Technical Reports Server (NTRS)

Sarbolouki, M. N.

1983-01-01

Tubular membranes made self-cleaning with aid of flow reversing valve. Sponge balls scrub membrane surfaces as they travel inside membrane tubes. A four-way flow-reversal valve automatically reverses flow in tubes at preset intervals so sponge balls reciprocate along tubes. Baskets at ends of tubes prevent sponges from escaping. Automatic cleaning feature added to existing membrane processing equipment with minimal modifications.

76 FR 6575 - Airworthiness Directives; BAE Systems (Operations) Limited Model BAe 146 and Avro 146-RJ Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

.... One operator reported a crack in a pre-modification main fitting. Shot peening was not present, as... received additional reports of cracked NLG main fittings. One operator reported a crack in a... optional closing action of EASA AD 2010-0001-E is embodiment of M-D B 146-32-150 (polishing and shot...

An in vitro study on the retentive strength of orthodontic bands cemented with CPP-ACP-containing GIC

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-12-01

Caries and white spot lesions around orthodontic bands are well known occurrences in fixed orthodontic treatment. There are several methods to overcome these problems. One of these includes modification of the band cement with remineralizing agents such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). However, it should be evaluated that the cement modification has no significant negative effects on the retentive strength of the cemented orthodontic bands. In a continuation of our previous studies on the effects of the addition of CPP-ACP on the mechanical properties of luting and lining glass ionomer cement (GIC), this study aimed to investigate the retentive strength of orthodontic bands cemented with CPP-ACP containing GIC. Sixty extracted human pre molars teeth were embedded in acrylic resin and randomly divided into two groups of 30 specimens. In group 1, bands were cemented to the tooth with a GIC. In group 2, CPP-ACP (1.56% w/w) was added to the GIC before cementation. The retentive strength of each groups was determined with a universal testing machine. Further, the amount of cement remaining on the tooth surface was evaluated under a stereomicroscope, and the adhesive remnant index (ARI) score was determined. Results of this study showed that there were no significant differences between the groups in retentive strength and ARI score. In conclusion, modification of GIC with 1.56% w/w CPP-ACP had no negative effects on the retentive strength of the bands so can be used during fixed orthodontic treatment.

Modification of the morphology of P(S-b-EO) templated thin TiO2 films by swelling with PS homopolymer.

PubMed

Perlich, J; Schulz, L; Abul Kashem, M M; Cheng, Y-J; Memesa, M; Gutmann, J S; Roth, S V; Müller-Buschbaum, P

2007-09-25

For the controlled modification of sol-gel-templated polymer nanocomposites, which are transferred to a nanostructured, crystalline TiO2 phase by a calcination process, the addition of a single homopolymer was investigated. For the preparation, the homopolymer polystyrene (PS) is added in different amounts to the diblock copolymer P(S-b-EO) acting as a templating agent. The homopolymer/diblock copolymer blend system is combined with sol-gel chemistry to provide and attach the TiO2 nanoparticles to the diblock copolymer. So-called good-poor solvent-pair-induced phase separation leads to the formation of nanostructures by film preparation via spin coating. The fabricated morphologies are studied as a function of added homopolymer before and after calcination with atomic force microscopy, field emission scanning electron microscopy, and grazing incidence small-angle X-ray scattering. The observed behavior is discussed in the framework of controlling the block copolymer morphologies by the addition of homopolymers. At small homopolymer concentrations, the increase in homopolymer concentration changes the structure size, whereas at high homopolymer concentrations, a change in morphology is triggered. Thus, the behavior of a pure polymer system is transferred to a more complex hybrid system.

Generation of an Adenovirus-Parvovirus Chimera with Enhanced Oncolytic Potential

PubMed Central

El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K.; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M.; Rommelaere, Jean

2012-01-01

In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells. PMID:22787235

Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential.

PubMed

El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M; Rommelaere, Jean; Marchini, Antonio

2012-10-01

In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells.

Thermal treatment to improve the hydrophobicity of ground CaCO3 particles modified with sodium stearate

NASA Astrophysics Data System (ADS)

Liang, Yong; Yu, Keyi; Zheng, Qinzhong; Xie, Jiuren; Wang, Ting-Jie

2018-04-01

The surface modification of calcium carbonate (CaCO3) particles, which is used as a filler, significantly affects the properties of the composed materials. The effects of thermal treatment on ground calcium carbonate (GCC) particles subjected to hydrophobic modification using sodium stearate (RCOONa) were studied. The contact angle of the modified GCC particles increased from 24.7° to 118.9° when the amount of RCOONa added was increased from 0% to 5% and then decreased to 97.5° when the RCOONa content was further increased to 10%. When a large amount of RCOONa was added, RCOO- reacts with Ca2+ and generates (RCOO)2Ca nuclei, which are adsorbed on the surface of the GCC particles, forming a discontinuous (RCOO)2Ca modified layer. After thermal treatment under sealed conditions, the contact angle of the GCC particles modified using 1.5% RCOONa/GCC increased from 112.8° to 139.6°. The thermal stability of the (RCOO)2Ca modified layer was increased, with the temperature increase of the mass-loss peak from 358.0 to 463.0 °C. It is confirmed that the spreading of melted (RCOO)2Ca nuclei on the surface of the GCC particles during the thermal treatment increased the continuity of the modified layer, converting the physical adsorption of the (RCOO)2Ca nuclei into chemisorption. The grafting density of RCOO- on the GCC particle surface after thermal treatment approximates to 5.00/nm2, which is close to the single-molecular-layer grafting density of RCOO-, indicating that excellent modification was achieved.

Acceptability and Feasibility of a Shared Decision-Making Model in Work Rehabilitation: A Mixed-Methods Study of Stakeholders' Perspectives.

PubMed

Coutu, Marie-France; Légaré, France; Durand, Marie-José; Stacey, Dawn; Labrecque, Marie-Elise; Corbière, Marc; Bainbridge, Lesley

2018-04-16

Purpose To establish the acceptability and feasibility of implementing a shared decision-making (SDM) model in work rehabilitation. Methods We used a sequential mixed-methods design with diverse stakeholder groups (representatives of private and public employers, insurers, and unions, as well as workers having participated in a work rehabilitation program). First, a survey using a self-administered questionnaire enabled stakeholders to rate their level of agreement with the model's acceptability and feasibility and propose modifications, if necessary. Second, eight focus groups representing key stakeholders (n = 34) and four one-on-one interviews with workers were conducted, based on the questionnaire results. For each stakeholder group, we computed the percentage of agreement with the model's acceptability and feasibility and performed thematic analyses of the transcripts. Results Less than 50% of each stakeholder group initially agreed with the overall acceptability and feasibility of the model. Stakeholders proposed 37 modifications to the objectives, 17 to the activities, and 39 to improve the model's feasibility. Based on in-depth analysis of the transcripts, indicators were added to one objective, an interview guide was added as proposed by insurers to ensure compliance of the SDM process with insurance contract requirements, and one objective was reformulated. Conclusion Despite initially low agreement with the model's acceptability on the survey, subsequent discussions led to three minor changes and contributed to the model's ultimate acceptability and feasibility. Later steps will involve assessing the extent of implementation of the model in real rehabilitation settings to see if other modifications are necessary before assessing its impact.

Electrode Modification and Optimization in Air-Cathode Single-Chamber Microbial Fuel Cells.

PubMed

Wang, Yanhua; Wu, Jiayan; Yang, Shengke; Li, Huihui; Li, Xiaoping

2018-06-27

Due to the known problems of microbial fuel cells (MFCs), such as low electricity generation performance and high cost of operation, we modified the electrode with graphene and polyaniline (PANI) is a single-chamber air-cathode MFC and then evaluated the effects of electrode modification on MFC electricity generation performance. Carbon cloth electrodes (unmodified, CC; graphene-modified, G/CC; and polyaniline-graphene-modified, PANI-G/CC) were prepared using the impregnation method. Sulfonated cobalt phthalocyanine (CoPcS) was then introduced as a cathode catalyst. The Co-PANI-G/CC cathode showed higher catalytic activity toward oxygen reduction compared with other electrodes. The maximum power density of the MFC with Co-PANI-G/CC cathode was 32.2 mW/m², which was 1.8 and 6.1 times higher than the value obtained with Co-G/CC and Co/CC cathodes, respectively. This indicates a significant improvement in the electricity generation of single-chamber MFCs and provides a simple, effective cathode modification method. Furthermore, we constructed single-chamber MFCs using the modified anode and cathode and analyzed electricity generation and oxytetracycline (OTC) degradation with different concentrations of OTC as the fuel. With increasing added OTC concentration, the MFC performance in both electricity generation and OTC degradation gradually decreased. However, when less than 50 mg/L OTC was added, the 5-day degradation rate of OTC reached more than 90%. It is thus feasible to process OTC-containing wastewater and produce electricity using single-chamber MFCs, which provides a new concept for wastewater treatment.

Effect of changes in an FFQ: comparing data from two national dietary survey instruments among 2-year-olds.

PubMed

Kristiansen, A L; Lillegaard, I T L; Lande, B; Andersen, L F

2013-01-28

In the interpretation of dietary trends, it is important to consider the potential effect of modifications in the dietary assessment method. Therefore, our objective was to explore the comparability of data obtained at two time points by a semi-quantitative FFQ (SFFQ) which has had slight modifications over time. In the national dietary surveys among Norwegian 2-year-olds, diet was assessed by an SFFQ which underwent modifications between the 1999 survey and the 2007 survey. In the present study, fifty-nine families with a 2-year-old child participated by completing both the SFFQ in a crossover design within a month's time. With regard to the reported intake of energy and nutrients, the largest significant differences observed between the two questionnaires were for carbohydrates and added sugar. According to intake of food groups, significant differences were observed for five out of sixteen food groups. Spearman's correlation coefficients for energy, nutrients and food groups ranged from 0.43 (Ca) to 0.85 (soft drinks). Most Bland-Altman plots indicated broad limits of agreement. The differences between the two questionnaires can be explained by changes in the questionnaires, changes in the food composition databases used and random variation. Comparing differences between the questionnaires by maternal educational level, number of children and type of day care revealed minor differences. In conclusion, this study showed that at the group level there was reasonable comparability between the two questionnaires, except for carbohydrates, added sugar and some food groups. Moreover, there were moderate to high correlations for energy, nutrients and food groups.

Consistent higher derivative gravitational theories with stable de Sitter and anti-de Sitter backgrounds

NASA Astrophysics Data System (ADS)

Biswas, Tirthabir; Koshelev, Alexey S.; Mazumdar, Anupam

2017-02-01

In this paper we provide the criteria for any generally covariant, parity preserving, and torsion-free theory of gravity to possess a stable de Sitter (dS) or anti-de Sitter (AdS) background. By stability we mean the absence of tachyonic or ghostlike states in the perturbative spectrum that can lead to classical instabilities and violation of quantum unitarity. While we find that the usual suspects, the F (R ) and F (G ) theories, can indeed possess consistent (A)dS backgrounds, G being the Gauss-Bonnet term, another interesting class of theories, string-inspired infinite derivative gravitational theories, can also be consistent around such curved vacuum solutions. Our study should not only be relevant for quantum gravity and early universe cosmology involving ultraviolet physics, but also for modifications of gravity in the infrared sector vying to replace dark energy.

Expanding the biomass derived chemical space

PubMed Central

Brun, Nicolas; Hesemann, Peter

2017-01-01

Biorefinery aims at the conversion of biomass and renewable feedstocks into fuels and platform chemicals, in analogy to conventional oil refinery. In the past years, the scientific community has defined a number of primary building blocks that can be obtained by direct biomass decomposition. However, the large potential of this “renewable chemical space” to contribute to the generation of value added bio-active compounds and materials still remains unexplored. In general, biomass derived building blocks feature a diverse range of chemical functionalities. In order to be integrated into value-added compounds, they require additional functionalization and/or covalent modification thereby generating secondary building blocks. The latter can be thus regarded as functional components of bio-active molecules or materials and represent an expansion of the renewable chemical space. This perspective highlights the most recent developments and opportunities for the synthesis of secondary biomass derived building blocks and their application to the preparation of value added products. PMID:28959397

Mindfulness programming for parents and teachers of children with ADHD.

PubMed

Miller, Carlin J; Brooker, Brianne

2017-08-01

Parents and teachers of children with attention-deficit/hyperactivity disorder (ADHD) are at-risk for a range of suboptimal psychosocial outcomes, including mental health difficulties and heightened stress, problems perhaps ameliorated through mindfulness-based programming. To show pilot data from an investigation of the outcomes of a purpose-built mindfulness training for parents and teachers of children with ADHD (N = 26). The program represents a purpose-driven modification of the Mindfulness-Based Stress Reduction (MBSR) curriculum. Namely, we reduced participant time commitment and added psychoeducation about ADHD with brief parent training. The measurement protocol included measures of stress, anxiety, depression, and mindfulness. Following the 8-week program, parents and teachers reported reduced perceived stress, reduced self-reported anxiety, and improvements in some facets of mindfulness. The work highlights the promise of specialized mindfulness-based interventions in promoting positive psychosocial outcomes in specific at-risk groups, such as the carers of children with ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of harbor modifications on the tsunami vulnerability of Crescent City, California

NASA Astrophysics Data System (ADS)

Dengler, L.; Uslu, B.

2008-12-01

Crescent City, California has experienced more damaging tsunami events in historic times than any other location on the West Coast of the United States. Thirty-one tsunamis have been observed at Crescent City since a tide gauge was established in 1933, including eleven events with maximum peak to trough wave range exceeding one meter and four that caused damage. The most damaging event occurred in 1964 as a result of the great Alaska earthquake. The ensuing tsunami flooded 29 city blocks and killed 11 in the Crescent City area. As a result of the 1964 tsunami and redevelopment projects, the Crescent City harbor was significantly modified in the early 1970s. A 200 x 300 meter small boat basin was carved into the preexisting shore line, a 123 meter dog leg extension was added to the central breakwater and significant deepening occurred on the eastern side of the harbor. In 2006, a Mw 8.3 earthquake in the Kuril Islands generated a moderate Pacific-wide tsunami. The only location with significant damage was the Crescent City harbor where strong currents damaged docks and boats, causing an estimated 9.2 million (US dollars) in damages. Strong currents estimated by the Harbor Master at 12 knots were observed near the entrance to the small boat basin. Past earthquakes from the northwestern Pacific including the 1933 M 8.3 Sanriku Japan earthquake may have produced similar amplitudes at Crescent City to the 2006 event but caused no damage. We have obtained the pre-modification harbor bathymetry and use the MOST model to compare tsunami water heights and current velocities for the 1933 and 2006 sources using modern and pre- modification bathymetry. We also examine model the 1964 inundation using the actual bathymetry and compare the results to numerical simulations that have only used the modern data.

Second Generation Integrated Composite Analyzer (ICAN) Computer Code

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.; Ginty, Carol A.; Sanfeliz, Jose G.

1993-01-01

This manual updates the original 1986 NASA TP-2515, Integrated Composite Analyzer (ICAN) Users and Programmers Manual. The various enhancements and newly added features are described to enable the user to prepare the appropriate input data to run this updated version of the ICAN code. For reference, the micromechanics equations are provided in an appendix and should be compared to those in the original manual for modifications. A complete output for a sample case is also provided in a separate appendix. The input to the code includes constituent material properties, factors reflecting the fabrication process, and laminate configuration. The code performs micromechanics, macromechanics, and laminate analyses, including the hygrothermal response of polymer-matrix-based fiber composites. The output includes the various ply and composite properties, the composite structural response, and the composite stress analysis results with details on failure. The code is written in FORTRAN 77 and can be used efficiently as a self-contained package (or as a module) in complex structural analysis programs. The input-output format has changed considerably from the original version of ICAN and is described extensively through the use of a sample problem.

Implementation and validation of an implant-based coordinate system for RSA migration calculation.

PubMed

Laende, Elise K; Deluzio, Kevin J; Hennigar, Allan W; Dunbar, Michael J

2009-10-16

An in vitro radiostereometric analysis (RSA) phantom study of a total knee replacement was carried out to evaluate the effect of implementing two new modifications to the conventional RSA procedure: (i) adding a landmark of the tibial component as an implant marker and (ii) defining an implant-based coordinate system constructed from implant landmarks for the calculation of migration results. The motivation for these two modifications were (i) to improve the representation of the implant by the markers by including the stem tip marker which increases the marker distribution (ii) to recover clinical RSA study cases with insufficient numbers of markers visible in the implant polyethylene and (iii) to eliminate errors in migration calculations due to misalignment of the anatomical axes with the RSA global coordinate system. The translational and rotational phantom studies showed no loss of accuracy with the two new measurement methods. The RSA system employing these methods has a precision of better than 0.05 mm for translations and 0.03 degrees for rotations, and an accuracy of 0.05 mm for translations and 0.15 degrees for rotations. These results indicate that the new methods to improve the interpretability, relevance, and standardization of the results do not compromise precision and accuracy, and are suitable for application to clinical data.

Modification of a Superficial X-Ray Therapy Machine for Rectal Contact Therapy

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

Barish, Robert J.; Donohue, Karen Episcopia

2015-01-15

X-ray therapy of superficial rectal cancers using a hand-held 50 kV contact unit (Philips RT-50) in a technique first described by Papillon had reached a point of widening clinical acceptability when the manufacturer of this equipment discontinued its production. To pursue this endocavitary approach to rectal therapy, technical modifications have to be made to conventional superficial x-ray therapy machines. Advantages over the original Papillon method include remote viewing of the lesion through the proctoscopic cone and a lower radiation exposure for the operator. We have evaluated a Bucky Combination Therapy Unit under conditions in which the operating voltage (65 kV),more » target skin distance (23.6 cm), and added filtration (0.39 mm Al) were selected in order to match as closely as possible the beam penetration characteristics of the “standard” (Papillon) technique. With this equipment, the thermal characteristics of the tube anode and housing limit the amount of radiation that can be delivered before a “rest period” for the machine is needed. In practice, 3 minutes of irradiation at an exposure rate of 500 R/min can be performed followed by an interval of 3 minutes before irradiation can be resumed.« less

Effects of the surface modification of silver nanoparticles on the surface-enhanced Raman spectroscopy of methylene blue for borohydride-reduced silver colloid

NASA Astrophysics Data System (ADS)

Dong, Xiao; Gu, Huaimin; Kang, Jian; Yuan, Xiaojuan; Wu, Jiwei

2010-12-01

The paper further investigated the relationship between the modification of the surface chemistry and the enhancement mechanisms of borohydride-reduced silver particles (BRSC). The bands of residual ions die down while the anomalous bands increase gradually with the increasing of the concentration of Cl - and Br -. It means the residual ions are displaced gradually by the added Cl - or Br - and the two halides can lead to the aggregation of the BRSC to a certain extent. However, the most strongly binding anions - I -, cannot cause any aggregation of silver particles. From the detection of methylene blue (MB), the relationship between the modification of silver surface chemistry and the enhancement mechanisms was discussed. Chloride gives the greatest enhancement while the iodide gives the lowest enhancement among the different kinds of anions. There are also some anomalous bands in the SERS spectra of MB, and these anomalous bands were given rational explanation in this paper.

Modification of the rheological properties of screen printing ceramic paints containing gold

NASA Astrophysics Data System (ADS)

Izak, P.; Mastalska-Poplawska, J.; Lis, J.; Stempkowska, A.

2017-01-01

This work presents the results of modification of rheological properties of screen printing paints containing gold. 15 wt% glossy gold paste and 15 wt% glossy liquid gold were used as modifiers containing gold. The study showed that the gold paint for screen printing can be obtained by evaporation of the 15 wt% liquid gold and the golden luster. The compaction process of liquid gold by evaporation is slow and easy to perform in industrial conditions. The second way to adapt the 15 wt% gold ceramic paint for screen printing application depended on adding the aniseed oil and the pine oil. The course of the flow curve of the gold paste without modification indicates that it is shear thinning and shows the desired effect of thixotropy, and even anti-thixotropy, at low shear rates (<50-1 s-1). The introduction of the essential oils eliminates this phenomenon and the paste converts itself from the non-rheostable to the rheostable liquid.

Applying Lean/Toyota production system principles to improve phlebotomy patient satisfaction and workflow.

PubMed

Melanson, Stacy E F; Goonan, Ellen M; Lobo, Margaret M; Baum, Jonathan M; Paredes, José D; Santos, Katherine S; Gustafson, Michael L; Tanasijevic, Milenko J

2009-12-01

Our goals were to improve the overall patient experience and optimize the blood collection process in outpatient phlebotomy using Lean principles. Elimination of non-value-added steps and modifications to operational processes resulted in increased capacity to handle workload during peak times without adding staff. The result was a reduction of average patient wait time from 21 to 5 minutes, with the goal of drawing blood samples within 10 minutes of arrival at the phlebotomy station met for 90% of patients. In addition, patient satisfaction increased noticeably as assessed by a 5-question survey. The results have been sustained for 10 months with staff continuing to make process improvements.

Study of the application of solar chemical dehumidification system to wind tunnel facilities of NASA Lewis Research Center at Cleveland, Ohio

NASA Technical Reports Server (NTRS)

1976-01-01

Energy utilization and cost payback analyses were prepared for proposed modifications. A 50,000 CFM standard compact packaged solid desiccant dehumidifier utilizing high temperature hot water (HTHW) for desiccant regeneration was added. The HTHW is generated by utilizing solar energy and is stored in a storage tank. A steam boiler is provided as a back-up for the solar system. A 50,000 CFM standard compact package solid desiccant dehumidifier utilizing high temperature hot water (HTHW) for desiccant regeneration was added. The HTHW is generated by utilizing a steam boiler and a heat exchanger and is stored in a storage tank.

Radion stabilization in higher curvature warped spacetime

NASA Astrophysics Data System (ADS)

Das, Ashmita; Mukherjee, Hiya; Paul, Tanmoy; SenGupta, Soumitra

2018-02-01

We consider a five dimensional AdS spacetime in presence of higher curvature term like F(R) = R + α R^2 in the bulk. In this model, we examine the possibility of modulus stabilization from the scalar degrees of freedom of higher curvature gravity free of ghosts. Our result reveals that the model stabilizes itself and the mechanism of modulus stabilization can be argued from a geometric point of view. We determine the region of the parametric space for which the modulus (or radion) can to be stabilized. We also show how the mass and coupling parameters of radion field are modified due to higher curvature term leading to modifications of its phenomenological implications on the visible 3-brane.

Mixed Phase Modeling in GlennICE with Application to Engine Icing

NASA Technical Reports Server (NTRS)

Wright, William B.; Jorgenson, Philip C. E.; Veres, Joseph P.

2011-01-01

A capability for modeling ice crystals and mixed phase icing has been added to GlennICE. Modifications have been made to the particle trajectory algorithm and energy balance to model this behavior. This capability has been added as part of a larger effort to model ice crystal ingestion in aircraft engines. Comparisons have been made to four mixed phase ice accretions performed in the Cox icing tunnel in order to calibrate an ice erosion model. A sample ice ingestion case was performed using the Energy Efficient Engine (E3) model in order to illustrate current capabilities. Engine performance characteristics were supplied using the Numerical Propulsion System Simulation (NPSS) model for this test case.

Dynamic Constraint Satisfaction with Reasonable Global Constraints

NASA Technical Reports Server (NTRS)

Frank, Jeremy

2003-01-01

Previously studied theoretical frameworks for dynamic constraint satisfaction problems (DCSPs) employ a small set of primitive operators to modify a problem instance. They do not address the desire to model problems using sophisticated global constraints, and do not address efficiency questions related to incremental constraint enforcement. In this paper, we extend a DCSP framework to incorporate global constraints with flexible scope. A simple approach to incremental propagation after scope modification can be inefficient under some circumstances. We characterize the cases when this inefficiency can occur, and discuss two ways to alleviate this problem: adding rejection variables to the scope of flexible constraints, and adding new features to constraints that permit increased control over incremental propagation.

First Direct Dating for the Construction and Modification of the Baphuon Temple Mountain in Angkor, Cambodia.

PubMed

Leroy, Stéphanie; Hendrickson, Mitch; Delqué-Kolic, Emmanuelle; Vega, Enrique; Dillmann, Philippe

2015-01-01

Architecture represents key evidence of dynastic practice and change in the archaeological world. Chronologies for many important buildings and sequences, including the iconic temples of medieval Angkor in Cambodia, are based solely on indirect associations from inscriptions and architectural styles. The Baphuon temple, one of the last major buildings in Angkor without textual or scientifically-derived chronological evidence, is crucial both for the context and date of its construction and the period when its western façade was modified into a unique, gigantic Reclining Buddha. Its construction was part of a major dynastic change and florescence of the Hindu-Mahayana Buddhist state and the modification is the key evidence of Theravada Buddhist power after Angkor's decline in the 15th century. Using a newly-developed approach based on AMS radiocarbon dating to directly date four iron crampons integrated into the structure we present the first direct evidence for the history of the Baphuon. Comprehensive study of ferrous elements shows that both construction and modification were critically earlier than expected. The Baphuon can now be considered as the major temple associated with the imperial reformations and territorial consolidation of Suryavarman I (1010-1050 AD) for whom no previous building to legitimize his reign could be identified. The Theravada Buddhist modification is a hundred years prior to the conventional 16th century estimation and is not associated with renewed use of Angkor. Instead it relates to the enigmatic Ayutthayan occupation of Angkor in the 1430s and 40s during a major period of climatic instability. Accurately dating iron with relatively low carbon content is a decisive step to test long-standing assumptions about architectural histories and political processes for states that incorporated iron into buildings (e.g., Ancient Greece, medieval India). Furthermore, this new approach has the potential to revise chronologies related to iron consumption practices since the origins of ferrous metallurgy three millennia ago.

First Direct Dating for the Construction and Modification of the Baphuon Temple Mountain in Angkor, Cambodia

PubMed Central

Leroy, Stéphanie; Hendrickson, Mitch; Delqué-Kolic, Emmanuelle; Vega, Enrique; Dillmann, Philippe

2015-01-01

Architecture represents key evidence of dynastic practice and change in the archaeological world. Chronologies for many important buildings and sequences, including the iconic temples of medieval Angkor in Cambodia, are based solely on indirect associations from inscriptions and architectural styles. The Baphuon temple, one of the last major buildings in Angkor without textual or scientifically-derived chronological evidence, is crucial both for the context and date of its construction and the period when its western façade was modified into a unique, gigantic Reclining Buddha. Its construction was part of a major dynastic change and florescence of the Hindu-Mahayana Buddhist state and the modification is the key evidence of Theravada Buddhist power after Angkor's decline in the 15th century. Using a newly-developed approach based on AMS radiocarbon dating to directly date four iron crampons integrated into the structure we present the first direct evidence for the history of the Baphuon. Comprehensive study of ferrous elements shows that both construction and modification were critically earlier than expected. The Baphuon can now be considered as the major temple associated with the imperial reformations and territorial consolidation of Suryavarman I (1010–1050 AD) for whom no previous building to legitimize his reign could be identified. The Theravada Buddhist modification is a hundred years prior to the conventional 16th century estimation and is not associated with renewed use of Angkor. Instead it relates to the enigmatic Ayutthayan occupation of Angkor in the 1430s and 40s during a major period of climatic instability. Accurately dating iron with relatively low carbon content is a decisive step to test long-standing assumptions about architectural histories and political processes for states that incorporated iron into buildings (e.g., Ancient Greece, medieval India). Furthermore, this new approach has the potential to revise chronologies related to iron consumption practices since the origins of ferrous metallurgy three millennia ago. PMID:26535895

Modifications of traps to reduce bycatch of freshwater turtles

USGS Publications Warehouse

Bury, R. Bruce

2011-01-01

Mortality of freshwater turtles varies among types and deployments of traps. There are few or no losses in hoop or fyke traps set where turtles may reach air, including placement in shallows, addition of floats on traps, and tying traps securely to a stake or to shore. Turtle mortality occurs when traps are set deep, traps are checked at intervals >1 day, and when turtles are captured as bycatch. Devices are available that exclude turtles from traps set for crab or game fish harvest. Slotted gates in front of the trap mouth reduce turtle entry, but small individuals still may be trapped. Incidental take of turtles is preventable by integrating several designs into aquatic traps, such as adding floats to the top of traps so turtles may reach air or an extension tube (chimney, ramp) that creates an escape route.

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation.

PubMed

Eastman, Peter; Friedrichs, Mark S; Chodera, John D; Radmer, Randall J; Bruns, Christopher M; Ku, Joy P; Beauchamp, Kyle A; Lane, Thomas J; Wang, Lee-Ping; Shukla, Diwakar; Tye, Tony; Houston, Mike; Stich, Timo; Klein, Christoph; Shirts, Michael R; Pande, Vijay S

2013-01-08

OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures. It is based on a layered architecture: the lower layers function as a reusable library that can be invoked by any application, while the upper layers form a complete environment for running molecular simulations. The library API hides all hardware-specific dependencies and optimizations from the users and developers of simulation programs: they can be run without modification on any hardware on which the API has been implemented. The current implementations of OpenMM include support for graphics processing units using the OpenCL and CUDA frameworks. In addition, OpenMM was designed to be extensible, so new hardware architectures can be accommodated and new functionality (e.g., energy terms and integrators) can be easily added.

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation

PubMed Central

Eastman, Peter; Friedrichs, Mark S.; Chodera, John D.; Radmer, Randall J.; Bruns, Christopher M.; Ku, Joy P.; Beauchamp, Kyle A.; Lane, Thomas J.; Wang, Lee-Ping; Shukla, Diwakar; Tye, Tony; Houston, Mike; Stich, Timo; Klein, Christoph; Shirts, Michael R.; Pande, Vijay S.

2012-01-01

OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures. It is based on a layered architecture: the lower layers function as a reusable library that can be invoked by any application, while the upper layers form a complete environment for running molecular simulations. The library API hides all hardware-specific dependencies and optimizations from the users and developers of simulation programs: they can be run without modification on any hardware on which the API has been implemented. The current implementations of OpenMM include support for graphics processing units using the OpenCL and CUDA frameworks. In addition, OpenMM was designed to be extensible, so new hardware architectures can be accommodated and new functionality (e.g., energy terms and integrators) can be easily added. PMID:23316124

Modifications of Fabrication of Vibratory Microgyroscopes

NASA Technical Reports Server (NTRS)

Bae, Sam Y.; Yee, Karl Y.; Wiberg, Dean

2005-01-01

A micromachining process for the fabrication of vibratory microgyroscopes from silicon wafers, and aspects of the microgyroscope design that are inextricably linked with the fabrication process, have been modified in an effort to increase production yields from perspectives of both quantity and quality. Prior to the modifications, the effective production yield of working microgyroscopes was limited to one or less per wafer. The modifications are part of a continuing effort to improve the design and increase production yields to more than 30 working microgyroscopes per wafer. A discussion of pertinent aspects of the unmodified design and the unmodified fabrication process is prerequisite to a meaningful description of the modifications. The design of the microgyroscope package was not conducive to high yield and rapid testing of many microgyroscopes. One of the major impediments to high yield and testing was found to lie in vibration- isolation beams around the four edges of each microgyroscope, which beams were found to be unnecessary for achieving high resonance quality factors (Q values) characterizing the vibrations of petallike cantilevers. The fabrication process included an 8- m-deep plasma etch. The purpose of the etch was to create 8- m vertical gaps, below which were to be placed large gold evaporated electrodes and sensing pads to drive and sense resonant vibrations of the "petals." The process also included a step in which bridges between dies were cut to separate the dies. The etched areas must be kept clean and smooth (free of debris and spikes), because any object close to 8 m high in those areas would stop the vibrations. However, it was found that after the etch, there remained some spikes with heights that were, variously, almost as high or as high as the etch depth. It also was found that the cutting of bridges created silicon debris, some of which lodged in the 8- m gaps and some of which landed on top of the petals. The masses added to the petals by the debris altered resonance frequencies and/or Q values to unacceptable degrees. Hence, the spikes and the debris have been conjectured to cause most of the observed malfunctions of newly fabricated microgyroscopes. Another pertinent aspect of the unmodified design and process was the fabrication of electrodes and the 8- m capacitance gap on a 500- m-thick wafer, and the fabrication of a 3-mm-thick baseplate from another wafer. It was necessary to bond these wafers to each other in an assembly step that was later found to be superfluous in that it could be eliminated by a suitable modification of the design.

Nucleosomes in the neighborhood

PubMed Central

Dorn, Elizabeth Suzanne

2011-01-01

The importance of local chromatin structure in regulating replication initiation has become increasingly apparent. Most recently, histone methylation and nucleosome positioning have been added to the list of modifications demonstrated to regulate origins. In particular, the methylation states of H3K4, H3K36 and H4K20 have been associated with establishing active, repressed or poised origins depending on the timing and extent of methylation. The stability and precise positioning of nucleosomes has also been demonstrated to affect replication efficiency. Although it is not yet clear how these modifications alter the behavior of specific replication factors, ample evidence establishes their role in maintaining coordinated replication. This review will summarize recent advances in understanding these aspects of chromatin structure in DNA replication origin control. PMID:21364325

Mapleson's Breathing Systems.

PubMed

Kaul, Tej K; Mittal, Geeta

2013-09-01

Mapleson breathing systems are used for delivering oxygen and anaesthetic agents and to eliminate carbon dioxide during anaesthesia. They consist of different components: Fresh gas flow, reservoir bag, breathing tubes, expiratory valve, and patient connection. There are five basic types of Mapleson system: A, B, C, D and E depending upon the different arrangements of these components. Mapleson F was added later. For adults, Mapleson A is the circuit of choice for spontaneous respiration where as Mapleson D and its Bains modifications are best available circuits for controlled ventilation. For neonates and paediatric patients Mapleson E and F (Jackson Rees modification) are the best circuits. In this review article, we will discuss the structure of the circuits and functional analysis of various types of Mapleson systems and their advantages and disadvantages.

The interplay of post-translational modification and gene therapy.

PubMed

Osamor, Victor Chukwudi; Chinedu, Shalom N; Azuh, Dominic E; Iweala, Emeka Joshua; Ogunlana, Olubanke Olujoke

2016-01-01

Several proteins interact either to activate or repress the expression of other genes during transcription. Based on the impact of these activities, the proteins can be classified into readers, modifier writers, and modifier erasers depending on whether histone marks are read, added, or removed, respectively, from a specific amino acid. Transcription is controlled by dynamic epigenetic marks with serious health implications in certain complex diseases, whose understanding may be useful in gene therapy. This work highlights traditional and current advances in post-translational modifications with relevance to gene therapy delivery. We report that enhanced understanding of epigenetic machinery provides clues to functional implication of certain genes/gene products and may facilitate transition toward revision of our clinical treatment procedure with effective fortification of gene therapy delivery.

A hybrid voice/data modulation for the VHF aeronautical channels

NASA Technical Reports Server (NTRS)

Akos, Dennis M.

1993-01-01

A method of improving the spectral efficiency of the existing Very High Frequency (VHF) Amplitude Modulation (AM) voice communication channels is proposed. The technique is to phase modulate the existing voice amplitude modulated carrier with digital data. This allows the transmission of digital information over an existing AM voice channel with no change to the existing AM signal format. There is no modification to the existing AM receiver to demodulate the voice signal and an additional receiver module can be added for processing of the digital data. The existing VHF AM transmitter requires only a slight modification for the addition of the digital data signal. The past work in the area is summarized and presented together with an improved system design and the proposed implementation.

Complex transcriptional and post-transcriptional regulation of an enzyme for Lipopolysaccharide modification

PubMed Central

Moon, Kyung; Six, David A.; Lee, Hyun-Jung; Raetz, Christian R.H.; Gottesman, Susan

2013-01-01

Summary The PhoQ/PhoP two-component system activates many genes for lipopolysaccharide (LPS) modification when cells are grown at low Mg2+ concentrations. An additional target of PhoQ and PhoP is MgrR, an Hfq-dependent small RNA that negatively regulates expression of eptB, also encoding a protein that carries out LPS modification. Examination of LPS confirmed that MgrR effectively silences EptB; the phosphoethanolamine modification associated with EptB is found in ΔmgrR::kan but not mgrR+ cells. Sigma E has been reported to positively regulate eptB, although the eptB promoter does not have the expected Sigma E recognition motifs. The effects of Sigma E and deletion of mgrR on levels of eptB mRNA were independent, and the same 5′ end was found in both cases. In vitro transcription and the behavior of transcriptional and translational fusions demonstrate that Sigma E acts directly at the level of transcription initiation for eptB, from the same start point as Sigma 70. The results suggest that when Sigma E is active, synthesis of eptB transcript outstrips MgrR-dependent degradation; presumably the modification of LPS is important under these conditions. Adding to the complexity of eptB regulation is a second sRNA, ArcZ, which also directly and negatively regulates eptB. PMID:23659637

Aqueous or solvent based surface modification: The influence of the combination solvent - organic functional group on the surface characteristics of titanium dioxide grafted with organophosphonic acids

NASA Astrophysics Data System (ADS)

Roevens, Annelore; Van Dijck, Jeroen G.; Geldof, Davy; Blockhuys, Frank; Prelot, Benedicte; Zajac, Jerzy; Meynen, Vera

2017-09-01

To alter the versatility of interactions at its surface, TiO2 is modified with organophosphonic acids (PA). A thorough understanding of the role of all synthesis conditions is necessary to achieve controlled functionalization. This study reports on the effect of using water, toluene and their mixtures when performing the modification of TiO2 with PA. Sorption and calorimetry measurements of surface interactions with various probing species clearly indicate that, by grafting PA in water, clear differences appear in the distribution of organic groups on the surface. Also the functional group of the PA determines the impact of using water as solvent. Modification in toluene results in a higher modification degree for propylphosphonic acid (3PA), as the solvent-solute interaction may hinder the grafting with phenylphosphonic acid (PhPA) in toluene. Water is preferred as solvent for PhPA modification as stabilizing π-OH interactions enhance surface grafting overcoming the competitive interaction of water at the surface as observed with 3PA. By using water in toluene mixtures for the functionalization of TiO2 with 3PA, the degree of functionalization is higher than when only water or toluene is used. Furthermore, adding small amounts of water leads to the formation of titanium propylphosphonates, next to surface grafting.

Phonetic Modification of Vowel Space in Storybook Speech to Infants up to 2 Years of Age

ERIC Educational Resources Information Center

Burnham, Evamarie B.; Wieland, Elizabeth A.; Kondaurova, Maria V.; McAuley, J. Devin; Bergeson, Tonya R.; Dilley, Laura C.

2015-01-01

Purpose: A large body of literature has indicated vowel space area expansion in infant-directed (ID) speech compared with adult-directed (AD) speech, which may promote language acquisition. The current study tested whether this expansion occurs in storybook speech read to infants at various points during their first 2 years of life. Method: In 2…

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

Podoshvedov, S. A., E-mail: podoshvedov@mail.ru

A method to generate Schroedinger cat states in free propagating optical fields based on the use of displaced states (or displacement operators) is developed. Some optical schemes with photon-added coherent states are studied. The schemes are modifications of the general method based on a sequence of displacements and photon additions or subtractions adjusted to generate Schroedinger cat states of a larger size. The effects of detection inefficiency are taken into account.

75 FR 47207 - Airworthiness Directives; Airbus Model A330-200 and -300 Series Airplanes, and Model A340-200...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... airplanes. The AD requires replacing or modifying the Halon dual-filter assemblies of the flow metering fire...-filter assembly P/N QA06753 is embodied in production through Airbus modification 40041. The Halon dual- filter assembly P/N QA06753-01 is only embodied in service through Airbus Service Bulletin A330-26-3030...

The non-steady state growth of pearlite outside the Hultgren extrapolation

DOE PAGES

Martin-Aranda, Maria; Rementeria, Rosalia; Hackenberg, Robert Errol; ...

2016-12-14

Here, the goal of this paper is to analyse the effect of adding Al on the non-steady pearlite growth occurring in a Fe–C–Mn system. The results are discussed in terms of the partitioning of elements across the austenite/ferrite and austenite/cementite interfaces, and the modification of the pearlite driving force related to the change in carbon activity in austenite.

Sorption of strontium-90 from fresh waters during sulfate modification of barium manganite

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

Ryzhen`kov, A.P.; Egorov, Yu.V.

1995-11-01

Recovery of strontium-90 with barium manganite from fresh waters (natural fresh waters of open basins) can be increased by adding agents that contain sulfate ions and thus modify the sorbent and chemically bind the sorbate. The treatment results in a heterogeneous anion-exchange transformation of barium manganite into barium sulfate-manganese dioxide and in simultaneous absorptive coprecipitation of strontium sulfate (microcomponent).

Feasibility Analysis and Prototyping of a Fast Autonomous Recon system

DTIC Science & Technology

2017-06-01

Test and Evaluation Interim Contractor Support System Assessment OPERATIONAL USE AND SYSTEM SUPPORT System Operation in the User Environment...Sustaining Maintenance and Logistics Support Operational Testing System Modifications for Improvement Contractor Support System Assessment...helicopter but has the added benefit of high -speed flight similar to a fixed-wing aircraft. Figure 1 shows the two different flight modes of the V-22

Differential Mass Spectrometry Profiles of Tau Protein in the Cerebrospinal Fluid of Patients with Alzheimer's Disease, Progressive Supranuclear Palsy, and Dementia with Lewy Bodies.

PubMed

Barthélemy, Nicolas R; Gabelle, Audrey; Hirtz, Christophe; Fenaille, François; Sergeant, Nicolas; Schraen-Maschke, Susanna; Vialaret, Jérôme; Buée, Luc; Junot, Christophe; Becher, François; Lehmann, Sylvain

2016-01-01

Microtubule-associated Tau proteins are major actors in neurological disorders, the so-called tauopathies. In some of them, and specifically in Alzheimer's disease (AD), hyperphosphorylated forms of Tau aggregate into neurofibrillary tangles. Following and understanding the complexity of Tau's molecular profile with its multiple isoforms and post-translational modifications represent an important issue, and a major analytical challenge. Immunodetection methods are, in fact, limited by the number, specificity, sensitivity, and capturing property of the available antibodies. Mass spectrometry (MS) has recently allowed protein quantification in complex biological fluids using isotope-labeled recombinant standard for absolute quantification (PSAQ). To study Tau proteins, which are found at very low concentrations within the cerebrospinal fluid (CSF), we relied on an innovative two-step pre-fractionation strategy, which was not dependent on immuno-enrichment. We then developed a sensitive multiplex peptide detection capability using targeted high-resolution MS to quantify Tau-specific peptides covering its entire sequence. This approach was used on a clinical cohort of patients with AD, progressive supranuclear palsy (PSP), and dementia with Lewy body (DLB) and with control non-neurodegenerative disorders. We uncovered a common CSF Tau molecular profile characterized by a predominance of central core expression and 1N/3R isoform detection. While PSP and DLB tau profiles showed minimal changes, AD was characterized by a unique pattern with specific modifications of peptide distribution. Taken together these results provide important information on Tau biology for future therapeutic interventions, and improved molecular diagnosis of tauopathies.

Flight test of a propulsion controlled aircraft system on the NASA F-15 airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.

1995-01-01

Flight tests of the propulsion controlled aircraft (PCA) system on the NASA F-15 airplane evolved as a result of a long series of simulation and flight tests. Initially, the simulation results were very optimistic. Early flight tests showed that manual throttles-only control was much more difficult than the simulation, and a flight investigation was flown to acquire data to resolve this discrepancy. The PCA system designed and developed by MDA evolved as these discrepancies were found and resolved, requiring redesign of the PCA software and modification of the flight test plan. Small throttle step inputs were flown to provide data for analysis, simulation update, and control logic modification. The PCA flight tests quickly revealed less than desired performance, but the extensive flexibility built into the flight PCA software allowed rapid evaluation of alternate gains, filters, and control logic, and within 2 weeks, the PCA system was functioning well. The initial objective of achieving adequate control for up-and-away flying and approaches was satisfied, and the option to continue to actual landings was achieved. After the PCA landings were accomplished, other PCA features were added, and additional maneuvers beyond those originally planned were flown. The PCA system was used to recover from extreme upset conditions, descend, and make approaches to landing. A heading mode was added, and a single engine plus rudder PCA mode was also added and flown. The PCA flight envelope was expanded far beyond that originally designed for. Guest pilots from the USAF, USN, NASA, and the contractor also flew the PCA system and were favorably impressed.

Clinical, behavioral, and treatment differences in nursing facility residents with dementia, with and without pseudobulbar affect symptomatology.

PubMed

Zarowitz, Barbara J; O'Shea, Terrence

2013-11-01

Characterize the prevalence and impact of crying and tearfulness as symptoms that may be suggestive of pseudobulbar affect (PBA) in residents of nursing facilities, including those with Alzheimer's disease (AD) and non-AD [non-AD-associated] associated dementia. Data were extracted retrospectively from a large repository of de-identified and linked Minimum Data Set 2.0 (MDS) and prescription claims records for the period between October 1, 2009, and September 30, 2010. A score of 1 or 2 on MDS item E1m ("crying, tearfulness") was used to identify potential PBA. 19,000 nursing facilities in 48 states. Prescription and MDS records of nursing facility residents. Comparison of concomitant diagnoses, MDS mood, and behavioral indicators, and psychopharmacologic medication use, in residents with crying/tearfulness to a control group matched for age, gender, diagnosis of AD or non-AD dementia, and diagnosis of depression. A total of 137,829 residents underwent at least one MDS assessment during the study period. Of these, 12,595 (9.1%) had item E1m ("crying, tearfulness") scored as a 1 or 2 on their MDS assessments. Ten thousand residents were then randomly selected from this group and matched to 10,000 controls without "crying, tearfulness" (MDS E1m = 0) for analysis. A total of 4,786 (47.9%) unique residents with "crying, tearfulness" had a diagnosis of AD (8.8%), non-AD dementia (31.5%), or both (7.6%). All of the MDS mood indicators were at least twice as prevalent in this group compared with those without "crying, tearfulness" Additionally, mood symptoms such as anger, worried/pained facial expressions, and repetitive verbalizations; and behavioral symptoms such as verbal/physical abuse and socially inappropriate/disruptive behavior, were more than twice as frequent in the "crying, tearfulness" group. Antipsychotic medications were also used more often in this group (50% vs. 36.1%), as were antidepressants (59.1% vs. 49.8%). In the absence of an International Classification of Diseases 9th edition, Clinical Modification code, the presence of "crying, tearfulness" on MDS 2.0 item E1m was used as a proxy to identify potential PBA. Nursing facility residents with "crying, tearfulness" had a higher prevalence of all mood and behavior indicators as well as psychopharmacological medication use, compared with matched controls without "crying, tearfulness." Similar results were seen in the subgroup of residents with an underlying diagnosis of AD and/or non-AD dementia. Further research should validate the actual prevalence of PBA in this population, and the corresponding impact on resident outcomes.

Neuropathologic features associated with Alzheimer disease diagnosis

PubMed Central

Grinberg, L.T.; Miller, B.; Kawas, C.; Yaffe, K.

2011-01-01

Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70–74 years: c statistic, 95% confidence interval: 0.93, 0.89–0.96; 75–84 years: 0.95, 0.87–0.95; ≥85 years: 0.83, 0.80–0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. PMID:22031532

Field and microcosm experiments to evaluate the effects of agricultural Cu treatment on the density and genetic structure of microbial communities in two different soils.

PubMed

Ranjard, Lionel; Echairi, Abdelwahad; Nowak, Virginie; Lejon, David P H; Nouaïm, Rachida; Chaussod, Rémi

2006-11-01

The effects of Cu amendment on indigenous soil microorganisms were investigated in two soils, a calcareous silty clay (Ep) and a sandy soil (Au), by means of a 1-year field experiment and a two-month microcosm incubation. Cu was added as 'Bordeaux mixture' [CuSO(4), Ca(OH)(2)] at the standard rate used in viticulture (B1=16 kg Cu kg(-1) soil) and at a higher level of contamination (B3=48 kg Cu ha(-1) soil). More extractable Cu was observed in sandy soil (Au) than in silty soil (Ep). Furthermore, total Cu and Cu-EDTA declined with time in Au soil, whereas they remained stable in Ep soil. Quantitative modifications of the microflora were assessed by C-biomass measurements and qualitative modifications were assessed by the characterization of the genetic structure of bacterial and fungal communities from DNA directly extracted from the soil, using B- and F-ARISA (bacterial and fungal automated ribosomal intergenic spacer analysis). In the field study, no significant modifications were observed in C-biomass whereas microcosm incubation showed a decrease in B3 contamination only. ARISA fingerprinting showed slight but significant modifications of bacterial and fungal communities in field and microcosm incubation. These modifications were transient in all cases, suggesting a short-term effect of Cu stress. Microcosm experiments detected the microbial community modifications with greater precision in the short-term, while field experiments showed that the biological effects of Cu contamination may be overcome or hidden by pedo-climatic variations.

Overview, hurdles, and future work in adaptive designs: perspectives from a National Institutes of Health-funded workshop.

PubMed

Coffey, Christopher S; Levin, Bruce; Clark, Christina; Timmerman, Cate; Wittes, Janet; Gilbert, Peter; Harris, Sara

2012-12-01

The clinical trials community has a never-ending search for dependable and reliable ways to improve clinical research. This exploration has led to considerable interest in adaptive clinical trial designs, which provide the flexibility to adjust trial characteristics on the basis of data reviewed at interim stages. Statisticians and clinical investigators have proposed or implemented a wide variety of adaptations in clinical trials, but specific approaches have met with differing levels of support. Within industry, investigators are actively exploring the benefits and pitfalls associated with adaptive designs (ADs). For example, a Drug Information Association (DIA) working group on ADs has engaged regulatory agencies in discussions. Many researchers working on publicly funded clinical trials, however, are not yet fully engaged in this discussion. We organized the Scientific Advances in Adaptive Clinical Trial Designs Workshop to begin a conversation about using ADs in publicly funded research. Held in November of 2009, the 1½-day workshop brought together representatives from the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the European Medicines Agency (EMA), the pharmaceutical industry, nonprofit foundations, the patient advocacy community, and academia. The workshop offered a forum for participants to address issues of ADs that arise at the planning, designing, and execution stages of clinical trials, and to hear the perspectives of influential members of the clinical trials community. The participants also set forth recommendations for guiding action to promote the appropriate use of ADs. These recommendations have since been presented, discussed, and vetted in a number of venues including the University of Pennsylvania Conference on Statistical Issues in Clinical Trials and the Society for Clinical Trials annual meeting. To provide a brief overview of ADs, describe the rationale behind conducting the workshop, and summarize the main recommendations that were produced as a result of this workshop. There is a growing interest in the use of adaptive clinical trial designs. However, a number of logistical barriers need to be addressed in order to obtain the potential advantages of an AD. Currently, the pharmaceutical industry is well ahead of academic trialists with respect to addressing these barriers. Academic trialists will need to address important issues such as education, infrastructure, modifications to existing funding models, and the impact on Data and Safety Monitoring Boards (DSMB) in order to achieve the possible benefits of adaptive clinical trial designs.

Organic light emitting diode with surface modification layer

DOEpatents

Basil, John D.; Bhandari, Abhinav; Buhay, Harry; Arbab, Mehran; Marietti, Gary J.

2017-09-12

An organic light emitting diode (10) includes a substrate (12) having a first surface (14) and a second surface (16), a first electrode (32), and a second electrode (38). An emissive layer (36) is located between the first electrode (32) and the second electrode (38). The organic light emitting diode (10) further includes a surface modification layer (18). The surface modification layer (18) includes a non-planar surface (30, 52).

Implications of Risk Factors for Alzheimer’s Disease in Canada’s Indigenous Population

PubMed Central

MacDonald, Julia Petrasek; Barnes, Deborah E.; Middleton, Laura E.

2015-01-01

Background Indigenous peoples in Canada have higher prevalence of modifiable risk factors for Alzheimer’s disease (AD). The relative importance of these risk factors on AD risk management is poorly understood. Methods Relative risks from literature and prevalence of risk factors from Statistics Canada or the First Nations Regional Health Survey were used to determine projected population attributable risk (PAR) associated with modifiable risk factors for AD (low education and vascular risk factors) among on- and off-reserve Indigenous and non-Indigenous people in Canada using the Levin formula. Results Physical inactivity had the highest PAR for AD among Indigenous and non-Indigenous peoples in Canada (32.5% [10.1%–51.1%] and 30.5% [9.2%–48.8%] respectively). The PAR for most modifiable risk factors was higher among Indigenous peoples in Canada, particularly among on-reserve groups. The greatest differences in PAR were for low educational attainment and smoking, which were approximately 10% higher among Indigenous peoples in Canada. The combined PAR for AD for all six modifiable risk factors was 79.6% among on-reserve Indigenous, 74.9% among off-reserve Indigenous, and 67.1% among non-Indigenous peoples in Canada. (All differences significant to p < .001.) Conclusions Modifiable risk factors are responsible for the most AD cases among Indigenous peoples in Canada. Further research is necessary to determine the prevalence of AD and the impact of risk factor modification among Indigenous peoples in Canada. PMID:26495049

Stress, Meditation, and Alzheimer’s Disease Prevention: Where The Evidence Stands

PubMed Central

Khalsa, Dharma Singh

2015-01-01

Abstract Although meditation is believed to be over five thousand years old, scientific research on it is in its infancy. Mitigating the extensive negative biochemical effects of stress is a superficially discussed target of Alzheimer’s disease (AD) prevention, yet may be critically important. This paper reviews lifestyle and stress as possible factors contributing to AD and meditation’s effects on cognition and well-being for reduction of neurodegeneration and prevention of AD. This review highlights Kirtan Kriya (KK), an easy, cost effective meditation technique requiring only 12 minutes a day, which has been successfully employed to improve memory in studies of people with subjective cognitive decline, mild cognitive impairment, and highly stressed caregivers, all of whom are at increased risk for subsequent development of AD. KK has also been shown to improve sleep, decrease depression, reduce anxiety, down regulate inflammatory genes, upregulate immune system genes, improve insulin and glucose regulatory genes, and increase telomerase by 43%; the largest ever recorded. KK also improves psycho-spiritual well-being or spiritual fitness, important for maintenance of cognitive function and prevention of AD. KK is easy to learn and practice by aging individuals. It is the premise of this review that meditation in general, and KK specifically, along with other modalities such as dietary modification, physical exercise, mental stimulation, and socialization, may be beneficial as part of an AD prevention program. PMID:26445019

Chemical substitutions in the selectivity filter of potassium channels do not rule out constricted-like conformations for C-type inactivation

PubMed Central

Li, Jing; Boulanger, Eliot; Rui, Huan; Perozo, Eduardo; Roux, Benoît

2017-01-01

In many K+ channels, prolonged activating stimuli lead to a time-dependent reduction in ion conduction, a phenomenon known as C-type inactivation. X-ray structures of the KcsA channel suggest that this inactivated state corresponds to a “constricted” conformation of the selectivity filter. However, the functional significance of the constricted conformation has become a matter of debate. Functional and structural studies based on chemically modified semisynthetic KcsA channels along the selectivity filter led to the conclusion that the constricted conformation does not correspond to the C-type inactivated state. The main results supporting this view include the observation that C-type inactivation is not suppressed by a substitution of D-alanine at Gly77, even though this modification is believed to lock the selectivity filter into its conductive conformation, whereas it is suppressed following amide-to-ester backbone substitutions at Gly77 and Tyr78, even though these structure-conserving modifications are not believed to prevent the selectivity filter from adopting the constricted conformation. However, several untested assumptions about the structural and functional impact of these chemical modifications underlie these arguments. To make progress, molecular dynamics simulations based on atomic models of the KcsA channel were performed. The computational results support the notion that the constricted conformation of the selectivity filter corresponds to the functional C-type inactivated state of the KcsA. Importantly, MD simulations reveal that the semisynthetic KcsAD-ala77 channel can adopt an asymmetrical constricted-like nonconductive conformation and that the amide-to-ester backbone substitutions at Gly77 and Tyr78 perturb the hydrogen bonding involving the buried water molecules stabilizing the constricted conformation. PMID:28973956

Modification of biochar for functionality improvement in soils

NASA Astrophysics Data System (ADS)

Zwart, Kor; Kuikman, Peter; Ross, Anrew; Takaya, Chibi; Singh, Surjit; Kocaturk, Pelin; Visser, Rian

2014-05-01

Application of biochar to soils is generally considered and practiced in order to improve specific soil functions such as CEC, moisture and nutrient retention and providing additional habitat for micro-organisms. Improvement of these soil functions should lead to a higher crop yield. This would be added value to the long term sequestration of carbon in soils and contribution to renewable energy from producing and using biochar. The concept of using biochar for soil amendment is predicated on biochar behaving in a similar manner as soil organic matter (SOM) does. However, if one critically compares the properties of biochar with the properties of SOM, it is evident that biochar is rather different from SOM [Zwart, 2013 ;Zwart & Kuikman, 2013]. We have has produced a range of biochar from different feedstock using pyrolysis, gasification and hydrothermal carbonisation resulting in chars with significantly different properties. The project also investigates and tested several possibilities for improving the functionality of biochar in soils by either(i) selection of feedstock, (ii), selection of processing conditions and (iii) chemical and physical modification of biochar during and after the production process. Post modification includes the chemical treatment of biochars with either H2O2, KOH, H2SO4 and transitional metals such as Fe and investigates their effect on surface functionality, porosity, surface area, CEC and phosphate sorption. The influence of the addition of chemical modifiers and oxidants during pyrolysis and gasification has also been investigated and their effect on surface functionality determined using similar techniques. The influence of the original biomass structure on the morphology of the resultant biochars has been investigated using scanning electron microscopy.

Diet and Eating Pattern Modifications Used by Community Living Adults to Manage Their Fecal Incontinence

PubMed Central

Croswell, Emily; Bliss, Donna Z.; Savik, Kay

2010-01-01

Purpose The study aimed to describe modifications in diet and eating patterns made by community-living people to manage fecal incontinence (FI) and to compare these differences according to sex, age, and FI severity. Subjects and Setting Subjects were 188 community-living adults (77% female, 92% white, 34% ≥ 65 years of age) in the upper Midwest who participated in a study about managing FI with dietary fiber. Methods Subjects were interviewed about diet and eating pattern changes that they made to manage FI and self reported demographic data. FI severity was recorded daily. Results Fifty-five percent of participants perceived that some foods worsen their FI (e.g., fatty or spicy foods and dairy products). More women than men (40 vs 18%, p=.008) reported avoiding foods in order to manage FI. A greater percentage of younger than older people believed that fatty/greasy foods (15% vs. 4%,) and alcohol (14% vs. 3%,) worsened their FI. Subjects with a higher FI severity score appeared to wait until FI was more severe before restricting caffeine than those with lower severity scores (22.2 ± 9.8 vs 11.69 ± 8.3, p = .034). One-third of subjects consumed foods rich in dietary fiber to prevent FI. Subjects also reported altered eating or cooking patterns; skipping meals, or eating at consistent times to manage FI. Conclusions Diet modification for managing FI incorporates involves restriction of some foods, along with adding others foods to the diet. Nursing assessments of self-care practices for FI should include diet and eating pattern changes when developing a plan of care. PMID:21076267

Autovideography: The Lived Experience of Recovery for Adults with Serious Mental Illness.

PubMed

Petros, Ryan; Solomon, Phyllis; Linz, Sheila; DeCesaris, Marissa; Hanrahan, Nancy P

2016-09-01

Mental health services have been transforming toward a recovery orientation for more than a decade, yet a robust understanding of recovery eludes many providers, and consensus on a conceptual definition has yet to be reached. This article examines mental health consumers' lived experience of recovery and evaluates the usefulness and comprehensiveness of CHIME, a major framework conceptually defining recovery for adults with serious mental illness. Researchers partnered with a mental health association in a major US city to engage in research with graduates of a recovery and education class for adults diagnosed with serious mental illness. Twelve participants were loaned video cameras and invited to "Tell us about your recovery" through autovideography. Of the 12 participants, six produced videos directly responding to the overall research question and were subsequently included in the present analysis. Data were analyzed thematically, and CHIME adequately represented the major domains presented in consumer videos with two notable modifications: subdomains of "reciprocity" within relationships and "contributing to others" were added to comprehensively represent consumer perspectives about recovery. Adding two subdomains to CHIME more effectively represents consumer narratives about recovery, contributes to the social construction of the personhood of people with serious mental illness, and offers a more robust description of the process of recovery.

Risk Assessment Using the Three Dimensions of Probability (Likelihood), Severity, and Level of Control

NASA Technical Reports Server (NTRS)

Watson, Clifford

2010-01-01

Traditional hazard analysis techniques utilize a two-dimensional representation of the results determined by relative likelihood and severity of the residual risk. These matrices present a quick-look at the Likelihood (Y-axis) and Severity (X-axis) of the probable outcome of a hazardous event. A three-dimensional method, described herein, utilizes the traditional X and Y axes, while adding a new, third dimension, shown as the Z-axis, and referred to as the Level of Control. The elements of the Z-axis are modifications of the Hazard Elimination and Control steps (also known as the Hazard Reduction Precedence Sequence). These steps are: 1. Eliminate risk through design. 2. Substitute less risky materials for more hazardous materials. 3. Install safety devices. 4. Install caution and warning devices. 5. Develop administrative controls (to include special procedures and training.) 6. Provide protective clothing and equipment. When added to the twodimensional models, the level of control adds a visual representation of the risk associated with the hazardous condition, creating a tall-pole for the least-well-controlled failure while establishing the relative likelihood and severity of all causes and effects for an identified hazard. Computer modeling of the analytical results, using spreadsheets and threedimensional charting gives a visual confirmation of the relationship between causes and their controls

Risk Assessment Using the Three Dimensions of Probability (Likelihood), Severity, and Level of Control

NASA Technical Reports Server (NTRS)

Watson, Clifford C.

2011-01-01

Traditional hazard analysis techniques utilize a two-dimensional representation of the results determined by relative likelihood and severity of the residual risk. These matrices present a quick-look at the Likelihood (Y-axis) and Severity (X-axis) of the probable outcome of a hazardous event. A three-dimensional method, described herein, utilizes the traditional X and Y axes, while adding a new, third dimension, shown as the Z-axis, and referred to as the Level of Control. The elements of the Z-axis are modifications of the Hazard Elimination and Control steps (also known as the Hazard Reduction Precedence Sequence). These steps are: 1. Eliminate risk through design. 2. Substitute less risky materials for more hazardous materials. 3. Install safety devices. 4. Install caution and warning devices. 5. Develop administrative controls (to include special procedures and training.) 6. Provide protective clothing and equipment. When added to the two-dimensional models, the level of control adds a visual representation of the risk associated with the hazardous condition, creating a tall-pole for the least-well-controlled failure while establishing the relative likelihood and severity of all causes and effects for an identified hazard. Computer modeling of the analytical results, using spreadsheets and three-dimensional charting gives a visual confirmation of the relationship between causes and their controls.

Risk Presentation Using the Three Dimensions of Likelihood, Severity, and Level of Control

NASA Technical Reports Server (NTRS)

Watson, Clifford

2010-01-01

Traditional hazard analysis techniques utilize a two-dimensional representation of the results determined by relative likelihood and severity of the residual risk. These matrices present a quick-look at the Likelihood (Y-axis) and Severity (X-axis) of the probable outcome of a hazardous event. A three-dimensional method, described herein, utilizes the traditional X and Y axes, while adding a new, third dimension, shown as the Z-axis, and referred to as the Level of Control. The elements of the Z-axis are modifications of the Hazard Elimination and Control steps (also known as the Hazard Reduction Precedence Sequence). These steps are: 1. Eliminate risk through design. 2. Substitute less risky materials for more hazardous materials. 3. Install safety devices. 4. Install caution and warning devices. 5. Develop administrative controls (to include special procedures and training.) 6. Provide protective clothing and equipment. When added to the two-dimensional models, the level of control adds a visual representation of the risk associated with the hazardous condition, creating a tall-pole for the leastwell-controlled failure while establishing the relative likelihood and severity of all causes and effects for an identified hazard. Computer modeling of the analytical results, using spreadsheets and three-dimensional charting gives a visual confirmation of the relationship between causes and their controls.

Targeting Palmitoyl Acyltransferases in Mutant NRAS-Driven Melanoma

DTIC Science & Technology

2015-10-01

activation in melanoma cells using chemical biology and functional genomic approaches. In the first year of the study, we have developed more potent...post-translational modification by adding a 16-carbon palmitate) is required for N-RAS proper membrane localization and its oncogenic activities ...RAS regulation could be a novel strategy to treat N-RAS mutant melanoma. We have developed chemical probes that covalently label the active sites of

Concepts of Ideal and Nonideal Explosives.

DTIC Science & Technology

1981-12-01

Akst and J. Hershkowitz, "Explosive Performance Modification by Cosolidifaction of Ammonium Nitrate with Fuels ," Technical Report 4987, Picatinny...explosives Equations of state Diameter effect Ammonium nitrate 20. ASSrRACr (ca’mes r w re t N netwezy ad identity by block number) The purpose of...this report is to stimulate discussion on the nonideality of ammonium nitrate and its composite explosives. The concept of ideal and non- ideal

Statistical classification techniques for engineering and climatic data samples

NASA Technical Reports Server (NTRS)

Temple, E. C.; Shipman, J. R.

1981-01-01

Fisher's sample linear discriminant function is modified through an appropriate alteration of the common sample variance-covariance matrix. The alteration consists of adding nonnegative values to the eigenvalues of the sample variance covariance matrix. The desired results of this modification is to increase the number of correct classifications by the new linear discriminant function over Fisher's function. This study is limited to the two-group discriminant problem.

Frame Transmission Efficiency-Based Cross-Layer Congestion Notification Scheme in Wireless Ad Hoc Networks.

PubMed

He, Huaguang; Li, Taoshen; Feng, Luting; Ye, Jin

2017-07-15

Different from the traditional wired network, the fundamental cause of transmission congestion in wireless ad hoc networks is medium contention. How to utilize the congestion state from the MAC (Media Access Control) layer to adjust the transmission rate is core work for transport protocol design. However, recent works have shown that the existing cross-layer congestion detection solutions are too complex to be deployed or not able to characterize the congestion accurately. We first propose a new congestion metric called frame transmission efficiency (i.e., the ratio of successful transmission delay to the frame service delay), which describes the medium contention in a fast and accurate manner. We further present the design and implementation of RECN (ECN and the ratio of successful transmission delay to the frame service delay in the MAC layer, namely, the frame transmission efficiency), a general supporting scheme that adjusts the transport sending rate through a standard ECN (Explicit Congestion Notification) signaling method. Our method can be deployed on commodity switches with small firmware updates, while making no modification on end hosts. We integrate RECN transparently (i.e., without modification) with TCP on NS2 simulation. The experimental results show that RECN remarkably improves network goodput across multiple concurrent TCP flows.

Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

PubMed

Richardson, Jason S; Yao, Michel K; Tran, Kaylie N; Croyle, Maria A; Strong, James E; Feldmann, Heinz; Kobinger, Gary P

2009-01-01

The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the molecular components of adenovirus-based vaccines can produce potent, optimized product, useful for vaccination and post-exposure therapy.

Effects of discontinuous drooped wing leading-edge modifications on the spinning characteristics of a low-wing general aviation airplane

NASA Technical Reports Server (NTRS)

Dicarlo, D. J.; Stough, H. P., III; Patton, J. M., Jr.

1980-01-01

Wind tunnel and flight tests were conducted to determine the effects of several discontinuous drooped wing leading-edge configurations on the spinning characteristics of a light, single-engine, low-wing research airplane. Particular emphasis was placed on the identification of modifications which would improve the spinning characteristics. The spanwise length of a discontinuous outboard droop was varied and several additional inboard segments were added to determine the influence of such leading-edge configurations on the spin behavior. Results of the study indicated that the use of only the discontinuous outboard droop, over a specific spanwise area, was most effective towards improving spin and spin recovery characteristics, whereas the segmented configurations having both inboard and outboard droop exhibited a tendency to enter a flat spin.

Structural modification in the formation of starch - silver nanocomposites

NASA Astrophysics Data System (ADS)

Begum, S. N. Suraiya; Aswal, V. K.; Ramasamy, Radha Perumal

2016-05-01

Polymer based nanocomposites have gained wide applications in field of battery technology. Starch is a naturally occurring polysaccharide with sustainable properties such as biodegradable, non toxic, excellent film forming capacity and it also act as reducing agent for the metal nanoparticles. In our research various concentration of silver nitrate (AgNO3) was added to the starch solution and films were obtained using solution casting method. Surface electron microscope (SEM) of the films shows modifications depending upon the concentration of AgNO3. Small angle neutron scattering (SANS) analysis showed that addition of silver nitrate modifies the starch to disc like structures and with increasing the AgNO3 concentration leads to the formation of fractals. This research could benefit battery technology where solid polymer membranes using starch is used.

Epigenetic mechanisms in heart development and disease.

PubMed

Martinez, Shannalee R; Gay, Maresha S; Zhang, Lubo

2015-07-01

Suboptimal intrauterine development has been linked to predisposition to cardiovascular disease in adulthood, a concept termed 'developmental origins of health and disease'. Although the exact mechanisms underlying this developmental programming are unknown, a growing body of evidence supports the involvement of epigenetic regulation. Epigenetic mechanisms such as DNA methylation, histone modifications and micro-RNA confer added levels of gene regulation without altering DNA sequences. These modifications are relatively stable signals, offering possible insight into the mechanisms underlying developmental origins of health and disease. This review will discuss the role of epigenetic mechanisms in heart development as well as aberrant epigenetic regulation contributing to cardiovascular disease. Additionally, we will address recent advances targeting epigenetic mechanisms as potential therapeutic approaches to cardiovascular disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced growth inhibition of prostate cancer in vitro and in vivo by a recombinant adenovirus-mediated dual-aptamer modified drug delivery system.

PubMed

Jing, Pei; Cao, Shousong; Xiao, Shuangli; Zhang, Xiaoqin; Ke, Siyun; Ke, Famin; Yu, Xin; Wang, Li; Wang, Shurong; Luo, Yuling; Zhong, Zhirong

2016-12-28

The peptide aptamer DUP-1 targets prostate-specific membrane antigen (PSMA)-negative cells, while the RNA aptamer A10-3.2 targets PSMA-positive prostate cancer cells. Moreover, the tumor-suppressor gene phosphatase and tensin homolog (PTEN) and the chemotherapeutic agent doxorubicin (DOX) effectively inhibit prostate cancer, and a recombinant adenovirus (Ad5) mediates high gene transfer efficiency. Here, we design a dual-aptamer modified tumor targeting gene and DOX delivery system mediated by recombinant adenovirus (A10-3.2(DOX)/DUP-1-PEG-Ad5, ADDP-Ad5). DUP-1 and A10-3.2 are connected to the adenovirus through polyethylene glycol (PEG), PTEN is integrated into Ad5, and DOX is embedded into the double chain of aptamer A10-3.2. The PEG-modification rate of Ad5 is 98.70 ± 2.43%. The DUP-1 and A10-3.2 modified products yield 80.40 ± 1.36% and 82.20 ± 2.14%, respectively. The uptake of ADDP-Ad5 and the expression of the reporter gene are enhanced by the system in PSMA-positive LNCaP and PSMA-negative PC3 human prostate cancer cells. ADDP-Ad5 significantly inhibits the cell growth of both LNCaP and PC3 cells. More importantly, ADDP-Ad5 is active in vivo against LNCaP and PC3 tumor xenografts and exhibits no significant toxicity to the mice. Therefore, ADDP-Ad5 may have clinical potential in prostate cancer therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An effective method for adenoviral-mediated delivery of small interfering RNA into mesenchymal stem cells.

PubMed

Forte, Amalia; Napolitano, Marco A; Cipollaro, Marilena; Giordano, Antonio; Cascino, Antonino; Galderisi, Umberto

2007-02-01

Mesenchymal stem cells (MSCs) promise as a main actor of cell-based therapeutic strategies, due to their intrinsic ability to differentiate along different mesenchymal cell lineages, able to repair the diseased or injured tissue in which they are localized. The application of MSCs in therapies requires an in depth knowledge of their biology and of the molecular mechanisms leading to MSC multilineage differentiation. The knockdown of target genes through small interfering RNA (siRNA) carried by adenoviruses (Ad) represents a valid tool for the study of the role of specific molecules in cell biology. Unfortunately, MSCs are poorly transfected by conventional Ad serotype 5 (Ad5) vectors. We set up a method to obtain a very efficient transduction of rat MSCs with low doses of unmodified Ad5, carrying the siRNA targeted against the mRNA coding for Rb2/p130 (Ad-siRNA-Rb2), which plays a fundamental role in cell differentiation. This method allowed a 95% transduction rate of Ad-siRNA in MSC, along with a siRNA-mediated 85% decrease of Rb2/p130 mRNA and a 70% decrease of Rb2/p130 protein 48 h after transduction with 50 multiplicities of infection (MOIs) of Ad5. The effect on Rb2/p130 protein persisted 15 days after transduction. Finally, Ad-siRNA did not compromise the viability of transduced MSCs neither induced any cell cycle modification. The effective Ad-siRNA-Rb2 we constructed, together with the efficient method of delivery in MSCs we set up, will allow an in depth analysis of the role of Rb2/p130 in MSC biology and multilineage differentiation.

Obstacle crossing with dual tasking is a danger for individuals with Alzheimer's disease and for healthy older people.

PubMed

Simieli, Lucas; Barbieri, Fabio Augusto; Orcioli-Silva, Diego; Lirani-Silva, Ellen; Stella, Florindo; Gobbi, Lilian Teresa Bucken

2015-01-01

The aim of this study was to analyze the effects of dual tasking on obstacle crossing during walking by individuals with Alzheimer's disease (AD) and by healthy older people. Thirty four elderly individuals (16 healthy subjects and 18 individuals with AD) were recruited to participate in this study. Three AD individuals and one control participant were excluded due to exclusion criteria. The participants were instructed to walk barefoot at their own speed along an 8 m long pathway. Each participant performed five trials for each condition (unobstructed walking, unobstructed walking with dual tasking, and obstacle crossing during walking with dual tasking). The trials were completely randomized for each participant. The mid-pathway stride was measured in the unobstructed walking trials and the stride that occurred during the obstacle avoidance was measured in the trials that involved obstacle crossing. The behavior of the healthy elderly subjects and individuals with AD was similar for obstacle crossing during walking with dual tasking. Both groups used the "posture first" strategy to prioritize stability and showed decreased attention to executive tasking while walking. Additionally, AD had a strong influence on the modifications that are made by the elderly while walking under different walking conditions.

Predicting the Rate of Cognitive Decline in Alzheimer Disease: Data From the ICTUS Study.

PubMed

Canevelli, Marco; Kelaiditi, Eirini; Del Campo, Natalia; Bruno, Giuseppe; Vellas, Bruno; Cesari, Matteo

2016-01-01

Different rates of cognitive progression have been observed among Alzheimer disease (AD) patients. The present study aimed at evaluating whether the rate of cognitive worsening in AD may be predicted by widely available and easy-to-assess factors. Mild to moderate AD patients were recruited in the ICTUS study. Multinomial logistic regression analysis was performed to measure the association between several sociodemographic and clinical variables and 3 different rates of cognitive decline defined by modifications (after 1 year of follow-up) of the Mini Mental State Examination (MMSE) score: (1) "slow" progression, as indicated by a decrease in the MMSE score ≤1 point; (2) "intermediate" progression, decrease in the MMSE score between 2 and 5 points; and (3) "rapid" progression, decrease in the MMSE score ≥6 points. A total of 1005 patients were considered for the present analyses. Overall, most of the study participants (52%) exhibited a slow cognitive course. Higher ADAS-Cog scores at baseline were significantly associated with both "intermediate" and "rapid" decline. Conversely, increasing age was negatively associated with "rapid" cognitive worsening. A slow progression of cognitive decline is common among AD patients. The influence of age and baseline cognitive impairment should always be carefully considered when designing AD trials and defining study populations.

Permit application modifications

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

NONE

1995-11-01

This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

KSC-07pd0158

NASA Image and Video Library

2007-01-23

KENNEDY SPACE CENTER, FLA. -- The right-hand orbital maneuvering system pod is being delivered to Orbiter Processing Facility bay 2 for installation on the orbiter Endeavour. The orbital maneuvering system/reaction control system left- and right-hand pods are attached to the upper aft fuselage left and right sides. Each pod is fabricated primarily of graphite epoxy composite and aluminum. Each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. The orbiter is being prepared for its first launch in just over four years. The vehicle has undergone an extensive modification period, including the addition of all of the return-to-flight safety upgrades added to both Discovery and Atlantis. Endeavour is targeted for launch of mission STS-118 on June 28. Photo credit: NASA/Kim Shiflett

KSC-07pd0159

NASA Image and Video Library

2007-01-23

KENNEDY SPACE CENTER, FLA. -- The right-hand orbital maneuvering system pod is driven past the Vehicle Assembly Building on its way to Orbiter Processing Facility bay 2 for installation on the orbiter Endeavour. The orbital maneuvering system/reaction control system left- and right-hand pods are attached to the upper aft fuselage left and right sides. Each pod is fabricated primarily of graphite epoxy composite and aluminum. Each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. The orbiter is being prepared for its first launch in just over four years. The vehicle has undergone an extensive modification period, including the addition of all of the return-to-flight safety upgrades added to both Discovery and Atlantis. Endeavour is targeted for launch of mission STS-118 on June 28. Photo credit: NASA/Kim Shiflett

Astigmatism error modification for absolute shape reconstruction using Fourier transform method

NASA Astrophysics Data System (ADS)

He, Yuhang; Li, Qiang; Gao, Bo; Liu, Ang; Xu, Kaiyuan; Wei, Xiaohong; Chai, Liqun

2014-12-01

A method is proposed to modify astigmatism errors in absolute shape reconstruction of optical plane using Fourier transform method. If a transmission and reflection flat are used in an absolute test, two translation measurements lead to obtain the absolute shapes by making use of the characteristic relationship between the differential and original shapes in spatial frequency domain. However, because the translation device cannot guarantee the test and reference flats rigidly parallel to each other after the translations, a tilt error exists in the obtained differential data, which caused power and astigmatism errors in the reconstructed shapes. In order to modify the astigmatism errors, a rotation measurement is added. Based on the rotation invariability of the form of Zernike polynomial in circular domain, the astigmatism terms are calculated by solving polynomial coefficient equations related to the rotation differential data, and subsequently the astigmatism terms including error are modified. Computer simulation proves the validity of the proposed method.

Computational fluid dynamic modelling of cavitation

NASA Technical Reports Server (NTRS)

Deshpande, Manish; Feng, Jinzhang; Merkle, Charles L.

1993-01-01

Models in sheet cavitation in cryogenic fluids are developed for use in Euler and Navier-Stokes codes. The models are based upon earlier potential-flow models but enable the cavity inception point, length, and shape to be determined as part of the computation. In the present paper, numerical solutions are compared with experimental measurements for both pressure distribution and cavity length. Comparisons between models are also presented. The CFD model provides a relatively simple modification to an existing code to enable cavitation performance predictions to be included. The analysis also has the added ability of incorporating thermodynamic effects of cryogenic fluids into the analysis. Extensions of the current two-dimensional steady state analysis to three-dimensions and/or time-dependent flows are, in principle, straightforward although geometrical issues become more complicated. Linearized models, however offer promise of providing effective cavitation modeling in three-dimensions. This analysis presents good potential for improved understanding of many phenomena associated with cavity flows.

Surface modification of active material structures in battery electrodes

DOEpatents

Erickson, Michael; Tikhonov, Konstantin

2016-02-02

Provided herein are methods of processing electrode active material structures for use in electrochemical cells or, more specifically, methods of forming surface layers on these structures. The structures are combined with a liquid to form a mixture. The mixture includes a surface reagent that chemically reacts and forms a surface layer covalently bound to the structures. The surface reagent may be a part of the initial liquid or added to the mixture after the liquid is combined with the structures. In some embodiments, the mixture may be processed to form a powder containing the structures with the surface layer thereon. Alternatively, the mixture may be deposited onto a current collecting substrate and dried to form an electrode layer. Furthermore, the liquid may be an electrolyte containing the surface reagent and a salt. The liquid soaks the previously arranged electrodes in order to contact the structures with the surface reagent.

Multimodal optical workstation for simultaneous linear, nonlinear microscopy and nanomanipulation: upgrading a commercial confocal inverted microscope.

PubMed

Mathew, Manoj; Santos, Susana I C O; Zalvidea, Dobryna; Loza-Alvarez, Pablo

2009-07-01

In this work we propose and build a multimodal optical workstation that extends a commercially available confocal microscope (Nikon Confocal C1-Si) to include nonlinear/multiphoton microscopy and optical manipulation/stimulation tools such as nanosurgery. The setup allows both subsystems (confocal and nonlinear) to work independently and simultaneously. The workstation enables, for instance, nanosurgery along with simultaneous confocal and brightfield imaging. The nonlinear microscopy capabilities are added around the commercial confocal microscope by exploiting all the flexibility offered by this microscope and without need for any mechanical or electronic modification of the confocal microscope systems. As an example, the standard differential interference contrast condenser and diascopic detector in the confocal microscope are readily used as a forward detection mount for second harmonic generation imaging. The various capabilities of this workstation, as applied directly to biology, are demonstrated using the model organism Caenorhabditis elegans.

The epidemiology of trauma in an intensive care unit in Bahrain.

PubMed

Ruehsen, M M; Abdul-Wahab, A W

1989-01-01

Injuries resulting from trauma are over-represented in Bahrain's intensive care unit beds. Using data from 1984 and 1985, this study examines the most severe etiologic agents and high-risk population groups among ICU trauma patients. Road traffic accidents were the principal cause of admission, accounting for 57% of all injury admissions. Most occurred in pedestrians suffering from severe head injury. Poisonings were the second largest category, followed by falls. In comparison with medical cases admitted to the ICU during the same 2-year period, the trauma cases included a disproportionate number of children and males in their most productive years of life, further adding to the economic burden which injuries have inflicted on this small country. The authors call for a new approach, namely passive prevention such as environmental modifications and legislation and tertiary prevention such as improvement of the country's underutilized ambulance service.

Universal Behavior of Extreme Price Movements in Stock Markets

PubMed Central

Fuentes, Miguel A.; Gerig, Austin; Vicente, Javier

2009-01-01

Many studies assume stock prices follow a random process known as geometric Brownian motion. Although approximately correct, this model fails to explain the frequent occurrence of extreme price movements, such as stock market crashes. Using a large collection of data from three different stock markets, we present evidence that a modification to the random model—adding a slow, but significant, fluctuation to the standard deviation of the process—accurately explains the probability of different-sized price changes, including the relative high frequency of extreme movements. Furthermore, we show that this process is similar across stocks so that their price fluctuations can be characterized by a single curve. Because the behavior of price fluctuations is rooted in the characteristics of volatility, we expect our results to bring increased interest to stochastic volatility models, and especially to those that can produce the properties of volatility reported here. PMID:20041178

Nutritional aspects to prevent heart diseases in traditional Persian medicine.

PubMed

Kordafshari, Gholamreza; Kenari, Hoorieh Mohammadi; Esfahani, Mohammad Mehdi; Ardakani, Mohammad Reza Shams; Keshavarz, Mansoor; Nazem, Esmaeil; Moghimi, Maryam; Zargaran, Arman

2015-01-01

Cardiovascular diseases are major health complications currently in various societies. Management of heart diseases as a prevention step or as treatment with low-cost procedures like lifestyle modifications including nutrition are important current trends. Although the term nutrition dates back to 2 past centuries, Persian physicians contributed to this term at least from 1000 years ago. Rhazes (865-925 AD) was one of the pioneers in this field. He preferred using foods in treating illnesses. "Foods and drinks" were 1 subject from 6 principles (Setteh Zarorieh) that Persian physicians believed can affect human health. In this review, we described some medieval Persian views on the role of nutrition in heart diseases and compare their prescriptions with current findings. Interestingly, current investigations mostly support Persian medicine principles. Historically, this work shows that the concept of nutrition in heart diseases has had a successful background at least from 1000 years ago in Persia. © The Author(s) 2014.

Biotechnological production of value-added carotenoids from microalgae: Emerging technology and prospects.

PubMed

Wichuk, Kristine; Brynjólfsson, Sigurður; Fu, Weiqi

2014-01-01

We recently evaluated the relationship between abiotic environmental stresses and lutein biosynthesis in the green microalga Dunaliella salina and suggested a rational design of stress-driven adaptive evolution experiments for carotenoids production in microalgae. Here, we summarize our recent findings regarding the biotechnological production of carotenoids from microalgae and outline emerging technology in this field. Carotenoid metabolic pathways are characterized in several representative algal species as they pave the way for biotechnology development. The adaptive evolution strategy is highlighted in connection with enhanced growth rate and carotenoid metabolism. In addition, available genetic modification tools are described, with emphasis on model species. A brief discussion on the role of lights as limiting factors in carotenoid production in microalgae is also included. Overall, our analysis suggests that light-driven metabolism and the photosynthetic efficiency of microalgae in photobioreactors are the main bottlenecks in enhancing biotechnological potential of carotenoid production from microalgae.

The new ClusterTrap setup

NASA Astrophysics Data System (ADS)

Martinez, F.; Marx, G.; Schweikhard, L.; Vass, A.; Ziegler, F.

2011-07-01

ClusterTrap has been designed to investigate properties of atomic clusters in the gas phase with particular emphasis on the dependence on the cluster size and charge state. The combination of cluster source, Penning trap and time-of-flight mass spectrometry allows a variety of experimental schemes including collision-induced dissociation, photo-dissociation, further ionization by electron impact, and electron attachment. Due to the storage capability of the trap extended-delay reaction experiments can be performed. Several recent modifications have resulted in an improved setup. In particular, an electrostatic quadrupole deflector allows the coupling of several sources or detectors to the Penning trap. Furthermore, a linear radio-frequency quadrupole trap has been added for accumulation and ion bunching and by switching the potential of a drift tube the kinetic energy of the cluster ions can be adjusted on their way towards or from the Penning trap. Recently, experiments on multiply negatively charged clusters have been resumed.

Overview of the Helios Version 2.0 Computational Platform for Rotorcraft Simulations

NASA Technical Reports Server (NTRS)

Sankaran, Venkateswaran; Wissink, Andrew; Datta, Anubhav; Sitaraman, Jayanarayanan; Jayaraman, Buvna; Potsdam, Mark; Katz, Aaron; Kamkar, Sean; Roget, Beatrice; Mavriplis, Dimitri;

Multiaxial Cyclic Thermoplasticity Analysis with Besseling's Subvolume Method

NASA Technical Reports Server (NTRS)

Mcknight, R. L.

1983-01-01

A modification was formulated to Besseling's Subvolume Method to allow it to use multilinear stress-strain curves which are temperature dependent to perform cyclic thermoplasticity analyses. This method automotically reproduces certain aspects of real material behavior important in the analysis of Aircraft Gas Turbine Engine (AGTE) components. These include the Bauschinger effect, cross-hardening, and memory. This constitutive equation was implemented in a finite element computer program called CYANIDE. Subsequently, classical time dependent plasticity (creep) was added to the program. Since its inception, this program was assessed against laboratory and component testing and engine experience. The ability of this program to simulate AGTE material response characteristics was verified by this experience and its utility in providing data for life analyses was demonstrated. In this area of life analysis, the multiaxial thermoplasticity capabilities of the method have proved a match for the actual AGTE life experience.

Cardiac sodium channel Markov model with temperature dependence and recovery from inactivation.

PubMed Central

Irvine, L A; Jafri, M S; Winslow, R L

1999-01-01

A Markov model of the cardiac sodium channel is presented. The model is similar to the CA1 hippocampal neuron sodium channel model developed by Kuo and Bean (1994. Neuron. 12:819-829) with the following modifications: 1) an additional open state is added; 2) open-inactivated transitions are made voltage-dependent; and 3) channel rate constants are exponential functions of enthalpy, entropy, and voltage and have explicit temperature dependence. Model parameters are determined using a simulated annealing algorithm to minimize the error between model responses and various experimental data sets. The model reproduces a wide range of experimental data including ionic currents, gating currents, tail currents, steady-state inactivation, recovery from inactivation, and open time distributions over a temperature range of 10 degrees C to 25 degrees C. The model also predicts measures of single channel activity such as first latency, probability of a null sweep, and probability of reopening. PMID:10096885

Efficacy of dietary behavior modification for preserving cardiovascular health and longevity.

PubMed

Pryde, Moira McAllister; Kannel, William Bernard

2010-12-28

Cardiovascular disease (CVD) and its predisposing risk factors are major lifestyle and behavioral determinants of longevity. Dietary lifestyle choices such as a heart healthy diet, regular exercise, a lean weight, moderate alcohol consumption, and smoking cessation have been shown to substantially reduce CVD and increase longevity. Recent research has shown that men and women who adhere to this lifestyle can substantially reduce their risk of coronary heart disease (CHD). The preventive benefits of maintaining a healthy lifestyle exceed those reported for using medication and procedures. Among the modifiable preventive measures, diet is of paramount importance, and recent data suggest some misconceptions and uncertainties that require reconsideration. These include commonly accepted recommendations about polyunsaturated fat intake, processed meat consumption, fish choices and preparation, transfatty acids, low carbohydrate diets, egg consumption, coffee, added sugar, soft drink beverages, glycemic load, chocolate, orange juice, nut consumption, vitamin D supplements, food portion size, and alcohol.

Cre/lox-Recombinase-Mediated Cassette Exchange for Reversible Site-Specific Genomic Targeting of the Disease Vector, Aedes aegypti.

PubMed

Häcker, Irina; Harrell Ii, Robert A; Eichner, Gerrit; Pilitt, Kristina L; O'Brochta, David A; Handler, Alfred M; Schetelig, Marc F

2017-03-07

Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.

Surface Modification of Intraocular Lenses

PubMed Central

Huang, Qi; Cheng, George Pak-Man; Chiu, Kin; Wang, Gui-Qin

2016-01-01

Objective: This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs). Data Sources: All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. Study Selection: The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded. Results: Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO2, heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments. Conclusion: The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs. PMID:26830993

The Black Hole Firewall and Top-Down Constructions of AdS/CFT

NASA Astrophysics Data System (ADS)

Almheiri, Ahmed Eid Khamis Thani

In the first part of this dissertation we argue that the following statements cannot be all true: (i) Black hole formation and evaporation is a unitary process as viewed by external observers, (ii) Physics outside some microscopic distance away from the event horizon is described by local effective quantum field theory, (iii) A black hole is a quantum system with a finite number of states given by the exponential of the Bekenstein Hawking entropy, and (iv) An infalling observer's experience in the vicinity of the horizon is well described by local effective quantum field theory in the infalling reference frame. We argue that the most conservative resolution is that an infalling observer will see drastic violations of effective field theory far away from the singularity, and encounter high energy quanta, a firewall, just behind the black hole event horizon. We address counter proposals to the firewall which involve, in one way or another, radical modifications of quantum mechanics or locality, and argue that they are unsatisfactory in their current formulation. We conclude this part with an investigation into the existence of firewalls in the two dimensional Einstein-dilaton gravity model of CGHS. We find that black holes in such models do not develop firewalls, but rather evaporate down to form small mass remnants. We elaborate on why this is inevitable in two dimensions and argue against a similar conclusion in higher dimensions. In the second part of this dissertation we construct AdS2 and AdS3 magnetic brane solutions within the abelian truncations of AdS4 x orbifolded S7 and AdS5 x S5 supergravity. We find a class of supersymmetric solutions of the bulk theory to assure stability. We perform a preliminary analysis demonstrating the stability of some nonsupersymmetric embeddings. We identify the dual field theory and compare the thermal entropies across the duality. We end with an investigatation into the effects of backreaction on holography in AdS2. We study a classically solvable toy model that contains an IR AdS2 throat, and find that backreaction behaves as a strongly relevant perturbation deep in the AdS2 region.

Design and Synthesis of Neuroprotective Methylthiazoles and Modification as NO-Chimeras for Neurodegenerative Therapy

PubMed Central

Qin, Zhihui; Luo, Jia; VandeVrede, Lawren; Tavassoli, Ehsan; Fa’, Mauro; Teich, Andrew; Arancio, Ottavio; Thatcher, Gregory R. J.

2012-01-01

Learning and memory deficits in Alzheimer’s disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described, which uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (MZ) derivatives were synthesized, based upon a lead neuroprotective pharmacophore acting in part by GABAA receptor potentiation. MZ derivatives were assayed for protection of primary neurons against oxygen-glucose deprivation and excitotoxicity. Selected neuroprotective derivatives were incorporated into NO-chimera prodrugs, coined nomethiazoles. To provide proof of concept for the nomethiazole drug class, selected examples were assayed for: restoration of synaptic function in hippocampal slices from AD-transgenic mice; reversal of cognitive deficits; and, brain bioavailability of the prodrug and its neuroprotective MZ metabolite. Taken together the assay data suggest that these chimeric nomethiazoles may be of use in treatment of multiple components of neurodegenerative disorders, such as AD. PMID:22779770

Ecological Effects of Weather Modification: A Problem Analysis.

ERIC Educational Resources Information Center

Cooper, Charles F.; Jolly, William C.

This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease.

PubMed

Siedlak, Sandra L; Casadesus, Gemma; Webber, Kate M; Pappolla, Miguel A; Atwood, Craig S; Smith, Mark A; Perry, George

2009-02-01

Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-beta protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-beta load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AbetaPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit.

Polydopamine as a new modification material to accelerate startup and promote anode performance in microbial fuel cells

NASA Astrophysics Data System (ADS)

Du, Qing; An, Jingkun; Li, Junhui; Zhou, Lean; Li, Nan; Wang, Xin

2017-03-01

The bacterial anode material is important to the performance of microbial fuel cells (MFCs) because its characteristics affect the biofilm formation and extracellular electron transfer. Here we find that a superhydrophilic semiconductor, polydopamine (PDA), is an effective modification material for the anode to accelerate startup and improve power density. When the activated carbon anode is added with 50% (wt.) PDA, the startup time is 14% shorter than the control (from 88 h to 76 h), with a 31% increase in maximum power density from 613 ± 9 to 803 ± 6 mW m-2, and the Columbic efficiency increases from 19% to 48%. These can be primarily attributed to the abundant functional groups (such as amino group, and catechol functions) introduced by PDA that improve hydrophilicity and extracellular electron transfer. PDA also increases proportions of Proteobacteria and Firmicutes families, indicating that PDA has a selective effect on anode microbial community. Our findings provide a new approach to accelerate anode biofilm formation and enhance MFC power output by modification of biocompatible PDA.

Effects of Inlet Modification and Rocket-Rack Extension on the Longitudinal Trim and Low-Lift Drag of the Douglas F5D-1 Airplane as Obtained with a 0.125-Scale Rocket-Boosted Model between Mach Numbers of 0.81 and 1.64, TED No. NACA AD 399

NASA Technical Reports Server (NTRS)

Hastings, Earl C., Jr.; Dickens, Waldo L.

1957-01-01

A flight investigation was conducted to determine the effects of an inlet modification and rocket-rack extension on the longitudinal trim and low-lift drag of the Douglas F5D-1 airplane. The investigation was conducted with a 0.125-scale rocket-boosted model which was flight tested at the Langley Pilotless Aircraft Research Station at Wallops Island, Va. Results indicate that the combined effects of the modified inlet and fully extended rocket racks on the trim lift coefficient and trim angle of attack were small between Mach numbers of 0.94 and 1.57. Between Mach numbers of 1.10 and 1.57 there was an average increase in drag coefficient of about o,005 for the model with modified inlet and extended rocket racks. The change in drag coefficient due to the inlet modification alone is small between Mach numbers of 1.59 and 1.64

Evaluation of modified titanium surfaces physical and chemical characteristics

NASA Astrophysics Data System (ADS)

Lukaszewska-Kuska, Magdalena; Leda, Bartosz; Gajdus, Przemyslaw; Hedzelek, Wieslaw

2017-11-01

Development of dental implantology is focused, among other things, on devising active surface of the implant, conditioning acceleration of the implant's integration with the bone. Increased roughness, characteristic for group of implants with developed surface, altered topography and chemically modified implant's surface determines increased implants stability. In this study four different titanium surfaces modifications: turned (TS); aluminium oxide-blasted (Al2O3); resorbable material blasted (RBM); sandblast and then etched with a mixture of acids (SAE), were evaluated in terms of surfaces topography and chemical composition prior to in vivo analysis. Topography analysis revealed two groups: one with smooth, anisotropic, undeveloped TS surface and the second group with remaining surfaces presenting rough, isotropic, developed surfaces with added during blasting procedure aluminium for Al2O3 and calcium and phosphorus for RBM. Physical and chemical modifications of titanium surface change its microstructure (typical for SAE) and increase its roughness (highest for Al2O3-blasted and RBM surfaces). The introduced modifications develop titanium surface - 10 times for SAE surfaces, 16 times for Al2O3-blasted surfaces, and 20 times for RBM surfaces.

Electric Propulsion Interactions Code (EPIC): Recent Enhancements and Goals for Future Capabilities

NASA Technical Reports Server (NTRS)

Gardner, Barbara M.; Kuharski, Robert A.; Davis, Victoria A.; Ferguson, Dale C.

2007-01-01

The Electric Propulsion Interactions Code (EPIC) is the leading interactive computer tool for assessing the effects of electric thruster plumes on spacecraft subsystems. EPIC, developed by SAIC under the sponsorship of the Space Environments and Effects (SEE) Program at the NASA Marshall Space Flight Center, has three primary modules. One is PlumeTool, which calculates plumes of electrostatic thrusters and Hall-effect thrusters by modeling the primary ion beam as well as elastic scattering and charge-exchange of beam ions with thruster-generated neutrals. ObjectToolkit is a 3-D object definition and spacecraft surface modeling tool developed for use with several SEE Program codes. The main EPIC interface integrates the thruster plume into the 3-D geometry of the spacecraft and calculates interactions and effects of the plume with the spacecraft. Effects modeled include erosion of surfaces due to sputtering, re-deposition of sputtered materials, surface heating, torque on the spacecraft, and changes in surface properties due to erosion and deposition. In support of Prometheus I (JIMO), a number of new capabilities and enhancements were made to existing EPIC models. Enhancements to EPIC include adding the ability to scale and view individual plume components, to import a neutral plume associated with a thruster (to model a grid erosion plume, for example), and to calculate the plume from new initial beam conditions. Unfortunately, changes in program direction have left a number of desired enhancements undone. Variable gridding over a surface and resputtering of deposited materials, including multiple bounces and sticking coefficients, would significantly enhance the erosion/deposition model. Other modifications such as improving the heating model and the PlumeTool neutral plume model, enabling time dependent surface interactions, and including EM1 and optical effects would enable EPIC to better serve the aerospace engineer and electric propulsion systems integrator. We review EPIC S overall capabilities and recent modifications, and discuss directions for future enhancements.

Surface-coated fly ash used as filler in biodegradable poly(vinyl alcohol) composite films: Part 1—The modification process

NASA Astrophysics Data System (ADS)

Nath, D. C. D.; Bandyopadhyay, S.; Gupta, S.; Yu, A.; Blackburn, D.; White, C.

2010-02-01

The surfaces of fly ash (FA) particles were modified by surfactant, sodium lauryl sulphate (SLS) and used in fabrication of composite films with polyvinyl alcohol (PVA). Both unmodified fly ash (FA) and modified fly ash (SLS-FA) samples were examined using a range of analytical tools including X-ray fluorescence spectroscopy (XRF), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). The distribution patterns of SLS-FA particles were shifted to the higher regions compared to FA by adding 1.2-4.2 μm in the ranges between 2 and 25 μm, whereas the modification process reduced the size of the particles over 25 μm due to grinding during the activation process. The increased 1.2-4.2 μm in average can be considered the thickness of the surfactant on the SLS-FA surface. On the oxides based chemical analysis by XRF, the compositions were almost unchanged. SEM and TEM were visualised the irregular sizes morphology mostly spherical of the particles, although it is impossible to capture the images of exactly same particles in modified and unmodified forms. The composite films reinforced with SLS-FA showed 33% higher strength than those of FA filled films. The enhancement of tensile strength attributed from the level of physical bonding between SLS-FA and PVA surfaces.

Renal hypertension prevents run training modification of cardiomyocyte diastolic Ca2+ regulation in male rats.

PubMed

Palmer, B M; Lynch, J M; Snyder, S M; Moore, R L

2001-06-01

The combined effects of endurance run training and renal hypertension on cytosolic Ca2+ concentration ([Ca2+]c) dynamics and Na+-dependent Ca2+ regulation in rat left ventricular cardiomyocytes were examined. Male Fischer 344 rats underwent stenosis of the left renal artery [hypertensive (Ht), n = 18] or a sham operation [normotensive (Nt), n = 20]. One-half of the rats from each group were treadmill trained for >16 wk. Cardiomyocyte fura 2 fluorescence ratio transients were recorded for 7 min during electrical pacing at 0.5 Hz, 2 mM extracellular Ca2+ concentration, and 29 degrees C. The rate of [Ca2+]c decline was not changed by run training in the Nt group but was reduced in the Ht group. At 7 min, cardiomyocytes were exposed to 10 mM caffeine in the absence of Na+ and Ca2+, which triggered sarcoplasmic reticular Ca2+ release and suppressed Ca2+ efflux via Na+/Ca2+ exchanger. External Na+ was then added, and Na+-dependent Ca2+ efflux rate was recorded. Treadmill training significantly enhanced Na+-dependent Ca2+ efflux rate under these conditions in the Nt group but not in the Ht group. These data provide evidence that renal hypertension prevents the normal run training-induced modifications in diastolic [Ca2+]c regulation mechanisms, including Na+/Ca2+ exchanger.

Adding 'epi-' to behaviour genetics: implications for animal domestication.

PubMed

Jensen, Per

2015-01-01

In this review, it is argued that greatly improved understanding of domestication may be gained from extending the field of behaviour genetics to also include epigenetics. Domestication offers an interesting framework of rapid evolutionary changes caused by well-defined selection pressures. Behaviour is an important phenotype in this context, as it represents the primary means of response to environmental challenges. An overview is provided of the evidence for genetic involvement in behavioural control and the presently used methods for finding so-called behaviour genes. This shows that evolutionary changes in behaviour are to a large extent correlated to changes in patterns of gene expression, which brings epigenetics into the focus. This area is concerned with the mechanisms controlling the timing and extent of gene expression, and a lot of focus has been placed on methylation of cytosine in promoter regions, usually associated with genetic downregulation. The review considers the available evidence that environmental input, for example stress, can modify methylation and other epigenetic marks and subsequently affect behaviour. Furthermore, several studies are reviewed, demonstrating that acquired epigenetic modifications can be inherited and cause trans-generational behaviour changes. In conclusion, epigenetics may signify a new paradigm in this respect, as it shows that genomic modifications can be caused by environmental signals, and random mutations in DNA sequence are therefore not the only sources of heritable genetic variation. © 2015. Published by The Company of Biologists Ltd.

The CRISPR-Cas system for plant genome editing: advances and opportunities.

PubMed

Kumar, Vinay; Jain, Mukesh

2015-01-01

Genome editing is an approach in which a specific target DNA sequence of the genome is altered by adding, removing, or replacing DNA bases. Artificially engineered hybrid enzymes, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), and the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated protein) system are being used for genome editing in various organisms including plants. The CRISPR-Cas system has been developed most recently and seems to be more efficient and less time-consuming compared with ZFNs or TALENs. This system employs an RNA-guided nuclease, Cas9, to induce double-strand breaks. The Cas9-mediated breaks are repaired by cellular DNA repair mechanisms and mediate gene/genome modifications. Here, we provide a detailed overview of the CRISPR-Cas system and its adoption in different organisms, especially plants, for various applications. Important considerations and future opportunities for deployment of the CRISPR-Cas system in plants for numerous applications are also discussed. Recent investigations have revealed the implications of the CRISPR-Cas system as a promising tool for targeted genetic modifications in plants. This technology is likely to be more commonly adopted in plant functional genomics studies and crop improvement in the near future. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

47 CFR 78.109 - Major and minor modifications to stations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Major and minor modifications to stations. 78... stations. (a) Amendments to applications and modifications to stations are classified as major or minor. A... new application. (b) Major modifications to a station or amendments to an application include, but are...

47 CFR 78.109 - Major and minor modifications to stations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Major and minor modifications to stations. 78... stations. (a) Amendments to applications and modifications to stations are classified as major or minor. A... new application. (b) Major modifications to a station or amendments to an application include, but are...

47 CFR 78.109 - Major and minor modifications to stations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Major and minor modifications to stations. 78... stations. (a) Amendments to applications and modifications to stations are classified as major or minor. A... new application. (b) Major modifications to a station or amendments to an application include, but are...

Study on the Modification of Bleached Eucalyptus Kraft Pulp Using Birch Xylan

Treesearch

Wenjia Han; Chuanshan Zhao; Thomas Elder; Rendang Yang; Dongho Kim; Yunqiao Pu; Jeffery Hsieh; Arthur J. Ragauskas

2012-01-01

In this study, birch xylan was deposited onto elementally chlorine free (ECF) bleached eucalyptus kraft pulp, and the corresponding changes in physical properties were determined. An aqueous 5% birch xylan solution at pH 9 was added to 5 wt% slurry of bleached kraft eucalyptus fibers, with stirring at 70 C for 15 min after which the pH was adjusted to 5–6. The xylan...

What’s The Hold Up Reconciling Acquisition Timeline Differences

DTIC Science & Technology

2016-02-16

methods might limit the flexibility of acquisition programs in terms of schedule and budget, resulting in a situation where program execution is...adapt to 12 future challenges.44 The intent, from the start, was to design for affordability, but Congress added a wrinkle . There were only two...54 The team attacked on all fronts. Two examples of their work follow. A redesign of the ship itself and modification to the construction method

Automatic Control of Personal Rapid Transit Vehicles

NASA Technical Reports Server (NTRS)

Smith, P. D.

1972-01-01

The requirements for automatic longitudinal control of a string of closely packed personal vehicles are outlined. Optimal control theory is used to design feedback controllers for strings of vehicles. An important modification of the usual optimal control scheme is the inclusion of jerk in the cost functional. While the inclusion of the jerk term was considered, the effect of its inclusion was not sufficiently studied. Adding the jerk term will increase passenger comfort.

Recurring Reports of Civilian Employment and Payrolls

DTIC Science & Technology

1989-09-11

Department of Defense -, ,• INSTRUCTION September 11, 1989AD-A272 768 NME 701 DA& M SUBJECT: Recurring Reports of Civilian Employment and Payrolls...Positions and Modification of TAPER Authority to Permit Promotion and Reassignment of these Employees," July 30, 1979 ( m ) Federal Personnel Manual (FPM...L. DD32 On-Site Inspection Agency (OSIA) M . DDOI: 1. Office of the Secretary of Defense (OSD) 2. Joint Chiefs of Staff (JCS)* 3. Defense Security

Modification in band gap of zirconium complexes

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

Sharma, Mayank, E-mail: mayank30134@gmail.com; Singh, J.; Chouhan, S.

2016-05-06

The optical properties of zirconium complexes with amino acid based Schiff bases are reported here. The zirconium complexes show interesting stereo chemical features, which are applicable in organometallic and organic synthesis as well as in catalysis. The band gaps of both Schiff bases and zirconium complexes were obtained by UV-Visible spectroscopy. It was found that the band gap of zirconium complexes has been modified after adding zirconium compound to the Schiff bases.

Electronic transport in methylated fragments of DNA

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

Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.

2015-11-16

We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics.

Electronic transport in methylated fragments of DNA

NASA Astrophysics Data System (ADS)

de Almeida, M. L.; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L.; Albuquerque, E. L.; Freire, V. N.; Caetano, E. W. S.; de Moura, F. A. B. F.; Lyra, M. L.

2015-11-01

We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics.

Scalability enhancement of AODV using local link repairing

NASA Astrophysics Data System (ADS)

Jain, Jyoti; Gupta, Roopam; Bandhopadhyay, T. K.

2014-09-01

Dynamic change in the topology of an ad hoc network makes it difficult to design an efficient routing protocol. Scalability of an ad hoc network is also one of the important criteria of research in this field. Most of the research works in ad hoc network focus on routing and medium access protocols and produce simulation results for limited-size networks. Ad hoc on-demand distance vector (AODV) is one of the best reactive routing protocols. In this article, modified routing protocols based on local link repairing of AODV are proposed. Method of finding alternate routes for next-to-next node is proposed in case of link failure. These protocols are beacon-less, means periodic hello message is removed from the basic AODV to improve scalability. Few control packet formats have been changed to accommodate suggested modification. Proposed protocols are simulated to investigate scalability performance and compared with basic AODV protocol. This also proves that local link repairing of proposed protocol improves scalability of the network. From simulation results, it is clear that scalability performance of routing protocol is improved because of link repairing method. We have tested protocols for different terrain area with approximate constant node densities and different traffic load.

Extension of the ADjoint Approach to a Laminar Navier-Stokes Solver

NASA Astrophysics Data System (ADS)

Paige, Cody

The use of adjoint methods is common in computational fluid dynamics to reduce the cost of the sensitivity analysis in an optimization cycle. The forward mode ADjoint is a combination of an adjoint sensitivity analysis method with a forward mode automatic differentiation (AD) and is a modification of the reverse mode ADjoint method proposed by Mader et al.[1]. A colouring acceleration technique is presented to reduce the computational cost increase associated with forward mode AD. The forward mode AD facilitates the implementation of the laminar Navier-Stokes (NS) equations. The forward mode ADjoint method is applied to a three-dimensional computational fluid dynamics solver. The resulting Euler and viscous ADjoint sensitivities are compared to the reverse mode Euler ADjoint derivatives and a complex-step method to demonstrate the reduced computational cost and accuracy. Both comparisons demonstrate the benefits of the colouring method and the practicality of using a forward mode AD. [1] Mader, C.A., Martins, J.R.R.A., Alonso, J.J., and van der Weide, E. (2008) ADjoint: An approach for the rapid development of discrete adjoint solvers. AIAA Journal, 46(4):863-873. doi:10.2514/1.29123.

An efficient approach for the assembly of mass and stiffness matrices of structures with modifications

NASA Astrophysics Data System (ADS)

Wagner, Andreas; Spelsberg-Korspeter, Gottfried

2013-09-01

The finite element method is one of the most common tools for the comprehensive analysis of structures with applications reaching from static, often nonlinear stress-strain, to transient dynamic analyses. For single calculations the expense to generate an appropriate mesh is often insignificant compared to the analysis time even for complex geometries and therefore negligible. However, this is not the case for certain other applications, most notably structural optimization procedures, where the (re-)meshing effort is very important with respect to the total runtime of the procedure. Thus it is desirable to find methods to efficiently generate mass and stiffness matrices allowing to reduce this effort, especially for structures with modifications of minor complexity, e.g. panels with cutouts. Therefore, a modeling approach referred to as Energy Modification Method is proposed in this paper. The underlying idea is to model and discretize the basis structure, e.g. a plate, and the modifications, e.g. holes, separately. The discretized energy expressions of the modifications are then subtracted from (or added to) the energy expressions of the basis structure and the coordinates are related to each other by kinematical constraints leading to the mass and stiffness matrices of the complete structure. This approach will be demonstrated by two simple examples, a rod with varying material properties and a rectangular plate with a rectangular or circular hole, using a finite element discretization as basis. Convergence studies of the method based on the latter example follow demonstrating the rapid convergence and efficiency of the method. Finally, the Energy Modification Method is successfully used in the structural optimization of a circular plate with holes, with the objective to split all its double eigenfrequencies.

Analysis of resources assisting in coping with swallowing difficulties for patients with Parkinson's disease: a cross-sectional study.

PubMed

Matsushima, Aiko; Matsushima, Junichi; Matsumoto, Akihisa; Moriwaka, Fumio; Honma, Sanae; Itoh, Kazunori; Yamada, Keiko; Shimohama, Shun; Ohnishi, Hirofumi; Mori, Mitsuru

2016-07-18

Malnutrition induced by swallowing difficulties (SD) impairs the quality of life and gives rise to SD-related costs in Parkinson's disease (PD) patients. With results of a swallowing difficulty questionnaire and data of resources specifically obtained such as SD-related costs, caregivers, and dietary therapies, this study is to suggest statistically supported ideas for improvements in arrangements for how participants cope with SD and maintain general well-being. We interviewed 237 PD patients. The SD-related costs involved those incurred by the provision of dietary modifications, care oriented foods, alternatives, and supplements. Dietary therapies included rice porridge and commercially available care foods. The relationships between BMI (body mass index) and the severity of SD assumed in this paper as indicators for general well-being and as resources for coping with SD for PD patients were statistically analyzed. A lower BMI was found in participants eating porridge consistency rice (p = 0.003) and eating porridge rice is significantly related to the severity of SD (p < 0.0001) and PD (p = 0.002). The severity of SD increased with age and PD duration (p = 0.035, p = 0.0005). Outlays for dietary modifications are the lowest reported here (p < 0.004) but the number of participants using dietary modifications is the largest among the SD-related items (n = 58). Eating care foods were reported for 11 older participants (p < 0.0001), most female (10/11). No lower BMI was found in participants eating care foods when compared with participants eating ordinary foods. Dietary modifications were performed by caregivers (OR: 6.8, CI: 3.1-15.2, p < 0.0001) and were related to the presence of children (OR: 3.4, CI: 1.2-11.4. p = 0.024). Older participants commonly live with spouses and children. Severe SD is associated with higher costs of coping with SD. A lower BMI is associated with modified foods, mostly eaten to cope with SD. Presence of caregivers and other persons residing with the participants here are related to dietary modifications but not to care food-related costs. Care foods may be effective in preventing malnutrition although the number who are able to cover the added expenses is limited because of the higher prices and shortage of information on the usefulness of care foods.

An epigenetic view of developmental diseases: new targets, new therapies.

PubMed

Xie, Pei; Zang, Li-Qun; Li, Xue-Kun; Shu, Qiang

2016-08-01

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. Original research articles and literature reviews published in PubMed-indexed journals. DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Translating government policy into recipes for success! Nutrition criteria promoting fruits and vegetables.

PubMed

Pollard, Christina M; Nicolson, Clemency; Pulker, Claire E; Binns, Colin W

2009-01-01

To develop nutrition criteria consistent with Australian dietary guidelines encouraging fruit and vegetable consumption for branding recipes with the Go for 2&5 campaign message. Dietary policies, guidelines, food selection guides, nutrient targets, existing consumer education programs' nutrition criteria, food habits, and eating styles were reviewed to develop nutrition criteria, which were then used to assess 128 recipes. Perth, Australia. Recipes were analyzed then assessed against criteria for fat, sodium, fiber, energy, added sugar, fruit, vegetables, cereal, and dairy content/per serving. Recipe nutrition criteria were devised, and 128 contemporary industry recipes were evaluated according to developed nutrition criteria. Recipe categories included main meals; light meals (includes breakfast); soups; salads; side dishes; snacks (includes drinks); desserts; bakery; and basic ingredients (eg, stocks, dips, and sauces). Nearly three quarters failed. Excess fat (45%) and sodium (30%) and inadequate cereal (24%) were the main reasons. Only minor modifications were required to meet criteria. "Healthful" recipes promoting fruits and vegetables were often high in fat and sodium and low in cereal content. Nutrition criteria developed for this study provided a practical way of assessing specific meals and snacks according to the dietary guidelines, making them suitable for nutrition promotions.