Mapping Base Modifications in DNA by Transverse-Current Sequencing

NASA Astrophysics Data System (ADS)

Alvarez, Jose R.; Skachkov, Dmitry; Massey, Steven E.; Kalitsov, Alan; Velev, Julian P.

2018-02-01

Sequencing DNA modifications and lesions, such as methylation of cytosine and oxidation of guanine, is even more important and challenging than sequencing the genome itself. The traditional methods for detecting DNA modifications are either insensitive to these modifications or require additional processing steps to identify a particular type of modification. Transverse-current sequencing in nanopores can potentially identify the canonical bases and base modifications in the same run. In this work, we demonstrate that the most common DNA epigenetic modifications and lesions can be detected with any predefined accuracy based on their tunneling current signature. Our results are based on simulations of the nanopore tunneling current through DNA molecules, calculated using nonequilibrium electron-transport methodology within an effective multiorbital model derived from first-principles calculations, followed by a base-calling algorithm accounting for neighbor current-current correlations. This methodology can be integrated with existing experimental techniques to improve base-calling fidelity.

System Safety and the Unintended Consequence

NASA Technical Reports Server (NTRS)

Watson, Clifford

2012-01-01

The analysis and identification of risks often result in design changes or modification of operational steps. This paper identifies the potential of unintended consequences as an over-looked result of these changes. Examples of societal changes such as prohibition, regulatory changes including mandating lifeboats on passenger ships, and engineering proposals or design changes to automobiles and spaceflight hardware are used to demonstrate that the System Safety Engineer must be cognizant of the potential for unintended consequences as a result of an analysis. Conclusions of the report indicate the need for additional foresight and consideration of the potential effects of analysis-driven design, processing changes, and/or operational modifications.

Assessment of potential positive effects of nZVI surface modification and concentration levels on TCE dechlorination in the presence of competing strong oxidants, using an experimental design.

PubMed

Kaifas, Delphine; Malleret, Laure; Kumar, Naresh; Fétimi, Wafa; Claeys-Bruno, Magalie; Sergent, Michelle; Doumenq, Pierre

2014-05-15

Nanoscale zero-valent iron (nZVI) particles are efficient for the remediation of aquifers polluted by trichloroethylene (TCE). But for on-site applications, their reactivity can be affected by the presence of common inorganic co-pollutants, which are equally reduced by nZVI particles. The aim of this study was to assess the potential positive effects of nZVI surface modification and concentration level on TCE removal in the concomitant presence of two strong oxidants, i.e., Cr(VI) and NO3(-). A design of experiments, testing four factors (i.e. nZVI concentration, nZVI surface modification, Cr(VI) concentration and NO3(-) concentration), was used to select the best trials for the identification of the main effects of the factors and of the factors interactions. The effects of these factors were studied by measuring the following responses: TCE removal rates at different times, degradation kinetic rates, and the transformation products formed. As expected, TCE degradation was delayed or inhibited in most of the experiments, due to the presence of inorganics. The negative effects of co-pollutants can be palliated by combining surface modification with a slight increase in nZVI concentration. Encouragingly, complete TCE removal was achieved for some given experimental conditions. Noteworthily, nZVI surface modification was found to promote the efficient degradation of TCE. When degradation occurred, TCE was mainly transformed into innocuous non-chlorinated transformation products, while hazardous chlorinated transformation products accounted for a small percentage of the mass-balance. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterizing the surface charge of synthetic nanomembranes by the streaming potential method

PubMed Central

Datta, Subhra; Conlisk, A. T.; Kanani, Dharmesh M.; Zydney, Andrew L.; Fissell, William H.; Roy, Shuvo

2010-01-01

The inference of the surface charge of polyethylene glycol (PEG)-coated and uncoated silicon membranes with nanoscale pore sizes from streaming potential measurements in the presence of finite electric double layer (EDL) effects is studied theoretically and experimentally. The developed theoretical model for inferring the pore wall surface charge density from streaming potential measurements is applicable to arbitrary pore cross-sectional shapes and accounts for the effect of finite salt concentration on the ionic mobilities and the thickness of the deposited layer of PEG. Theoretical interpretation of the streaming potential data collected from silicon membranes having nanoscale pore sizes, with/without pore wall surface modification with PEG, indicates that finite electric double layer (EDL) effects in the pore-confined electrolyte significantly affect the interpretation of the membrane charge and that surface modification with PEG leads to a reduction in the pore wall surface charge density. The theoretical model is also used to study the relative significance of the following uniquely nanoscale factors affecting the interpretation of streaming potential in moderate to strongly charged pores: altered net charge convection by applied pressure differentials, surface-charge effects on ionic conduction, and electroosmotic convection of charges. PMID:20462592

A review of the design and modification of lactoferricins and their derivatives.

PubMed

Hao, Ya; Yang, Na; Teng, Da; Wang, Xiumin; Mao, Ruoyu; Wang, Jianhua

2018-06-01

Lactoferricin (Lfcin), a multifunction short peptide with a length of 25 residues, is derived from the whey protein lactoferrin by acidic pepsin hydrolysis. It has potent nutritional enhancement, antimicrobial, anticancer, antiviral, antiparasitic, and anti-inflammatory activities. This review describes the research advantages of the above biological functions, with attention to the molecular design and modification of Lfcin. In this examination of design and modification studies, research on the identification of Lfcin active derivatives and crucial amino acid residues is also reviewed. Many strategies for Lfcin optimization have been studied in recent decades, but we mainly introduce chemical modification, cyclization, chimera and polymerization of this peptide. Modifications such as incorporation of D-amino acids, acetylation and/or amidation could effectively improve the activity and stability of these compounds. Due to their wide array of bio-functions and applications, Lfcins have great potential to be developed as biological agents with multiple functions involved with nutritional enhancement, as well as disease preventive and therapeutic effects.

Cysteine Oxidative Post-translational Modifications: Emerging Regulation in the Cardiovascular System

PubMed Central

Chung, Heaseung S.; Wang, Sheng-Bing; Venkatraman, Vidya; Murray, Christopher I.; Van Eyk, Jennifer E.

2014-01-01

In the cardiovascular system, changes in the oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the post-translational modification of proteins at critical cysteine (Cys) thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. While the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understanding how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various Cys oxidative post-translational modifications (Ox-PTMs) and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other post-translational modifications' signaling pathways though cross-talk. Finally, we review the growing number of tools being developed to identify and quantify the various Cys Ox-PTMs and how this will advance our understanding of redox-regulation. PMID:23329793

Effect modification of the association between temperature variability and daily cardiovascular mortality by air pollutants in three Chinese cities.

PubMed

Luo, Kai; Li, Runkui; Wang, Zongshuang; Zhang, Ruiming; Xu, Qun

2017-11-01

There is limited evidence showing the mortality effects of temperature variability (TV) on cardiovascular diseases. The joint effects between TV and air pollutants are also less well-established. This study aims to assess the effect modification of TV-cardiovascular mortality by air pollutants in three Chinese cities (Beijing, Nanjing and Chengdu). Data of daily mortality, air pollutants and meteorological factors from 2008 to 2011 was collected from each city. TV was calculated as the standard deviation of daily maximum and minimum temperatures over exposure days. The city-specific effect estimates of TV on cardiovascular mortality were calculated using a quasi-Poisson regression model, adjusting for potential confounders (e.g., seasonality and temperature). An interaction term of TV and a three-level air pollutants stratum indicator was included in the models. Effect modifications by air pollutants were assessed by comparing the estimates of TV's effect between pollutant stratums and calculating the corresponding 95% confidential interval of the differences. Multivariate meta-analysis was conducted to obtain the pooled estimates. The data showed that TV was associated with increased risk of cardiovascular mortality, especially for longer TV exposure days (0-8 days, TV08). This association was still observed after adjusting for air pollutants on current day or the previous two days. Stronger estimates were observed in females, but no significant difference between males and females was detected, indicating the absence of evidence of effect modification by gender. Estimates of TV-cardiovascular mortality varied across two season periods (warm and cool season) and age groups, but the evidence of effect modification by age and seasons was absent. Regarding the effect modification of TV-cardiovascular mortality association by air pollutants, a significant effect modification was identified for PM 10, but not for NO 2 and SO 2 in the whole population for all TV exposure days. This finding also persisted in subgroups, specifically in females and the elderly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Constantly evolving safety assessment protocols for GM foods.

PubMed

Sesikeran, B; Vasanthi, Siruguri

2008-01-01

he introduction of GM foods has led to the evolution of a food safety assessment paradigm that establishes safety of the GM food relative to its conventional counterpart. The GM foods currently approved and marketed in several countries have undergone extensive safety testing under a structured safety assessment framework evolved by international organizations like FAO, WHO, Codex and OECD. The major elements of safety assessment include molecular characterization of inserted genes and stability of the trait, toxicity and allergenicity potential of the expressed substances, compositional analysis, potential for gene transfer to gut microflora and unintentional effects of the genetic modification. As more number and type of food crops are being brought under the genetic modification regime, the adequacy of existing safety assessment protocols for establishing safety of these foods has been questioned. Such crops comprise GM crops with higher agronomic vigour, nutritional or health benefit/ by modification of plant metabolic pathways and those expressing bioactive substances and pharmaceuticals. The safety assessment challenges of these foods are the potential of the methods to detect unintentional effects with higher sensitivity and rigor. Development of databases on food compositions, toxicants and allergens is currently seen as an important aid to development of safety protocols. With the changing global trends in genetic modification technology future challenge would be to develop GM crops with minimum amount of inserted foreign DNA so as to reduce the burden of complex safety assessments while ensuring safety and utility of the technology.

Protein Arginine Methylation and Citrullination in Epigenetic Regulation

PubMed Central

2015-01-01

The post-translational modification of arginine residues represents a key mechanism for the epigenetic control of gene expression. Aberrant levels of histone arginine modifications have been linked to the development of several diseases including cancer. In recent years, great progress has been made in understanding the physiological role of individual arginine modifications and their effects on chromatin function. The present review aims to summarize the structural and functional aspects of histone arginine modifying enzymes and their impact on gene transcription. We will discuss the potential for targeting these proteins with small molecules in a variety of disease states. PMID:26686581

Evaluating the Cost-Effectiveness of Lifestyle Modification versus Metformin Therapy for the Prevention of Diabetes in Singapore

PubMed Central

Png, May Ee; Yoong, Joanne Su-Yin

2014-01-01

Background In Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective. Methodology Cost effectiveness was analysed from 2010–2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars. Principal Findings The total economic cost for non-diabetic subjects from the societal perspective was US$25,867, US$28,108 and US$26,177 for placebo, lifestyle modification and metformin intervention respectively. For diabetic patients, the total economic cost from the societal perspective was US$32,921, US$35,163 and US$33,232 for placebo, lifestyle modification and metformin intervention respectively. Lifestyle modification relative to placebo is likely to be associated with an incremental cost per QALY gained at US$36,663 while that of metformin intervention is likely to be US$6,367 from a societal perspective. Conclusion Based on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However, the cost of lifestyle modification from the societal perspective would have to be reduced in order to match the cost-effectiveness of metformin intervention. PMID:25203633

Artificial Intelligence, DNA Mimicry, and Human Health.

PubMed

Stefano, George B; Kream, Richard M

2017-08-14

The molecular evolution of genomic DNA across diverse plant and animal phyla involved dynamic registrations of sequence modifications to maintain existential homeostasis to increasingly complex patterns of environmental stressors. As an essential corollary, driver effects of positive evolutionary pressure are hypothesized to effect concerted modifications of genomic DNA sequences to meet expanded platforms of regulatory controls for successful implementation of advanced physiological requirements. It is also clearly apparent that preservation of updated registries of advantageous modifications of genomic DNA sequences requires coordinate expansion of convergent cellular proofreading/error correction mechanisms that are encoded by reciprocally modified genomic DNA. Computational expansion of operationally defined DNA memory extends to coordinate modification of coding and previously under-emphasized noncoding regions that now appear to represent essential reservoirs of untapped genetic information amenable to evolutionary driven recruitment into the realm of biologically active domains. Additionally, expansion of DNA memory potential via chemical modification and activation of noncoding sequences is targeted to vertical augmentation and integration of an expanded cadre of transcriptional and epigenetic regulatory factors affecting linear coding of protein amino acid sequences within open reading frames.

Characterization of Cell Wall Components and Their Modifications during Postharvest Storage of Asparagus officinalis L.: Storage-Related Changes in Dietary Fiber Composition.

PubMed

Schäfer, Judith; Wagner, Steffen; Trierweiler, Bernhard; Bunzel, Mirko

2016-01-20

Changes in cell wall composition during storage of plant foods potentially alter the physiological effects of dietary fiber components. To investigate postharvest cell wall modifications of asparagus and their consequences in terms of insoluble dietary fiber structures, asparagus was stored at 20 and 1 °C for different periods of time. Structural analyses demonstrated postharvest changes in the polysaccharide profile, dominated by decreased portions of galactans. Increasing lignin contents correlated with compositional changes (monolignol ratios and linkage types) of the lignin polymer as demonstrated by chemical and two-dimensional nuclear magnetic resonance (2D-NMR) methods. Depending on the storage time and temperature, syringyl units were preferentially incorporated into the lignin polymer. Furthermore, a drastic increase in the level of ester-linked phenolic monomers (i.e., p-coumaric acid and ferulic acid) and polymer cross-links (di- and triferulic acids) was detected. The attachment of p-coumaric acid to lignin was demonstrated by 2D-NMR experiments. Potential consequences of postharvest modifications on physiological effects of asparagus dietary fiber are discussed.

Surface modification of malachite with ethanediamine and its effect on sulfidization flotation

NASA Astrophysics Data System (ADS)

Feng, Qicheng; Zhao, Wenjuan; Wen, Shuming

2018-04-01

Ethanediamine was used to modify the mineral surface of malachite to improve its sulfidization and flotation behavior. The activation mechanism was investigated by adsorption experiments, X-ray photoelectron spectroscopy (XPS) analysis, and zeta potential measurements. Microflotation experiments showed that the flotation recovery of malachite was enhanced after the pretreatment of the mineral particles with ethanediamine prior to the addition of Na2S. Adsorption tests revealed that numerous sulfide ion species in the pulp solution were transferred onto the mineral surface through the formation of more copper sulfide species. This finding was confirmed by the results of the XPS measurements. Ethanediamine modification not only increased the contents of copper sulfide species on the malachite surface but also enhanced the reactivity of the sulfidization products. During sulfidization, Cu(II) species on the mineral surface were reduced into Cu(I) species, and the percentages of S22- and Sn2- relative to the total S increased after modification, resulting in increased surface hydrophobicity. The results of zeta potential measurements showed that the ethanediamine-modified mineral surface adsorbed with more sulfide ion species was advantageous to the attachment of xanthate species, thereby improving malachite floatability. The proposed ethanediamine modification followed by sulfidization xanthate flotation exhibits potential for industrial application.

Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na{sub v}1.6 sodium channels

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

Tan Jianguo; Soderlund, David M., E-mail: dms6@cornell.ed

2010-09-15

We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}{sub 1} and {beta}{sub 2} auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 {mu}M), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were {approx}more » 9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 {mu}M), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 {mu}M), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin {approx} 15-fold and that tefluthrin was {approx} 10-fold more potent than deltamethrin as a use-dependent modifier of Na{sub v}1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na{sub v}1.2 sodium channel coexpressed with the rat {beta}{sub 1} and {beta}{sub 2} subunits in oocytes showed that the Na{sub v}1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na{sub v}1.2 isoform. These results implicate sodium channels containing the Na{sub v}1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.« less

Electrochemical surface modification of carbon mesh anode to improve the performance of air-cathode microbial fuel cells.

PubMed

Luo, Jianmei; Chi, Meiling; Wang, Hongyu; He, Huanhuan; Zhou, Minghua

2013-12-01

A convenient and promising alternative to surface modification of carbon mesh anode was fulfilled by electrochemical oxidation in the electrolyte of nitric acid or ammonium nitrate at ambient temperature. It was confirmed that such an anode modification method was low cost and effective not only in improving the efficiency of power generation in microbial fuel cells (MFCs) for synthetic wastewater treatment, but also helping to reduce the period for MFCs start-up. The MFCs with anode modification in electrolyte of nitric acid performed the best, achieving a Coulombic efficiency enhancement of 71 %. As characterized, the electrochemical modification resulted in the decrease of the anode potential and internal resistance but the increase of current response and nitrogen-containing and oxygen-containing functional groups on the carbon surface, which might contribute to the enhancement on the performances of MFCs.

Assessment of the effects of multiple extreme floods on flow and transport processes under competing flood protection and environmental management strategies.

PubMed

Tu, Tongbi; Carr, Kara J; Ercan, Ali; Trinh, Toan; Kavvas, M Levent; Nosacka, John

2017-12-31

Extreme floods are regarded as one of the most catastrophic natural hazards and can result in significant morphological changes induced by pronounced sediment erosion and deposition processes over the landscape. However, the effects of extreme floods of different return intervals on the floodplain and river channel morphological evolution with the associated sediment transport processes are not well explored. Furthermore, different basin management action plans, such as engineering structure modifications, may also greatly affect the flood inundation, sediment transport, solute transport and morphological processes within extreme flood events. In this study, a coupled two-dimensional hydrodynamic, sediment transport and morphological model is applied to evaluate the impact of different river and basin management strategies on the flood inundation, sediment transport dynamics and morphological changes within extreme flood events of different magnitudes. The 10-year, 50-year, 100-year and 200-year floods are evaluated for the Lower Cache Creek system in California under existing condition and a potential future modification scenario. Modeling results showed that select locations of flood inundation within the study area tend to experience larger inundation depth and more sediment is likely to be trapped in the study area under potential modification scenario. The proposed two dimensional flow and sediment transport modeling approach implemented with a variety of inflow conditions can provide guidance to decision-makers when considering implementation of potential modification plans, especially as they relate to competing management strategies of large water bodies, such as the modeling area in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

Survey of High-Pressure Effects in Solids.

DTIC Science & Technology

1979-11-01

phenomenological Lennard - Jones and Morse potentials . The resulting study of the GrUneisen parameter is most illuminating. A more am- bitious program would to...the Gordon-Kim-Boyer scheme with our suggested modifications; use of the exchange-correlation potential in the local-density approximation i such an...Xenon Hugoniot Calculations and Experiments .......... 41 3.8. Xenon Intermolecular Potentials ...................... 42 3.9. Xenon Hugoniot Calculations

Synthesis and physico-chemical characterization of modified starches from banana (Musa AAB) and its biological activities in diabetic rats.

PubMed

Reddy, Chagam Koteswara; Suriya, M; Vidya, P V; Haripriya, Sundaramoorthy

2017-01-01

This study describes a simple method of preparation and physico-chemical properties of modified starches (type-3 resistant starches) from banana (Musa AAB), and the modified starches investigated as functional food with a beneficial effect on type-2 diabetes. RS3 was prepared using a method combined with debranching modification and physical modification; native and modifies starches were characterized by scanning electron microscope (SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and rapid visco analyzer (RVA). Use of the enzymatic and physical modification methodology, improved the yield of RS (26.62%) from Musa AAB. A reduced viscosity and swelling power; increased transition temperatures, water absorption capacity and solubility index with B-type crystalline pattern and loss of granular appearance were observed during the debranching modification and physical modification. The modified starches exhibited beneficial health effects in diabetic and HFD rats who consumed it. These results recommend that dietary feeding of RS3 was effective in the regulation of glucose and lipid profile in serum and suppressing the oxidative stress in rats under diabetic and HFD condition. This current study provides new bioactive starches, with potential applications in the food and non-food industries. Copyright © 2016 Elsevier B.V. All rights reserved.

Landscape changes as a factor affecting the course and consequences of extreme floods in the Otava river basin, Czech Republic.

PubMed

Langhammer, Jakub; Vilímek, Vít

2008-09-01

The paper presents the analysis of anthropogenical modifications of the landscape in relation to the course and consequences of floods. The research was conducted in the Otava river basin which represents the core zone of the extreme flood in August 2002 in Central Europe. The analysis was focused on the key indicators of landscape modification potentially affecting the runoff process - the long-term changes of land-use, changes of land cover structure, land drainage, historical shortening of the river network and the modifications of streams and floodplains. The information on intensity and spatial distribution of modifications was derived from different data sources--historical maps, available GIS data, remote sensing and field mapping. The results revealed a high level of spatial diversity of anthropogenical modifications in different parts of the river basin. The intensive modifications in most of indicators were concentrated in the lowland region of the river basin due to its agricultural use; however important changes were also recorded in the headwater region of the basin. The high spatial diversity of the modifications may result in their varying effect on the course and consequences of floods in different parts of the river basin. This effect is demonstrated by the cluster analysis based on the matrix of indicators of stream and floodplain modification, physiogeographical characteristics and geomorphological evidences of the flood in August 2002, derived from the individual thematic layers using GIS.

High-temperature annealing of graphite: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Petersen, Andrew; Gillette, Victor

2018-05-01

A modified AIREBO potential was developed to simulate the effects of thermal annealing on the structure and physical properties of damaged graphite. AIREBO parameter modifications were made to reproduce Density Functional Theory interstitial results. These changes to the potential resulted in high-temperature annealing of the model, as measured by stored-energy reduction. These results show some resemblance to experimental high-temperature annealing results, and show promise that annealing effects in graphite are accessible with molecular dynamics and reactive potentials.

Investigation of the Effect of Oil Modification on Critical Characteristics of Asphalt Binders

NASA Astrophysics Data System (ADS)

Golalipour, Amir

Thermally induced cracking of asphalt pavement continues to be a serious issue in cold climate regions as well as in areas which experience extreme daily temperature differentials. Low temperature cracking of asphalt pavements is attributed to thermal stresses and strains developed during cooling cycles. Improving asphalt binder low temperature fracture and stiffness properties continues to be a subject of particular concern. Therefore, significant amount of research has been focused on improving asphalt binder properties through modification. In recent years, wide ranges of oil based modifications have been introduced to improve asphalt binder performance, especially at the low service temperatures. Although, significant use of these oils is seen in practice, knowledge of the fundamental mechanisms of oil modification and their properties for achieving optimum characteristics is limited. Hence, this study focuses on better understanding of the effect of oil modifiers which would help better material selection and achieve optimum performance in terms of increasing the life span of pavements. In this study, the effect of oil modification on the rheological properties of the asphalt binder is investigated. To examine the effect of oil modification on binder characteristics, low temperature properties as well as high temperature performance of oil modified binders were evaluated. It is found that oils vary in their effects on asphalt binder performance. However, for all oils used in the study, adding an oil to binder can improve binder low temperature performance, and this result mainly attributed to the softening effect. In addition to that, a simple linear model is proposed to predict the performance grade of oil modified binder based on the properties of its constituents at high and low temperatures. Another part of this study focuses on the oil modification effect on asphalt binder thermal strain and stresses. A viscoelastic analytical procedure is combined with experimentally derived failure stress and strain envelopes to determine the controlling failure mechanism, strain tolerance or critical stress, in thermal cracking of oil modified binders. The low temperature failure results depict that oil modification has a good potential of improving the cracking resistance of asphalt binders during thermal cycles.

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

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

Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin,more » arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome wide site specific changes as detected with DREAM • Compound/class specific effects suggested by pyrosequence of specific targets • Zebrafish embryo may be a screening model for epigenetic effects.« less

Effect of plasma grid bias on extracted currents in the RF driven surface-plasma negative ion source

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

Belchenko, Yu., E-mail: belchenko@inp.nsk.su; Ivanov, A.; Sanin, A.

2016-02-15

Extraction of negative ions from the large inductively driven surface-plasma negative ion source was studied. The dependencies of the extracted currents vs plasma grid (PG) bias potential were measured for two modifications of radio-frequency driver with and without Faraday screen, for different hydrogen feeds and for different levels of cesium conditioning. The maximal PG current was independent of driver modification and it was lower in the case of inhibited cesium. The maximal extracted negative ion current depends on the potential difference between the near-PG plasma and the PG bias potentials, while the absolute value of plasma potential in the drivermore » and in the PG area is less important for the negative ion production. The last conclusion confirms the main mechanism of negative ion production through the surface conversion of fast atoms.« less

Effects of daily food processing on allergenicity.

PubMed

Cabanillas, Beatriz; Novak, Natalija

2017-08-11

Daily food processing has the potential to alter the allergenicity of foods due to modification of the physico-chemical properties of proteins. The degree of such modifications depends on factors such as processing conditions, type of food considered, allergenic content, etc. The impact of daily food processing like boiling, roasting, frying or baking on food allergenicity have been extensively studied. The influence of other thermal treatments such as microwave heating or pressure cooking on allergenicity has also been analyzed. Non-thermal treatment such as peeling impacts on the allergenic content of certain foods such as fruits. In this review, we give an updated overview of the effects of daily processing treatments on the allergenicity of a wide variety of foods. The different variables that contribute to the modification of food allergenicity due to processing are also reviewed and discussed.

Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

PubMed

Sen, Dilara; Keung, Albert J

2018-01-01

The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.

Efficiency of plasma actuator ionization in shock wave modification in a rarefied supersonic flow over a flat plate

NASA Astrophysics Data System (ADS)

Joussot, Romain; Lago, Viviana; Parisse, Jean-Denis

2014-12-01

This paper describes experimental and numerical investigations focused on the shock wave modification, induced by a dc glow discharge, of a Mach 2 flow under rarefied regime. The model under investigation is a flat plate equipped with a plasma actuator composed of two electrodes. The glow discharge is generated by applying a negative potential to the upstream electrode, enabling the creation of a weakly ionized plasma. The natural flow (i.e. without the plasma) exhibits a thick laminar boundary layer and a shock wave with a hyperbolic shape. Images of the flow obtained with an ICCD camera revealed that the plasma discharge induces an increase in the shock wave angle. Thermal effects (volumetric, and at the surface) and plasma effects (ionization, and thermal non-equilibrium) are the most relevant processes explaining the observed modifications. The effect induced by the heating of the flat plate surface is studied experimentally by replacing the upstream electrode by a heating element, and numerically by modifying the thermal boundary condition of the model surface. The results show that for a similar temperature distribution over the plate surface, modifications induced by the heating element are lower than those produced by the plasma. This difference shows that other effects than purely thermal effects are involved with the plasma actuator. Measurements of the electron density with a Langmuir probe highlight the fact that the ionization degree plays an important role into the modification of the flow. The gas properties, especially the isentropic exponent, are indeed modified by the plasma above the actuator and upstream the flat plate. This leads to a local modification of the flow conditions, inducing an increase in the shock wave angle.

Enhancing the functional properties of thermophilic enzymes by chemical modification and immobilization.

PubMed

Cowan, Don A; Fernandez-Lafuente, Roberto

2011-09-10

The immobilization of proteins (mostly typically enzymes) onto solid supports is mature technology and has been used successfully to enhance biocatalytic processes in a wide range of industrial applications. However, continued developments in immobilization technology have led to more sophisticated and specialized applications of the process. A combination of targeted chemistries, for both the support and the protein, sometimes in combination with additional chemical and/or genetic engineering, has led to the development of methods for the modification of protein functional properties, for enhancing protein stability and for the recovery of specific proteins from complex mixtures. In particular, the development of effective methods for immobilizing large multi-subunit proteins with multiple covalent linkages (multi-point immobilization) has been effective in stabilizing proteins where subunit dissociation is the initial step in enzyme inactivation. In some instances, multiple benefits are achievable in a single process. Here we comprehensively review the literature pertaining to immobilization and chemical modification of different enzyme classes from thermophiles, with emphasis on the chemistries involved and their implications for modification of the enzyme functional properties. We also highlight the potential for synergies in the combined use of immobilization and other chemical modifications. Copyright © 2011 Elsevier Inc. All rights reserved.

Creation and implementation of an effective physician compensation methodology for a nonprofit medical foundation.

PubMed

Ferch, A W

2000-01-01

The foundation has determined that the adjusted gross billing methodology is a viable method to be considered for a nonprofit medical foundation in compensating physicians. The foundation continues to experiment with the margin formula and is exploring other potential formulas, but believes with certain modifications the percentage of adjusted gross billing methodology can be effective and useful because of its simplicity, ease of administration, and motivational effect on the physicians. The primary improvement to the model needed would be the ability to adjust the formula on a frequent basis for individual practice variations. Modifications will continue to be made as circumstances change, but the basic principles will remain constant.

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure.

PubMed

Bouwmeester, Manon C; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; Kamstra, Jorke H; Jelinek, Jaroslav; Issa, Jean-Pierre J; Legler, Juliette; van der Ven, Leo T M

2016-01-15

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Research supporting potential modification of the NASA specification for dry heat microbial reduction of spacecraft hardware

NASA Astrophysics Data System (ADS)

Spry, James A.; Beaudet, Robert; Schubert, Wayne

Dry heat microbial reduction (DHMR) is the primary method currently used to reduce the microbial load of spacecraft and component parts to comply with planetary protection re-quirements. However, manufacturing processes often involve heating flight hardware to high temperatures for purposes other than planetary protection DHMR. At present, the specifica-tion in NASA document NPR8020.12, describing the process lethality on B. atrophaeus (ATCC 9372) bacterial spores, does not allow for additional planetary protection bioburden reduction credit for processing outside a narrow temperature, time and humidity window. Our results from a comprehensive multi-year laboratory research effort have generated en-hanced data sets on four aspects of the current specification: time and temperature effects in combination, the effect that humidity has on spore lethality, and the lethality for spores with exceptionally high thermal resistance (so called "hardies"). This paper describes potential modifications to the specification, based on the data set gener-ated in the referenced studies. The proposed modifications are intended to broaden the scope of the current specification while still maintaining confidence in a conservative interpretation of the lethality of the DHMR process on microorganisms.

Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

PubMed

Tharmalingam, Sujeenthar; Sreetharan, Shayenthiran; Kulesza, Adomas V; Boreham, Douglas R; Tai, T C

2017-10-01

Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (<100 mGy) and oxidative stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood

PubMed Central

Harris, Donald G.; Quinn, Kevin J.; French, Beth M.; Schwartz, Evan; Kang, Elizabeth; Dahi, Siamak; Phelps, Carol J.; Ayares, David L.; Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

2014-01-01

Background Genetically modified pigs are a promising potential source of lung xenografts. Ex-vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. Methods Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had 1 genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 hours of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. Results Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 hours generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55 or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. Conclusion This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury, and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival. PMID:25470239

Protein requirements for long term missions

NASA Astrophysics Data System (ADS)

Stein, T. P.

1994-11-01

A key component of the diet for a space mission is protein. This first part of this paper reviews the reasons for emphasizing protein nutrition and then discusses what the requirements are likely to be. The second part discusses potential advantages of modifying these requirements and describes potential approaches to effecting these modifications based on well established ground based models.

Thermal-based treatment options for localized prostate cancer.

PubMed

Koch, Michael O; Gardner, Thomas A

2005-09-01

It seems clear that thermal-based therapies of prostate cancer have the potential to completely eradicate the prostate gland. Technical modifications continue to improve our ability to use these modalities more effectively, which can be seen in the ever decreasing morbidity from damage to adjacent structures. These treatments offer potential major advantages over surgery and radiation-based treatment modalities.

Addressing the human factors issues associated with control room modifications

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

O`Hara, J.; Stubler, W.; Kramer, J.

1998-03-01

Advanced human-system interface (HSI) technology is being integrated into existing nuclear plants as part of plant modifications and upgrades. The result of this trend is that hybrid HSIs are created, i.e., HSIs containing a mixture of conventional (analog) and advanced (digital) technology. The purpose of the present research is to define the potential effects of hybrid HSIs on personnel performance and plant safety and to develop human factors guidance for safety reviews of them where necessary. In support of this objective, human factors issues associated with hybrid HSIs were identified. The issues were evaluated for their potential significance to plantmore » safety, i.e., their human performance concerns have the potential to compromise plant safety. The issues were then prioritized and a subset was selected for design review guidance development.« less

Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study

PubMed Central

Meng, Xiangfei; Brunet, Alain; Turecki, Gustavo; Liu, Aihua; D'Arcy, Carl; Caron, Jean

2017-01-01

Objective Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study. Methods Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence. Results The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases. Conclusions Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted. PMID:28601831

Mental Health on the Go: Effects of a Gamified Attention Bias Modification Mobile Application in Trait Anxious Adults.

PubMed

Dennis, Tracy A; O'Toole, Laura

2014-09-01

Interest in the use of mobile technology to deliver mental health services has grown in light of the economic and practical barriers to treatment. Yet, research on alternative delivery strategies that are more affordable, accessible, and engaging is in its infancy. Attention bias modification training (ABMT), has potential to reduce treatment barriers as a mobile intervention for stress and anxiety, but the degree to which ABMT can be embedded in a mobile gaming format and its potential for transfer of benefits is unknown. The present study examined effects of a gamified ABMT mobile application in highly trait anxious participants ( N = 78). A single session of the active compared to placebo training reduced subjective anxiety and observed stress reactivity. Critically, the long (45 minutes) but not short (25 minutes) active training condition reduced the core cognitive process implicated in ABMT (threat bias) as measured by an untrained, gold-standard protocol.

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

PubMed Central

Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

Assessing the potential and side effects of ocean albedo modification in the Arctic

NASA Astrophysics Data System (ADS)

Mengis, N.; Oschlies, A.; Keller, D. P.; Martin, T.

2015-12-01

The ice albedo feedbacks in the Arctic are a key factor of the positive feedback mechanisms, which amplify climate change in the high northern latitudes. This study assesses the potential and side effects of an idealised Arctic ocean albedo modification (AOAM) experiment under varying emissions scenarios. A first finding is the fact that the decreasing trend in the Arctic summer sea ice extent could only be offset rather than reversed by the implementation of AOAM under increasing atmospheric CO2 emissions. What becomes evident in this study is that the Earth system regulates its internal heat budgets. Therefore a local cooling at the high northern latitudes causes compensatory heat fluxes in the atmosphere and the ocean. Meaning that firstly, the effectiveness of local scale climate intervention will, in the long term, be lowered by these compensatory fluxes and secondly that there are consequences, such as the subsurface warming signal found in this study, which are unexpected and unintended.

Influence of linear profile modification and loading conditions on the dynamic tooth load and stress of high contact ratio gears

NASA Technical Reports Server (NTRS)

Lee, Chinwai; Lin, Hsiang Hsi; Oswald, Fred B.; Townsend, Dennis P.

1990-01-01

A computer simulation for the dynamic response of high-contact-ratio spur gear transmissions is presented. High contact ratio gears have the potential to produce lower dynamic tooth loads and minimum root stress but they can be sensitive to tooth profile errors. The analysis presented examines various profile modifications under realistic loading conditions. The effect of these modifications on the dynamic load (force) between mating gear teeth and the dynamic root stress is presented. Since the contact stress is dependent on the dynamic load, minimizing dynamic loads will also minimize contact stresses. It is shown that the combination of profile modification and the applied load (torque) carried by a gear system has a significant influence on gear dynamics. The ideal modification at one value of applied load will not be the best solution for a different load. High-contact-ratio gears were found to require less modification than standard low-contact-ratio gears. High-contact-ratio gears are more adversely affected by excess modification than by under modification. In addition, the optimal profile modification required to minimize the dynamic load (hence the contact stress) on a gear tooth differs from the optimal modification required to minimize the dynamic root (bending) stress. Computer simulation can help find the design tradeoffs to determine the best profile modification to satisfy the conflicting constraints of minimizing both the load and root stress in gears which must operate over a range of applied loads.

Transgenerational effects of insecticides-implications for rapid pest evolution in agroecosystems.

PubMed

Brevik, Kristian; Lindström, Leena; McKay, Stephanie D; Chen, Yolanda H

2018-04-01

Although pesticides are a major selective force in driving the evolution of insect pests, the evolutionary processes that give rise to insecticide resistance remain poorly understood. Insecticide resistance has been widely observed to increase with frequent and intense insecticide exposure, but can be lost following the relaxation of insecticide use. One possible but rarely explored explanation is that insecticide resistance may be associated with epigenetic modifications, which influence the patterning of gene expression without changing underlying DNA sequence. Epigenetic modifications such as DNA methylation, histone modifications, and small RNAs have been observed to be heritable in arthropods, but their role in the context of rapid evolution of insecticide resistance remain poorly understood. Here, we discuss evidence supporting how: firstly, insecticide-induced effects can be transgenerationally inherited; secondly, epigenetic modifications are heritable; and thirdly, epigenetic modifications are responsive to pesticide and xenobiotic stress. Therefore, pesticides may drive the evolution of resistance via epigenetic processes. Moreover, insect pests primed by pesticides may be more tolerant of other stress, further enhancing their success in adapting to agroecosystems. Resolving the role of epigenetic modifications in the rapid evolution of insect pests has the potential to lead to new approaches for integrated pest management as well as improve our understanding of how anthropogenic stress may drive the evolution of insect pests. Copyright © 2018 Elsevier Inc. All rights reserved.

Oligo/Polynucleotide-Based Gene Modification: Strategies and Therapeutic Potential

PubMed Central

Sargent, R. Geoffrey; Kim, Soya

2011-01-01

Oligonucleotide- and polynucleotide-based gene modification strategies were developed as an alternative to transgene-based and classical gene targeting-based gene therapy approaches for treatment of genetic disorders. Unlike the transgene-based strategies, oligo/polynucleotide gene targeting approaches maintain gene integrity and the relationship between the protein coding and gene-specific regulatory sequences. Oligo/polynucleotide-based gene modification also has several advantages over classical vector-based homologous recombination approaches. These include essentially complete homology to the target sequence and the potential to rapidly engineer patient-specific oligo/polynucleotide gene modification reagents. Several oligo/polynucleotide-based approaches have been shown to successfully mediate sequence-specific modification of genomic DNA in mammalian cells. The strategies involve the use of polynucleotide small DNA fragments, triplex-forming oligonucleotides, and single-stranded oligodeoxynucleotides to mediate homologous exchange. The primary focus of this review will be on the mechanistic aspects of the small fragment homologous replacement, triplex-forming oligonucleotide-mediated, and single-stranded oligodeoxynucleotide-mediated gene modification strategies as it relates to their therapeutic potential. PMID:21417933

Hunting for unexpected post-translational modifications by spectral library searching with tier-wise scoring.

PubMed

Ma, Chun Wai Manson; Lam, Henry

2014-05-02

Discovering novel post-translational modifications (PTMs) to proteins and detecting specific modification sites on proteins is one of the last frontiers of proteomics. At present, hunting for post-translational modifications remains challenging in widely practiced shotgun proteomics workflows due to the typically low abundance of modified peptides and the greatly inflated search space as more potential mass shifts are considered by the search engines. Moreover, most popular search methods require that the user specifies the modification(s) for which to search; therefore, unexpected and novel PTMs will not be detected. Here a new algorithm is proposed to apply spectral library searching to the problem of open modification searches, namely, hunting for PTMs without prior knowledge of what PTMs are in the sample. The proposed tier-wise scoring method intelligently looks for unexpected PTMs by allowing mass-shifted peak matches but only when the number of matches found is deemed statistically significant. This allows the search engine to search for unexpected modifications while maintaining its ability to identify unmodified peptides effectively at the same time. The utility of the method is demonstrated using three different data sets, in which the numbers of spectrum identifications to both unmodified and modified peptides were substantially increased relative to a regular spectral library search as well as to another open modification spectral search method, pMatch.

Changes to histone modifications following prenatal alcohol exposure: An emerging picture.

PubMed

Chater-Diehl, Eric J; Laufer, Benjamin I; Singh, Shiva M

2017-05-01

Epigenetic mechanisms are important for facilitating gene-environment interactions in many disease etiologies, including Fetal Alcohol Spectrum Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs in animal models has illuminated the complex role of these mechanisms in FASD. In contrast, histone modifications have not been as well researched, due in part to being less stable than DNA methylation and less well-characterized in disease. It is now apparent that even changes in transient marks can have profound effects if they alter developmental trajectories. In addition, many histone methylations are now known to be relatively stable and can propagate themselves. As technologies and knowledge have advanced, a small group has investigated the role of histone modifications in FASD. Here, we synthesize the data on the effects of prenatal alcohol exposure (PAE) on histone modifications. Several key points are evident. AS with most alcohol-induced outcomes, timing and dosage differences yield variable effects. Nevertheless, these studies consistently find enrichment of H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone acetyltransferases and methyltransferases. The consistency of these alterations may implicate them as key mechanisms underlying FASD. Histone modification changes do not often correlate with gene expression changes, though some important examples exist. Encouragingly, attempts to reproduce specific histone modification changes are very often successful. We comment on possible directions for future studies, focusing on further exploration of current trends, expansion of time-point and dosage regimes, and evaluation of biomarker potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Epigenetics in myeloid derived suppressor cells: a sheathed sword towards cancer

PubMed Central

Zhang, Chao; Wang, Shuo; Liu, Yufeng; Yang, Cheng

2016-01-01

Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells composed of progenitors and precursors to myeloid cells, are deemed to participate in the development of tumor-favoring immunosuppressive microenvironment. Thus, the regulatory strategies targeting MDSCs' expansion, differentiation, accumulation and function could possibly be effective “weapons” in anti-tumor immunotherapies. Epigenetic mechanisms, which involve DNA modification, covalent histone modification and RNA interference, result in the heritable down-regulation or silencing of gene expression without a change in DNA sequences. Epigenetic modification of MDSC's functional plasticity leads to the remodeling of its characteristics, therefore reframing the microenvironment towards countering tumor growth and metastasis. This review summarized the pertinent findings on the DNA methylation, covalent histone modification, microRNAs and small interfering RNAs targeting MDSC in cancer genesis, progression and metastasis. The potentials as well as possible obstacles in translating into anti-cancer therapeutics were also discussed. PMID:27458169

Versatile Method for the Site-Specific Modification of DNA with Boron Clusters: Anti-Epidermal Growth Factor Receptor (EGFR) Antisense Oligonucleotide Case.

PubMed

Ebenryter-Olbińska, Katarzyna; Kaniowski, Damian; Sobczak, Milena; Wojtczak, Błażej A; Janczak, Sławomir; Wielgus, Ewelina; Nawrot, Barbara; Leśnikowski, Zbigniew J

2017-11-21

A general and convenient approach for the incorporation of different types of boron clusters into specific locations of the DNA-oligonucleotide chain based on the automated phosphoramidite method of oligonucleotide synthesis and post-synthetic "click chemistry" modification has been developed. Pronounced effects of boron-cluster modification on the physico- and biochemical properties of the antisense oligonucleotides were observed. The silencing activity of antisense oligonucleotides bearing a single boron cluster modification in the middle of the oligonucleotide chain was substantially higher than that of unmodified oligonucleotides. This finding may be of importance for the design of therapeutic nucleic acids with improved properties. The proposed synthetic methodology broadens the availability of nucleic acid-boron cluster conjugates and opens up new avenues for their potential practical use. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The ethics of molecular memory modification.

PubMed

Hui, Katrina; Fisher, Carl E

2015-07-01

Novel molecular interventions have recently shown the potential to erase, enhance and alter specific long-term memories. Unique features of this form of memory modification call for a close examination of its possible applications. While there have been discussions of the ethics of memory modification in the literature, molecular memory modification (MMM) can provide special insights. Previously raised ethical concerns regarding memory enhancement, such as safety issues, the 'duty to remember', selfhood and personal identity, require re-evaluation in light of MMM. As a technology that exploits the brain's updating processes, MMM helps correct the common misconception that memory is a static entity by demonstrating how memory is plastic and subject to revision even in the absence of external manipulation. Furthermore, while putatively safer than other speculative technologies because of its high specificity, MMM raises notable safety issues, including potential insidious effects on the agent's emotions and personal identity. Nonetheless, MMM possesses characteristics of a more permissible form of modification, not only because it is theoretically safer, but because its unique mechanism of action requires a heightened level of cooperation from the agent. Discussions of memory modification must consider the specific mechanisms of action, which can alter the weight and relevance of various ethical concerns. MMM also highlights the need for conceptual accuracy regarding the term 'enhancement'; this umbrella term will have to be differentiated as new technologies are applied to a widening array of purposes. 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.

A Growing Role for Gender Analysis in Air Pollution Epidemiology

PubMed Central

Clougherty, Jane E.

2010-01-01

Objective Epidemiologic studies of air pollution effects on respiratory health report significant modification by sex, although results are not uniform. Importantly, it remains unclear whether modifications are attributable to socially derived gendered exposures, to sex-linked physiological differences, or to some interplay thereof. Gender analysis, which aims to disaggregate social from biological differences between males and females, may help to elucidate these possible sources of effect modification. Data sources and data extraction A PubMed literature search was performed in July 2009, using the terms “respiratory” and any of “sex” or “gender” or “men and women” or “boys and girls” and either “PM2.5” (particulate matter ≥ 2.5 μm in aerodynamic diameter) or “NO2” (nitrogen dioxide). I reviewed the identified studies, and others cited therein, to summarize current evidence of effect modification, with attention to authors’ interpretation of observed differences. Owing to broad differences in exposure mixes, outcomes, and analytic techniques, with few studies examining any given combination thereof, meta-analysis was not deemed appropriate at this time. Data synthesis More studies of adults report stronger effects among women, particularly for older persons or where using residential exposure assessment. Studies of children suggest stronger effects among boys in early life and among girls in later childhood. Conclusions The qualitative review describes possible sources of difference in air pollution response between women and men, which may vary by life stage, coexposures, hormonal status, or other factors. The sources of observed effect modifications remain unclear, although gender analytic approaches may help to disentangle gender and sex differences in pollution response. A framework for incorporating gender analysis into environmental epidemiology is offered, along with several potentially useful methods from gender analysis. PMID:20123621

Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties

PubMed Central

Marzaioli, Viviana; Aguilar-Pimentel, Juan Antonio; Weichenmeier, Ingrid; Luxenhofer, Georg; Wiemann, Martin; Landsiedel, Robert; Wohlleben, Wendel; Eiden, Stefanie; Mempel, Martin; Behrendt, Heidrun; Schmidt-Weber, Carsten; Gutermuth, Jan; Alessandrini, Francesca

2014-01-01

Background Silica (SiO2) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems. Objective To assess the potential impact of SiO2 NP exposure and NPs chemical modifications in allergic airway inflammation. Methods Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO2 NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue. Results Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO2 NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis. Conclusion Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO2 NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans. PMID:24940059

Modified lysozymes as novel broad spectrum natural antimicrobial agents in foods.

PubMed

Aminlari, Ladan; Hashemi, Marjan Mohammadi; Aminlari, Mahmoud

2014-06-01

In recent years much attention and interest have been directed toward application of natural antimicrobial agents in foods. Some naturally occurring proteins such as lactoperoxidase, lactoferrin, and lysozyme have received considerable attention and are being considered as potential antimicrobial agents in foods. Lysozyme kills bacteria by hydrolyzing the peptidoglycan layer of the cell wall of certain bacterial species, hence its application as a natural antimicrobial agent has been suggested. However, limitations in the action of lysozyme against only Gram-positive bacteria have prompted scientists to extend the antimicrobial effects of lysozyme by several types of chemical modifications. During the last 2 decades extensive research has been directed toward modification of lysozyme in order to improve its antimicrobial properties. This review will report on the latest information available on lysozyme modifications and examine the applicability of the modified lysozymes in controlling growth of Gram-positive and Gram-negative bacteria in foods. The results of modifications of lysozyme using its conjugation with different small molecule, polysaccharides, as well as modifications using proteolytic enzymes will be reviewed. These types of modifications have not only increased the functional properties of lysozyme (such as solubility and heat stability) but also extended the antimicrobial activity of lysozyme. Many examples will be given to show that modification can decrease the count of Gram-negative bacteria in bacterial culture and in foods by as much as 5 log CFU/mL and in some cases essentially eliminated Escherichia coli. In conclusion this review demonstrates that modified lysozymes are excellent natural food preservatives, which can be used in food industry. The subject described in this review article can lead to the development of methods to produce new broad-spectrum natural antimicrobial agents, based on modification of chicken egg white lysozyme, which might potentially replace the currently used synthetic food preservatives. © 2014 Institute of Food Technologists®

Short-term effects of air temperature on mortality and effect modification by air pollution in three cities of Bavaria, Germany: a time-series analysis.

PubMed

Breitner, Susanne; Wolf, Kathrin; Devlin, Robert B; Diaz-Sanchez, David; Peters, Annette; Schneider, Alexandra

2014-07-01

Air temperature has been shown to be associated with mortality; however, only very few studies have been conducted in Germany. This study examined the association between daily air temperature and cause-specific mortality in Bavaria, Southern Germany. Moreover, we investigated effect modification by age and ambient air pollution. We obtained data from Munich, Nuremberg as well as Augsburg, Germany, for the period 1990 to 2006. Data included daily cause-specific death counts, mean daily meteorology and air pollution concentrations (particulate matter with a diameter<10 μm [PM10] and maximum 8-h ozone). We used Poisson regression models combined with distributed lag non-linear models adjusting for long-term trend, calendar effects, and meteorological factors. Air pollutant concentrations were categorized into three levels, and an interaction term was included to quantify potential effect modification of the air temperature effects. The temperature-mortality relationships were non-linear for all cause-specific mortality categories showing U- or J-shaped curves. An increase from the 90th (20.0 °C) to the 99th percentile (24.8 °C) of 2-day average temperature led to an increase in non-accidental mortality by 11.4% (95% CI: 7.6%-15.3%), whereas a decrease from the 10th (-1.0 °C) to the 1st percentile (-7.5 °C) in the 15-day average temperature resulted in an increase of 6.2% (95% CI: 1.8%-10.8%). The very old were found to be most susceptible to heat effects. Results also suggested some effect modification by ozone, but not for PM10. Results indicate that both very low and very high air temperature increase cause-specific mortality in Bavaria. Results also pointed to the importance of considering effect modification by age and ozone in assessing temperature effects on mortality. Copyright © 2014 Elsevier B.V. All rights reserved.

Sequence tagging reveals unexpected modifications in toxicoproteomics

PubMed Central

Dasari, Surendra; Chambers, Matthew C.; Codreanu, Simona G.; Liebler, Daniel C.; Collins, Ben C.; Pennington, Stephen R.; Gallagher, William M.; Tabb, David L.

2010-01-01

Toxicoproteomic samples are rich in posttranslational modifications (PTMs) of proteins. Identifying these modifications via standard database searching can incur significant performance penalties. Here we describe the latest developments in TagRecon, an algorithm that leverages inferred sequence tags to identify modified peptides in toxicoproteomic data sets. TagRecon identifies known modifications more effectively than the MyriMatch database search engine. TagRecon outperformed state of the art software in recognizing unanticipated modifications from LTQ, Orbitrap, and QTOF data sets. We developed user-friendly software for detecting persistent mass shifts from samples. We follow a three-step strategy for detecting unanticipated PTMs in samples. First, we identify the proteins present in the sample with a standard database search. Next, identified proteins are interrogated for unexpected PTMs with a sequence tag-based search. Finally, additional evidence is gathered for the detected mass shifts with a refinement search. Application of this technology on toxicoproteomic data sets revealed unintended cross-reactions between proteins and sample processing reagents. Twenty five proteins in rat liver showed signs of oxidative stress when exposed to potentially toxic drugs. These results demonstrate the value of mining toxicoproteomic data sets for modifications. PMID:21214251

Nutrition and prevention of Alzheimer’s dementia

PubMed Central

Swaminathan, Arun; Jicha, Gregory A.

2014-01-01

A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer’s dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may specifically disrupt pathogenic pathways in the development of AD. Nutritional modifications have the advantage of being cost effective, easy to implement, socially acceptable and generally safe and devoid of significant adverse events in most cases. Many nutritional interventions have been studied and continue to be evaluated in hopes of finding a successful agent, combination of agents, or dietary modifications that can be used for the prevention and or treatment of AD. The current review focuses on several key nutritional compounds and dietary modifications that have been studied in humans, and further discusses the rationale underlying their potential utility for the prevention and treatment of AD. PMID:25368575

Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-only, ADHD and conduct problems, and controls.

PubMed

Helseth, Sarah A; Waschbusch, Daniel A; Gnagy, Elizabeth M; Onyango, Adia N; Burrows-MacLean, Lisa; Fabiano, Gregory A; Coles, Erika K; Chacko, Anil; Wymbs, Brian T; Walker, Kathryn S; Wymbs, Frances A; Garefino, Allison; Massetti, Greta M; Robb Mazzant, Jessica; Hoffman, Martin T; Waxmonsky, James G; Nichols-Lopez, Kristin; Pelham, William E

2015-04-01

This study compared the unique and combined effects of evidence-based treatments for ADHD-stimulant medication and behavior modification-on children's rates of reinforcement for deviant peer behavior (RDPB). Using a within-subjects design, 222 elementary school-age children attending a summer treatment program, including 151 children with ADHD (127 male), with and without comorbid conduct problems, and 71 control children (57 male), received varying combinations of behavior modification (no, low-intensity, and high-intensity) and methylphenidate (placebo, 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg). RDPB was measured through direct observation and compared across all behavior modification and medication conditions. Children with ADHD reinforced the deviant behavior of their peers at a significantly higher rate than control children in the absence of either intervention. However, that difference largely disappeared in the presence of both behavior modification and medication. Both low and high-intensity behavior modification, as well as medium (0.30 mg/kg) and high (0.60 mg/kg) doses of methylphenidate, significantly reduced the rate of ADHD children's RDPB to levels similar to the control group. Results indicate that although untreated children with ADHD do engage in RDPB at a greater rate than their non-ADHD peers, existing evidence-based interventions can substantially decrease the presence of RDPB, thereby limiting potential iatrogenic effects in group-based treatment settings. (c) 2015 APA, all rights reserved).

View of Soviet ionospheric modification research

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

Duncan, L.M.; Showen, R.L.

1990-10-01

We have reviewed and provided a technical assessment of Soviet research of the past five to ten years in ionospheric modification by high-power radio waves. This review includes a comprehensive survey of Soviet published literature, conference proceedings, and direct discussions with the involved Soviet researchers. The current state of the art for Soviet research in this field is evaluated, identifying areas of potential breakthrough discoveries, and discussing implications of this work for emerging technologies and future applications. This assessment is divided into the categories of basic research, advanced research, and applications. Basic research is further subdivided into studies of themore » modified natural geophysical environment, nonlinear plasma physics, and polar geophysical studies. Advanced research topics include the generation of artificial ionization mirrors and high-power oblique propagation effects. A separate comparative assessment of Soviet theoretical work also is included in this analysis. Our evaluation of practical and potential applications of this research discusses the utility of ionospheric modification in creating disturbed radio wave propagation environments, and its role in current and future remote-sensing and telecommunications systems. This technical assessment does not include consideration of ionospheric modification by means other than high-power radio waves. The Soviet effort in ionospheric modification sustains theoretical and experimental research at activity levels considerably greater than that found in comparable programs in the West. Notable strengths of the Soviet program are its breadth of coverage, large numbers of scientific participation, theoretical creativity and insight, and its powerful radio wave transmitting facilities.« less

Reconsidering the Status of Title IX.

ERIC Educational Resources Information Center

Hammer, Ben

2003-01-01

Discusses the controversy over Title IX and women's participation in college athletics. Critics say the mandate shortchanges men's teams, while proponents say that women's sports programs remain underfunded in spite of Title IX. Describes some proposed modifications to Title IX and their potential effects. (SLD)

Rotational excitation of symmetric top molecules by collisions with atoms: Close coupling, coupled states, and effective potential calculations for NH3-He

NASA Technical Reports Server (NTRS)

Green, S.

1976-01-01

The formalism for describing rotational excitation in collisions between symmetric top rigid rotors and spherical atoms is presented both within the accurate quantum close coupling framework and also the coupled states approximation of McGuire and Kouri and the effective potential approximation of Rabitz. Calculations are reported for thermal energy NH3-He collisions, treating NH3 as a rigid rotor and employing a uniform electron gas (Gordon-Kim) approximation for the intermolecular potential. Coupled states are found to be in nearly quantitative agreement with close coupling results while the effective potential method is found to be at least qualitatively correct. Modifications necessary to treat the inversion motion in NH3 are discussed.

Augmented liver targeting of exosomes by surface modification with cationized pullulan.

PubMed

Tamura, Ryo; Uemoto, Shinji; Tabata, Yasuhiko

2017-07-15

Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes. Surface modification can be achieved by a simple mixing of original exosomes and cationized pullulan and through an electrostatic interaction of both substances. The exosomes modified with cationized pullulan were internalized into HepG2 cells in vitro to a significantly greater extent than unmodified ones and this internalization was induced through the asialoglycoprotein receptor that was specifically expressed on HepG2 cells and hepatocytes. When injected intravenously into mice with concanavalin A-induced liver injury, the modified exosomes accumulated in the liver tissue, resulting in an enhanced anti-inflammatory effect in vivo. It is concluded that the surface modification with cationized pullulan promoted accumulation of the exosomes in the liver and the subsequent biological function, resulting in a greater therapeutic effect on liver injury. Exosomes have shown potentials as therapeutics for various inflammatory disease models. This study is the first to show the specific accumulation of exosomes in the liver and enhanced anti-inflammatory effect via the surface modification of exosomes using pullulan, which is specifically recognized by the asialoglycoprotein receptor (AGPR) on HepG2 cells and hepatocytes. The pullulan was expressed on the surface of PKH-labeled exosomes, and it led increased accumulation of PKH into HepG2 cells, whereas the accumulation was canceled by AGPR inhibitor. In the mouse liver injury model, the modification of PKH-labeled exosomes with pullulan enabled increased accumulation of PKH specifically in the injured liver. Furthermore the greater therapeutic effects against the liver injury compared with unmodified original exosomes was observed. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel Fabrication of Biodegradable Superabsorbent Microspheres with Diffusion Barrier through Thermo-Chemical Modification and Their Potential Agriculture Applications for Water Holding and Sustained Release of Fertilizer.

PubMed

Feng, Diejing; Bai, Bo; Wang, Honglun; Suo, Yourui

2017-07-26

Synergistic utilization of water and fertilizer has vital contribution to the modern production of agriculture. This work reports on a simple and facile strategy to prepare biodegradable yeast/sodium alginate/poly(vinyl alcohol) superabsorbent microspheres with a diffusion barrier merit by thermo-chemical modification route. The integrated performances, including water absorbency, water retention, water evaporation ratio, leaching loss control, sustained-release behaviors, and degradation in soil, were systematically investigated. The results revealed that the modified microspheres were a triumphant water and fertilizer manager to effectively hold water and control the unexpected leakage of fertilizer for sustained release. Therefore, this work provides a promising approach to ameliorate the utilization efficiency of water and fertilizer in potential agriculture applications.

Ion beam modification of zinc white pigment characterized by ex situ and in situ μ-Raman and XPS

NASA Astrophysics Data System (ADS)

Beck, L.; Gutiérrez, P. C.; Miro, S.; Miserque, F.

2017-10-01

Zinc oxide, known as zinc white, is one of the principal white pigments developed in the 18th century and was used by the Impressionist painters. ZnO as artists' pigment has occasionally been characterized by X-ray and ion beam techniques, but these studies are limited by the potential for visible radiation effect. Ion beam modifications of zinc oxide have extensively been investigated, but mainly for electronic and industrial applications. In this paper, we focus our investigation on ion beam modification of ZnO used as pigment. Two irradiation conditions have been used: an external 3 MeV proton micro-beam representative of PIXE analysis and 2 MeV H+ and 1.2 MeV Au + beams in vacuum to investigate irradiation modifications in electronic and nuclear energy loss regimes. Ion beam modification was characterized by ex situ and in situ micro-Raman spectrometry and XPS. The results shows that IBA of zinc white can be carried out safely in historical paintings with low current and dose.

Effect of Ultrasonic Nano-Crystal Surface Modification (UNSM) on the Passivation Behavior of Aged 316L Stainless Steel

PubMed Central

Kim, Ki-Tae; Lee, Jung-Hee; Kim, Young-Sik

2017-01-01

Stainless steels have good corrosion resistance in many environments but welding or aging can decrease their resistance. This work focused on the effect of aging time and ultrasonic nano-crystal surface modification on the passivation behavior of 316L stainless steel. In the case of slightly sensitized 316L stainless steel, increasing the aging time drastically decreased the pitting potential, increased the passive current density, and decreased the resistance of the passive film, even though aging did not form chromium carbide and a chromium depletion zone. This behavior is due to the micro-galvanic corrosion between the matrix and carbon segregated area, and this shows the importance of carbon segregation in grain boundaries to the pitting corrosion resistance of stainless steel, in addition to the formation of the chromium depletion zone. UNSM (Ultrasonic Nano Crystal Surface Modification)-treatment to the slightly sensitized 316L stainless steel increased the pitting potential, decreased the passive current density, and increased the resistance of the passive film. However, in the case of heavily sensitized 316L stainless steel, UNSM-treatment decreased the pitting potential, increased the passive current density, and decreased the resistance of the passive film. This behavior is due to the dual effects of the UNSM-treatment. That is, the UNSM-treatment reduced the carbon segregation, regardless of whether the stainless steel 316L was slightly or heavily sensitized. However, since this treatment made mechanical flaws in the outer surface in the case of the heavily sensitized stainless steel, UNSM-treatment may eliminate chromium carbide, and this flaw can be a pitting initiation site, and therefore decrease the pitting corrosion resistance. PMID:28773067

Effect of Ultrasonic Nano-Crystal Surface Modification (UNSM) on the Passivation Behavior of Aged 316L Stainless Steel.

PubMed

Kim, Ki-Tae; Lee, Jung-Hee; Kim, Young-Sik

2017-06-27

Stainless steels have good corrosion resistance in many environments but welding or aging can decrease their resistance. This work focused on the effect of aging time and ultrasonic nano-crystal surface modification on the passivation behavior of 316L stainless steel. In the case of slightly sensitized 316L stainless steel, increasing the aging time drastically decreased the pitting potential, increased the passive current density, and decreased the resistance of the passive film, even though aging did not form chromium carbide and a chromium depletion zone. This behavior is due to the micro-galvanic corrosion between the matrix and carbon segregated area, and this shows the importance of carbon segregation in grain boundaries to the pitting corrosion resistance of stainless steel, in addition to the formation of the chromium depletion zone. UNSM (Ultrasonic Nano Crystal Surface Modification)-treatment to the slightly sensitized 316L stainless steel increased the pitting potential, decreased the passive current density, and increased the resistance of the passive film. However, in the case of heavily sensitized 316L stainless steel, UNSM-treatment decreased the pitting potential, increased the passive current density, and decreased the resistance of the passive film. This behavior is due to the dual effects of the UNSM-treatment. That is, the UNSM-treatment reduced the carbon segregation, regardless of whether the stainless steel 316L was slightly or heavily sensitized. However, since this treatment made mechanical flaws in the outer surface in the case of the heavily sensitized stainless steel, UNSM-treatment may eliminate chromium carbide, and this flaw can be a pitting initiation site, and therefore decrease the pitting corrosion resistance.

Engineering the mobility increment in pentacene-based field-effect transistors by fast cooling of polymeric modification layer

NASA Astrophysics Data System (ADS)

Ling, Haifeng; Zhang, Chenxi; Chen, Yan; Shao, Yaqing; Li, Wen; Li, Huanqun; Chen, Xudong; Yi, Mingdong; Xie, Linghai; Huang, Wei

2017-06-01

In this work, we investigate the effect of the cooling rate of polymeric modification layers (PMLs) on the mobility improvement of pentacene-based organic field-effect transistors (OFETs). In contrast to slow cooling (SC), the OFETs fabricated through fast cooling (FC) with PMLs containing side chain-phenyl rings, such as polystyrene (PS) and poly (4-vinylphenol) (PVP), show an obvious mobility incensement compared with that of π-group free polymethylmethacrylate (PMMA). Atomic force microscopy (AFM) images and x-ray diffraction (XRD) characterizations have showed that fast-cooled PMLs could effectively enhance the crystallinity of pentacene, which might be related to the optimized homogeneity of surface energy on the surface of polymeric dielectrics. Our work has demonstrated that FC treatment could be a potential strategy for performance modulation of OFETs.

Long-term Effect of Biomineralized Insulin Nanoparticles on Type 2 Diabetes Treatment

PubMed Central

Xiao, Yun; Wang, Xiaoyu; Wang, Ben; Liu, Xueyao; Xu, Xurong; Tang, Ruikang

2017-01-01

Intracellular insulin may exhibit a long-term effect in regulating protein synthesis, DNA synthesis, and gene transcription. However, the intracellular delivery of insulin is a great challenge. Here, we describe how a simple biomineralization modification of insulin can transport it into intact cells on a large scale, leading to a long-term therapeutic effect on diabetes mellitus. Using insulin-resistant HepG2 cell and diabetic KKAy mice as models, in vitro and in vivo assessments have demonstrated that biomineralized insulin nanoparticles can trigger glucose metabolism, and this improvement extends after the treatment. The potential exists to improve the current treatment of type 2 diabetes mellitus through biomineralized modifications of insulin. This study provides a new paradigm of biomimetic nanotechnology for biomedical applications. PMID:29158827

Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein modification--an in vitro study.

PubMed

Kurien, Biji T; Scofield, R Hal

2007-03-21

Free radical mediated lipid peroxidation has been implicated in multiple diseases. A major oxidation by-product of this deleterious process is 4-hydroxy-2-nonenal (HNE). HNE is cytotoxic, mutagenic and genotoxic and is involved in disease pathogenesis. Curcumin, a non-steroidal anti-inflammatory agent (occurring as the yellow pigment found in the rhizomes of the perennial herb Curcuma longa known as turmeric), has emerged as the newest "nutraceutical" agent that has been shown to be efficacious against colon cancer and other disorders, including correcting cystic fibrosis defects. Since curcumin has been reported to have anti-oxidant properties we hypothesized that it will inhibit HNE-modification of a protein substrate. Using an ELISA that employed HNE-modification of solid phase antigen following immobilization, we found that the curcumin solubilized in dilute alkali (5mM sodium hydroxide, pH 11) inhibited HNE-protein modification by 65%. Turmeric also inhibited HNE-protein modification similarly (65%) but at a much lower alkali level (130muM sodium hydroxide, pH 7.6). Alkali by itself (5mM sodium hydroxide, pH 11) was found to enhance HNE modification by as much as 267%. Curcumin/turmeric has to inhibit this alkali enhanced HNE-modification prior to inhibiting the normal HNE protein modification induced by HNE. Thus, inhibition of HNE-modification could be a mechanism by which curcumin exerts its antioxidant effects. The pH at which the inhibition of HNE modification of substrate was observed was close to the physiological pH, making this formulation of curcumin potentially useful practically.

Handling Qualities Prediction of an F-16XL-Based Reduced Sonic Boom Aircraft

NASA Technical Reports Server (NTRS)

Cogan, Bruce; Yoo, Seung

2010-01-01

A major goal of the Supersonics Project under NASA s Fundamental Aeronautics program is sonic boom reduction of supersonic aircraft. An important part of this effort is development and validation of sonic boom prediction tools used in aircraft design. NASA Dryden s F- 16XL was selected as a potential testbed aircraft to provide flight validation. Part of this task was predicting the handling qualities of the modified aircraft. Due to the high cost of modifying the existing F-16XL control laws, it was desirable to find modifications that reduced the aircraft sonic boom but did not degrade baseline aircraft handling qualities allowing for the potential of flight test without changing the current control laws. This was not a requirement for the initial modification design work, but an important consideration for proceeding to the flight test option. The primary objective of this work was to determine an aerodynamic and mass properties envelope of the F-16XL aircraft. The designers could use this envelope to determine the effect of proposed modifications on aircraft handling qualities.

Methodologic ramifications of paying attention to sex and gender differences in clinical research.

PubMed

Prins, Martin H; Smits, Kim M; Smits, Luc J

2007-01-01

Methodologic standards for studies on sex and gender differences should be developed to improve reporting of studies and facilitate their inclusion in systematic reviews. The essence of these studies lies within the concept of effect modification. This article reviews important methodologic issues in the design and reporting of pharmacogenetic studies. Differences in effect based on sex or gender should preferably be expressed in absolute terms (risk differences) to facilitate clinical decisions on treatment. Information on the distribution of potential effect modifiers or prognostic factors should be available to prevent a biased comparison of differences in effect between genotypes. Other considerations included the possibility of selective nonavailability of biomaterial and the choice of a statistical model to study effect modification. To ensure high study quality, additional methodologic issues should be taken into account when designing and reporting studies on sex and gender differences.

Improving the quality of aquatic toxicity tests: Lessons learned and proficiency needs

EPA Science Inventory

Aquatic toxicity testing methodologies have been widely used to assess potential adverse effects of chemicals and wastewater discharges on aquatic life in the United States since the 1970’s. Over the years, continued method modifications, increased training, and technical r...

Reversal of the asymmetry in a cylindrical coaxial capacitively coupled Ar/Cl 2 plasma

DOE PAGES

Upadhyay, Janardan; Im, Do; Popović, Svetozar; ...

2015-10-08

The reduction of the asymmetry in the plasma sheath voltages of a cylindrical coaxial capacitively coupled plasma is crucial for efficient surface modification of the inner surfaces of concave three-dimensional structures, including superconducting radio frequency cavities. One critical asymmetry effect is the negative dc self-bias, formed across the inner electrode plasma sheath due to its lower surface area compared to the outer electrode. The effect on the self-bias potential with the surface enhancement by geometric modification on the inner electrode structure is studied. The shapes of the inner electrodes are chosen as cylindrical tube, large and small pitch bellows, andmore » disc-loaded corrugated structure (DLCS). The dc self-bias measurements for all these shapes were taken at different process parameters in Ar/Cl 2 discharge. Lastly, the reversal of the negative dc self-bias potential to become positive for a DLCS inner electrode was observed and the best etch rate is achieved due to the reduction in plasma asymmetry.« less

N-Acetylcysteine treatment of dystrophic mdx mice results in protein thiol modifications and inhibition of exercise induced myofibre necrosis.

PubMed

Terrill, Jessica R; Radley-Crabb, Hannah G; Grounds, Miranda D; Arthur, Peter G

2012-05-01

Oxidative stress is implicated as a factor that increases necrosis of skeletal muscles in Duchenne Muscular Dystrophy (DMD) and the dystrophic mdx mouse. Consequently, drugs that minimize oxidative stress are potential treatments for muscular dystrophy. This study examined the in vivo benefits to mdx mice of an antioxidant treatment with the cysteine precursor N-acetylcysteine (NAC), administered in drinking water. NAC was completely effective in preventing treadmill exercise-induced myofibre necrosis (assessed histologically) and the increased blood creatine kinase levels (a measure of sarcolemma leakiness) following exercise were significantly lower in the NAC treated mice. While NAC had no effect on malondialdehyde level or protein carbonylation (two indicators of irreversible oxidative damage), treatment with NAC for one week significantly decreased the oxidation of glutathione and protein thiols, and enhanced muscle protein thiol content. These data provide in vivo evidence for protective benefits of NAC treatment on dystropathology, potentially via protein thiol modifications. Copyright © 2011 Elsevier B.V. All rights reserved.

Mental Health on the Go: Effects of a Gamified Attention Bias Modification Mobile Application in Trait Anxious Adults

PubMed Central

Dennis, Tracy A.; O’Toole, Laura

2015-01-01

Interest in the use of mobile technology to deliver mental health services has grown in light of the economic and practical barriers to treatment. Yet, research on alternative delivery strategies that are more affordable, accessible, and engaging is in its infancy. Attention bias modification training (ABMT), has potential to reduce treatment barriers as a mobile intervention for stress and anxiety, but the degree to which ABMT can be embedded in a mobile gaming format and its potential for transfer of benefits is unknown. The present study examined effects of a gamified ABMT mobile application in highly trait anxious participants (N = 78). A single session of the active compared to placebo training reduced subjective anxiety and observed stress reactivity. Critically, the long (45 minutes) but not short (25 minutes) active training condition reduced the core cognitive process implicated in ABMT (threat bias) as measured by an untrained, gold-standard protocol. PMID:26029490

Engineered/designer biochar for contaminant removal/immobilization from soil and water: Potential and implication of biochar modification.

PubMed

Rajapaksha, Anushka Upamali; Chen, Season S; Tsang, Daniel C W; Zhang, Ming; Vithanage, Meththika; Mandal, Sanchita; Gao, Bin; Bolan, Nanthi S; Ok, Yong Sik

2016-04-01

The use of biochar has been suggested as a means of remediating contaminated soil and water. The practical applications of conventional biochar for contaminant immobilization and removal however need further improvements. Hence, recent attention has focused on modification of biochar with novel structures and surface properties in order to improve its remediation efficacy and environmental benefits. Engineered/designer biochars are commonly used terms to indicate application-oriented, outcome-based biochar modification or synthesis. In recent years, biochar modifications involving various methods such as, acid treatment, base treatment, amination, surfactant modification, impregnation of mineral sorbents, steam activation and magnetic modification have been widely studied. This review summarizes and evaluates biochar modification methods, corresponding mechanisms, and their benefits for contaminant management in soil and water. Applicability and performance of modification methods depend on the type of contaminants (i.e., inorganic/organic, anionic/cationic, hydrophilic/hydrophobic, polar/non-polar), environmental conditions, remediation goals, and land use purpose. In general, modification to produce engineered/designer biochar is likely to enhance the sorption capacity of biochar and its potential applications for environmental remediation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study.

PubMed

Meng, Xiangfei; Brunet, Alain; Turecki, Gustavo; Liu, Aihua; D'Arcy, Carl; Caron, Jean

2017-06-10

Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study. Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence. The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases. Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Electron-phonon mediated heat flow in disordered graphene

NASA Astrophysics Data System (ADS)

Chen, Wei; Clerk, Aashish A.

2012-09-01

We calculate the heat flux and electron-phonon thermal conductance in a disordered graphene sheet, going beyond a Fermi’s golden rule approach to fully account for the modification of the electron-phonon interaction by disorder. Using the Keldysh technique combined with standard impurity averaging methods in the regime kFl≫1 (where kF is the Fermi wave vector and l is the mean free path), we consider both scalar potential (i.e., deformation potential) and vector-potential couplings between electrons and phonons. We also consider the effects of electronic screening at the Thomas-Fermi level. We find that the temperature dependence of the heat flux and thermal conductance is sensitive to the presence of disorder and screening, and reflects the underlying chiral nature of electrons in graphene and the corresponding modification of their diffusive behavior. In the case of weak screening, disorder enhances the low-temperature heat flux over the clean system (changing the associated power law from T4 to T3), and the deformation potential dominates. For strong screening, both the deformation potential and vector-potential couplings make comparable contributions, and the low-temperature heat flux obeys a T5 power law.

MOSFET Electric-Charge Sensor

NASA Technical Reports Server (NTRS)

Robinson, Paul A., Jr.

1988-01-01

Charged-particle probe compact and consumes little power. Proposed modification enables metal oxide/semiconductor field-effect transistor (MOSFET) to act as detector of static electric charges or energetic charged particles. Thickened gate insulation acts as control structure. During measurements metal gate allowed to "float" to potential of charge accumulated in insulation. Stack of modified MOSFET'S constitutes detector of energetic charged particles. Each gate "floats" to potential induced by charged-particle beam penetrating its layer.

Plasma control by modification of helicon wave propagation in low magnetic fields

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

Lafleur, T.; Charles, C.; Boswell, R. W.

2010-07-15

By making use of nonuniform magnetic fields, it is shown experimentally that control of helicon wave propagation can be achieved in a low pressure (0.08 Pa) expanding plasma. The m=1 helicon waves are formed during a direct capacitive to wave mode transition that occurs in a low diverging magnetic field (B{sub 0}<3 mT). In this initial configuration, waves are prevented from reaching the downstream region, but slight modifications to the magnetic field allows the axial distance over which waves can propagate to be controlled. By changing the effective propagation distance in this way, significant modification of the density and plasmamore » potential profiles can be achieved, showing that the rf power deposition can be spatially controlled as well. Critical to the modification of the wave propagation behavior is the magnetic field strength (and geometry) near the exit of the plasma source region, which gives electron cyclotron frequencies close to the wave frequency of 13.56 MHz.« less

Genetic modification of Anopheles stephensi for resistance to multiple Plasmodium falciparum strains does not influence susceptibility to o'nyong'nyong virus or insecticides, or Wolbachia-mediated resistance to the malaria parasite.

PubMed

Pike, Andrew; Dimopoulos, George

2018-01-01

Mosquitoes that have been genetically engineered for resistance to human pathogens are a potential new tool for controlling vector-borne disease. However, genetic modification may have unintended off-target effects that could affect the mosquitoes' utility for disease control. We measured the resistance of five genetically modified Plasmodium-suppressing Anopheles stephensi lines to o'nyong'nyong virus, four classes of insecticides, and diverse Plasmodium falciparum field isolates and characterized the interactions between our genetic modifications and infection with the bacterium Wolbachia. The genetic modifications did not alter the mosquitoes' resistance to either o'nyong'nyong virus or insecticides, and the mosquitoes were equally resistant to all tested P. falciparum strains, regardless of Wolbachia infection status. These results indicate that mosquitoes can be genetically modified for resistance to malaria parasite infection and remain compatible with other vector-control measures without becoming better vectors for other pathogens.

Atomic states in optical traps near a planar surface

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

Messina, Riccardo; Pelisson, Sophie; Angonin, Marie-Christine

2011-05-15

In this paper, we discuss the atomic states in a vertical optical lattice in proximity of a surface. We study the modifications to the ordinary Wannier-Stark states in the presence of a surface, and we characterize the energy shifts produced by the Casimir-Polder interaction between atom and mirror. In this context, we introduce an effective model describing the finite size of the atom in order to regularize the energy corrections. In addition, the modifications to the energy levels due to a hypothetical non-Newtonian gravitational potential as well as their experimental observability are investigated.

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.

Recent Development of Plasmonic Resonance-Based Photocatalysis and Photovoltaics for Solar Utilization.

PubMed

Fan, Wenguang; Leung, Michael K H

2016-02-02

Increasing utilization of solar energy is an effective strategy to tackle our energy and energy-related environmental issues. Both solar photocatalysis (PC) and solar photovoltaics (PV) have high potential to develop technologies of many practical applications. Substantial research efforts are devoted to enhancing visible light activation of the photoelectrocatalytic reactions by various modifications of nanostructured semiconductors. This review paper emphasizes the recent advancement in material modifications by means of the promising localized surface plasmonic resonance (LSPR) mechanisms. The principles of LSPR and its effects on the photonic efficiency of PV and PC are discussed here. Many research findings reveal the promise of Au and Ag plasmonic nanoparticles (NPs). Continual investigation for increasing the stability of the plasmonic NPs will be fruitful.

Potential sensitivity of warm season precipitation to urbanization extents: Modeling study in Beijing-Tianjin-Hebei urban agglomeration in China

NASA Astrophysics Data System (ADS)

Wang, Jun; Feng, Jinming; Yan, Zhongwei

2015-09-01

In this study, we investigated how different degrees of urbanization affect local and regional rainfall using high-resolution simulations based on the Weather Research and Forecasting Model. The extreme rainfall event of 21 July 2012 in Beijing was simulated for three representative urban land use distributions (no urbanization, early urbanization level of 1980, and recent urbanization level of 2009). Results suggest that urban modification of rainfall is potentially sensitive to urban land use condition. Rainfall was increased significantly over the downwind Beijing metropolis because of the effects of early urbanization; however, recent conditions of high urban development caused no significant increase. Further comparative analysis revealed that positive urban thermodynamical effects (i.e., urban warming, increased sensible heat transportation, and enhanced convergence and vertical motions) play major roles in urban modification of rainfall during the early urbanization stage. However, after cities expand to a certain extent (i.e., urban agglomeration), the regional moisture depression induced by the prevalence of impervious urban land has an effect on atmospheric instability energy, which might negate the city's positive impact on regional rainfall. Additional results from regional climate simulations for 10 Julys confirm this supposition. Given the explosive urban population growth and increasing demand for freshwater in cities, the potential negative effects of the urban environment on precipitation are worth investigation, particularly in rapidly developing countries and regions.

Modification of trout sperm membranes associated with activation and cryopreservation. Implications for fertilizing potential

USDA-ARS?s Scientific Manuscript database

Abstract We investigated the effects of two trout sperm activation solutions on sperm physiology and membrane organization prior to and following cryopreservation using flow cytometry and investigated their impact on in vitro fertility. Cryopreservation caused greater phospholipid disorder (high pl...

BIRTH DEFECTS RISK ASSOCIATED WITH MATERNAL SPORT FISH CONSUMPTION: POTENTIAL EFFECT MODIFICATION BY SEX OF OFFSPRING

EPA Science Inventory

Contaminated sport fish consumption may result in exposure to various reproductive and developmental toxicants, including pesticides and other suspected endocrine disruptors. We investigated the relation between maternal sport fish meals and risk of major birth defects among infa...

Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

PubMed

Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

2017-04-01

Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Prerequisites for understanding climate-change impacts on northern prairie wetlands

USGS Publications Warehouse

Anteau, Michael J.; Wiltermuth, Mark T.; Post van der Burg, Max; Pearse, Aaron T.

2016-01-01

The Prairie Pothole Region (PPR) contains ecosystems that are typified by an extensive matrix of grasslands and depressional wetlands, which provide numerous ecosystem services. Over the past 150 years the PPR has experienced numerous landscape modifications resulting in agricultural conversion of 75–99 % of native prairie uplands and drainage of 50–90 % of wetlands. There is concern over how and where conservation dollars should be spent within the PPR to protect and restore wetland basins to support waterbird populations that will be robust to a changing climate. However, while hydrological impacts of landscape modifications appear substantial, they are still poorly understood. Previous modeling efforts addressing impacts of climate change on PPR wetlands have yet to fully incorporate interacting or potentially overshadowing impacts of landscape modification. We outlined several information needs for building more informative models to predict climate change effects on PPR wetlands. We reviewed how landscape modification influences wetland hydrology and present a conceptual model to describe how modified wetlands might respond to climate variability. We note that current climate projections do not incorporate cyclical variability in climate between wet and dry periods even though such dynamics have shaped the hydrology and ecology of PPR wetlands. We conclude that there are at least three prerequisite steps to making meaningful predictions about effects of climate change on PPR wetlands. Those evident to us are: 1) an understanding of how physical and watershed characteristics of wetland basins of similar hydroperiods vary across temperature and moisture gradients; 2) a mechanistic understanding of how wetlands respond to climate across a gradient of anthropogenic modifications; and 3) improved climate projections for the PPR that can meaningfully represent potential changes in climate variability including intensity and duration of wet and dry periods. Once these issues are addressed, we contend that modeling efforts will better inform and quantify ecosystem services provided by wetlands to meet needs of waterbird conservation and broader societal interests such as flood control and water quality.

Cost-effectiveness of a complex workplace dietary intervention: an economic evaluation of the Food Choice at Work study

PubMed Central

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

2018-01-01

Objective To evaluate the costs, benefits and cost-effectiveness of complex workplace dietary interventions, involving nutrition education and system-level dietary modification, from the perspective of healthcare providers and employers. Design Single-study economic evaluation of a cluster-controlled trial (Food Choice at Work (FCW) study) with 1-year follow-up. Setting Four multinational manufacturing workplaces in Cork, Ireland. Participants 517 randomly selected employees (18–65 years) from four workplaces. Interventions Cost data were obtained from the FCW study. Nutrition education included individual nutrition consultations, nutrition information (traffic light menu labelling, posters, leaflets and emails) and presentations. System-level dietary modification included menu modification (restriction of fat, sugar and salt), increase in fibre, fruit discounts, strategic positioning of healthier alternatives and portion size control. The combined intervention included nutrition education and system-level dietary modification. No intervention was implemented in the control. Outcomes The primary outcome was an improvement in health-related quality of life, measured using the EuroQoL 5 Dimensions 5 Levels questionnaire. The secondary outcome measure was reduction in absenteeism, which is measured in monetary amounts. Probabilistic sensitivity analysis (Monte Carlo simulation) assessed parameter uncertainty. Results The system-level intervention dominated the education and combined interventions. When compared with the control, the incremental cost-effectiveness ratio (€101.37/quality-adjusted life-year) is less than the nationally accepted ceiling ratio, so the system-level intervention can be considered cost-effective. The cost-effectiveness acceptability curve indicates there is some decision uncertainty surrounding this, arising from uncertainty surrounding the differences in effectiveness. These results are reiterated when the secondary outcome measure is considered in a cost–benefit analysis, whereby the system-level intervention yields the highest net benefit (€56.56 per employee). Conclusions System-level dietary modification alone offers the most value per improving employee health-related quality of life and generating net benefit for employers by reducing absenteeism. While system-level dietary modification strategies are potentially sustainable obesity prevention interventions, future research should include long-term outcomes to determine if improvements in outcomes persist. Trial registration number ISRCTN35108237; Post-results. PMID:29502090

Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.

PubMed

Jhun, Min A; Hu, Howard; Schwartz, Joel; Weisskopf, Marc G; Nie, Linda H; Sparrow, David; Vokonas, Pantel S; Park, Sung Kyun

2015-01-13

Although the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness. We examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements. Adjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 μg/g) and patella lead (20 μg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1. This study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.

An entropy and viscosity corrected potential method for rotor performance prediction

NASA Technical Reports Server (NTRS)

Bridgeman, John O.; Strawn, Roger C.; Caradonna, Francis X.

1988-01-01

An unsteady Full-Potential Rotor code (FPR) has been enhanced with modifications directed at improving its drag prediction capability. The shock generated entropy has been included to provide solutions comparable to the Euler equations. A weakly interacted integral boundary layer has also been coupled to FPR in order to estimate skin-friction drag. Pressure distributions, shock positions, and drag comparisons are made with various data sets derived from two-dimensional airfoil, hovering, and advancing high speed rotor tests. In all these comparisons, the effect of the nonisentropic modification improves (i.e., weakens) the shock strength and wave drag. In addition, the boundary layer method yields reasonable estimates of skin-friction drag. Airfoil drag and hover torque data comparisons are excellent, as are predicted shock strength and positions for a high speed advancing rotor.

A fluid description of plasma double-layers

NASA Technical Reports Server (NTRS)

Levine, J. S.; Crawford, F. W.

1979-01-01

The space-charge double-layer that forms between two plasmas with different densities and thermal energies was investigated using three progressively realistic models which are treated by fluid theory, and take into account four species of particles: electrons and ions reflected by the double-layer, and electrons and ions transmitted through it. The two plasmas are assumed to be cold, and the self-consistent potential, electric field and space-charge distributions within the double-layer are determined. The effects of thermal velocities are taken into account for the reflected particles, and the modifications to the cold plasma solutions are established. Further modifications due to thermal velocities of the transmitted particles are examined. The applicability of a one dimensional fluid description, rather than plasma kinetic theory, is discussed. Theoretical predictions are compared with double layer potentials and lengths deduced from laboratory and space plasma experiments.

Chemical modification of L-asparaginase from Cladosporium sp. for improved activity and thermal stability.

PubMed

Mohan Kumar, N S; Kishore, Vijay; Manonmani, H K

2014-01-01

L-Asparaginase (ASNase), an antileukemia enzyme, is facing problems with antigenicity in the blood. Modification of L-asparaginase from Cladosporium sp. was tried to obtain improved stability and improved functionality. In our experiment, modification of the enzyme was tried with bovine serum albumin, ovalbumin by crosslinking using glutaraldehyde, N-bromosuccinimide, and mono-methoxy polyethylene glycol. Modified enzymes were studied for activity, temperature stability, rate constants (kd), and protection to proteolytic digestion. Modification with ovalbumin resulted in improved enzyme activity that was 10-fold higher compared to native enzyme, while modification with bovine serum albumin through glutaraldehyde cross-linking resulted in high stability of L-asparaginase that was 8.5- and 7.62-fold more compared to native enzyme at 28°C and 37°C by the end of 24 hr. These effects were dependent on the quantity of conjugate formed. Modification also markedly prolonged L-asparaginase half-life and serum stability. N-Bromosuccinimide-modified ASNase presented greater stability with prolonged in vitro half-life of 144 hr to proteolytic digestion relative to unmodified enzyme (93 h). The present work could be seen as producing a modified L-asparaginase with improved activity and stability and can be a potential source for developing therapeutic agents for cancer treatment.

A systematic review of recommended modifications of CBT for people with cognitive impairments following brain injury.

PubMed

Gallagher, Melanie; McLeod, Hamish J; McMillan, Thomas M

2016-11-22

Due to diverse cognitive, emotional and interpersonal changes that can follow brain injury, psychological therapies often need to be adapted to suit the complex needs of this population. The aims of the study were to synthesise published recommendations for therapy modifications following brain injury from non-progressive traumatic, vascular, or metabolic causes and to determine how often such modifications have been applied to cognitive behavioural therapy (CBT) for post-injury emotional adjustment problems. A systematic review and narrative synthesis of therapy modifications recommended in review articles and reported in intervention studies was undertaken. Database and manual searches identified 688 unique papers of which eight review articles and 16 intervention studies met inclusion criteria. The review articles were thematically analysed and a checklist of commonly recommended modifications composed. The checklist items clustered under themes of: therapeutic education and formulation; attention; communication; memory; and executive functioning. When this checklist was applied to the intervention studies, memory aids and an emphasis on socialising patients to the CBT model were most frequently reported as adaptations. It was concluded that the inconsistent reporting of psychological therapy adaptations for people with brain injury is a barrier to developing effective and replicable therapies. We present a comprehensive account of potential modifications that should be used to guide future research and practice.

Biocrusts in the context of global change

USGS Publications Warehouse

Reed, Sasha C.; Maestre, Fernando T.; Ochoa-Hueso, Raul; Kuske, Cheryl; Darrouzet-Nardi, Anthony N.; Darby, Brian; Sinsabaugh, Bob; Oliver, Mel; Sancho, Leo; Belnap, Jayne

2016-01-01

A wide range of studies show global environmental change will profoundly affect the structure, function, and dynamics of terrestrial ecosystems. The research synthesized here underscores that biocrust communities are also likely to respond significantly to global change drivers, with a large potential for modification to their abundance, composition, and function. We examine how elevated atmospheric CO2 concentrations, climate change (increased temperature and altered precipitation), and nitrogen deposition affect biocrusts and the ecosystems they inhabit. We integrate experimental and observational data, as well as physiological, community ecology, and biogeochemical perspectives. Taken together, these data highlight the potential for biocrust organisms to respond dramatically to environmental change and show how changes to biocrust community composition translate into effects on ecosystem function (e.g., carbon and nutrient cycling, soil stability, energy balance). Due to the importance of biocrusts in regulating dryland ecosystem processes and the potential for large modifications to biocrust communities, an improved understanding and predictive capacity regarding biocrust responses to environmental change are of scientific and societal relevance.

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

PubMed

Tsuchiya, Naho; Pathipvanich, Panita; Wichukchinda, Nuanjun; Rojanawiwat, Archawin; Auwanit, Wattana; Ariyoshi, Koya; Sawanpanyalert, Pathom

2014-10-30

Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand. All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models. Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification. HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia.

Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

NASA Astrophysics Data System (ADS)

Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

2008-11-01

The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic material of a new prosthesis generation, more extended tests and experiments are necessary.

The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment.

PubMed

Basse, Clémence; Arock, Michel

2015-12-15

Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore, epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then expose the future role that control of epigenetic modifications might play in prevention, prognostication, follow-up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi-drugs might have an increasing potential of development in the next future. However, if DNA methyltransferase inhibitors and histone desacetylase inhibitors have shown encouraging results in BC, their action remains nonspecific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in cotreatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi-drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of isothiocyanates from cruciferous vegetables or of Genistein from soybean in a dietary program that might potentially reduce the risk of BC in large populations. © 2014 UICC.

Studies of satellite support to weather modification in the western US region

NASA Technical Reports Server (NTRS)

Cotton, W. R.; Grant, L. O.; Vonderhaar, T. H.

1978-01-01

The applications of meteorological satellite data to both summer and winter weather modification programs are addressed. Appraisals of the capability of satellites to assess seedability, to provide real-time operational support, and to assist in the post-experiment analysis of a seeding experiment led to the incorporation of satellite observing systems as a major component in the Bureau of Reclamations weather modification activities. Satellite observations are an integral part of the South Park Area cumulus experiment (SPACE) which aims to formulate a quantitative hypothesis for enhancing precipitation from orographically induced summertime mesoscale convective systems (orogenic mesoscale systems). Progress is reported in using satellite observations to assist in classifying the important mesoscale systems, and in defining their frequency and coverage, and potential area of effect. Satellite studies of severe storms are also covered.

Potential Safety Effects of Lane Width and Shoulder Width on Two-Lane Rural State Highways in Idaho

DOT National Transportation Integrated Search

2012-07-01

This study provides a comprehensive evaluation of the relationship between crash rates and shoulder width and lane width for two-lane rural state highways in Idaho. Crash Modification Factors (CMFs) for shoulder width and lane width were developed us...

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. I. Multimode effect on early membrane events.

PubMed

Rocher, Françoise; Dédaldéchamp, Fabienne; Saeedi, Saed; Fleurat-Lessard, Pierrette; Chollet, Jean-Francois; Roblin, Gabriel

2014-11-01

A study of the structure-activity relationship carried out on several benzoic acid-related phenolics indicates that this type of compounds hinders the osmocontractile reaction of pulvinar cells in the range of 0-100%. Tentatively, we tried to find a way that could explain this differential action. With this aim, the relationship between the inhibitory effect and important molecular physico-chemical parameters (namely lipophilicity and degree of dissociation) was drawn. In addition, the effect of a variety of these compounds was investigated on their capacity to modify the electrical transmembrane potential and induce modifications in proton fluxes. Finally, using plasma membrane vesicles purified from pulvinar tissues, we examined the effects of some selected compounds on the proton pump activity and catalytic activity of the plasma membrane H(+)-ATPase. Taken together, the results indicate that a modification of the molecular structure of phenolics may induce important variation in the activity of the compound on these early membrane events. Among the tested phenolics, salicylic acid (SA) and acetylsalicylic acid (ASA, aspirin) are of particuler note, as they showed atypical effects on the physiological processes studied. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Detecting the impact of bank and channel modification on invertebrate communities in Mediterranean temporary streams (Sardinia, SW Italy).

PubMed

Buffagni, Andrea; Tenchini, Roberta; Cazzola, Marcello; Erba, Stefania; Balestrini, Raffaella; Belfiore, Carlo; Pagnotta, Romano

2016-09-15

We hypothesized that reach-scale, bank and channel modification would impact benthic communities in temporary rivers of Sardinia, when pollution and water abstraction are not relevant. A range of variables were considered, which include both artificial structures/alterations and natural features observed in a stream reach. Multivariate regression trees (MRT) were used to assess the effects of the explanatory variables on invertebrate assemblages and five groups, characterized by different habitat modification and/or features, were recognized. Four node variables determined the splits in the MRT analysis: channel reinforcement, tree-related bank and channel habitats, channel modification and bank modification. Continuity of trees in the river corridor diverged among MRT groups and significant differences among groups include presence of alders, extent of channel shading and substrate diversity. Also, the percentage of in-stream organic substrates, in particular CPOM/Xylal, showed highly significant differences among groups. For practical applications, thresholds for the extent of channel reinforcement (40%) and modification (10%) and for bank alteration (≈30%) were provided, that can be used to guide the implementation of restoration measures. In moderately altered river reaches, a significant extent of tree-related habitats (≈5%) can noticeably mitigate the effects of morphological alteration on aquatic invertebrates. The outcomes highlight the importance of riparian zone management as an opportune, achievable prospect in the restoration of Mediterranean temporary streams. The impact of bank and channel modification on ecological status (sensu WFD) was investigated and the tested benthic metrics, especially those based on abundance data, showed legible differences among MRT groups. Finally, bank and channel modification appears to be a potential threat for the conservation of a few Sardo-Corsican endemic species. The introduction of management criteria that openly use information on endemic species seems crucial to reduce the risk of improving overall ecological status while depleting biodiversity. Copyright © 2016 Elsevier B.V. All rights reserved.

Making Better Scar: Emerging Approaches for Modifying Mechanical and Electrical Properties Following Infarction and Ablation

PubMed Central

Holmes, Jeffrey W.; Laksman, Zachary; Gepstein, Lior

2015-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function – maintaining integrity of the heart wall against enormous mechanical forces – but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. PMID:26615948

Solution of the Quantum Harmonic Oscillator Plus a Delta-Function Potential at the Origin: The "Oddness" of Its Even-Parity Solutions

ERIC Educational Resources Information Center

Viana-Gomes, J.; Peres, N. M. R.

2011-01-01

We derive the energy levels associated with the even-parity wavefunctions of the harmonic oscillator with an additional delta-function potential at the origin. Our results bring to the attention of students a non-trivial and analytical example of a modification of the usual harmonic oscillator potential, with emphasis on the modification of the…

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.

Alcohol consumption and the risk of type 2 diabetes mellitus: effect modification by hypercholesterolemia: the Third Korea National Health and Nutrition Examination Survey (2005).

PubMed

Jang, Hyeongap; Jang, Won-Mo; Park, Jong-Heon; Oh, Juhwan; Oh, Mu-Kyung; Hwang, Soo-Hee; Kim, Yong-Ik; Lee, Jin-Seok

2012-01-01

While the protective nature of moderate alcohol consumption against diabetes mellitus is well known, inconsistent findings continue to be reported. The possibility of different mixes of effect modifiers has been raised as a reason for those inconsistent findings. Our study aim was to examine potential effect modifiers that can change the effect of alcohol consumption on type 2 diabetes. From data in the third Korea National Health and Nutrition Examination Survey, 3,982 individuals over the age of 30 years who had not been diagnosed with diabetes were selected for inclusion in the study population. Breslow and Day's test and the Wald test between hypercholesterolemia and alcohol consumption in a multiple logistic regression model were used to assess effect modification. Odds ratios for diabetes stratified by alcohol consumption strata and assessed using Breslow and Day's tests for homogeneity indicated that hypercholesterolemia was not a significant confounding factor (p=0.01). However, the Wald test for interaction terms, which is a conservative method of effect modification, was significant (p=0.03). The results indicate that moderate alcohol consumption is not necessarily protective for type 2 diabetes mellitus, if a person has hypercholesterolemia. People who have hypercholesterolemia should be aware of the risk associated with alcohol consumption, a risk that contrasts with the reported protective effect of moderate alcohol consumption on diabetes.

Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

PubMed

Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

2017-10-01

Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Adsorptive Removal of Metal Ions from Water using Functionalized Biomaterials.

PubMed

Deshpande, Kanchanmala

2017-01-01

Synthesis and modification of cost-effective sorbents for removing heavy metals from water resources is an area of significance. It had been reported that materials with biological origins, such as agricultural and animal waste, are excellent alternatives to conventional adsorbents due to their higher affinity, capacity and selectivity towards metal ions. These properties of biomaterials help to reduce or detoxify metal ions concentration in contaminated water to acceptable regulatory standards. Synthesis of novel, efficient, cost effective, eco-friendly biomaterials for heavy metal adsorption from water is still an area of challenge. In this comprehensive review, acompilation of patents as well as published articles is carried out to outline the properties of different biomaterials based on their precursors along withdetailed description of biomaterial morphology and various surface modification approaches. A detailed study of the performance of adsorbents and the role of physical and chemical modification in terms of enhancing their potential for metal adsorption from water is compiled here. The factors affecting adsorption behavior i.e., capacity and affinity of e biomaterials is also compiled. This paper presents a concise review of reported studies on the synthesis and modification of biomaterials, their use for heavy metal removal from waters and future prospects of this technology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Is Graphene a Promising Nano-Material for Promoting Surface Modification of Implants or Scaffold Materials in Bone Tissue Engineering?

PubMed Central

Gu, Ming; Liu, Yunsong; Chen, Tong; Du, Feng; Zhao, Xianghui; Xiong, Chunyang

2014-01-01

Bone tissue engineering promises to restore bone defects that are caused by severe trauma, congenital malformations, tumors, and nonunion fractures. How to effectively promote the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field. Many researchers are studying the ways of conferring a pro-osteodifferentiation or osteoinductive capability on implants or scaffold materials, where osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of coating material that may confer the pro-osteodifferentiation capability on implants and scaffold materials by surface modification. Here, we review recent studies on the effects of graphene on surface modifications of implants or scaffold materials. The ability of graphene to improve the mechanical and biological properties of implants or scaffold materials, such as nitinol and carbon nanotubes, and its ability to promote the adhesion, proliferation, and osteogenic differentiation of MSCs or osteoblasts have been demonstrated in several studies. Most previous studies were performed in vitro, but further studies will explore the mechanisms of graphene's effects on bone regeneration, its in vivo biocompatibility, its ability to promote osteodifferentiation, and its potential applications in bone tissue engineering. PMID:24447041

Is graphene a promising nano-material for promoting surface modification of implants or scaffold materials in bone tissue engineering?

PubMed

Gu, Ming; Liu, Yunsong; Chen, Tong; Du, Feng; Zhao, Xianghui; Xiong, Chunyang; Zhou, Yongsheng

2014-10-01

Bone tissue engineering promises to restore bone defects that are caused by severe trauma, congenital malformations, tumors, and nonunion fractures. How to effectively promote the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field. Many researchers are studying the ways of conferring a pro-osteodifferentiation or osteoinductive capability on implants or scaffold materials, where osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of coating material that may confer the pro-osteodifferentiation capability on implants and scaffold materials by surface modification. Here, we review recent studies on the effects of graphene on surface modifications of implants or scaffold materials. The ability of graphene to improve the mechanical and biological properties of implants or scaffold materials, such as nitinol and carbon nanotubes, and its ability to promote the adhesion, proliferation, and osteogenic differentiation of MSCs or osteoblasts have been demonstrated in several studies. Most previous studies were performed in vitro, but further studies will explore the mechanisms of graphene's effects on bone regeneration, its in vivo biocompatibility, its ability to promote osteodifferentiation, and its potential applications in bone tissue engineering.

Targeting aging for disease modification in osteoarthritis.

PubMed

Collins, John A; Diekman, Brian O; Loeser, Richard F

2018-01-01

Age is a key risk factor for the development of osteoarthritis and age-related changes within the joint might represent targets for therapy. The recent literature was reviewed to find studies that provide new insight into the role of aging in osteoarthritis, with a focus on the potential for disease modification. Preclinical studies using isolated cells and animal models provide evidence that two hallmarks of aging (cellular senescence and mitochondrial dysfunction) contribute to the development of osteoarthritis. Senescent cells secrete pro-inflammatory mediators and matrix degrading enzymes, and killing these cells with 'senolytic' compounds has emerged as a potential disease-modifying therapy. Mitochondrial dysfunction is associated with increased levels of reactive oxygen species (ROS) that can promote osteoarthritis by disrupting homeostatic intracellular signaling. Reducing ROS production in the mitochondria, stimulating antioxidant gene expression through Nrf2 activation, or inhibiting specific redox-sensitive signaling proteins represent additional approaches to disease modification in osteoarthritis that require further investigation. Although no human clinical trials for osteoarthritis have specifically targeted aging, preclinical studies suggest that targeting cellular senescence and/or mitochondrial dysfunction and the effects of excessive ROS may lead to novel interventions that could slow the progression of osteoarthritis.

Lysine Methylation of Nuclear Co-repressor Receptor Interacting Protein 140

PubMed Central

Huq, MD Mostaqul; Ha, Sung Gil; Barcelona, Helene; Wei, Li-Na

2009-01-01

Receptor interacting protein 140 (RIP140) undergoes extensive posttranslational modifications (PTMs), including phosphorylation, acetylation, arginine methylation, and pyridoxylation. PTMs affect its sub-cellular distribution, protein-protein interaction, and biological activity in adipocyte differentiation. Arginine methylation on Arg240, Arg650, and Arg948 suppresses the repressive activity of RIP140. Here we find that endogenous RIP140 in differentiated 3T3-L1 cells is also modified by lysine methylation. Three lysine residues, Lys591, Lys653, and Lys757 are mapped as potential methylation sites by mass spectrometry. Site-directed mutagenesis study shows that lysine methylation enhances its gene repressive activity. Mutation of lysine methylation sites enhances arginine methylation, while mutation on arginine methylation sites has little effect on its lysine methylation, suggesting a relationship between lysine methylation and arginine methylation. Kinetic analysis of PTMs of endogenous RIP140 in differentiated 3T3-L1 cells demonstrates sequential modifications on RIP140, initiated from constitutive lysine methylation, followed by increased arginine methylation later in differentiation. This study reveals a potential hierarchy of modifications, at least for lysine and arginine methylation, which bi-directionally regulate the functionality of a non-histone protein. PMID:19216533

Bacterial attachment to RO membranes surface-modified by concentration-polarization-enhanced graft polymerization.

PubMed

Bernstein, Roy; Belfer, Sofia; Freger, Viatcheslav

2011-07-15

Concentration polarization-enhanced radical graft polymerization, a facile surface modification technique, was examined as an approach to reduce bacterial deposition onto RO membranes and thus contribute to mitigation of biofouling. For this purpose an RO membrane ESPA-1 was surface-grafted with a zwitterionic and negatively and positively charged monomers. The low monomer concentrations and low degrees of grafting employed in modifications moderately reduced flux (by 20-40%) and did not affect salt rejection, yet produced substantial changes in surface chemistry, charge and hydrophilicity. The propensity to bacterial attachment of original and modified membranes was assessed using bacterial deposition tests carried out in a parallel plate flow setup using a fluorescent strain of Pseudomonas fluorescens. Compared to unmodified ESPA-1 the deposition (mass transfer) coefficient was significantly increased for modification with the positively charged monomer. On the other hand, a substantial reduction in bacterial deposition rates was observed for membranes modified with zwitterionic monomer and, still more, with very hydrophilic negatively charged monomers. This trend is well explained by the effects of surface charge (as measured by ζ-potential) and hydrophilicity (contact angle). It also well correlated with force distance measurements by AFM using surrogate spherical probes with a negative surface charge mimicking the bacterial surface. The positively charged surface showed a strong hysteresis with a large adhesion force, which was weaker for unmodified ESPA-1 and still weaker for zwitterionic surface, while negatively charged surface showed a long-range repulsion and negligible hysteresis. These results demonstrate the potential of using the proposed surface- modification approach for varying surface characteristics, charge and hydrophilicity, and thus minimizing bacterial deposition and potentially reducing propensity biofouling.

The Laughlin liquid in an external potential

NASA Astrophysics Data System (ADS)

Rougerie, Nicolas; Yngvason, Jakob

2018-04-01

We study natural perturbations of the Laughlin state arising from the effects of trapping and disorder. These are N-particle wave functions that have the form of a product of Laughlin states and analytic functions of the N variables. We derive an upper bound to the ground state energy in a confining external potential, matching exactly a recently derived lower bound in the large N limit. Irrespective of the shape of the confining potential, this sharp upper bound can be achieved through a modification of the Laughlin function by suitably arranged quasi-holes.

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...

Medication for Behavior Modification in Birds.

PubMed

van Zeeland, Yvonne

2018-01-01

The use of behavior modifying drugs may be considered in birds with behavior problems, especially those refractory to behavior modification therapy and environmental management. To accomplish behavior change, a variety of drugs can be used, including psychoactive drugs, hormones, antihistamines, analgesics, and anticonvulsants. Because their prescription to birds is off-label, these drugs are considered appropriate only when a sound rationale can be provided for their use. This requires a (correct) behavioral diagnosis to be established. In addition, regular monitoring and follow-up are warranted to determine the efficacy of the treatment and evaluate the occurrence of potential adverse side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Particle creation and reheating in a braneworld inflationary scenario

NASA Astrophysics Data System (ADS)

Bilić, Neven; Domazet, Silvije; Djordjevic, Goran S.

2017-10-01

We study the cosmological particle creation in the tachyon inflation based on the D-brane dynamics in the Randall-Sundrum (RSII) model extended to include matter in the bulk. The presence of matter modifies the warp factor which results in two effects: a modification of the RSII cosmology and a modification of the tachyon potential. Besides, a string theory D-brane supports among other fields a U(1) gauge field reflecting open strings attached to the brane. We demonstrate how the interaction of the tachyon with the U(1) gauge field drives cosmological creation of massless particles and estimate the resulting reheating at the end of inflation.

Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

PubMed Central

Ong, Thomas Prates; Moreno, Fernando Salvador; Ross, Sharon Ann

2012-01-01

Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated. PMID:22353664

Inclusion of methoxy groups inverts the thermodynamic stabilities of DNA-RNA hybrid duplexes: A molecular dynamics simulation study.

PubMed

Suresh, Gorle; Priyakumar, U Deva

2015-09-01

Modified nucleic acids have found profound applications in nucleic acid based technologies such as antisense and antiviral therapies. Previous studies on chemically modified nucleic acids have suggested that modifications incorporated in furanose sugar especially at 2'-position attribute special properties to nucleic acids when compared to other modifications. 2'-O-methyl modification to deoxyribose sugars of DNA-RNA hybrids is one such modification that increases nucleic acid stability and has become an attractive class of compounds for potential antisense applications. It has been reported that modification of DNA strands with 2'-O-methyl group reverses the thermodynamic stability of DNA-RNA hybrid duplexes. Molecular dynamics simulations have been performed on two hybrid duplexes (DR and RD) which differ from each other and 2'-O-methyl modified counterparts to investigate the effect of 2'-O-methyl modification on their duplex stability. The results obtained suggest that the modification drives the conformations of both the hybrid duplexes towards A-RNA like conformation. The modified hybrid duplexes exhibit significantly contrasting dynamics and hydration patterns compared to respective parent duplexes. In line with the experimental results, the relative binding free energies suggest that the introduced modifications stabilize the less stable DR hybrid, but destabilize the more stable RD duplex. Binding free energy calculations suggest that the increased hydrophobicity is primarily responsible for the reversal of thermodynamic stability of hybrid duplexes. Free energy component analysis further provides insights into the stability of modified duplexes. Copyright © 2015 Elsevier Inc. All rights reserved.

INVESTIGATION OF THE MUTAGENIC POTENTIAL OF EMISSIONS FROM ASPHALT FORMULATIONS WITH AND WITHOUT CRUMB-RUBBER MODIFICATION

EPA Science Inventory

INVESTIGATION OF THE MUTAGENIC POTENTIAL OF EMISSIONS FROM ASPHALT FORMULATIONS WITH AND WITHOUT CRUMB-RUBBER MODIFICATION

Larry D. Olsen', Virginia S. Houk2, Sarah H. Warren2, Larry D. Claxton2, Kevin W. Hanley', Aubrey K. Miller3, Gregory A Burr', Daniel Almaguer', Grego...

NASA Lewis Stirling SPRE testing and analysis with reduced number of cooler tubes

NASA Technical Reports Server (NTRS)

Wong, Wayne A.; Cairelli, James E.; Swec, Diane M.; Doeberling, Thomas J.; Lakatos, Thomas F.; Madi, Frank J.

1992-01-01

Free-piston Stirling power converters are candidates for high capacity space power applications. The Space Power Research Engine (SPRE), a free-piston Stirling engine coupled with a linear alternator, is being tested at the NASA Lewis Research Center in support of the Civil Space Technology Initiative. The SPRE is used as a test bed for evaluating converter modifications which have the potential to improve the converter performance and for validating computer code predictions. Reducing the number of cooler tubes on the SPRE has been identified as a modification with the potential to significantly improve power and efficiency. Experimental tests designed to investigate the effects of reducing the number of cooler tubes on converter power, efficiency and dynamics are described. Presented are test results from the converter operating with a reduced number of cooler tubes and comparisons between this data and both baseline test data and computer code predictions.

Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-only, ADHD and conduct problems, and controls

PubMed Central

Helseth, Sarah A.; Waschbusch, Daniel A.; Gnagy, Elizabeth M.; Onyango, Adia N.; Burrows-MacLean, Lisa; Fabiano, Gregory A.; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Wymbs, Frances A.; Garefino, Allison; Massetti, Greta M.; Mazzant, Jessica Robb; Hoffman, Martin T.; Waxmonsky, James G.; Nichols-Lopez, Kristin; Pelham, William E.

2015-01-01

Objective This study compared the unique and combined effects of evidence-based treatments for ADHD —stimulant medication and behavior modification—on children’s rates of reinforcement for deviant peer behavior (RDPB). Method Using a within-subjects design, 222 elementary school-age children attending a summer treatment program, including 151 children with ADHD (127 male), with and without comorbid conduct problems, and 71 control children (57 male), received varying combinations of behavior modification (no, low-intensity, and high-intensity) and methylphenidate (placebo, 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg). RDPB was measured through direct observation and compared across all behavior modification and medication conditions. Results Children with ADHD reinforced the deviant behavior of their peers at a significantly higher rate than control children in the absence of either intervention. However, that difference largely disappeared in the presence of both behavior modification and medication. Both low and high-intensity behavior modification, as well as medium (0.30 mg/kg) and high (0.60 mg/kg) doses of methylphenidate, significantly reduced the rate of ADHD children’s RDPB to levels similar to the control group. Conclusions Results indicate that although untreated children with ADHD do engage in RDPB at a greater rate than their non-ADHD peers, existing evidence-based interventions can substantially decrease the presence of RDPB, thereby limiting potential iatrogenic effects in group-based treatment settings. Public Health Significance Statement This study found that children with behavior disorders reinforced their peers' deviant behaviors much more than typically developing children. However, behavior modification and medication treatments both reduced reinforcement rates, indicating that peer contagion can easily be managed in group-based treatments for children PMID:25495357

Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus.

PubMed

Rezaei-Ghaleh, Nasrollah; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

2016-07-29

Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-β (Aβ) peptide and investigate how phosphorylation at serine 8 affects the structure of Aβ aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Aβ, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Aβ phosphorylation at serine 8 causes structural changes in the N-terminal region of Aβ aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Aβ aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Barrier modification in sub-barrier fusion reaction 64Ni+100Mo using Wong formula with Skyrme forces in semiclassical formalism

NASA Astrophysics Data System (ADS)

Kumar, Raj; Gupta, Raj K.

2011-09-01

We obtain the nuclear proximity potential by using semiclassical extended Thomas Fermi (ETF) approach in Skyrme energy density formalism (SEDF), and use it in the extended l-summed Wong formula under frozen density approximation. This method has the advantage of allowing the use of different Skyrme forces, giving different barriers. Thus, for a given reaction, we could choose a Skyrme force with proper barrier characteristics, not-requiring extra "barrier lowering" or "barrier narrowing" for a best fit to data. For the 64Ni+100Mo reaction, the l-summed Wong formula, with effects of deformations and orientations of nuclei included, fits the fusion-evaporation cross section data exactly for the force GSkI, requiring additional barrier modifications for forces SIII and SV. However, the same for other similar reactions, like 58,64Ni+58,64Ni, fit the data best for SIII force. Hence, the barrier modification effects in l-summed Wong expression depend on the choice of Skyrme force in semiclassical ETF method.

Design of patient-specific gait modifications for knee osteoarthritis rehabilitation.

PubMed

Fregly, Benjamin J; Reinbolt, Jeffrey A; Rooney, Kelly L; Mitchell, Kim H; Chmielewski, Terese L

2007-09-01

Abstract-Gait modification is a nonsurgical approach for reducing the external knee adduction torque in patients with knee osteoarthritis (OA). The magnitude of the first adduction torque peak in particular is strongly associated with knee OA progression. While toeing out has been shown to reduce the second peak, no clinically realistic gait modifications have been identified that effectively reduce both peaks simultaneously. This study predicts novel patient-specific gait modifications that achieve this goal without changing the foot path. The modified gait motion was designed for a single patient with knee OA using dynamic optimization of a patient-specific, full-body gait model. The cost function minimized the knee adduction torque subject to constraints limiting how much the new gait motion could deviate from the patient's normal gait motion. The optimizations predicted a "medial-thrust" gait pattern that reduced the first adduction torque peak between 32% and 54% and the second peak between 34% and 56%. The new motion involved three synergistic kinematic changes: slightly decreased pelvis obliquity, slightly increased leg flexion, and slightly increased pelvis axial rotation. After gait retraining, the patient achieved adduction torque reductions of 39% to 50% in the first peak and 37% to 55% in the second one. These reductions are comparable to those reported after high tibial osteotomy surgery. The associated kinematic changes were consistent with the predictions except for pelvis obliquity, which showed little change. This study demonstrates that it is feasible to design novel patient-specific gait modifications with potential clinical benefit using dynamic optimization of patient-specific, full-body gait models. Further investigation is needed to assess the extent to which similar gait modifications may be effective for other patients with knee OA.

ADAPTATION OF THE ADVANCED STATISTICAL TRAJECTORY REGIONAL AIR POLLUTION (ASTRAP) MODEL TO THE EPA VAX COMPUTER - MODIFICATIONS AND TESTING

EPA Science Inventory

The Advanced Statistical Trajectory Regional Air Pollution (ASTRAP) model simulates long-term transport and deposition of oxides of and nitrogen. t is a potential screening tool for assessing long-term effects on regional visibility from sulfur emission sources. owever, a rigorou...

HDAC inhibitors and immunotherapy; a double edged sword?

PubMed Central

Kroesen, Michiel; Armandari, Inna; Hoogerbrugge, Peter M.; Adema, Gosse J.

2014-01-01

Epigenetic modifications, like histone acetylation, are essential for regulating gene expression within cells. Cancer cells acquire pathological epigenetic modifications resulting in gene expression patterns that facilitate and sustain tumorigenesis. Epigenetic manipulation therefore is emerging as a novel targeted therapy for cancer. Histone Acetylases (HATs) and Histone Deacetylases (HDACs) regulate histone acetylation and hence gene expression. Histone deacetylase (HDAC) inhibitors are well known to affect cancer cell viability and biology and are already in use for the treatment of cancer patients. Immunotherapy can lead to clinical benefit in selected cancer patients, especially in patients with limited disease after tumor debulking. HDAC inhibitors can potentially synergize with immunotherapy by elimination of tumor cells. The direct effects of HDAC inhibitors on immune cell function, however, remain largely unexplored. Initial data have suggested HDAC inhibitors to be predominantly immunosuppressive, but more recent reports have challenged this view. In this review we will discuss the effects of HDAC inhibitors on tumor cells and different immune cell subsets, synergistic interactions and possible mechanisms. Finally, we will address future challenges and potential application of HDAC inhibitors in immunocombination therapy of cancer. PMID:25115382

Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals

PubMed Central

Thess, Andreas; Grund, Stefanie; Mui, Barbara L; Hope, Michael J; Baumhof, Patrick; Fotin-Mleczek, Mariola; Schlake, Thomas

2015-01-01

Being a transient carrier of genetic information, mRNA could be a versatile, flexible, and safe means for protein therapies. While recent findings highlight the enormous therapeutic potential of mRNA, evidence that mRNA-based protein therapies are feasible beyond small animals such as mice is still lacking. Previous studies imply that mRNA therapeutics require chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system. Here we show that chemically unmodified mRNA can achieve those goals as well by applying sequence-engineered molecules. Using erythropoietin (EPO) driven production of red blood cells as the biological model, engineered Epo mRNA elicited meaningful physiological responses from mice to nonhuman primates. Even in pigs of about 20 kg in weight, a single adequate dose of engineered mRNA encapsulated in lipid nanoparticles (LNPs) induced high systemic Epo levels and strong physiological effects. Our results demonstrate that sequence-engineered mRNA has the potential to revolutionize human protein therapies. PMID:26050989

Post isolation modification of exosomes for nanomedicine applications.

PubMed

Hood, Joshua L

2016-07-01

Exosomes are extracellular nanovesicles. They innately possess ideal structural and biocompatible nanocarrier properties. Exosome components can be engineered at the cellular level. Alternatively, when exosome source cells are unavailable for customized exosome production, exosomes derived from a variety of biological origins can be modified post isolation which is the focus of this article. Modification of exosome surface structures allows for exosome imaging and tracking in vivo. Exosome membranes can be loaded with hydrophobic therapeutics to increase drug stability and efficacy. Hydrophilic therapeutics such as RNA can be encapsulated in exosomes to improve cellular delivery. Despite advances in post isolation exosome modification strategies, many challenges to effectively harnessing their therapeutic potential remain. Future topics of exploration include: matching exosome subtypes with nanomedicine applications, optimizing exosomal nanocarrier formulation and investigating how modified exosomes interface with the immune system. Research into these areas will greatly facilitate personalized exosome-based nanomedicine endeavors.

Post isolation modification of exosomes for nanomedicine applications

PubMed Central

Hood, Joshua L

2016-01-01

Exosomes are extracellular nanovesicles. They innately possess ideal structural and biocompatible nanocarrier properties. Exosome components can be engineered at the cellular level. Alternatively, when exosome source cells are unavailable for customized exosome production, exosomes derived from a variety of biological origins can be modified post isolation which is the focus of this article. Modification of exosome surface structures allows for exosome imaging and tracking in vivo. Exosome membranes can be loaded with hydrophobic therapeutics to increase drug stability and efficacy. Hydrophilic therapeutics such as RNA can be encapsulated in exosomes to improve cellular delivery. Despite advances in post isolation exosome modification strategies, many challenges to effectively harnessing their therapeutic potential remain. Future topics of exploration include: matching exosome subtypes with nanomedicine applications, optimizing exosomal nanocarrier formulation and investigating how modified exosomes interface with the immune system. Research into these areas will greatly facilitate personalized exosome-based nanomedicine endeavors. PMID:27348448

Recent progress in plasma-assisted synthesis and modification of 2D materials

NASA Astrophysics Data System (ADS)

Han, Zhao Jun; Murdock, Adrian T.; Seo, Dong Han; Bendavid, Avi

2018-07-01

Plasma represents an important technique for both the synthesis and modification of two-dimensional (2D) materials, owing to the unique plasma-material interactions which can enable effective energy transfer at the nanoscale. Non-equilibrium and non-thermal plasma techniques have been widely applied on various 2D materials, including graphene, silicene, germanene, phosphorene, hexagonal boron nitride (h-BN), and transition metal dichalcogenides such as MoS2 and WS2. Here, we review the recent progress in plasma-assisted synthesis and modification (e.g. functionalisation, doping and etching) of 2D materials and discuss the potential applications of this unique branch of 2D materials. Challenges and future research opportunities in the relevant research field are also discussed. The primary aim of this Review is to provide a better understanding of the plasma-assisted processes and to promote the utilization of 2D materials for advanced electronic, optoelectronic, sensing and energy storage applications.

Tissue modification with feedback: the smart scalpel

NASA Astrophysics Data System (ADS)

Sebern, Elizabeth L.; Brenan, Colin J. H.; Anderson, R. Rox; Hunter, Ian W.

1998-10-01

While feedback control is widespread throughout many engineering fields, there are almost no examples of surgical instruments that utilize a real-time detection and intervention strategy. This concept of closed loop feedback can be applied to the development of autonomous or semi- autonomous minimally invasive robotic surgical systems for efficient excision or modification of diseased tissue. Spatially localized regions of the tissue are first probed to distinguish pathological from healthy tissue based on differences in histochemical and morphological properties. Energy is directed to only the diseased tissue, minimizing collateral damage by leaving the adjacent healthy tissue intact. Continuous monitoring determines treatment effectiveness and, if needed, enables real-time treatment modifications to produce optimal therapeutic outcomes. The present embodiment of this general concept is a microsurgical instrument we call the Smart Scalpel, designed to treat skin angiodysplasias such as port wine stains. Other potential Smart Scalpel applications include psoriasis treatment and early skin cancer detection and intervention.

Numerical modeling analysis of stress transfer modification concepts for deep longwall mines. Report of investigations/1995

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

Vandergrift, T.L.; Jude, C.V.

1995-12-31

This U.S. Bureau of Mines (USBM) report evaluates three stress-transfer-modification concepts for their potential in reducing longwall gate road stresses and closures. In each of the three concepts--packwalling, gob infilling, and entry filling--support structures are constructed on the headgate side of the panel parallel with or inby the face line. When the headgate becomes the tailgate of the adjacent panel, these structures are in place to accept stresses transferred from the mined-out panel. Using the USBM nonlinear boundary-element program MULSIM/NL, baseline models of typical longwall stress transfer behavior were developed for both intermediate depth and deep mining conditions. These modelsmore » were verified by comparing model results with field measurements and observations. The stress-transfer-modification concepts were then incorporated into the deep baseline model to quantify the effects of each concept on tailgate closure.« less

Structuring of material parameters in lithium niobate crystals with low-mass, high-energy ion radiation

NASA Astrophysics Data System (ADS)

Peithmann, K.; Eversheim, P.-D.; Goetze, J.; Haaks, M.; Hattermann, H.; Haubrich, S.; Hinterberger, F.; Jentjens, L.; Mader, W.; Raeth, N. L.; Schmid, H.; Zamani-Meymian, M.-R.; Maier, K.

2011-10-01

Ferroelectric lithium niobate crystals offer a great potential for applications in modern optics. To provide powerful optical components, tailoring of key material parameters, especially of the refractive index n and the ferroelectric domain landscape, is required. Irradiation of lithium niobate crystals with accelerated ions causes strong structured modifications in the material. The effects induced by low-mass, high-energy ions (such as 3He with 41 MeV, which are not implanted, but transmit through the entire crystal volume) are reviewed. Irradiation yields large changes of the refractive index Δn, improved domain engineering capability within the material along the ion track, and waveguiding structures. The periodic modification of Δn as well as the formation of periodically poled lithium niobate (PPLN) (supported by radiation damage) is described. Two-step knock-on displacement processes, 3He→Nb and 3He→O causing thermal spikes, are identified as origin for the material modifications.

Longitudinal study of diet quality and change in asthma symptoms in adults, according to smoking status.

PubMed

Li, Zhen; Kesse-Guyot, Emmanuelle; Dumas, Orianne; Garcia-Aymerich, Judith; Leynaert, Bénédicte; Pison, Christophe; Le Moual, Nicole; Romieu, Isabelle; Siroux, Valérie; Camargo, Carlos A; Nadif, Rachel; Varraso, Raphaëlle

2017-02-01

It has been hypothesised that increased asthma prevalence in westernised countries is associated with changes in lifestyle factors, including a poorer diet. However, little is known regarding the association between diet quality and asthma. In the diet-asthma association, the role of BMI as a potential mediator needs clarification; moreover, potential effect modification by non-diet sources of oxidants, such as smoking, merits investigation. We investigated the association between diet quality and change in asthma symptoms, as well as assessed effect modification by smoking, while accounting for BMI as a potential mediator. Using data from the French prospective Epidemiological study on the Genetics and Environment of Asthma study, we assessed diet quality using the Alternate Healthy Eating Index 2010 (AHEI-2010) at baseline and change in asthma symptoms (stable (reference), worsening, improved; mean follow-up time: 7 years). Mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by BMI. The analyses included 969 adults (mean age 43 years; 49 % men; 42 % ever asthma). We observed a significant interaction between smoking and AHEI-2010 on change in asthma symptoms (P for interaction=0·04). Among never smokers (n 499), we observed a positive total effect (multivariable OR 1·39; 95 % CI 1·07, 1·80) and a positive direct effect (OR 1·41; 95 % CI 1·09, 1·80) of the AHEI-2010 (per ten-point increment) on improved symptoms. No indirect effect mediated through BMI was observed (OR 0·99; 95 % CI 0·91, 1·07). Among former and current smokers, all effects were statistically non-significant. Better diet quality was associated with improved asthma symptoms over time in never smokers, independently of BMI.

Soil modification by invasive plants: Effects on native and invasive species of mixed-grass prairies

USGS Publications Warehouse

Jordan, N.R.; Larson, D.L.; Huerd, S.C.

2008-01-01

Invasive plants are capable of modifying attributes of soil to facilitate further invasion by conspecifics and other invasive species. We assessed this capability in three important plant invaders of grasslands in the Great Plains region of North America: leafy spurge (Euphorbia esula), smooth brome (Bromus inermis) and crested wheatgrass (Agropyron cristatum). In a glasshouse, these three invasives or a group of native species were grown separately through three cycles of growth and soil conditioning in both steam-pasteurized and non-pasteurized soils, after which we assessed seedling growth in these soils. Two of the three invasive species, Bromus and Agropyron, exhibited significant self-facilitation via soil modification. Bromus and Agropyron also had significant facilitative effects on other invasives via soil modification, while Euphorbia had significant antagonistic effects on the other invasives. Both Agropyron and Euphorbia consistently suppressed growth of two of three native forbs, while three native grasses were generally less affected. Almost all intra- and interspecific effects of invasive soil conditioning were dependent upon presence of soil biota from field sites where these species were successful invaders. Overall, these results suggest that that invasive modification of soil microbiota can facilitate plant invasion directly or via 'cross-facilitation' of other invasive species, and moreover has potential to impede restoration of native communities after removal of an invasive species. However, certain native species that are relatively insensitive to altered soil biota (as we observed in the case of the forb Linum lewisii and the native grasses), may be valuable as 'nurse'species in restoration efforts. ?? 2007 Springer Science+Business Media B.V.

Heterogeneity in the Relationship between Disinfection By-Products in Drinking Water and Cancer: A Systematic Review.

PubMed

Benmarhnia, Tarik; Delpla, Ianis; Schwarz, Lara; Rodriguez, Manuel J; Levallois, Patrick

2018-05-14

The epidemiological evidence demonstrating the effect of disinfection by-products (DBPs) from drinking water on colon and rectal cancers is well documented. However, no systematic assessment has been conducted to assess the potential effect measure modification (EMM) in the relationship between DBPs and cancer. The objective of this paper is to conduct a systematic literature review to determine the extent to which EMM has been assessed in the relationship between DBPs in drinking water in past epidemiological studies. Selected articles ( n = 19) were reviewed, and effect estimates and covariates that could have been used in an EMM assessment were gathered. Approximately half of the studies assess EMM ( n = 10), but the majority of studies only estimate it relative to sex subgroups ( n = 6 for bladder cancer and n = 2 both for rectal and colon cancers). Although EMM is rarely assessed, several variables that could have a potential modification effect are routinely collected in these studies, such as socioeconomic status or age. The role of environmental exposures through drinking water can play an important role and contribute to cancer disparities. We encourage a systematic use of subgroup analysis to understand which populations or territories are more vulnerable to the health impacts of DBPs.

Heterogeneity in the Relationship between Disinfection By-Products in Drinking Water and Cancer: A Systematic Review

PubMed Central

Delpla, Ianis; Schwarz, Lara; Rodriguez, Manuel J.; Levallois, Patrick

2018-01-01

The epidemiological evidence demonstrating the effect of disinfection by-products (DBPs) from drinking water on colon and rectal cancers is well documented. However, no systematic assessment has been conducted to assess the potential effect measure modification (EMM) in the relationship between DBPs and cancer. The objective of this paper is to conduct a systematic literature review to determine the extent to which EMM has been assessed in the relationship between DBPs in drinking water in past epidemiological studies. Selected articles (n = 19) were reviewed, and effect estimates and covariates that could have been used in an EMM assessment were gathered. Approximately half of the studies assess EMM (n = 10), but the majority of studies only estimate it relative to sex subgroups (n = 6 for bladder cancer and n = 2 both for rectal and colon cancers). Although EMM is rarely assessed, several variables that could have a potential modification effect are routinely collected in these studies, such as socioeconomic status or age. The role of environmental exposures through drinking water can play an important role and contribute to cancer disparities. We encourage a systematic use of subgroup analysis to understand which populations or territories are more vulnerable to the health impacts of DBPs. PMID:29757939

Epigenetics and the Developmental Origins of Health and ...

EPA Pesticide Factsheets

Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). DNA methylation, posttranslational histone protei n modifications, noncoding RNAs and recruited protein complexes are elements of the epigenetic regulation of gene transcription. These heritable but reversible changes in gene function are dynamic and labile during specific stages of the reproductive cycle and development. Epigenetic marks may be maintained throughout an individual's lifespan and can alter the life-long risk of disease; the nature of these epigenetic marks and their potential alteration by environmental factors is an area of active research. This chapter provides an overview of epigenetic regulation, particularly as it occurs as an essential component of embryo-fetal development. In this chapter we will present key features of DNA methylation and histone protein modifications, including the enzymes involved and the effects of these modifications on gene transcription. We will discuss the interplay of these dynamic modifications and the emerging role of noncoding RNAs in epigenetic gene regulation.

Surface modification of upconverting nanoparticles by layer-by-layer assembled polyelectrolytes and metal ions.

PubMed

Palo, Emilia; Salomäki, Mikko; Lastusaari, Mika

2017-12-15

Modificating and protecting the upconversion luminescence nanoparticles is important for their potential in various applications. In this work we demonstrate successful coating of the nanoparticles by a simple layer-by-layer method using negatively charged polyelectrolytes and neodymium ions. The layer fabrication conditions such as number of the bilayers, solution concentrations and selected polyelectrolytes were studied to find the most suitable conditions for the process. The bilayers were characterized and the presence of the desired components was studied and confirmed by various methods. In addition, the upconversion luminescence of the bilayered nanoparticles was studied to see the effect of the surface modification on the overall intensity. It was observed that with selected deposition concentrations the bilayer successfully shielded the particle resulting in stronger upconversion luminescence. The layer-by-layer method offers multiple possibilities to control the bilayer growth even further and thus gives promises that the use of upconverting nanoparticles in applications could become even easier with less modification steps in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Bias modification training can alter approach bias and chocolate consumption.

PubMed

Schumacher, Sophie E; Kemps, Eva; Tiggemann, Marika

2016-01-01

Recent evidence has demonstrated that bias modification training has potential to reduce cognitive biases for attractive targets and affect health behaviours. The present study investigated whether cognitive bias modification training could be applied to reduce approach bias for chocolate and affect subsequent chocolate consumption. A sample of 120 women (18-27 years) were randomly assigned to an approach-chocolate condition or avoid-chocolate condition, in which they were trained to approach or avoid pictorial chocolate stimuli, respectively. Training had the predicted effect on approach bias, such that participants trained to approach chocolate demonstrated an increased approach bias to chocolate stimuli whereas participants trained to avoid such stimuli showed a reduced bias. Further, participants trained to avoid chocolate ate significantly less of a chocolate muffin in a subsequent taste test than participants trained to approach chocolate. Theoretically, results provide support for the dual process model's conceptualisation of consumption as being driven by implicit processes such as approach bias. In practice, approach bias modification may be a useful component of interventions designed to curb the consumption of unhealthy foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Double-plasma enhanced carbon shield for spatial/interfacial controlled electrodes in lithium ion batteries via micro-sized silicon from wafer waste

NASA Astrophysics Data System (ADS)

Chen, Bing-Hong; Chuang, Shang-I.; Duh, Jenq-Gong

2016-11-01

Using spatial and interfacial control, the micro-sized silicon waste from wafer slurry could greatly increase its retention potential as a green resource for silicon-based anode in lithium ion batteries. Through step by step spatial and interfacial control for electrode, the cyclability of recycled waste gains potential performance from its original poor retention property. In the stages of spatial control, the electrode stabilizers of active, inactive and conductive additives were mixed into slurries for maintaining architecture and conductivity of electrode. In addition, a fusion electrode modification of interfacial control combines electrolyte additive, technique of double-plasma enhanced carbon shield (D-PECS) to convert the chemical bond states and to alter the formation of solid electrolyte interphases (SEIs) in the first cycle. The depth profiles of chemical composition from external into internal electrode illustrate that the fusion electrode modification not only forms a boundary to balance the interface between internal and external electrodes but also stabilizes the SEIs formation and soothe the expansion of micro-sized electrode. Through these effect approaches, the performance of micro-sized Si waste electrode can be boosted from its serious capacity degradation to potential retention (200 cycles, 1100 mAh/g) and better meet the requirements for facile and cost-effective in industrial production.

AH-1S communication switch integration program

NASA Technical Reports Server (NTRS)

Haworth, Loran; Szoboszlay, Zoltan; Shively, Robert; Bick, Frank J.

1989-01-01

The C-6533/ARC communication system as installed on the test AH-1E Cobra helicopter was modified to allow discrete radio selection of all aircraft radios at the cyclic radio/intercommunication system switch. The current Cobra-fleet use of the C-6533 system is cumbersome, particularly during low-altitude operations. Operationally, the current system C-6533 configuration and design requires the pilot to estimate when he can safely remove his hand from an active flight control to select radios during low-altitude flight. The pilot must then physically remove his hand from the flight control, look inside the cockpit to select and verify the radio selection and then effect the selected radio transmission by activating the radio/ICS switch on the cyclic. This condition is potentially hazardous, especially during low-level flight at night in degraded weather. To improve pilot performance, communications effectiveness, and safety, manprint principles were utilized in the selection of a design modification. The modified C-6533 design was kept as basic as possible for potential Cobra-fleet modification. The communications system was modified and the design was subsequently flight-tested by the U.S. Army Aeroflightdynamics Directorate and NASA at the NASA Ames Research Center, Mountain View, California. The design modification enables the Cobra pilot to maintain hands-on flight controls while selecting radios during nap-of-the-Earth (NOE) flight without looking inside the cockpit which resulted in reduced pilot workload ratings, better pilot handling quality ratings and increased flight safety for the NOE flight environment.

Functional Modification of Thioether Groups in Peptides, Polypeptides, and Proteins.

PubMed

Deming, Timothy J

2017-03-15

Recent developments in the modification of methionine and other thioether-containing residues in peptides, polypeptides, and proteins are reviewed. Properties and potential applications of the resulting functionalized products are also discussed. While much of this work is focused on natural Met residues, modifications at other side-chain residues have also emerged as new thioether-containing amino acids have been incorporated into peptidic materials. Functional modification of thioether-containing amino acids has many advantages and is a complementary methodology to the widely utilized methods for modification at cysteine residues.

Cost-effectiveness of a complex workplace dietary intervention: an economic evaluation of the Food Choice at Work study.

PubMed

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

2018-03-03

To evaluate the costs, benefits and cost-effectiveness of complex workplace dietary interventions, involving nutrition education and system-level dietary modification, from the perspective of healthcare providers and employers. Single-study economic evaluation of a cluster-controlled trial (Food Choice at Work (FCW) study) with 1-year follow-up. Four multinational manufacturing workplaces in Cork, Ireland. 517 randomly selected employees (18-65 years) from four workplaces. Cost data were obtained from the FCW study. Nutrition education included individual nutrition consultations, nutrition information (traffic light menu labelling, posters, leaflets and emails) and presentations. System-level dietary modification included menu modification (restriction of fat, sugar and salt), increase in fibre, fruit discounts, strategic positioning of healthier alternatives and portion size control. The combined intervention included nutrition education and system-level dietary modification. No intervention was implemented in the control. The primary outcome was an improvement in health-related quality of life, measured using the EuroQoL 5 Dimensions 5 Levels questionnaire. The secondary outcome measure was reduction in absenteeism, which is measured in monetary amounts. Probabilistic sensitivity analysis (Monte Carlo simulation) assessed parameter uncertainty. The system-level intervention dominated the education and combined interventions. When compared with the control, the incremental cost-effectiveness ratio (€101.37/quality-adjusted life-year) is less than the nationally accepted ceiling ratio, so the system-level intervention can be considered cost-effective. The cost-effectiveness acceptability curve indicates there is some decision uncertainty surrounding this, arising from uncertainty surrounding the differences in effectiveness. These results are reiterated when the secondary outcome measure is considered in a cost-benefit analysis, whereby the system-level intervention yields the highest net benefit (€56.56 per employee). System-level dietary modification alone offers the most value per improving employee health-related quality of life and generating net benefit for employers by reducing absenteeism. While system-level dietary modification strategies are potentially sustainable obesity prevention interventions, future research should include long-term outcomes to determine if improvements in outcomes persist. ISRCTN35108237; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Self-energy effect and Coulomb potential modulation of the exciton in monolayer MoS2 on polar substrate

NASA Astrophysics Data System (ADS)

Wang, Zi-Wu; Xiao, Yao; Li, Run-Ze; Li, Wei-Ping; Li, Zhi-Qing

2017-11-01

We theoretically investigate the correction of exciton binding energy in monolayer MoS2 resulting from the exciton couples with surface optical (SO) phonons induced by polar substrate. The total correction of binding energy can be divided into the self-energy effect and modification of Coulomb potential using the unitary transformation method. We find that both the self-energy and Coulomb potential vary from tens of meV to several hundreds of meV depending on the cut-off wave vector of SO phonon modes, polarizability of substrate materials and internal distance between the monolayer MoS2 and polar substrate. An effective Coulomb potential is obtained by combining the modified term into the Coulomb potential. This potentially could be widely used in various two-dimensional materials. Our theoretical results not only propose the ways to externally control the exciton binding energy in experiment, but also enrich the understanding of the exciton properties in the dielectric environment.

The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.

PubMed

Raju, S Vamsee; Lin, Vivian Y; Liu, Limbo; McNicholas, Carmel M; Karki, Suman; Sloane, Peter A; Tang, Liping; Jackson, Patricia L; Wang, Wei; Wilson, Landon; Macon, Kevin J; Mazur, Marina; Kappes, John C; DeLucas, Lawrence J; Barnes, Stephen; Kirk, Kevin; Tearney, Guillermo J; Rowe, Steven M

2017-01-01

Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-μm resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.

Characterization of organo-modified bentonite sorbents: The effect of modification conditions on adsorption performance

NASA Astrophysics Data System (ADS)

Parolo, María E.; Pettinari, Gisela R.; Musso, Telma B.; Sánchez-Izquierdo, María P.; Fernández, Laura G.

2014-11-01

The organic modification of a natural bentonite was evaluated using two methods: exchanging the interlayer cations by hexadecyltrimethylammonium (HDTMA) and grafting with vinyltrimethoxysilane (VTMS) and γ-methacryloyloxy propyl trimethoxysilane (TMSPMA) on montmorillonite surface. The physicochemical characterization of all materials was made by X-ray diffraction (XRD), IR spectroscopy, thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET) surface area techniques. HDTMA cations and organosilanes were intercalated into the interlayer space of montmorillonite, as deduced from the increase of the basal spacing. IR spectroscopy, TGA and BET area give evidence of successful organic modification. The studies show a decrease in the IR absorption band intensity at 3465 cm-1 with surfactant modification, and also a decrease of mass loss due to adsorbed water observed in two samples: the organoclay and functionalized bentonites, which are evidences of a lower interlayer hydrophilicity. The efficiency of aniline removal onto natural bentonite, organobentonite and functionalized bentonites from aqueous solutions was evaluated. Aniline sorption on natural bentonite was studied using batch experiments, XRD and IR spectroscopy. The hydrophobic surface of organobentonite and functionalized bentonites increased the retention capacity for nonionic organic substances such as aniline on bentonites. The sorption properties of modified bentonite, through different modification methods, enhanced the potential industrial applications of bentonites in water decontamination.

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

PubMed

Ren, Xiangkui; Feng, Yakai; Guo, Jintang; Wang, Haixia; Li, Qian; Yang, Jing; Hao, Xuefang; Lv, Juan; Ma, Nan; Li, Wenzhong

2015-08-07

Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

The Development of a Design and Construction Process Protocol to Support the Home Modification Process Delivered by Occupational Therapists

PubMed Central

Ormerod, Marcus; Newton, Rita

2018-01-01

Modifying the home environments of older people as they age in place is a well-established health and social care intervention. Using design and construction methods to redress any imbalance caused by the ageing process or disability within the home environment, occupational therapists are seen as the experts in this field of practice. However, the process used by occupational therapists when modifying home environments has been criticised for being disorganised and not founded on theoretical principles and concepts underpinning the profession. To address this issue, research was conducted to develop a design and construction process protocol specifically for home modifications. A three-stage approach was taken for the analysis of qualitative data generated from an online survey, completed by 135 occupational therapists in the UK. Using both the existing occupational therapy intervention process model and the design and construction process protocol as the theoretical frameworks, a 4-phase, 9-subphase design and construction process protocol for home modifications was developed. Overall, the study is innovative in developing the first process protocol for home modifications, potentially providing occupational therapists with a systematic and effective approach to the design and delivery of home modification services for older and disabled people. PMID:29682348

The Development of a Design and Construction Process Protocol to Support the Home Modification Process Delivered by Occupational Therapists.

PubMed

Russell, Rachel; Ormerod, Marcus; Newton, Rita

2018-01-01

Modifying the home environments of older people as they age in place is a well-established health and social care intervention. Using design and construction methods to redress any imbalance caused by the ageing process or disability within the home environment, occupational therapists are seen as the experts in this field of practice. However, the process used by occupational therapists when modifying home environments has been criticised for being disorganised and not founded on theoretical principles and concepts underpinning the profession. To address this issue, research was conducted to develop a design and construction process protocol specifically for home modifications. A three-stage approach was taken for the analysis of qualitative data generated from an online survey, completed by 135 occupational therapists in the UK. Using both the existing occupational therapy intervention process model and the design and construction process protocol as the theoretical frameworks, a 4-phase, 9-subphase design and construction process protocol for home modifications was developed. Overall, the study is innovative in developing the first process protocol for home modifications, potentially providing occupational therapists with a systematic and effective approach to the design and delivery of home modification services for older and disabled people.

Making Healthy Food Choices Using Nutrition Facts Panels: The Roles of Knowledge, Motivation, Dietary Modifications Goals, and Age

PubMed Central

Cassady, Diana L.

2012-01-01

Nutrition facts panels (NFPs) contain a rich assortment of nutrition information and are available on most food packages. The importance of this information is potentially even greater among older adults due to their increased risk for diet-related diseases, as well as those with goals for dietary modifications that may impact food choice. Despite past work suggesting that knowledge and motivation impact attitudes surrounding and self-reported use of NFPs, we know little about how (i.e., strategies used) and how well (i.e., level of accuracy) younger and older individuals process NFP information when evaluating healthful qualities of foods. We manipulated the content of NFPs and, using eye tracking methodology, examined strategies associated with deciding which of two NFPs, presented side-by-side, was healthier. We examined associations among strategy use and accuracy as well as age, dietary modification status, knowledge, and motivation. Results showed that, across age groups, those with dietary modification goals made relatively more comparisons between NFPs with increasing knowledge and motivation; but that strategy effectiveness (relationship to accuracy) depended on age and motivation. Results also showed that knowledge and motivation may protect against declines in accuracy in later life and that, across age and dietary modification status, knowledge mediates the relationship between motivation and decision accuracy. PMID:22524999

Comparison of the physiological characteristics of transgenic insect-resistant cotton and conventional lines.

PubMed

Li, Xiaogang; Ding, Changfeng; Wang, Xingxiang; Liu, Biao

2015-03-04

The introduction of transgenic insect-resistant cotton into agricultural ecosystems has raised concerns regarding its ecological effects. Many studies have been conducted to compare the differences in characteristics between transgenic cotton and conventional counterparts. However, few studies have focused on the different responses of transgenic cotton to stress conditions, especially to the challenges of pathogens. The aim of this work is to determine the extent of variation in physiological characteristics between transgenic insect-resistant cotton and the conventional counterpart infected by cotton soil-borne pathogens. The results showed that the difference in genetic backgrounds is the main factor responsible for the effects on biochemical characteristics of transgenic cotton when incubating with cotton Fusarium oxysporum. However, genetic modification had a significantly greater influence on the stomatal structure of transgenic cotton than the effects of cotton genotypes. Our results highlight that the differences in genetic background and/or genetic modifications may introduce variations in physiological characteristics and should be considered to explore the potential unexpected ecological effects of transgenic cotton.

Assessing management of raptor predation management for snowy plover recovery

Treesearch

Bruce G. Marcot; Daniel C. Elbert

2015-01-01

On February 4, 2014, a seven-member expert panel provided objective technical information on the potential effectiveness and feasibility of activities to manage raptors (northern harriers and great horned owls) to aid the recovery of western snowy plovers. The panel discussed and scored the 26 raptor control techniques in nine main categories of habitat modification,...

SU-E-T-267: Construction and Evaluation of a Neutron Wall to Shield a 15 MV Linac in a Low-Energy Vault.

PubMed

Speiser, M; Hager, F; Foster, R; Solberg, T

2012-06-01

To design and quantify the shielding efficacy of an inner Borated Polyethylene (BPE)wall for a 15 MV linac in a low energy vault. A Varian TrueBeam linac with a maximum photon energy of 15 MV was installed in asmaller, preexisting vault. This vault originally housed a low-energy machine and did not havesufficient maze length recommended for neutron attenuation. Effective dose rate calculationswere performed using the Modified Kersey's Method as detailed in NCRP Report No. 151 andfound to be unacceptably high. An initial survey following the machine installation confirmedthese calculations. Rather than restrict the linac beam energy to 10 MV, BPE was investigatedas a neutron moderating addition. An inner wall and door were planned and constructed using4'×8'×1″ thick 5% BPE sheets. The resulting door and wall had 2″ of BPE; conduits and ductwork were also redesigned and shielded. A survey was conducted following construction of thewall. The vault modification reduced the expected effective dose at the vault door from 36.23to 0.010 mSv/week. As specific guidelines for vault modification are lacking, this project quantitativelydemonstrates the potential use of BPE for vault modification. Such modifications may provide alow-cost shielding solution to allow for the use of high energy modes in smaller treatment vaults. © 2012 American Association of Physicists in Medicine.

The effectiveness of workplace dietary modification interventions: a systematic review.

PubMed

Geaney, F; Kelly, C; Greiner, B A; Harrington, J M; Perry, I J; Beirne, P

2013-11-01

To evaluate the effectiveness of workplace dietary modification interventions alone or in combination with nutrition education on employees' dietary behaviour, health status, self-efficacy, perceived health, determinants of food choice, nutrition knowledge, co-worker support, job satisfaction, economic cost and food-purchasing patterns. Data sources included PubMed, Medline, Embase, Psych Info., Web of Knowledge and Cochrane Library (November 2011). This review was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were randomised controlled trials and controlled studies. Interventions were implemented for at least three months. Cochrane Collaboration's risk of bias tool measured potential biases. Heterogeneity precluded meta-analysis. Results were presented in a narrative summary. Six studies conducted in Brazil, the USA, Netherlands and Belgium met the inclusion criteria. Four studies reported small increases in fruit and vegetable consumption (≤half serving/day). These studies involved workplace dietary modifications and three incorporated nutrition education. Other outcomes reported included health status, co-worker support, job satisfaction, perceived health, self-efficacy and food-purchasing patterns. All studies had methodological limitations that weakened confidence in the results. Limited evidence suggests that workplace dietary modification interventions alone and in combination with nutrition education increase fruit and vegetable intakes. These interventions should be developed with recommended guidelines, workplace characteristics, long-term follow-up and objective outcomes for diet, health and cost. © 2013.

Technological capabilities of surface layers formation on implant made of Ti-6Al-4V ELI alloy.

PubMed

Kiel-Jamrozik, Marta; Szewczenko, Janusz; Basiaga, Marcin; Nowińska, Katarzyna

2015-01-01

The aim of the presented research was to find a combination of surface modification methods of implants made of the Ti-6Al-4V ELI alloy, that lead to formation of effective barrier for metallic ions that may infiltrate into solution. To this end, the following tests were carried out: roughness measurement, the voltamperometric tests (potentiodynamic and potentiostatic), and the ion infiltration test. The electropolishing process resulted in the lowering of surface roughness in comparison with mechanical treatment of the surface layer. The anodization process and steam sterilization increased corrosion resistance regardless of the mechanical treatment or electropolishing. The crevice corrosion tests revealed that independent of the modification method applied, the Ti-6Al-4V ELI alloy has excellent crevice corrosion resistance. The smallest quantity of ions infiltrated to the solution was observed for surface modification consisting in the mechanical treatment and anodization with the potential of 97 V. Electric parameters deter- mined during studies were the basis for effectiveness estimation of particular surface treatment methods. The research has shown that the anodization process significantly influences the pitting corrosion resistance of the Ti-6Al-4V ELI alloy independent of the previous surface treatment methods (mechanical and electrochemical). The surface layer after such modification is a protective barrier for metallic ions infiltrated to solution and protects titanium alloy against corrosive environment influence.

The relative abundances of Sn, Te, Xe, Ba and Ce. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Krombel, K. E.

1983-01-01

Elements with even atomic number (Z) in the interval 50 or = Z or = 58 were resolved in the cosmic radiation using the Heavy Nuclei Experiment on the HEAO-3 satellite. Their relative abundances were compared with the results expected from pure r-process material, pure s-process material, and solar system material, both with and without a modification due to possible first ionization potential effects. Such effects may be the result of the preferential acceleration, and hence enhancement in the cosmic rays, of those elements having low first ionization potentials. Measurements were found to be inconsistent with pure r-process material at the greater than 98% confidence level whether or not the first ionization potential adjustments are made.

Improvement of charge separation in TiO{sub 2} by its modification with different tungsten compounds

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

Tryba, B., E-mail: beata.tryba@zut.edu.pl; Tygielska, M.; Grzeskowiak, M.

2016-04-15

Highlights: • Ammonium m-tungstate doped to TiO{sub 2} highly improved charge separation in TiO{sub 2}. • Negative electrokinetic potential of TiO{sub 2} facilitates holes migration to its surface. • Fast migration of holes to TiO{sub 2} surfaces increased yield of OH radicals formation. • Adsorption of dyes on photocatalyst increased its decomposition under visible light. - Abstract: Three different tungsten precursors were used for TiO{sub 2} modification: H{sub 2}WO{sub 4}, WO{sub 2}, and ammonium m-tungstate. It was proved that modification of TiO{sub 2} with tungsten compounds enhanced its photocatalytic activity through the improvement of charge separation. This effect was obtainedmore » by coating of TiO{sub 2} particles with tungsten compound, which changed their surficial electrokinetical potential from positive onto negative. The most efficient tungsten compound, which caused enhanced separation of free carriers was ammonium m-tungstate (AMT). Two dyes with different ionic potential were used for the photocatalytic decomposition. It appeared that cationic dye—Methylene Blue was highly adsorbed on the negatively charged surface of TiO{sub 2} modified by AMT and decomposed, however this photocatalyst was quickly deactivated whereas anionic dye—acid red was better adsorbed on the less acidic surface of TiO{sub 2} and was rapidly decomposed with almost the same rate in the five following cycles.« less

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.

Functional Interplay between Small Non-Coding RNAs and RNA Modification in the Brain.

PubMed

Leighton, Laura J; Bredy, Timothy W

2018-06-07

Small non-coding RNAs are essential for transcription, translation and gene regulation in all cell types, but are particularly important in neurons, with known roles in neurodevelopment, neuroplasticity and neurological disease. Many small non-coding RNAs are directly involved in the post-transcriptional modification of other RNA species, while others are themselves substrates for modification, or are functionally modulated by modification of their target RNAs. In this review, we explore the known and potential functions of several distinct classes of small non-coding RNAs in the mammalian brain, focusing on the newly recognised interplay between the epitranscriptome and the activity of small RNAs. We discuss the potential for this relationship to influence the spatial and temporal dynamics of gene activation in the brain, and predict that further research in the field of epitranscriptomics will identify interactions between small RNAs and RNA modifications which are essential for higher order brain functions such as learning and memory.

Retrospective study of a TTR FAP cohort to modify NIS+7 for therapeutic trials.

PubMed

Suanprasert, N; Berk, J L; Benson, M D; Dyck, P J B; Klein, C J; Gollob, J A; Bettencourt, B R; Karsten, V; Dyck, P J

2014-09-15

Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials. Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve - than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of heat waves on mortality: effect modification and confounding by air pollutants.

PubMed

Analitis, Antonis; Michelozzi, Paola; D'Ippoliti, Daniela; De'Donato, Francesca; Menne, Bettina; Matthies, Franziska; Atkinson, Richard W; Iñiguez, Carmen; Basagaña, Xavier; Schneider, Alexandra; Lefranc, Agnès; Paldy, Anna; Bisanti, Luigi; Katsouyanni, Klea

2014-01-01

Heat waves and air pollution are both associated with increased mortality. Their joint effects are less well understood. We explored the role of air pollution in modifying the effects of heat waves on mortality, within the EuroHEAT project. Daily mortality, meteorologic, and air pollution data from nine European cities for the years 1990-2004 were assembled. We defined heat waves by taking both intensity and duration into account. The city-specific effects of heat wave episodes were estimated using generalized estimating equation models, adjusting for potential confounders with and without inclusion of air pollutants (particles, ozone, nitrogen dioxide, sulphur dioxide, carbon monoxide). To investigate effect modification, we introduced an interaction term between heat waves and each single pollutant in the models. Random effects meta-analysis was used to summarize the city-specific results. The increase in the number of daily deaths during heat wave episodes was 54% higher on high ozone days compared with low, among people age 75-84 years. The heat wave effect on high PM10 days was increased by 36% and 106% in the 75-84 year and 85+ year age groups, respectively. A similar pattern was observed for effects on cardiovascular mortality. Effect modification was less evident for respiratory mortality, although the heat wave effect itself was greater for this cause of death. The heat wave effect was smaller (15-30%) after adjustment for ozone or PM10. The heat wave effect on mortality was larger during high ozone or high PM10 days. When assessing the effect of heat waves on mortality, lack of adjustment for ozone and especially PM10 overestimates effect parameters. This bias has implications for public health policy.

Introduction to the thematic minireview series on redox-active protein modifications and signaling.

PubMed

Banerjee, Ruma

2013-09-13

The dynamics of redox metabolism necessitate cellular strategies for sensing redox changes and for responding to them. A common mechanism for receiving and transmitting redox changes is via reversible modifications of protein cysteine residues. A plethora of cysteine modifications have been described, including sulfenylation, glutathionylation, and disulfide formation. These post-translational modifications have the potential to alter protein structure and/or function and to modulate cellular processes ranging from division to death and from circadian rhythms to secretion. The focus of this thematic minireview series is cysteine modifications in response to reactive oxygen and nitrogen species.

Molecular docking and ADME-toxicity studies of potential compounds of medicinal plants grown in Indonesia as an anti-rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Awaluddin, Rizki; Muhtadi, Wildan Khairi; Chabib, Lutfi; Ikawati, Zullies; Martien, Ronny; Ismail, Hilda

2017-03-01

Rheumatoid arthritis (RA) is an autoimmune disease with recurrent bone destruction around the joints that could lead to permanent joint damage. DMARDs (Disease Modifying Anti-Rheumatoid Drugs) and NSAIDs (Non-Steroid Anti-Inflammatory Drugs) are the RA therapies with many side effects on long term use. Based on the ethnomedicine, there are many plants that could be found in Indonesia that contain the potential compounds as alternative RA therapies. The aim of this study is to assess the potential of compounds of various medicinal plants against multiple proteins that play an important role on RA through the molecular docking study and pharmacokinetic prediction. Hesperidin, EGCG (Epigallocatechin gallate), and mangiferin showed higher activity compared to the other compounds against TACE (TNF-α converting enzyme) which play an important role in the inhibition of TNF-α. Inhibition on it could suppress macrophage cell and T-cell activity by suppressing the regulation of cytokine secretion against inflammation. Furthermore, hesperidin, EGCG, and mangiferin did not show effects on CYP450 (cytochrome P450). Modification of drug delivery system must be done to increase the bioavailability of the compounds. It can be concluded that hesperidin, EGCG, and mangiferin are potential to be developed as an RA therapy with a modification of drug delivery system. This study suggest the encapsulation method using liposome as the drug carrier, which is suitable with the charactheristic of hesperidine, EGCG, and mangiferin.

Probiotics as potential antioxidants: a systematic review.

PubMed

Mishra, Vijendra; Shah, Chandni; Mokashe, Narendra; Chavan, Rupesh; Yadav, Hariom; Prajapati, Jashbhai

2015-04-15

Probiotics are known for their health beneficial effects and are established as dietary adjuncts. Probiotics have been known for many beneficial health effects. In this view, there is interest to find the potential probiotic strains that can exhibit antioxidant properties along with health benefits. In vitro and in vivo studies indicate that probiotics exhibit antioxidant potential. In this view, consumption of probiotics alone or foods supplemented with probiotics may reduce oxidative damage, free radical scavenging rate, and modification in activity of crucial antioxidative enzymes in human cells. Incorporation of probiotics in foods can provide a good strategy to supply dietary antioxidants, but more studies are needed to standardize methods and evaluate antioxidant properties of probiotics before they can be recommended for antioxidant potential. In this paper, the literature related to known antioxidant potential of probiotics and proposing future perspectives to conduct such studies has been reviewed.

A parametrisation of modified gravity on nonlinear cosmological scales

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

Lombriser, Lucas, E-mail: llo@roe.ac.uk

2016-11-01

Viable modifications of gravity on cosmological scales predominantly rely on screening mechanisms to recover Einstein's Theory of General Relativity in the Solar System, where it has been well tested. A parametrisation of the effects of such modifications in the spherical collapse model is presented here for the use of modelling the modified nonlinear cosmological structure. The formalism allows an embedding of the different screening mechanisms operating in scalar-tensor theories through large values of the gravitational potential or its first or second derivatives as well as of linear suppression effects or more general transitions between modified and Einstein gravity limits. Eachmore » screening or suppression mechanism is parametrised by a time, mass, and environment dependent screening scale, an effective modified gravitational coupling in the fully unscreened limit that can be matched to linear theory, the exponent of a power-law radial profile of the screened coupling, determined by derivatives, symmetries, and potentials in the scalar field equation, and an interpolation rate between the screened and unscreened limits. Along with generalised perturbative methods, the parametrisation may be used to formulate a nonlinear extension to the linear parametrised post-Friedmannian framework to enable generalised tests of gravity with the wealth of observations from the nonlinear cosmological regime.« less

Early Exposure to Traffic-Related Air Pollution, Respiratory Symptoms at 4 Years of Age, and Potential Effect Modification by Parental Allergy, Stressful Family Events, and Sex: A Prospective Follow-up Study of the PARIS Birth Cohort

PubMed Central

Rancière, Fanny; Bougas, Nicolas; Viola, Malika; Momas, Isabelle

2016-01-01

Background: The relation between traffic-related air pollution (TRAP) exposure and the incidence of asthma/allergy in preschool children has been widely studied, but results remain heterogeneous, possibly due to differences in methodology and susceptibility to TRAP. Objectives: We aimed to study the relation of early TRAP exposure with the development of respiratory/allergic symptoms and asthma during preschool years, and to investigate parental allergy, “stressful” family events, and sex as possible effect modifiers. Methods: We examined data of 2,015 children from the PARIS birth cohort followed up with repeated questionnaires completed by parents until age 4 years. TRAP exposure in each child’s first year of life was estimated by nitrogen oxides (NOx) air dispersion modeling, taking into account both home and day care locations. Association between TRAP exposure and patterns of wheezing, dry night cough, and rhinitis symptoms was studied using multinomial logistic regression models adjusted for potential confounders. Effect modification by parental history of allergy, stressful family events, and sex was investigated. Results: An interquartile range (26 μg/m3) increase in NOx levels was associated with an increased odds ratio (OR) of persistent wheezing at 4 years (adjusted OR = 1.27; 95% confidence interval: 1.09, 1.47). TRAP exposure was positively associated with persistent wheeze, dry cough, and rhinitis symptoms among children with a parental allergy, those experiencing stressful family events, and boys, but not in children whose parents did not have allergies or experience stressful events, or in girls (all interaction p-values < 0.2). Conclusions: This study supports the hypothesis that not all preschool children are equal regarding TRAP health effects. Parental history of allergy, stressful family events, and male sex may increase their susceptibility to adverse respiratory effects of early TRAP exposure. Citation: Rancière F, Bougas N, Viola M, Momas I. 2017. Early exposure to traffic-related air pollution, respiratory symptoms at 4 years of age, and potential effect modification by parental allergy, stressful family events, and sex: a prospective follow-up study of the PARIS birth cohort. Environ Health Perspect 125:737–745; http://dx.doi.org/10.1289/EHP239 PMID:27219743

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation.

PubMed

Holmes, Jeffrey W; Laksman, Zachary; Gepstein, Lior

2016-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function - maintaining integrity of the heart wall against enormous mechanical forces - but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aerodynamic and Acoustic Flight Test Results and Results for the Stratospheric Observatory for Infrared Astronomy

NASA Technical Reports Server (NTRS)

Cumming, Stephen B.; Smith, Mark S.; Cliatt, Larry J.; Frederick, Michael A.

2014-01-01

As part of the Stratospheric Observatory for Infrared Astronomy program, a 747SP airplane was modified to carry a 2.5-m telescope in the aft section of the fuselage. The resulting airborne observatory allows for observations above 99 percent of the water vapor in the atmosphere. The open cavity created by the modifications had the potential to significantly affect the airplane in the areas of aerodynamics and acoustics. Several series of flight tests were conducted to clear the operating envelope of the airplane for astronomical observations, planned to be performed between the altitudes of 35,000 ft and 45,000 ft. The flight tests were successfully completed. Cavity acoustics were below design limits, and the overall acoustic characteristics of the cavity were better than expected. The modification did have some effects on the stability and control of the airplane, but these effects were not significant. Airplane air data systems were not affected by the modifications. This paper describes the methods used to examine the aerodynamics and acoustic data from the flight tests and provides a discussion of the flight-test results in the areas of cavity acoustics, stability and control, and air data.

Aerodynamic and Acoustic Flight Test Results for the Stratospheric Observatory for Infrared Astronomy

NASA Technical Reports Server (NTRS)

Cumming, Stephen B.; Cliatt, Larry James; Frederick, Michael A.; Smith, Mark S.

2013-01-01

As part of the Stratospheric Observatory for Infrared Astronomy (SOFIA) program, a 747SP airplane was modified to carry a 2.5 meter telescope in the aft section of the fuselage. The resulting airborne observatory allows for observations above 99 percent of the water vapor in the atmosphere. The open cavity created by the modifications had the potential to significantly affect the airplane in the areas of aerodynamics and acoustics. Several series of flight tests were conducted to clear the airplanes operating envelope for astronomical observations, planned to be performed between the altitudes of 39,000 feet and 45,000 feet. The flight tests were successfully completed. Cavity acoustics were below design limits, and the overall acoustic characteristics of the cavity were better than expected. The modification did have some effects on the stability and control of the airplane, but these effects were not significant. Airplane air data systems were not affected by the modifications. This paper describes the methods used to examine the aerodynamics and acoustic data from the flight tests and provides a discussion of the flight test results in the areas of cavity acoustics, stability and control, and air data.

Correlation between physicochemical properties of modified clinoptilolite and its performance in the removal of ammonia-nitrogen.

PubMed

Dong, Yingbo; Lin, Hai; He, Yinhai

2017-03-01

The physicochemical properties of the 24 modified clinoptilolite samples and their ammonia-nitrogen removal rates were measured to investigate the correlation between them. The modified clinoptilolites obtained by acid modification, alkali modification, salt modification, and thermal modification were used to adsorb ammonia-nitrogen. The surface area, average pore width, macropore volume, mecropore volume, micropore volume, cation exchange capacity (CEC), zeta potential, silicon-aluminum ratios, and ammonia-nitrogen removal rate of the 24 modified clinoptilolite samples were measured. Subsequently, the linear regression analysis method was used to research the correlation between the physicochemical property of the different modified clinoptilolite samples and the ammonia-nitrogen removal rate. Results showed that the CEC was the major physicochemical property affecting the ammonia-nitrogen removal performance. According to the impacts from strong to weak, the order was CEC > silicon-aluminum ratios > mesopore volume > micropore volume > surface area. On the contrary, the macropore volume, average pore width, and zeta potential had a negligible effect on the ammonia-nitrogen removal rate. The relational model of physicochemical property and ammonia-nitrogen removal rate of the modified clinoptilolite was established, which was ammonia-nitrogen removal rate = 1.415[CEC] + 173.533 [macropore volume] + 0.683 [surface area] + 4.789[Si/Al] - 201.248. The correlation coefficient of this model was 0.982, which passed the validation of regression equation and regression coefficients. The results of the significance test showed a good fit to the correlation model.

Nanotubular surface modification of metallic implants via electrochemical anodization technique.

PubMed

Wang, Lu-Ning; Jin, Ming; Zheng, Yudong; Guan, Yueping; Lu, Xin; Luo, Jing-Li

2014-01-01

Due to increased awareness and interest in the biomedical implant field as a result of an aging population, research in the field of implantable devices has grown rapidly in the last few decades. Among the biomedical implants, metallic implant materials have been widely used to replace disordered bony tissues in orthopedic and orthodontic surgeries. The clinical success of implants is closely related to their early osseointegration (ie, the direct structural and functional connection between living bone and the surface of a load-bearing artificial implant), which relies heavily on the surface condition of the implant. Electrochemical techniques for modifying biomedical implants are relatively simple, cost-effective, and appropriate for implants with complex shapes. Recently, metal oxide nanotubular arrays via electrochemical anodization have become an attractive technique to build up on metallic implants to enhance the biocompatibility and bioactivity. This article will thoroughly review the relevance of electrochemical anodization techniques for the modification of metallic implant surfaces in nanoscale, and cover the electrochemical anodization techniques used in the development of the types of nanotubular/nanoporous modification achievable via electrochemical approaches, which hold tremendous potential for bio-implant applications. In vitro and in vivo studies using metallic oxide nanotubes are also presented, revealing the potential of nanotubes in biomedical applications. Finally, an outlook of future growth of research in metallic oxide nanotubular arrays is provided. This article will therefore provide researchers with an in-depth understanding of electrochemical anodization modification and provide guidance regarding the design and tuning of new materials to achieve a desired performance and reliable biocompatibility.

Nanotubular surface modification of metallic implants via electrochemical anodization technique

PubMed Central

Wang, Lu-Ning; Jin, Ming; Zheng, Yudong; Guan, Yueping; Lu, Xin; Luo, Jing-Li

2014-01-01

Due to increased awareness and interest in the biomedical implant field as a result of an aging population, research in the field of implantable devices has grown rapidly in the last few decades. Among the biomedical implants, metallic implant materials have been widely used to replace disordered bony tissues in orthopedic and orthodontic surgeries. The clinical success of implants is closely related to their early osseointegration (ie, the direct structural and functional connection between living bone and the surface of a load-bearing artificial implant), which relies heavily on the surface condition of the implant. Electrochemical techniques for modifying biomedical implants are relatively simple, cost-effective, and appropriate for implants with complex shapes. Recently, metal oxide nanotubular arrays via electrochemical anodization have become an attractive technique to build up on metallic implants to enhance the biocompatibility and bioactivity. This article will thoroughly review the relevance of electrochemical anodization techniques for the modification of metallic implant surfaces in nanoscale, and cover the electrochemical anodization techniques used in the development of the types of nanotubular/nanoporous modification achievable via electrochemical approaches, which hold tremendous potential for bio-implant applications. In vitro and in vivo studies using metallic oxide nanotubes are also presented, revealing the potential of nanotubes in biomedical applications. Finally, an outlook of future growth of research in metallic oxide nanotubular arrays is provided. This article will therefore provide researchers with an in-depth understanding of electrochemical anodization modification and provide guidance regarding the design and tuning of new materials to achieve a desired performance and reliable biocompatibility. PMID:25258532

A high-throughput and rapid computational method for screening of RNA post-transcriptional modifications that can be recognized by target proteins.

PubMed

Orr, Asuka A; Gonzalez-Rivera, Juan C; Wilson, Mark; Bhikha, P Reena; Wang, Daiqi; Contreras, Lydia M; Tamamis, Phanourios

2018-02-01

There are over 150 currently known, highly diverse chemically modified RNAs, which are dynamic, reversible, and can modulate RNA-protein interactions. Yet, little is known about the wealth of such interactions. This can be attributed to the lack of tools that allow the rapid study of all the potential RNA modifications that might mediate RNA-protein interactions. As a promising step toward this direction, here we present a computational protocol for the characterization of interactions between proteins and RNA containing post-transcriptional modifications. Given an RNA-protein complex structure, potential RNA modified ribonucleoside positions, and molecular mechanics parameters for capturing energetics of RNA modifications, our protocol operates in two stages. In the first stage, a decision-making tool, comprising short simulations and interaction energy calculations, performs a fast and efficient search in a high-throughput fashion, through a list of different types of RNA modifications categorized into trees according to their structural and physicochemical properties, and selects a subset of RNA modifications prone to interact with the target protein. In the second stage, RNA modifications that are selected as recognized by the protein are examined in-detail using all-atom simulations and free energy calculations. We implement and experimentally validate this protocol in a test case involving the study of RNA modifications in complex with Escherichia coli (E. coli) protein Polynucleotide Phosphorylase (PNPase), depicting the favorable interaction between 8-oxo-7,8-dihydroguanosine (8-oxoG) RNA modification and PNPase. Further advancement of the protocol can broaden our understanding of protein interactions with all known RNA modifications in several systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Epigenetics Reactivation of Nrf2 in Prostate TRAMP C1 Cells by Curcumin Analogue FN1.

PubMed

Li, Wenji; Pung, Doug; Su, Zheng-Yuan; Guo, Yue; Zhang, Chengyue; Yang, Anne Yuqing; Zheng, Xi; Du, Zhi-Yun; Zhang, Kun; Kong, Ah-Ng

2016-04-18

It has previously been shown that curcumin can effectively inhibit prostate cancer proliferation and progression in TRAMP mice, potentially acting through the hypomethylation of the Nrf2 gene promoter and hence activation of the Nrf2 pathway to enhance cell antioxidative defense. FN1 is a synthetic curcumin analogue that shows stronger anticancer activity than curcumin in other reports. We aimed to explore the epigenetic modification of FN1 that restores Nrf2 expression in TRAMP-C1 cells. Stably transfected HepG2-C8 cells were used to investigate the effect of FN1 on the Nrf2- antioxidant response element (ARE) pathway. Real-time quantitative PCR and Western blotting were applied to study the influence of FN1 on endogenous Nrf2 and its downstream genes. Bisulfite genomic sequencing (BGS) and methylated DNA immunoprecipitation (MeDIP) were then performed to examine the methylation profile of the Nrf2 promoter. An anchorage-independent colony-formation analysis was conducted to examine the tumor inhibition activity of FN1. Epigenetic modification enzymes, including DNMTs and HDACs, were investigated by Western blotting. The luciferase reporter assay indicated that FN1 was more potent than curcumin in activating the Nrf2-ARE pathway. FN1 increased the expression of Nrf2 and its downstream detoxifying enzymes. FN1 significantly inhibited the colony formation of TRAMP-C1 cells. BGS and MeDIP assays revealed that FN1 treatment (250 nM for 3 days) reduced the percentage of CpG methylation of the Nrf2 promoter. FN1 also downregulated epigenetic modification enzymes. In conclusion, our results suggest that FN1 is a novel anticancer agent for prostate cancer. In the TRAMP-C1 cell line, FN1 can increase the level of Nrf2 and downstream genes via activating the Nrf2-ARE pathway and inhibit the colony formation potentially through the decreased expression of keap1 coupled with CpG demethylation of the Nrf2 promoter. This CpG demethylation effect may come from decreased epigenetic modification enzymes, such as DNMT1, DNMT3a, DNMT3b, and HDAC4.

For Whom the Bell Tolls: Neurocognitive Individual Differences in the Acute Stress-Reduction Effects of an Attention Bias Modification Game for Anxiety

PubMed Central

Dennis-Tiwary, Tracy; Egan, Laura J.; Babkirk, Sarah; Denefrio, Samantha

2016-01-01

The efficacy of attention bias modification training (ABMT) for anxiety is debated, in part because individual differences in task engagement and pre-training threat bias impact training efficacy. In the present study, an engaging, gamified ABMT mobile application, or “app,” was utilized in 42 (21 females) trait-anxious adults. EEG was recorded during pre- and post-training threat bias assessment to generate scalp-recorded event-related potentials (ERPs) reflecting neurocognitive responses to threat. Following app play (ABMT versus placebo), subjective anxiety and stress responses (observed and self-reported) were measured. ABMT, versus placebo, resulted in improved behavioral performance during the stress task for females only. No difference was found between training groups in self-reported anxiety. ABMT resulted in improved performance during the stress task among those evidencing specific pre-training ERP responses: decreased P1 amplitudes, suggesting less attention allocation, but potentiated N170 amplitudes, suggesting enhanced attention selection and discrimination. Individual differences in behavioral threat bias did not moderate training effects. Results suggest that efficient initial allocation of attention to threat combined with enhanced recruitment of sensory gain mechanisms may underlie positive ABMT effects on anxiety-related stress. Targeting neurocognitive responses to threat to personalize ABMT and develop more effective methods of treatment delivery, such as gamification, are discussed. PMID:26745621

Non-strictly black body spectrum from the tunnelling mechanism

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

Corda, Christian, E-mail: cordac.galilei@gmail.com

2013-10-15

The tunnelling mechanism is widely used to explain Hawking radiation. However, in many cases the analysis used to obtain the Hawking temperature only involves comparing the emission probability for an outgoing particle with the Boltzmann factor. Banerjee and Majhi improved this approach by explicitly finding a black body spectrum associated with black holes. Their result, obtained using a reformulation of the tunnelling mechanism, is in contrast to that of Parikh and Wilczek, who found an emission probability that is compatible with a non-strictly thermal spectrum. Using the recently identified effective state for a black hole, we solve this contradiction viamore » a slight modification of the analysis by Banerjee and Majhi. The final result is a non-strictly black body spectrum from the tunnelling mechanism. We also show that for an effective temperature, we can express the corresponding effective metric using Hawking’s periodicity arguments. Potential important implications for the black hole information puzzle are discussed. -- Highlights: •We review an important result by Banerjee and Majhi on the tunnelling mechanism in the framework of Hawking radiation. •This result is in contrast to another result reported by Parikh and Wilczek. •We introduce the effective state of a black hole. •We explain the contrast via a slight modification of the analysis by Banerjee and Majhi. •We discuss potential important implications for the black hole information puzzle.« less

Assessing environmental impacts of genetically modified plants on non-target organisms: The relevance of in planta studies.

PubMed

Arpaia, Salvatore; Birch, A Nicholas E; Kiss, Jozsef; van Loon, Joop J A; Messéan, Antoine; Nuti, Marco; Perry, Joe N; Sweet, Jeremy B; Tebbe, Christoph C

2017-04-01

In legal frameworks worldwide, genetically modified plants (GMPs) are subjected to pre-market environmental risk assessment (ERA) with the aim of identifying potential effects on the environment. In the European Union, the EFSA Guidance Document introduces the rationale that GMPs, as well as their newly produced metabolites, represent the potential stressor to be evaluated during ERA. As a consequence, during several phases of ERA for cultivation purposes, it is considered necessary to use whole plants or plant parts in experimental protocols. The importance of in planta studies as a strategy to address impacts of GMPs on non-target organisms is demonstrated, to evaluate both effects due to the intended modification in plant phenotype (e.g. expression of Cry proteins) and effects due to unintended modifications in plant phenotype resulting from the transformation process (e.g. due to somaclonal variations or pleiotropic effects). In planta tests are also necessary for GMPs in which newly expressed metabolites cannot easily be studied in vitro. This paper reviews the scientific literature supporting the choice of in planta studies as a fundamental tool in ERA of GMPs in cultivation dossiers; the evidence indicates they can realistically mimic the ecological relationships occurring in their receiving environments and provide important insights into the biology and sustainable management of GMPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel roles for biogenic monoamines: from monoamines in transglutaminase-mediated post-translational protein modification to monoaminylation deregulation diseases.

PubMed

Walther, Diego J; Stahlberg, Silke; Vowinckel, Jakob

2011-12-01

Functional protein serotonylation is a newly recognized post-translational modification with the primary biogenic monoamine (PBMA) serotonin (5-HT). This covalent protein modification is catalyzed by transglutaminases (TGs) and, for example, acts in the constitutive activation of small GTPases. Multiple physiological roles have been identified since its description in 2003 and, importantly, deregulated serotonylation was shown in the etiology of bleeding disorders, primary pulmonary hypertension and diabetes. The PBMAs 5-HT, histamine, dopamine, and norepinephrine all act as neurotransmitters in the nervous system and as hormones in non-neuronal tissues, which points out their physiological importance. In analogy to serotonylation we have found that also the other PBMAs act through the TG-catalyzed mechanisms of 'histaminylation', 'dopaminylation' and 'norepinephrinylation'. Therefore, PBMAs deploy a considerable portion of their effects via protein monoaminylation in addition to their canonical receptor-mediated signaling. Here, the implications of these newly identified post-translational modifications are presented and discussed. Furthermore, the potential regulatory roles of protein monoaminylation in small GTPase, heterotrimeric G-protein and lipid signaling, as well as in modulating metabolic enzymes and nuclear processes, are critically assessed. © 2011 The Authors Journal compilation © 2011 FEBS.

Epigenomics in cancer management

PubMed Central

Costa, Fabricio F

2010-01-01

The identification of all epigenetic modifications implicated in gene expression is the next step for a better understanding of human biology in both normal and pathological states. This field is referred to as epigenomics, and it is defined as epigenetic changes (ie, DNA methylation, histone modifications and regulation by noncoding RNAs such as microRNAs) on a genomic scale rather than a single gene. Epigenetics modulate the structure of the chromatin, thereby affecting the transcription of genes in the genome. Different studies have already identified changes in epigenetic modifications in a few genes in specific pathways in cancers. Based on these epigenetic changes, drugs against different types of tumors were developed, which mainly target epimutations in the genome. Examples include DNA methylation inhibitors, histone modification inhibitors, and small molecules that target chromatin-remodeling proteins. However, these drugs are not specific, and side effects are a major problem; therefore, new DNA sequencing technologies combined with epigenomic tools have the potential to identify novel biomarkers and better molecular targets to treat cancers. The purpose of this review is to discuss current and emerging epigenomic tools and to address how these new technologies may impact the future of cancer management. PMID:21188117

Mechanistic understanding of the cysteine capping modifications of antibodies enables selective chemical engineering in live mammalian cells.

PubMed

Zhong, Xiaotian; He, Tao; Prashad, Amar S; Wang, Wenge; Cohen, Justin; Ferguson, Darren; Tam, Amy S; Sousa, Eric; Lin, Laura; Tchistiakova, Lioudmila; Gatto, Scott; D'Antona, Aaron; Luan, Yen-Tung; Ma, Weijun; Zollner, Richard; Zhou, Jing; Arve, Bo; Somers, Will; Kriz, Ronald

2017-04-20

Protein modifications by intricate cellular machineries often redesign the structure and function of existing proteins to impact biological networks. Disulfide bond formation between cysteine (Cys) pairs is one of the most common modifications found in extracellularly-destined proteins, key to maintaining protein structure. Unpaired surface cysteines on secreted mammalian proteins are also frequently found disulfide-bonded with free Cys or glutathione (GSH) in circulation or culture, the mechanism for which remains unknown. Here we report that these so-called Cys-capping modifications take place outside mammalian cells, not in the endoplasmic reticulum (ER) where oxidoreductase-mediated protein disulfide formation occurs. Unpaired surface cysteines of extracellularly-arrived proteins such as antibodies are uncapped upon secretion before undergoing disulfide exchange with cystine or oxidized GSH in culture medium. This observation has led to a feasible way to selectively modify the nucleophilic thiol side-chain of cell-surface or extracellular proteins in live mammalian cells, by applying electrophiles with a chemical handle directly into culture medium. These findings provide potentially an effective approach for improving therapeutic conjugates and probing biological systems. Copyright © 2017 Elsevier B.V. All rights reserved.

A review on the application of inorganic nano-structured materials in the modification of textiles: focus on anti-microbial properties.

PubMed

Dastjerdi, Roya; Montazer, Majid

2010-08-01

Textiles can provide a suitable substrate to grow micro-organisms especially at appropriate humidity and temperature in contact to human body. Recently, increasing public concern about hygiene has been driving many investigations for anti-microbial modification of textiles. However, using many anti-microbial agents has been avoided because of their possible harmful or toxic effects. Application of inorganic nano-particles and their nano-composites would be a good alternative. This review paper has focused on the properties and applications of inorganic nano-structured materials with good anti-microbial activity potential for textile modification. The discussed nano-structured anti-microbial agents include TiO(2) nano-particles, metallic and non-metallic TiO(2) nano-composites, titania nanotubes (TNTs), silver nano-particles, silver-based nano-structured materials, gold nano-particles, zinc oxide nano-particles and nano-rods, copper nano-particles, carbon nanotubes (CNTs), nano-clay and its modified forms, gallium, liposomes loaded nano-particles, metallic and inorganic dendrimers nano-composite, nano-capsules and cyclodextrins containing nano-particles. This review is also concerned with the application methods for the modification of textiles using nano-structured materials. Copyright 2010 Elsevier B.V. All rights reserved.

Using ant-behavior-based simulation model AntWeb to improve website organization

NASA Astrophysics Data System (ADS)

Li, Weigang; Pinheiro Dib, Marcos V.; Teles, Wesley M.; Morais de Andrade, Vlaudemir; Alves de Melo, Alba C. M.; Cariolano, Judas T.

2002-03-01

Some web usage mining algorithms showed the potential application to find the difference among the organizations expected by visitors to the website. However, there are still no efficient method and criterion for a web administrator to measure the performance of the modification. In this paper, we developed an AntWeb, a model inspired by ants' behavior to simulate the sequence of visiting the website, in order to measure the efficient of the web structure. We implemented a web usage mining algorithm using backtrack to the intranet website of the Politec Informatic Ltd., Brazil. We defined throughput (the number of visitors to reach their target pages per time unit relates to the total number of visitors) as an index to measure the website's performance. We also used the link in a web page to represent the effect of visitors' pheromone trails. For every modification in the website organization, for example, putting a link from the expected location to the target object, the simulation reported the value of throughput as a quick answer about this modification. The experiment showed the stability of our simulation model, and a positive modification to the intranet website of the Politec.

Genetic modification of plant cell walls to enhance biomass yield and biofuel production in bioenergy crops.

PubMed

Wang, Yanting; Fan, Chunfen; Hu, Huizhen; Li, Ying; Sun, Dan; Wang, Youmei; Peng, Liangcai

2016-01-01

Plant cell walls represent an enormous biomass resource for the generation of biofuels and chemicals. As lignocellulose property principally determines biomass recalcitrance, the genetic modification of plant cell walls has been posed as a powerful solution. Here, we review recent progress in understanding the effects of distinct cell wall polymers (cellulose, hemicelluloses, lignin, pectin, wall proteins) on the enzymatic digestibility of biomass under various physical and chemical pretreatments in herbaceous grasses, major agronomic crops and fast-growing trees. We also compare the main factors of wall polymer features, including cellulose crystallinity (CrI), hemicellulosic Xyl/Ara ratio, monolignol proportion and uronic acid level. Furthermore, the review presents the main gene candidates, such as CesA, GH9, GH10, GT61, GT43 etc., for potential genetic cell wall modification towards enhancing both biomass yield and enzymatic saccharification in genetic mutants and transgenic plants. Regarding cell wall modification, it proposes a novel groove-like cell wall model that highlights to increase amorphous regions (density and depth) of the native cellulose microfibrils, providing a general strategy for bioenergy crop breeding and biofuel processing technology. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Graphite Fiber/Polyimide PMCs from Hot Melt vs Solution Prepreg

NASA Technical Reports Server (NTRS)

Shin, E. Eugene; Sutter, James K.; Eakin, Howard; Inghram, Linda; McCorkle, Linda; Scheiman, Dan; Papadopoulos, Demetrios; Thesken, John; Fink, Jeffrey E.

2002-01-01

Carbon fiber reinforced high temperature polymer matrix composites (PMC) have been extensively investigated as potential weight reduction replacements of various metallic components in next generation high performance propulsion rocket engines. The initial phase involves development of comprehensive composite material-process-structure-design-property-in-service performance correlations and database, especially for a high stiffness facesheet of various sandwich structures. Overview of the program plan, technical approaches and current multi-team efforts will be presented. During composite fabrication, it was found that the two large volume commercial prepregging methods (hot-melt vs. solution) resulted in considerably different composite cure behavior. Details of the process-induced physical and chemical modifications in the prepregs, their effects on composite processing, and systematic cure cycle optimization studies will be discussed. The combined effects of prepregging method and cure cycle modification on composite properties and isothermal aging performance were also evaluated.

Nanopipette delivery: influence of surface charge.

PubMed

Shi, Wenqing; Sa, Niya; Thakar, Rahul; Baker, Lane A

2015-07-21

In this report, transport through a nanopipette is studied and the interplay between current rectification and ion delivery for small pipettes is examined. First, surface charge dependence of concentration polarization effects in a quartz nanopipette was investigated. Electrical characterization was performed through current-potential (I-V) measurements. In addition, fluorescein (an anionic fluorescent probe) was utilized to optically map ion enrichment and ion depletion in the nanopipette tip. Bare nanopipettes and polyethylenimine (PEI)-modified nanopipettes were examined. Results confirm that concentration polarization is a surface charge dependent phenomenon and delivery can be controlled through modification of surface charge. The relationship between concentration polarization effects and voltage-driven delivery of charged electroactive species was investigated with a carbon ring/nanopore electrode fabricated from pyrolyzed parylene C (PPC). Factors such as surface charge polarity of the nanopipette, electrolyte pH, and electrolyte concentration were investigated. Results indicate that with modification of surface charge, additional control over delivery of charged species can be achieved.

Germline Editing: Editors Cautionary.

PubMed

Krishan, K; Kanchan, T; Singh, B; Baryah, N; Puri, S

2018-01-01

This communication is regarding the recent editing of the genome of the human embryo with CRISPR/Cas9 which generated a debate amongst the biological scientists around the world. Editing human germline genes may act as godsend in some serious genetic and other disorders as the genes related to these disorders can be replaced effectively. The scientists are in dilemma whether the human germline gene modification is a boon or bane for the human society. Though editing human germline genes may be an answer to many serious genetic disorders however; it may have unpredictable effects on future generations. The ethical issues regarding the germline editing need further discussion which may have implications on human race and on-going human evolution. Thus, the researchers need to be doubly cautious and some stringent regulations should be framed regarding the various aspects of germ line gene modifications and any potential conflict with nature for future outcome.

Physicochemical modifications accompanying UV laser induced surface structures on poly(ethylene terephthalate) and their effect on adhesion of mesenchymal cells.

PubMed

Rebollar, Esther; Pérez, Susana; Hernández, Margarita; Domingo, Concepción; Martín, Margarita; Ezquerra, Tiberio A; García-Ruiz, Josefa P; Castillejo, Marta

2014-09-07

This work reports on the formation of different types of structures on the surface of polymer films upon UV laser irradiation. Poly(ethylene terephthalate) was irradiated with nanosecond UV pulses at 193 and 266 nm. The polarization of the laser beam and the irradiation angle of incidence were varied, giving rise to laser induced surface structures with different shapes and periodicities. The irradiated surfaces were topographically characterized by atomic force microscopy and the chemical modifications induced by laser irradiation were inspected via micro-Raman and fluorescence spectroscopies. Contact angle measurements were performed with different liquids, and the results evaluated in terms of surface free energy components. Finally, in order to test the influence of surface properties for a potential application, the modified surfaces were used for mesenchymal stem cell culture assays and the effect of nanostructure and surface chemistry on cell adhesion was evaluated.

8 MeV electron beam induced modifications in the thermal, structural and electrical properties of nanophase CeO2 for potential electronics applications

NASA Astrophysics Data System (ADS)

Babitha, K. K.; Sreedevi, A.; Priyanka, K. P.; Ganesh, S.; Varghese, Thomas

2018-06-01

The effect of 8 MeV electron beam irradiation on the thermal, structural and electrical properties of CeO2 nanoparticles synthesized by chemical precipitation route was investigated. The dose dependent effect of electron irradiation was studied using various characterization techniques such as, thermogravimetric and differential thermal analyses, X-ray diffraction, Fourier transformed infrared spectroscopy and impedance spectroscopy. Systematic investigation based on the results of structural studies confirm that electron beam irradiation induces defects and particle size variation on CeO2 nanoparticles, which in turn results improvements in AC conductivity, dielectric constant and loss tangent. Structural modifications and high value of dielectric constant for CeO2 nanoparticles due to electron beam irradiation make it as a promising material for the fabrication of gate dielectric in metal oxide semiconductor devices.

Evaluation of Graphite Fiber/Polyimide PMCs from Hot Melt versus Solution Prepreg

NASA Technical Reports Server (NTRS)

Shin, Eugene E.; Sutter, James K.; Eakin, Howard; Inghram, Linda; McCorkle, Linda; Scheiman, Dan; Papadopoulos, Demetrios; Thesken, John; Fink, Jeffrey E.; Gray, Hugh R. (Technical Monitor)

2002-01-01

Carbon fiber reinforced high temperature polymer matrix composites (PMC) have been extensively investigated as potential weight reduction replacements of various metallic components in next generation high performance propulsion rocket engines. The initial phase involves development of comprehensive composite material-process-structure-design-property in-service performance correlations and database, especially for a high stiffness facesheet of various sandwich structures. Overview of the program plan, technical approaches and current multi-team efforts will be presented. During composite fabrication, it was found that the two large volume commercial prepregging methods (hot-melt vs. solution) resulted in considerably different composite cure behavior. Details of the process-induced physical and chemical modifications in the prepregs, their effects on composite processing, and systematic cure cycle optimization studies will be discussed. The combined effects of prepregging method and cure cycle modification on composite properties and isothermal aging performance were also evaluated.

Carotid Artery Stenting, Endarterectomy, or Medical Treatment Alone: The Debate Is Not Over

PubMed Central

Kassaian, Seyed Ebrahim; Goodarzynejad, Hamidreza

2011-01-01

The management of carotid artery stenosis reduces the risk of stroke and its related deaths. Management options include risk factor modification and medical therapy, carotid endarterectomy (CEA), and carotid artery stenting (CAS). Although several randomized controlled trials (RCTs), mostly conducted in late-1980s and mid-1990s, have proved CEA to be effective in the prevention of ipsilateral ischemic events in selected patients with carotid artery stenosis, aggressive risk factor modification and medical therapy with recently introduced antiplatelet agents, statins, and more effective antihypertensive medications may have reduced compelling indications for immediate surgery in asymptomatic populations. Also recently, due to improvements in percutaneous techniques and carotid stents, CAS has received wide attention as a potential alternative to CEA. Herein, we review the recent data on the management options of carotid artery stenosis and seek to identify the most appropriate treatment strategy in selected patients with carotid artery stenosis. PMID:23074598

Local epigenetic reprograming induced by G-quadruplex ligands

PubMed Central

Recolin, Bénédicte; Campbell, Beth C.; Maiter, Ahmed; Sale, Julian E.; Balasubramanian, Shankar

2017-01-01

DNA and histone modifications regulate transcriptional activity and thus represent valuable targets to reprogram the activity of genes. Current epigenetic therapies target the machinery that regulates these modifications, leading to global transcriptional reprogramming with the potential for extensive undesired effects. Epigenetic information can also be modified as a consequence of disrupting processive DNA replication. Here we demonstrate that impeding replication by small molecule-mediated stabilisation of G-quadruplex nucleic acid secondary structures triggers local epigenetic plasticity. We report the use of the BU-1 locus of chicken DT40 cells to screen for small molecules able to induce G-quadruplex-dependent transcriptional reprogramming. Further characterisation of the top hit compound revealed its ability to induce a dose-dependent inactivation of BU-1 expression in two steps, first loss of H3K4me3 and subsequently DNA cytosine methylation, changes that were heritable across cell divisions even after the compound was removed. Targeting DNA secondary structures thus represents a potentially new approach for locus-specific epigenetic reprogramming. PMID:29064488

Local epigenetic reprogramming induced by G-quadruplex ligands

NASA Astrophysics Data System (ADS)

Guilbaud, Guillaume; Murat, Pierre; Recolin, Bénédicte; Campbell, Beth C.; Maiter, Ahmed; Sale, Julian E.; Balasubramanian, Shankar

2017-11-01

DNA and histone modifications regulate transcriptional activity and thus represent valuable targets to reprogram the activity of genes. Current epigenetic therapies target the machinery that regulates these modifications, leading to global transcriptional reprogramming with the potential for extensive undesired effects. Epigenetic information can also be modified as a consequence of disrupting processive DNA replication. Here, we demonstrate that impeding replication by small-molecule-mediated stabilization of G-quadruplex nucleic acid secondary structures triggers local epigenetic plasticity. We report the use of the BU-1 locus of chicken DT40 cells to screen for small molecules able to induce G-quadruplex-dependent transcriptional reprogramming. Further characterization of the top hit compound revealed its ability to induce a dose-dependent inactivation of BU-1 expression in two steps: the loss of H3K4me3 and then subsequent DNA cytosine methylation, changes that were heritable across cell divisions even after the compound was removed. Targeting DNA secondary structures thus represents a potentially new approach for locus-specific epigenetic reprogramming.

Modification of the surfaces of medical devices to prevent microbial adhesion and biofilm formation.

PubMed

Desrousseaux, C; Sautou, V; Descamps, S; Traoré, O

2013-10-01

The development of devices with surfaces that have an effect against microbial adhesion or viability is a promising approach to the prevention of device-related infections. To review the strategies used to design devices with surfaces able to limit microbial adhesion and/or growth. A PubMed search of the published literature. One strategy is to design medical devices with a biocidal agent. Biocides can be incorporated into the materials or coated or covalently bonded, resulting either in release of the biocide or in contact killing without release of the biocide. The use of biocides in medical devices is debated because of the risk of bacterial resistance and potential toxicity. Another strategy is to modify the chemical or physical surface properties of the materials to prevent microbial adhesion, a complex phenomenon that also depends directly on microbial biological structure and the environment. Anti-adhesive chemical surface modifications mostly target the hydrophobicity features of the materials. Topographical modifications are focused on roughness and nanostructures, whose size and spatial organization are controlled. The most effective physical parameters to reduce bacterial adhesion remain to be determined and could depend on shape and other bacterial characteristics. A prevention strategy based on reducing microbial attachment rather than on releasing a biocide is promising. Evidence of the clinical efficacy of these surface-modified devices is lacking. Additional studies are needed to determine which physical features have the greatest potential for reducing adhesion and to assess the usefulness of antimicrobial coatings other than antibiotics. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Relationship between size and surface modification of silica particles and enhancement and suppression of inflammatory cytokine production by lipopolysaccharide- or peptidoglycan-stimulated RAW264.7 macrophages

NASA Astrophysics Data System (ADS)

Uemura, Eiichiro; Yoshioka, Yasuo; Hirai, Toshiro; Handa, Takayuki; Nagano, Kazuya; Higashisaka, Kazuma; Tsutsumi, Yasuo

2016-06-01

Although nanomaterials are used in an increasing number of commodities, the relationships between their immunotoxicity and physicochemical properties such as size or surface characteristics are not fully understood. Here we demonstrated that pretreatment with amorphous silica particles (SPs) of various sizes (diameters of 10-1000 nm), with or without amine surface modification, significantly decreased interleukin 6 production by RAW264.7 macrophages following lipopolysaccharide or peptidoglycan stimulation. Furthermore, nanosized, but not microsized, SPs significantly enhanced tumor necrosis factor-α production in macrophages stimulated with lipopolysaccharide. This altered cytokine response was distinct from the inflammatory responses induced by treatment with the SPs alone. Additionally, the uptake of SPs into macrophages by phagocytosis was found to be crucial for the suppression of macrophage immune response to occur, irrespective of particle size or surface modification. Together, these results suggest that SPs may not only increase susceptibility to microbial infection, but that they may also be potentially effective immunosuppressants.

On the Klein–Gordon oscillator subject to a Coulomb-type potential

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

Bakke, K., E-mail: kbakke@fisica.ufpb.br; Furtado, C., E-mail: furtado@fisica.ufpb.br

2015-04-15

By introducing the scalar potential as modification in the mass term of the Klein–Gordon equation, the influence of a Coulomb-type potential on the Klein–Gordon oscillator is investigated. Relativistic bound states solutions are achieved to both attractive and repulsive Coulomb-type potentials and the arising of a quantum effect characterized by the dependence of angular frequency of the Klein–Gordon oscillator on the quantum numbers of the system is shown. - Highlights: • Interaction between the Klein–Gordon oscillator and a modified mass term. • Relativistic bound states for both attractive and repulsive Coulomb-type potentials. • Dependence of the Klein–Gordon oscillator frequency on themore » quantum numbers. • Relativistic analogue of a position-dependent mass system.« less

Modern and prospective technologies for weather modification activities: A look at integrating unmanned aircraft systems

NASA Astrophysics Data System (ADS)

Axisa, Duncan; DeFelice, Tom P.

2016-09-01

Present-day weather modification technologies are scientifically based and have made controlled technological advances since the late 1990s, early 2000s. The technological advances directly related to weather modification have primarily been in the decision support and evaluation based software and modeling areas. However, there have been some technological advances in other fields that might now be advanced enough to start considering their usefulness for improving weather modification operational efficiency and evaluation accuracy. We consider the programmatic aspects underlying the development of new technologies for use in weather modification activities, identifying their potential benefits and limitations. We provide context and initial guidance for operators that might integrate unmanned aircraft systems technology in future weather modification operations.

Handling Qualities Flight Testing of the Stratospheric Observatory for Infrared Astronomy (SOFIA)

NASA Technical Reports Server (NTRS)

Glaser, Scott T.; Strovers, Brian K.

2011-01-01

Airborne infrared astronomy has a long successful history, albeit relatively unknown outside of the astronomy community. A major problem with ground based infrared astronomy is the absorption and scatter of infrared energy by water in the atmosphere. Observing the universe from above 40,000 ft puts the observation platform above 99% of the water vapor in the atmosphere, thereby addressing this problem at a fraction of the cost of space based systems. The Stratospheric Observatory For Infrared Astronomy (SOFIA) aircraft is the most ambitious foray into the field of airborne infrared astronomy in history. Using a 747SP (The Boeing Company, Chicago, Illinois) aircraft modified with a 2.5m telescope located in the aft section of the fuselage, the SOFIA endeavors to provide views of the universe never before possible and at a fraction of the cost of space based systems. The modification to the airplane includes moveable doors and aperture that expose the telescope assembly. The telescope assembly is aimed and stabilized using a multitude of on board systems. This modification has the potential to cause aerodynamic anomalies that could induce undesired forces either at the cavity itself or indirectly due to interference with the empennage, both of which could cause handling qualities issues. As a result, an extensive analysis and flight test program was conducted from December 2009 through March 2011. Several methods, including a Lower Order Equivalent Systems analysis and pilot assessment, were used to ascertain the effects of the modification. The SOFIA modification was found to cause no adverse handling qualities effects and the aircraft was cleared for operational use. This paper discusses the history and modification to the aircraft, development of test procedures and analysis, results of testing and analysis, lessons learned for future projects and justification for operational certification.

Making healthy food choices using nutrition facts panels. The roles of knowledge, motivation, dietary modifications goals, and age.

PubMed

Miller, Lisa M Soederberg; Cassady, Diana L

2012-08-01

Nutrition facts panels (NFPs) contain a rich assortment of nutrition information and are available on most food packages. The importance of this information is potentially even greater among older adults due to their increased risk for diet-related diseases, as well as those with goals for dietary modifications that may impact food choice. Despite past work suggesting that knowledge and motivation impact attitudes surrounding and self-reported use of NFPs, we know little about how (i.e., strategies used) and how well (i.e., level of accuracy) younger and older individuals process NFP information when evaluating healthful qualities of foods. We manipulated the content of NFPs and, using eye tracking methodology, examined strategies associated with deciding which of two NFPs, presented side-by-side, was healthier. We examined associations among strategy use and accuracy as well as age, dietary modification status, knowledge, and motivation. Results showed that, across age groups, those with dietary modification goals made relatively more comparisons between NFPs with increasing knowledge and motivation; but that strategy effectiveness (relationship to accuracy) depended on age and motivation. Results also showed that knowledge and motivation may protect against declines in accuracy in later life and that, across age and dietary modification status, knowledge mediates the relationship between motivation and decision accuracy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Note: Modification of the Gay-Berne potential for improved accuracy and speed

NASA Astrophysics Data System (ADS)

Persson, Rasmus A. X.

2012-06-01

A modification of the Gay-Berne (GB) potential is proposed which is about 10% to 20% more speed efficient and statistically more accurate in reproducing the energy of interaction of two linear Lennard-Jones tetratomics when averaged over all orientations. For the special cases of end-to-end and side-by-side configurations, the new potential is equivalent to the GB one. A simple generalization to dissimilar particles of D∞h symmetry is presented but does not retain the superior agreement with respect to its GB counterpart, except at close range.

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.

Histones and their modifications in ovarian cancer - drivers of disease and therapeutic targets.

PubMed

Marsh, Deborah J; Shah, Jaynish S; Cole, Alexander J

2014-01-01

Epithelial ovarian cancer has the highest mortality of the gynecological malignancies. High grade serous epithelial ovarian cancer (SEOC) is the most common subtype, with the majority of women presenting with advanced disease where 5-year survival is around 25%. Platinum-based chemotherapy in combination with paclitaxel remains the most effective treatment despite platinum therapies being introduced almost 40 years ago. Advances in molecular medicine are underpinning new strategies for the treatment of cancer. Major advances have been made by international initiatives to sequence cancer genomes. For SEOC, with the exception of TP53 that is mutated in virtually 100% of these tumors, there is no other gene mutated at high frequency. There is extensive copy number variation, as well as changes in methylation patterns that will influence gene expression. To date, the role of histones and their post-translational modifications in ovarian cancer is a relatively understudied field. Post-translational histone modifications play major roles in gene expression as they direct the configuration of chromatin and so access by transcription factors. Histone modifications include methylation, acetylation, and monoubiquitination, with involvement of enzymes including histone methyltransferases, histone acetyltransferases/deacetylases, and ubiquitin ligases/deubiquitinases, respectively. Complexes such as the Polycomb repressive complex also play roles in the control of histone modifications and more recently roles for long non-coding RNA and microRNAs are emerging. Epigenomic-based therapies targeting histone modifications are being developed and offer new approaches for the treatment of ovarian cancer. Here, we discuss histone modifications and their aberrant regulation in malignancy and specifically in ovarian cancer. We review current and upcoming histone-based therapies that have the potential to inform and improve treatment strategies for women with ovarian cancer.

Array automated assembly task, phase 2. Low cost silicon solar array project

NASA Technical Reports Server (NTRS)

Rhee, S. S.; Jones, G. T.; Allison, K. T.

1978-01-01

Several modifications instituted in the wafer surface preparation process served to significantly reduce the process cost to 1.55 cents per peak watt in 1975 cents. Performance verification tests of a laser scanning system showed a limited capability to detect hidden cracks or defects, but with potential equipment modifications this cost effective system could be rendered suitable for applications. Installation of electroless nickel plating system was completed along with an optimization of the wafer plating process. The solder coating and flux removal process verification test was completed. An optimum temperature range of 500-550 C was found to produce uniform solder coating with the restriction that a modified dipping procedure is utilized. Finally, the construction of the spray-on dopant equipment was completed.

Investigating the Potential of Land Use Modifications to Mitigate the Respiratory Health Impacts of NO2: A Case Study in the Portland-Vancouver Metropolitan Area

NASA Astrophysics Data System (ADS)

Rao, Meenakshi

The health impacts of urban air pollution are a growing concern in our rapidly urbanizing world. Urban air pollutants show high intra-urban spatial variability linked to urban land use and land cover (LULC). This correlation of air pollutants with LULC is widely recognized; LULC data is an integral input into a wide range of models, especially land use regression models developed by epidemiologists to study the impact of air pollution on human health. Given the demonstrated links between LULC and urban air pollution, and between urban air pollution and health, an interesting question arises: what is the potential of LULC modifications to mitigate the health impacts of urban air pollution? In this dissertation we assess the potential of LULC modifications to mitigate the health impacts of NO2, a respiratory irritant and strong marker for combustion-related air pollution, in the Portland-Vancouver metropolitan area in northwestern USA. We begin by measuring summer and winter NO2 in the area using a spatially dense network of passive NO 2 samplers. We next develop an annual average model for NO2 based on the observational data, using random forest--for the first time in the realm of urban air pollution--to disentangle the effects of highly correlated LULC variables on ambient NO2 concentrations. We apply this random forest (LURF) model to a 200m spatial grid covering the study area, and use this 200m LURF model to quantify the effect of different urban land use categories on ambient concentrations of NO2. Using the changes in ambient NO2 concentrations resulting from land use modifications as input to BenMAP (a health benefits assessment tool form the US EPA), we assess the NO2-related health impact associated with each land use category and its modifications. We demonstrate how the LURF model can be used to assess the respiratory health benefits of competing land use modifications, including city-wide and local-scale mitigation strategies based on modifying tree canopy and vehicle miles traveled (VMT). Planting trees is a common land cover modification strategy undertaken by cities to reduce air pollution. Statistical models such as LUR and LURF demonstrate a correlation between tree cover and reduced air pollution, but they cannot demonstrate causation. Hence, we run the atmospheric chemistry and transport model CMAQ to examine to what extent the dry deposition mechanism can explain the reduction of NO2 which statistical models associate with tree canopy. Results from our research indicate that even though the Portland-Vancouver area is in compliance with the US EPA NO2 standards, ambient concentrations of NO2 still create an annual health burden of at least 40 million USD. Our model suggests that NO2 associated with high intensity development and VMT may be creating an annual health burden of 7 million and 3.3 million USD respectively. Existing tree canopy, on the other hand, is associated with an annual health benefit of 1.4 million USD. LULC modifications can mitigate some fraction of this health burden. A 2% increase in tree canopy across the study area may reduce incidence rates of asthma exacerbation by as much as 7%. We also find that increasing tree canopy is a more effective strategy than reducing VMT in terms of mitigating the health burden of NO 2. CMAQ indicates that the amount of NO2 removed by dry deposition is an order of magnitude smaller than that predicted by our statistical model. About one-third of the difference can be explained by the lower NO2 values predicted by CMAQ, and one-third may be attributable to parameterization of stomatal uptake.

Reversal of Apixaban Induced Alterations in Hemostasis by Different Coagulation Factor Concentrates: Significance of Studies In Vitro with Circulating Human Blood

PubMed Central

Arellano-Rodrigo, Eduardo; Roquer, Jaume; Reverter, Joan Carles; Sanz, Victoria Veronica; Molina, Patricia; Lopez-Vilchez, Irene; Diaz-Ricart, Maribel; Galan, Ana Maria

2013-01-01

Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s−1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM and perfusion studies. Our results indicate that rFVIIa, PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban. PMID:24244342

Modelling and simulation of complex sociotechnical systems: envisioning and analysing work environments

PubMed Central

Hettinger, Lawrence J.; Kirlik, Alex; Goh, Yang Miang; Buckle, Peter

2015-01-01

Accurate comprehension and analysis of complex sociotechnical systems is a daunting task. Empirically examining, or simply envisioning the structure and behaviour of such systems challenges traditional analytic and experimental approaches as well as our everyday cognitive capabilities. Computer-based models and simulations afford potentially useful means of accomplishing sociotechnical system design and analysis objectives. From a design perspective, they can provide a basis for a common mental model among stakeholders, thereby facilitating accurate comprehension of factors impacting system performance and potential effects of system modifications. From a research perspective, models and simulations afford the means to study aspects of sociotechnical system design and operation, including the potential impact of modifications to structural and dynamic system properties, in ways not feasible with traditional experimental approaches. This paper describes issues involved in the design and use of such models and simulations and describes a proposed path forward to their development and implementation. Practitioner Summary: The size and complexity of real-world sociotechnical systems can present significant barriers to their design, comprehension and empirical analysis. This article describes the potential advantages of computer-based models and simulations for understanding factors that impact sociotechnical system design and operation, particularly with respect to process and occupational safety. PMID:25761227

Assessing Stream Restoration Potential of Recreational Enhancements on an Urban Stream, Springfield, OH

NASA Astrophysics Data System (ADS)

Ritter, J. B.; Evelsizor, A.; Minter, K.; Rigsby, C.; Shaw, K.; Shearer, K.

2010-12-01

Restoration potential of urban streams is inherently constrained by urban infrastructure. Roads and built structures may necessitate a static stream planform while water, sewage, and electrical utilities buried in the stream channel require a stable grade. A privately-led initiative to improve the recreational potential of a 9-km reach of Buck Creek and its tributary Beaver Creek in Springfield, Ohio, includes the modification of four lowhead dams with hydraulic heights up to 3 m. Modifications to the dams include replacing their hydraulic height with a series of drop structures engineered to create hydraulics conducive to kayak play. Two of the lowhead dams have been modified to date. The purpose of this study is to assess the potential benefits of modifications designed for their recreational value for stream restoration. The drop structure is a constructed channel constriction comprised of a hard step in the long stream profile immediately upstream of a scour pool, forming a morphologic sequence of constriction, step, and pool. Up to 4 drop structures are used along a given stream reach, constructed in the area of the former dam, its scour pool and a portion of the impounded area. Though not designed for stream restoration purposes, these structures potentially act as series a riffle-pool sequences. Changes in the stream habitat, water chemistry, and macroinvertebrates in response to dam modification highlight the potential for incorporating stream restoration into the engineering design. Following modification of two of the dams, the in-stream habitat quality, as measured by physical and biological indices, increased at one site and decreased at the other site, depending on whether the uppermost drop structure at the site reduced or expanded the impounded area. In the best case, channel sands and gravels, free of fine sand, silt, and organics, have deposited in a crescentic-shaped bar paralleling and grading to the constriction and step. Greater abundance and diversity of pollution-intolerant macroinvertebrates, supported by higher dissolved oxygen in the substrate, characterizes riffles at these sites.

Effects of tooth profile modification on dynamic responses of a high speed gear-rotor-bearing system

NASA Astrophysics Data System (ADS)

Hu, Zehua; Tang, Jinyuan; Zhong, Jue; Chen, Siyu; Yan, Haiyan

2016-08-01

A finite element node dynamic model of a high speed gear-rotor-bearing system considering the time-varying mesh stiffness, backlash, gyroscopic effect and transmission error excitation is developed. Different tooth profile modifications are introduced into the gear pair and corresponding time-varying mesh stiffness curves are obtained. Effects of the tooth profile modification on mesh stiffness are analyzed, and the natural frequencies and mode shapes of the gear-rotor-bearing transmission system are given. The dynamic responses with respect to a wide input speed region including dynamic factor, vibration amplitude near the bearing and dynamic transmission error are obtained by introducing the time-varying mesh stiffness in different tooth profile modification cases into the gear-rotor-bearing dynamic system. Effects of the tooth profile modification on the dynamic responses are studied in detail. The numerical simulation results show that both the short profile modification and the long profile modification can affect the mutation of the mesh stiffness when the number of engaging tooth pairs changes. A short profile modification with an appropriate modification amount can improve the dynamic property of the system in certain work condition.

Use of meteorological satellite observations in weather modification programs

NASA Technical Reports Server (NTRS)

Dennis, A. S.; Smith, P. L., Jr.; Biswas, K. R.

1973-01-01

The potential value of weather satellite data in field operations of weather modification is appraised. It was found that satellites could play a useful role in operational weather modification projects, particularly in the recognition of treatment opportunities. Satellite cloud photographs and infrared observations appear promising in the identification of treatment opportunities in seeding orographic cloud systems for increased snowpack, in seeding convective clouds for increased rainfall, in identifying hail threats, and in tracking and observing hurricanes as an aid to timing and location of seeding treatments. It was concluded that the potential value of satellite data in the treatment and evaluation phases of operational projects is not as great as in the recognition of treatment opportunity.

Recent Advances in Attention Bias Modification for Substance Addictions

PubMed Central

Zhang, Melvyn Weibin; Ying, Jiang Bo; Song, Guo; Fung, Daniel S. S.; Smith, Helen E.

2018-01-01

Research on attentional bias modification has increased since 2014. A recent meta-analysis demonstrates evidence for bias modification for substance disorders, including alcohol and tobacco use disorders. Several pharmacological trials have shown that pharmacological agents can attenuate and modify such attentional bias. The pharmacological trials that have appeared to date have produced mixed results, which has clinical implications. Developments in Internet and mobile technologies have transformed how attention bias modification is currently being achieved. There remains great potential for further research that examines the efficacy of technology-aided attention bias interventions. PMID:29617325

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

Fromm, Andrea; Bonitz, Michael; Dufty, James

The idea of treating quantum systems by semiclassical representations using effective quantum potentials (forces) has been successfully applied in equilibrium by many authors, see e.g. [D. Bohm, Phys. Rev. 85 (1986) 166 and 180; D.K. Ferry, J.R. Zhou, Phys. Rev. B 48 (1993) 7944; A.V. Filinov, M. Bonitz, W. Ebeling, J. Phys. A 36 (2003) 5957 and references cited therein]. Here, this idea is extended to nonequilibrium quantum systems in an external field. A gauge-invariant quantum kinetic theory for weakly inhomogeneous charged particle systems in a strong electromagnetic field is developed within the framework of nonequilibrium Green's functions. The equationmore » for the spectral density is simplified by introducing a classical (local) form for the kinetics. Nonlocal quantum effects are accounted for in this way by replacing the bare external confinement potential with an effective quantum potential. The equation for this effective potential is identified and solved for weak inhomogeneity in the collisionless limit. The resulting nonequilibrium spectral function is used to determine the density of states and the modification of the Born collision operator in the kinetic equation for the Wigner function due to quantum confinement effects.« less

Effects of pretreatment processes for Zr electrorefining of oxidized Zircaloy-4 cladding tubes

NASA Astrophysics Data System (ADS)

Hwa Lee, Chang; Lee, Yoo Lee; Jeon, Min Ku; Choi, Yong Taek; Kang, Kweon Ho; Park, Geun Il

2014-06-01

The effect of pretreatment processes for the Zr electrorefining of oxidized Zircaloy-4 cladding tubes is examined in LiCl-KCl-ZrCl4 molten salts at 500 °C. The cyclic voltammetries reveal that the Zr dissolution kinetics is highly dependent on the thickness of a Zr oxide layer formed at 500 °C under air atmosphere. For the Zircaloy-4 tube covered with a 1 μm thick oxide layer, the Zr dissolution process is initiated from a non-stoichiometric Zr oxide surface through salt treatment at an open circuit potential in the molten salt electrolyte. The Zr dissolution of the samples in the middle range of oxide layer thickness appears to be more effectively derived by the salt treatment coupled with an anodic potential application at an oxidation potential of Zr. A modification of the process scheme offers an applicability of Zr electrorefining for the treatment of oxidized cladding hull wastes.

Magnetic fluids effect upon growth processes in plants

NASA Astrophysics Data System (ADS)

Sala, F.

1999-07-01

The metabolic processes of plants growth and development take place according to some organic rules which are specific to their genetic potential. These processes may exhibit modifications of intensity, rhythm, sense, under the influence of the environmental conditions of agricultural systems, through certain factors and bioregulators artificially introduced by man. The results of some investigations regarding effects of biocompatible magnetic fluids (LMW 100 G) on the vegetal organism's (growth, development, fructifying, the level and quality of the yield precocity) are presented.

Effect of deformation on the structural state of piracetam

NASA Astrophysics Data System (ADS)

Kanunnikova, O. M.; Mikhailova, S. S.; Karban', O. V.; Mukhgalin, V. V.; Aksenova, V. V.; Sen'kovskii, B. V.; Pechina, E. A.; Lad'yanov, V. I.

2016-04-01

The effect of various deformation actions on the structure-phase transformations in piracetam of modifications I and II with a sodium acetate addition is studied. Mechanical activation and pressing are shown to cause the polymorphic transformation of modification I into modification II, and modification III forms predominantly during severe plastic deformation by torsion. The structural difference between the piracetam molecules of modifications I and II is found to be retained in aqueous solutions.

Attenuation of glycation-induced multiple protein modifications by Indian antidiabetic plant extracts.

PubMed

Tupe, Rashmi S; Kemse, Nisha G; Khaire, Amrita A; Shaikh, Shamim A

2017-12-01

Protein glycation is the major contributing factor in the development of diabetic complications. The antiglycation potential of medicinal plants provides a promising opportunity as complementary interventions for complications. To investigate the antiglycation potential of 19 medicinal plants extracts using albumin by estimating different indicators: (1) glycation (early and late), (2) albumin oxidation, and (3) amyloid aggregation. The effect of aqueous plant extracts (1% w/v) on protein glycation was assessed by incubating albumin (10 mg/mL) with fructose (250 mM) for 4 days. Degree of protein glycation in the absence and presence of plant extracts was assessed by estimating fructosamine, advanced glycation end products (AGEs), carbonyls, free thiol group and β-amyloid aggregation. Petroselinum crispum, Boerhavia diffusa, Terminalia chebula, Swertia chirayita and Glycyrrhiza glabra showed significant antiglycating activity. P. crispum and A. barbadensis inhibited the carbonyl stress and protected the thiol group from oxidative damage. There was significant correlation between protein thiols and amyloid inhibition (R = -.69, p < .001). P. crispum, B. diffusa and T. chebula had the most potent antiglycation activity. These plant exerted noticeable antiglycation activity at different glycation modifications of albumin. These findings are important for identifying plants with potential to combat diabetic complications.

Spacesuit Radiation Shield Design Methods

NASA Technical Reports Server (NTRS)

Wilson, John W.; Anderson, Brooke M.; Cucinotta, Francis A.; Ware, J.; Zeitlin, Cary J.

2006-01-01

Meeting radiation protection requirements during EVA is predominantly an operational issue with some potential considerations for temporary shelter. The issue of spacesuit shielding is mainly guided by the potential of accidental exposure when operational and temporary shelter considerations fail to maintain exposures within operational limits. In this case, very high exposure levels are possible which could result in observable health effects and even be life threatening. Under these assumptions, potential spacesuit radiation exposures have been studied using known historical solar particle events to gain insight on the usefulness of modification of spacesuit design in which the control of skin exposure is a critical design issue and reduction of blood forming organ exposure is desirable. Transition to a new spacesuit design including soft upper-torso and reconfigured life support hardware gives an opportunity to optimize the next generation spacesuit for reduced potential health effects during an accidental exposure.

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

NASA Technical Reports Server (NTRS)

Barber, Peter W.; Demerdash, Nabeel A. O.; Wang, R.; Hurysz, B.; Luo, Z.

1991-01-01

The goal is to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom.The approach consists of four steps: (1) develop analytical tools (models and computer programs); (2) conduct parameterization studies; (3) predict the global space station EMI environment; and (4) provide a basis for modification of EMI standards.

Wood surface modification by in-situ sol-gel deposition of hybrid inorganic-organic thin films

Treesearch

Mandla A. Tshabalala; Li-Piin Sung

2007-01-01

Interest in the use of nanoparticles of iron, titanium, aluminum, and zinc oxides in transparent coatings for wood is increasing. Such nano-composite coatings have the potential of not only preserving the natural color of the wood, but also stabilizing the wood surface against the combined degradative effects of sunlight and moisture. The nanoparticles can be used as...

Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy.

PubMed

Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

2016-06-01

Despite remarkable advancements, clinical evaluations of adenovirus (Ad)-mediated cancer gene therapies have highlighted the need for improved delivery and targeting. Genetic modification of Ad capsid proteins has been extensively attempted. Although genetic modification enhances the therapeutic potential of Ad, it is difficult to successfully incorporate extraneous moieties into the capsid and the engineering process is laborious. Recently, chemical modification of the Ad surface with nanomaterials and targeting moieties has been found to enhance Ad internalization into the target by both passive and active mechanisms. Alternatively, external stimulus-mediated targeting can result in selective accumulation of Ad in the tumor and prevent dissemination of Ad into surrounding nontarget tissues. In the present review, we discuss various genetic, chemical, and mechanical engineering strategies for overcoming the challenges that hinder the therapeutic efficacy of Ad-based approaches. Surface modification of Ad by genetic, chemical, or mechanical engineering strategies enables Ad to overcome the shortcomings of conventional Ad and enhances delivery efficiency through distinct and unique mechanisms that unmodified Ad cannot mimic. However, although the therapeutic potential of Ad-mediated gene therapy has been enhanced by various surface modification strategies, each strategy still possesses innate limitations that must be addressed, requiring innovative ideas and designs.

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial.

PubMed

Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

2009-05-21

Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. http://www.clinicaltrials.gov identifier NCT00847769.

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

PubMed Central

Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

2009-01-01

Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration identifier NCT00847769. PMID:19460169

Undoped and Ni-doped CoO x surface modification of porous BiVO 4 photoelectrodes for water oxidation

DOE PAGES

Liu, Ya; Guo, Youhong; Schelhas, Laura T.; ...

2016-09-29

Surface modification of photoanodes with oxygen evolution reaction (OER) catalysts is an effective approach to enhance water oxidation kinetics, to reduce external bias, and to improve the energy harvesting efficiency of photoelectrochemical (PEC) water oxidation. Here, the surface of porous BiVO 4 photoanodes was modified by the deposition of undoped and Ni-doped CoO x via nitrogen flow assisted electrostatic spray pyrolysis. This newly developed atmospheric pressure deposition technique allows for surface coverage throughout the porous structure with thickness and composition control. PEC testing of modified BiVO 4 photoanodes shows that after deposition of an undoped CoO x surface layer, themore » onset potential shifts negatively by ca. 420 mV and the photocurrent density reaches 2.01 mA cm –2 at 1.23 vs V RHE under AM 1.5G illumination. Modification with Ni-doped CoO x produces even more effective OER catalysis and yields a photocurrent density of 2.62 mA cm –2 at 1.23 V RHE under AM 1.5G illumination. Furthermore, the valence band X-ray photoelectron spectroscopy and synchrotron-based X-ray absorption spectroscopy results show the Ni doping reduces the Fermi level of the CoO x layer; the increased surface band bending produced by this effect is partially responsible for the superior PEC performance.« less

Cost Savings Potential of Modification to the Standard Light Rail Vehicle Specification

DOT National Transportation Integrated Search

1979-02-01

This report describes an assessment of the Standard Light Rail Vehicle (SLRV) specification to determine whether the relaxation or modification of some requirements could result in a significant reduction in vehicle costs. A Technique of Assessment b...

Memantine reverses social withdrawal induced by ketamine in rats.

PubMed

Uribe, Ezequiel; Landaeta, José; Wix, Richard; Eblen, Antonio

2013-03-01

The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.

A multitechnique evaluation of topical corticosteroid treatment.

PubMed

Josse, G; Rouvrais, C; Mas, A; Haftek, M; Delalleau, A; Ferraq, Y; Ossant, F; George, J; Lagarde, J M; Schmitt, A M

2009-02-01

Corticosteroids are widely prescribed for systemic or local treatment of inflammatory autoimmune disorders. Long-term therapy is associated with side effects and causes cutaneous atrophy of the epidermis and the dermis. The present study aims to evaluate with several noninvasive techniques, the skin modifications observed during corticosteroids treatment. The potential of skin mechanical measurement and ultrasound radio frequency (RF) signal analysis are proposed as new measures more closely related to the functional impairments. Thirteen young healthy women volunteers had two applications per day on one arm of topical Clobetasol propionate 0.05% for 28 days, and they were followed for 28 days more. Skin modifications were studied by high-frequency ultrasound imaging, ultrasound RF signal analysis, optical coherence tomography and by the suction test. For all the techniques, a statistically significant change is observed with treatment. Large variations, around 30%, are observed for all techniques, but less for ultrasound imaging (10%). Dermis and epidermis thickness presented stable measurements on the nontreated zone. At the end of the study, measures returned to normal. The dynamic is mainly observed within the first 14 days of treatment and within the first 14 days after its cessation. Similar dynamics of skin modification during corticosteroid treatment was observed with very different techniques. Moreover, the potential of RF ultrasound analysis and mechanical skin measurement for characterizing skin structural and functional impairments has been evaluated.

Antidepressant-Like Effects of Acupuncture-Insights From DNA Methylation and Histone Modifications of Brain-Derived Neurotrophic Factor.

PubMed

Jiang, Huili; Zhang, Xuhui; Lu, Jun; Meng, Hong; Sun, Yang; Yang, Xinjing; Zhao, Bingcong; Bao, Tuya

2018-01-01

Sensitive and stable biomarkers that facilitate depression detection and monitor the antidepressant efficiency are currently unavailable. Thus, the objective is to investigate the potential of DNA methylation and histone modifications of brain-derived neurotrophic factor (BDNF) in monitoring severity and antidepressive effects of acupuncture. The depression rat model was imitated by social isolation and chronic unpredicted mild stress (CUMS). The expression of serum BDNF was detected by enzyme-linked immunosorbent assay (ELISA), the hippocampal BDNF, acetylation levels in histone H3 lysine 9 (acH3K9), and HDAC2 by Western blot, the hippocampal mRNA of BDNF by RT-polymerase chain reaction (PCR). The DNA methylation patterns of the promoter I of BDNF was detected by MS-PCR. We investigated that the expression of BDNF in serum and hippocampus were significantly downregulated compared with controls. The same trend was found in mRNA of BDNF. Notably, acupuncture reversed the downregulation of BDNF in serum and hippocampus and mRNA of BDNF compared with model group. Acupuncture reversed the CUMS-induced downregulation of hippocampal acH3K9. On the contrary, the CUMS-induced upregulation of hippocampal HDAC2 in model group was significantly reversed by acupuncture. Collectively, the antidepressant effect of acupuncture might be mediated by regulating the DNA methylation and histone modifications of BDNF, which may represent novel biomaker for detection of depression and monitoring severity and antidepressive effects.

Cancer Chemoprevention by Dietary Polyphenols: Promising Role for Epigenetics

PubMed Central

Link, Alexander; Balaguer, Francesc; Goel, Ajay

2010-01-01

Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans. In this article, we first discuss the contribution of diet and environmental factors on epigenetic alterations; subsequently, we provide a comprehensive review of literature on the role of various dietary polyphenols. In particular, we summarize the current knowledge on a large number of dietary agents and their effects on DNA methylation, histone modifications and regulation of expression of non-coding miRNAs in various in vitro and in vivo models. We emphasize how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopreventive strategies for reducing the health burden of cancer and other diseases in humans. PMID:20599773

Cognitive Modification and Systematic Desensitization with Test Anxious High School Students.

ERIC Educational Resources Information Center

Leal, Lois L.; And Others

1981-01-01

Compares the relative effectiveness of cognitive modification and systematic desensitization with test anxious high school students (N=30). The systematic desensitization treatment appeared to be significantly more effective on the performance measure while cognitive modification was more effective on one of the self-report measures. (Author/JAC)

Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

PubMed

Lester, Kathryn J; Field, Andy P; Muris, Peter

2011-01-01

This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

Sorption of lead ions on diatomite and manganese oxides modified diatomite.

PubMed

Al-Degs, Y; Khraisheh, M A; Tutunji, M F

2001-10-01

Naturally occurring diatomaceous earth (diatomite) has been tested as a potential sorbent for Pb(II) ions. The intrinsic exchange properties were further improved by modification with manganese oxides. Modified adsorbent (referred to as Mn-diatomite) showed a higher tendency for adsorbing lead ions from solution at pH 4. The high performance exhibited by Mn-diatomite was attributed to increased surface area and higher negative surface charge after modification. Scanning electron microscope pictures revealed a birnessite structure of manganese oxides, which was featured by a plate-like-crystal structure. Diatomite filtration quality was improved after modification by manganese oxides. Good filtration qualities combined with high exchange capacity emphasised the potential use of Mn-diatomite in filtration systems.

Cellular Pressure-Actuated Joint

NASA Technical Reports Server (NTRS)

McGuire, John R.

2003-01-01

A modification of a pressure-actuated joint has been proposed to improve its pressure actuation in such a manner as to reduce the potential for leakage of the pressurizing fluid. The specific joint for which the modification is proposed is a field joint in a reusable solid-fuel rocket motor (RSRM), in which the pressurizing fluid is a mixture of hot combustion gases. The proposed modification could also be applicable to other pressure-actuated joints of similar configuration.

Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo

NASA Astrophysics Data System (ADS)

Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

2015-04-01

The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01439e

The effect of chemically modified alginates on macrophage phenotype and biomolecule transport.

PubMed

Bygd, Hannah C; Bratlie, Kaitlin M

2016-07-01

Macrophage (MΦ) reprogramming has received significant attention in applications such as cancer therapeutics and tissue engineering where the host immune response to biomaterials is crucial in determining the success or failure of an implanted device. Polymeric systems can potentially be used to redirect infiltrating M1 MΦs toward a proangiogenic phenotype. This work exploits the concept of MΦ reprogramming in the engineering of materials for improving the longevity of tissue engineering scaffolds. We have investigated the effect of 13 different chemical modifications of alginate on MΦ phenotype. Markers of the M1 response-tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase-and the M2 response-arginase-were measured and used to determine the ability of the materials to alter MΦ phenotype. It was found that some modifications were able to reduce the pro-inflammatory response of M1 MΦs, others appeared to amplify the M2 phenotype, and the results for two materials suggested they were able to reprogram a MΦ population from M1 to M2. These findings were supplemented by studies done to examine the permselectivity of the materials. Diffusion of TNF-α was completely prevented through some of these materials, while up to 84% was found to diffuse through others. The diffusion of insulin through the materials was statistically consistent. These results suggest that the modification of these materials might alter mass transport in beneficial ways. The ability to control polarization of MΦ phenotypes with immunoprotective materials has the potential to augment the success of tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1707-1719, 2016. © 2016 Wiley Periodicals, Inc.

Oxidative stress and mitochondria-mediated cell death mechanisms triggered by the familial Danish dementia ADan amyloid

PubMed Central

Todd, Krysti; Ghiso, Jorge; Rostagno, Agueda

2015-01-01

Familial Danish Dementia (FDD), an early-onset non-amyloid-β (Aβ) cerebral amyloidosis, is neuropathologically characterized by widespread cerebral amyloid angiopathy, parenchymal amyloid and preamyloid deposits, as well as neurofibrillary degeneration indistinguishable to that seen in Alzheimer’s disease (AD). The main amyloid subunit composing FDD lesions, a 34-amino acid de-novo generated peptide ADan, is the direct result of a genetic defect at the 3’-end of the BRI2 gene and the physiologic action of furin-like proteolytic processing at the C-terminal region of the ADan precursor protein. We aimed to study the impact of the FDD mutation, the additional formation of the pyroglutamate (pE) posttranslational modification as well as the relevance of C-terminal truncations –all major components of the heterogeneous FDD deposits–on the structural and neurotoxic properties of the molecule. Our data indicates that whereas the mutation generated a β-sheet-rich hydrophobic ADan subunit of high oligomerization/fibrillization propensity and the pE modification further enhanced these properties, C-terminal truncations had the opposite effect mostly abolishing these features. The potentiation of pro-amyloidogenic properties correlated with the initiation of neuronal cell death mechanisms involving oxidative stress, perturbation of mitochondrial membrane potential, release of mitochondrial cytochrome c, and downstream activation of caspase-mediated apoptotic pathways. The amyloid-induced toxicity was inhibited by targeting specific components of these detrimental cellular pathways, using reactive oxygen scavengers and monoclonal antibodies recognizing the pathological amyloid subunit. Taken together, the data indicate that the FDD mutation and the pE posttranslational modification are both primary elements driving intact ADan into an amyloidogenic/neurotoxic pathway while truncations at the C-terminus eliminate the pro-amyloidogenic characteristics of the molecule, likely reflecting effect of physiologic clearance mechanisms. PMID:26459115

De novo design and engineering of functional metal and porphyrin-binding protein domains

NASA Astrophysics Data System (ADS)

Everson, Bernard H.

In this work, I describe an approach to the rational, iterative design and characterization of two functional cofactor-binding protein domains. First, a hybrid computational/experimental method was developed with the aim of algorithmically generating a suite of porphyrin-binding protein sequences with minimal mutual sequence information. This method was explored by generating libraries of sequences, which were then expressed and evaluated for function. One successful sequence is shown to bind a variety of porphyrin-like cofactors, and exhibits light- activated electron transfer in mixed hemin:chlorin e6 and hemin:Zn(II)-protoporphyrin IX complexes. These results imply that many sophisticated functions such as cofactor binding and electron transfer require only a very small number of residue positions in a protein sequence to be fixed. Net charge and hydrophobic content are important in determining protein solubility and stability. Accordingly, rational modifications were made to the aforementioned design procedure in order to improve its overall success rate. The effects of these modifications are explored using two `next-generation' sequence libraries, which were separately expressed and evaluated. Particular modifications to these design parameters are demonstrated to effectively double the purification success rate of the procedure. Finally, I describe the redesign of the artificial di-iron protein DF2 into CDM13, a single chain di-Manganese four-helix bundle. CDM13 acts as a functional model of natural manganese catalase, exhibiting a kcat of 0.08s-1 under steady-state conditions. The bound manganese cofactors have a reduction potential of +805 mV vs NHE, which is too high for efficient dismutation of hydrogen peroxide. These results indicate that as a high-potential manganese complex, CDM13 may represent a promising first step toward a polypeptide model of the Oxygen Evolving Complex of the photosynthetic enzyme Photosystem II.

Covalent modification of a ten-residue cationic antimicrobial peptide with levofloxacin

NASA Astrophysics Data System (ADS)

Rodriguez, Carlos; Papanastasiou, Emilios; Juba, Melanie; Bishop, Barney

2014-09-01

The rampant spread of antibiotic resistant bacteria has spurred interest in alternative strategies for developing next-generation antibacterial therapies. As such, there has been growing interest in cationic antimicrobial peptides (CAMPs) and their therapeutic applications. Modification of CAMPs via conjugation to auxiliary compounds, including small molecule drugs, is a new approach to developing effective, broad-spectrum antibacterial agents with novel physicochemical properties and versatile antibacterial mechanisms. Here, we’ve explored design parameters for engineering CAMPs conjugated to small molecules with favorable physicochemical and antibacterial properties by covalently affixing a fluoroquinolone antibiotic, levofloxacin, to the ten-residue CAMP Pep-4. Relative to the unmodified Pep-4, the conjugate was found to demonstrate substantially increased antibacterial potency under high salt concentrations. Historically, it has been observed that most CAMPs lose antibacterial effectiveness in such high ionic strength environments, a fact that has presented a challenge to their development as therapeutics. Physicochemical studies revealed that P4LC was more hydrophobic than Pep-4, while mechanistic findings indicated that the conjugate was more effective at disrupting bacterial membrane integrity. Although the inherent antibacterial effect of the incorporated levofloxacin molecules did not appear to be substantially realized in this conjugate, these findings nevertheless suggest that covalent attachment of small molecule antibiotics with favorable physicochemical properties to CAMPs could be a promising strategy for enhancing peptide performance and overall therapeutic potential. These results have broader applicability to the development of future CAMP-antibiotic conjugates for potential therapeutic applications.

Proposed modification to the specification for dry heat microbial reduction of spacecraft hardware for future US missions

NASA Astrophysics Data System (ADS)

James; Spry, A.; Beaudet, Robert; Schubert, Wayne

Dry heat microbial reduction (DHMR) is the primary technique used to reduce the microbial load of spacecraft and component parts to comply with planetary protection requirements. Often, manufacturing processes involve heating flight hardware to high temperatures for purposes other than planetary protection DHMR. At present, the existing specification in NASA document NPR8020.12C, describing the process lethality on B. atrophaeus (ATCC 9372) bacterial spores, does not allow for additional planetary protection bioburden reduction credit for processing outside a narrow temperature, time and humidity window. However, recent studies (Schubert et al., COSPAR 2008) from a comprehensive multi-year laboratory research effort have generated enhanced data sets on four aspects of the current specification: time and temperature combination effects, the effect that humidity has on spore lethality, the lethality for spores with exceptionally high thermal resistance (so called "hardies"), and the extended exposure requirement for encapsulated microorganisms. This paper describes proposed modifications to the specification, based on the data set generated in the referenced study. The proposed modifications are intended to broaden the scope of the current specification while still maintaining a confident conservative interpretation of the lethality of the DHMR process on microorganisms. Potential cost and schedule benefits to future missions utilizing the revised specification will be highlighted.

Improving efficacy of cancer immunotherapy by genetic modification of natural killer cells.

PubMed

Burga, Rachel A; Nguyen, Tuongvan; Zulovich, Jane; Madonna, Sarah; Ylisastigui, Loyda; Fernandes, Rohan; Yvon, Eric

2016-11-01

Natural killer (NK) cells are members of the innate immune system that recognize target cells via activating and inhibitory signals received through cell receptors. Derived from the lymphoid lineage, NK cells are able to produce cytokines and exert a cytotoxic effect on viral infected and malignant cells. It is their unique ability to lyse target cells rapidly and without prior education that renders NK cells a promising effector cell for adoptive cell therapy. However, both viruses and tumors employ evasion strategies to avoid attack by NK cells, which represent biological challenges that need to be harnessed to fully exploit the cytolytic potential of NK cells. Using genetic modification, the function of NK cells can be enhanced to improve their homing, cytolytic activity, in vivo persistence and safety. Examples include gene modification to express chemokine, high-affinity Fc receptor and chimeric antigen receptors, suicide genes and the forced expression of cytokines such as interleukin (IL)-2 and IL-15. Preclinical studies have clearly demonstrated that such approaches are effective in improving NK-cell function, homing and safety. In this review, we summarize the recent advances in the genetic manipulations of NK cells and their application for cellular immunotherapeutic strategies. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Pore channel surface modification for enhancing anti-fouling membrane distillation

NASA Astrophysics Data System (ADS)

Qiu, Haoran; Peng, Yuelian; Ge, Lei; Villacorta Hernandez, Byron; Zhu, Zhonghua

2018-06-01

Membrane surface modification by forming a functional layer is an effective way to improve the anti-fouling properties of membranes; however, the additional layer and the potential blockage of bulk pores may increase the mass transfer resistance and reduce the permeability. In this study, we applied a novel method of preparing anti-fouling membranes for membrane distillation by dispersing graphene oxide (GO) on the channel surface of polyvinylidene fluoride membranes. The surface morphology and properties were characterized by scanning electron microscopy, atomic force microscope, and Fourier transform infrared spectrometry. Compared to the membrane surface modification by nanoparticles (e.g. SiO2), GO was mainly located on the pore surface of the membrane bulk, rather than being formed as an individual layer onto the membrane surface. The performance was evaluated via a direct-contact membrane distillation process with anionic and cationic surfactants as the foulants, separately. Compared to the pristine PVDF membrane, the anti-fouling behavior and distillate flux of the GO-modified membranes were improved, especially when using the anionic surfactant as the foulant. The enhanced anti-fouling performance can be attributed to the oxygen containing functional groups in GO and the healing of the membrane pore defects. This method may provide an effective route to manipulate membrane pore surface properties for anti-fouling separation without increasing mass transfer resistance.

Substrate-specific modifications on magnetic iron oxide nanoparticles as an artificial peroxidase for improving sensitivity in glucose detection.

PubMed

Liu, Yanping; Yu, Faquan

2011-04-08

Magnetic iron oxide nanoparticles (MION) were recently found to act as a peroxidase with intrinsic advantages over natural counterparts. Their limited affinity toward catalysis substrates, however, dramatically reduces their utility. In this paper, some effective groups were screened out and conjugated on MION as substrate-specific modifications for improving MION's affinity to substrates and hence utility. Nanoparticles of four different superficial structures were synthesized and characterized by TEM, size, zeta potential and SQUID, and assayed for peroxidase activity. Glucose detection was selected as an application model system to evaluate the bonus thereof. Catalysis was found to follow Michaelis-Menten kinetics. Sulfhydryl groups incorporated on MION (SH-MION) notably improve the affinity toward a substrate (hydrogen peroxide) and so do amino groups (NH₂-MION) toward another substrate, proved by variation in the determined kinetic parameters. A synergistically positive effect was observed and an apparently elevated detection sensitivity and a significantly lowered detection limit of glucose were achieved when integrated with both sulfhydryl and amino groups (SH-NH₂-MION). Our findings suggest that substrate-specific surface modifications are a straightforward and robust strategy to improve MION peroxidase-like activity. The high activity extends magnetic nanoparticles to wide applications other than glucose detection.

Adaptation of a Simple Microfluidic Platform for High-Dimensional Quantitative Morphological Analysis of Human Mesenchymal Stromal Cells on Polystyrene-Based Substrates.

PubMed

Lam, Johnny; Marklein, Ross A; Jimenez-Torres, Jose A; Beebe, David J; Bauer, Steven R; Sung, Kyung E

2017-12-01

Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.

Recent Achievements in Characterizing the Histone Code and Approaches to Integrating Epigenomics and Systems Biology.

PubMed

Janssen, K A; Sidoli, S; Garcia, B A

2017-01-01

Functional epigenetic regulation occurs by dynamic modification of chromatin, including genetic material (i.e., DNA methylation), histone proteins, and other nuclear proteins. Due to the highly complex nature of the histone code, mass spectrometry (MS) has become the leading technique in identification of single and combinatorial histone modifications. MS has now overcome antibody-based strategies due to its automation, high resolution, and accurate quantitation. Moreover, multiple approaches to analysis have been developed for global quantitation of posttranslational modifications (PTMs), including large-scale characterization of modification coexistence (middle-down and top-down proteomics), which is not currently possible with any other biochemical strategy. Recently, our group and others have simplified and increased the effectiveness of analyzing histone PTMs by improving multiple MS methods and data analysis tools. This review provides an overview of the major achievements in the analysis of histone PTMs using MS with a focus on the most recent improvements. We speculate that the workflow for histone analysis at its state of the art is highly reliable in terms of identification and quantitation accuracy, and it has the potential to become a routine method for systems biology thanks to the possibility of integrating histone MS results with genomics and proteomics datasets. © 2017 Elsevier Inc. All rights reserved.

Enhanced cell attachment and hemocompatibility of titanium by nanoscale surface modification through severe plastic integration of magnesium-rich islands and porosification.

PubMed

Rezaei, Masoud; Tamjid, Elnaz; Dinari, Ali

2017-10-11

Besides the wide applications of titanium and its alloys for orthopedic and biomedical implants, the biocompatible nature of titanium has emerged various surface modification techniques to enhance its bioactivity and osteointegration with living tissues. In this work, we present a new procedure for nanoscale surface modification of titanium implants by integration of magnesium-rich islands combined with controlled formation of pores and refinement of the surface grain structure. Through severe plastic deformation of the titanium surface with fine magnesium hydride powder, Mg-rich islands with varying sizes ranging from 100 nm to 1000 nm can be integrated inside a thin surface layer (100-500 µm) of the implant. Selective etching of the surface forms a fine structure of surface pores which their average size varies in the range of 200-500 nm depending on the processing condition. In vitro biocompatibility and hemocompatibility assays show that the Mg-rich islands and the induced surface pores significantly enhance cell attachment and biocompatibility without an adverse effect on the cell viability. Therefore, severe plastic integration of Mg-rich islands on titanium surface accompanying with porosification is a new and promising procedure with high potential for nanoscale modification of biomedical implants.

Structural behavior of the space shuttle SRM Tang-Clevis joint

NASA Technical Reports Server (NTRS)

Greene, W. H.; Knight, N. F., Jr.; Stockwell, A. E.

1986-01-01

The space shuttle Challenger accident investigation focused on the failure of a tang-clevis joint on the right solid rocket motor. The existence of relative motion between the inner arm of the clevis and the O-ring sealing surface on the tang has been identified as a potential contributor to this failure. This motion can cause the O-rings to become unseated and therefore lose their sealing capability. Finite element structural analyses have been performed to predict both deflections and stresses in the joint under the primary, pressure loading condition. These analyses have demonstrated the difficulty of accurately predicting the structural behavior of the tang-clevis joint. Stresses in the vicinity of the connecting pins, obtained from elastic analyses, considerably exceed the material yield allowables indicating that inelastic analyses are probably necessary. Two modifications have been proposed to control the relative motion between the inner clevis arm and the tang at the O-ring sealing surface. One modification, referred to as the capture feature, uses additional material on the inside of the tang to restrict motion of the inner clevis arm. The other modification uses external stiffening rings above and below the joint to control the local bending in the shell near the joint. Both of these modifications are shown to be effective in controlling the relative motion in the joint.

Structural behavior of the space shuttle SRM tang-clevis joint

NASA Technical Reports Server (NTRS)

Greene, William H.; Knight, Norman F., Jr.; Stockwell, Alan E.

1988-01-01

The space shuttle Challenger accident investigation focused on the failure of a tang-clevis joint on the right solid rocket motor. The existence of relative motion between the inner arm of the clevis and the O-ring sealing surface on the tang has been identified as a potential contributor to this failure. This motion can cause the O-rings to become unseated and therefore lose their sealing capability. Finite element structural analyses have been performed to predict both deflections and stresses in the joint under the primary, pressure loading condition. These analyses have demonstrated the difficulty of accurately predicting the structural behavior of the tang-clevis joint. Stresses in the vicinity of the connecting pins, obtained from elastic analyses, considerably exceed the material yield allowables indicating that inelastic analyses are probably necessary. Two modifications have been proposed to control the relative motion between the inner clevis arm and the tang at the O-ring sealing surface. One modification, referred to as the capture feature, uses additional material on the inside of the tang to restrict motion of the inner clevis arm. The other modification uses external stiffening rings above and below the joint to control the local bending in the shell near the joint. Both of these modifications are shown to be effective in controlling the relative motion in the joint.

Activated carbon with excellent chromium(VI) adsorption performance prepared by acid-base surface modification.

PubMed

Liu, S X; Chen, X; Chen, X Y; Liu, Z F; Wang, H L

2007-03-06

In the present work, activated carbon (AC) with excellent Cr(VI) adsorption performance especially at low concentrations was prepared by an acid-base surface modification method. Raw activated carbon (AC(0)) was first oxidized in boiling HNO(3) (AC(1)), then treated with a mixture of NaOH and NaCl (AC(2)). Batch equilibrium and continuous column adsorption were conducted to evaluate the adsorption performance. Boehm titration, elemental analysis, and N(2)/77K adsorption isotherm methods were used to characterize the surface properties and pore structure of modified ACs. The results revealed that the modified AC exhibited excellent Cr(VI) adsorption performance in terms of adsorption capacity and adsorption rate: AC(2)>AC(1)>AC(0). Modification caused S(BET) to decrease and the total number of surface oxygen acidic groups to increase. HNO(3) oxidization produced positive acid groups, and subsequently NaOH treatment replaced H(+) of surface acid groups by Na(+), and the acidity of AC decreased. The main cause of higher Cr(VI) adsorption capacity and rate for AC(2) was the presence of more oxygen surface acidic groups and suitable surface acidity. HNO(3)-NaOH modification shows potential for the preparation of high quality AC for the effective removal of low concentrations of Cr(VI).

siRNAmod: A database of experimentally validated chemically modified siRNAs.

PubMed

Dar, Showkat Ahmad; Thakur, Anamika; Qureshi, Abid; Kumar, Manoj

2016-01-28

Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod.

Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations.

PubMed

Jiang, Jun; Aduri, Raviprasad; Chow, Christine S; SantaLucia, John

2014-04-01

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson-Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity.

Functional Electrospun Nanofibrous Scaffolds for Biomedical Applications

PubMed Central

Liang, Dehai; Hsiao, Benjamin S.; Chu, Benjamin

2009-01-01

Functional nanofibrous scaffolds produced by electrospinning have great potential in many biomedical applications, such as tissue engineering, wound dressing, enzyme immobilization and drug (gene) delivery. For a specific successful application, the chemical, physical and biological properties of electrospun scaffolds should be adjusted to match the environment by using a combination of multi-component compositions and fabrication techniques where electrospinning has often become a pivotal tool. The property of the nanofibrous scaffold can be further improved with innovative development in electrospinning processes, such as two-component electrospinning and in-situ mixing electrospinning. Post modifications of electrospun membranes also provide effective means to render the electrospun scaffolds with controlled anisotropy and porosity. In this review, we review the materials, techniques and post modification methods to functionalize electrospun nanofibrous scaffolds suitable for biomedical applications. PMID:17884240

DNA and histone methylation in gastric carcinogenesis

PubMed Central

Calcagno, Danielle Queiroz; Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Burbano, Rommel Rodriguez; Smith, Marília de Arruda Cardoso

2013-01-01

Epigenetic alterations contribute significantly to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches that target DNA methylation and histone modifications have emerged. A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment. Here, we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome. PMID:23482412

Health Benefits of Fasting and Caloric Restriction.

PubMed

Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

2017-10-23

Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

Computer-aided design of high-contact-ratio gears for minimum dynamic load and stress

NASA Technical Reports Server (NTRS)

Lin, Hsiang Hsi; Lee, Chinwai; Oswald, Fred B.; Townsend, Dennis P.

1990-01-01

A computer aided design procedure is presented for minimizing dynamic effects on high contact ratio gears by modification of the tooth profile. Both linear and parabolic tooth profile modifications of high contact ratio gears under various loading conditions are examined and compared. The effects of the total amount of modification and the length of the modification zone were systematically studied at various loads and speeds to find the optimum profile design for minimizing the dynamic load and the tooth bending stress. Parabolic profile modification is preferred over linear profile modification for high contact ratio gears because of its lower sensitivity to manufacturing errors. For parabolic modification, a greater amount of modification at the tooth tip and a longer modification zone are required. Design charts are presented for high contact ratio gears with various profile modifications operating under a range of loads. A procedure is illustrated for using the charts to find the optimum profile design.

Circles within circles: crosstalk between protein Ser/Thr/Tyr-phosphorylation and Met oxidation

USDA-ARS?s Scientific Manuscript database

Background: Reversible posttranslational protein modifications such as phosphorylation of Ser/Thr/Tyr and Met oxidation are critical for both metabolic regulation and cellular signalling. Although these modifications are typically studied individually, herein we describe the potential for cross-talk...

Listener Responses According to Stuttering Self-Acknowledgment and Modification

ERIC Educational Resources Information Center

Lee, Kyungjae; Manning, Walter H.

2010-01-01

Given the well-documented understanding that stuttering behavior elicits stereotypically negative responses from listeners, two experiments explored the equivocal results of earlier investigations concerning the potential for self-acknowledgment and modification of stuttering to elicit positive responses from naive (unfamiliar with stuttering)…

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

Electric-field-induced modification in Curie temperature of Co monolayer on Pt(111)

NASA Astrophysics Data System (ADS)

Nakamura, Kohji; Oba, Mikito; Akiyama, Toru; Ito, Tomonori; Weinert, Michael

2015-03-01

Magnetism induced by an external electric field (E-field) has received much attention as a potential approach for controlling magnetism at the nano-scale with the promise of ultra-low energy power consumption. Here, the E-field-induced modification of the Curie temperature for a prototypical transition-metal thin layer of a Co monolayer on Pt(111) is investigated by first-principles calculations by using the full-potential linearized augmented plane wave method that treats spin-spiral structures in an E-field. An applied E-field modifies the magnon (spin-spiral formation) energies by a few meV, which leads to a modification of the exchange pair interaction parameters within the classical Heisenberg model. With inclusion of the spin-orbit coupling (SOC), the magnetocrystalline anisotropy and the Dzyaloshinskii-Morita interaction are obtained by the second variation SOC method. An E-field-induced modification of the Curie temperature is demonstrated by Monte Carlo simulations, in which a change in the exchange interaction is found to play a key role.

Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface-Enhanced Raman Scattering: The Case of Cytosine.

PubMed

Morla-Folch, Judit; Xie, Hai-nan; Gisbert-Quilis, Patricia; Gómez-de Pedro, Sara; Pazos-Perez, Nicolas; Alvarez-Puebla, Ramon A; Guerrini, Luca

2015-11-09

Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single- and double-stranded DNA. The minute amount of DNA required per measurement, in the sub-nanogram regime, removes the necessity of pre-amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low-cost and high-throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Semiclassical anomalies of the quantum mechanical systems and their modifications for the asymptotic matching

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

Deniz, Coskun, E-mail: coskun.deniz@ege.edu.tr

JWKB solutions to the Initial Value Problems (IVPs) of the Time Independent Schrodinger's Equation (TISE) for the Simple Linear Potentials (SLPs) with a turning point parameter have been studied according to the turning points by graphical analysis to test the results of the JWKB solutions and suggested modifications. The anomalies happening in the classically inaccessible region where the SLP function is smaller than zero and the results of the suggested modifications, which are in consistent with the quantum mechanical theories, to remove these anomalies in this region have been presented. The origins of the anomalies and verifications of the suggestedmore » modifications showing a great success in the results have also been studied in terms of a suggested M{sub ij}=S{sup {approx}}{sub i-1,j} matrix elements made up of the JWKB expansion terms, S{sub i-1,j} (where i = 1, 2, 3 and j 1, 2). The results of the modifications for the IVPs and their application to the Bound State Problems (BSPs) with an example application of the Harmonic Oscillator (HO) have been presented and their generalization for any potential function have been discussed and classified accordingly.« less

Interplay between the miRNome and the epigenetic machinery: Implications in health and disease.

PubMed

Poddar, Shagun; Kesharwani, Devesh; Datta, Malabika

2017-11-01

Epigenetics refers to functionally relevant genomic changes that do not involve changes in the basic nucleotide sequence. Majorly, these are of two types: DNA methylation and histone modifications. Small RNA molecules called miRNAs are often thought to mediate post-transcriptional epigenetic changes by mRNA degradation or translational attenuation. While DNA methylation and histone modifications have their own independent effects on various cellular events, several reports are suggestive of an obvious interplay between these phenomena and the miRNA regulatory program within the cell. Several miRNAs like miR-375, members of miR-29 family, miR-34, miR-200, and others are regulated by DNA methylation and histone modifications in various types of cancers and metabolic diseases. On the other hand, miRNAs like miR-449a, miR-148, miR-101, miR-214, and miR-128 target members of the epigenetic machinery and their dysregulation leads to diverse cellular aberrations. In spite of being independent cellular events, emergence of such reports that suggest a connection between DNA methylation, histone modification, and miRNA function in several diseases indicate that this connecting axis offers a valuable target with great therapeutic potential that might be exploited for disease management. We review the current status of crosstalk between the major epigenetic modifications and the miRNA machinery and discuss this in the context of health and disease. © 2017 Wiley Periodicals, Inc.

Irreversible modification of sodium channel inactivation in toad myelinated nerve fibres by the oxidant chloramine-T.

PubMed Central

Wang, G K

1984-01-01

The effects of externally applied chloramine-T on the excitability of single toad myelinated nerve fibres were studied. Chloramine-T is a mild oxidant which reacts specifically with the cysteine and methionine residues of proteins. Chloramine-T prolongs the action potential of a single myelinated fibre by more than 1000-fold. This effect is concentration- and time-dependent; higher concentrations and longer incubation times increase prolongation. Under voltage-clamp conditions, sodium channel inactivation is markedly inhibited by chloramine-T while sodium channel activation remains normal. Prolonged depolarization of the membrane leads to a maintained sodium current. The maintained sodium currents show activation kinetics, dependence on membrane potential, and reversal potentials which are similar to those of normal, inactivating sodium currents in untreated fibres. Both the maintained and the peak sodium currents are equally inhibited by tetrodotoxin. After partial removal of sodium inactivation by brief exposures to chloramine-T, the voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by about 20 mV, even after correction for the non-inactivating component contributed by the maintained current. The phenomena described here imply that cysteine or methionine residues are critical for the sodium channel inactivation processes. The two different modifications of inactivation, its removal shown by the maintained current, and the shift in the voltage-dependence of the remaining inactivatable channels, reveal that at least two separate residues are modified by chloramine-T. PMID:6321714

Human factors engineering and design validation for the redesigned follitropin alfa pen injection device.

PubMed

Mahony, Mary C; Patterson, Patricia; Hayward, Brooke; North, Robert; Green, Dawne

2015-05-01

To demonstrate, using human factors engineering (HFE), that a redesigned, pre-filled, ready-to-use, pre-asembled follitropin alfa pen can be used to administer prescribed follitropin alfa doses safely and accurately. A failure modes and effects analysis identified hazards and harms potentially caused by use errors; risk-control measures were implemented to ensure acceptable device use risk management. Participants were women with infertility, their significant others, and fertility nurse (FN) professionals. Preliminary testing included 'Instructions for Use' (IFU) and pre-validation studies. Validation studies used simulated injections in a representative use environment; participants received prior training on pen use. User performance in preliminary testing led to IFU revisions and a change to outer needle cap design to mitigate needle stick potential. In the first validation study (49 users, 343 simulated injections), in the FN group, one observed critical use error resulted in a device design modification and another in an IFU change. A second validation study tested the mitigation strategies; previously reported use errors were not repeated. Through an iterative process involving a series of studies, modifications were made to the pen design and IFU. Simulated-use testing demonstrated that the redesigned pen can be used to administer follitropin alfa effectively and safely.

Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

NASA Astrophysics Data System (ADS)

Cazzola, Martina; Corazzari, Ingrid; Prenesti, Enrico; Bertone, Elisa; Vernè, Enrica; Ferraris, Sara

2016-03-01

Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H2O2 highlighting scavenging activity of the bioactive glass.

Robust aptamer-polydopamine-functionalized M-PLGA-TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy.

PubMed

Xu, Guojun; Yu, Xinghua; Zhang, Jinxie; Sheng, Yingchao; Liu, Gan; Tao, Wei; Mei, Lin

2016-01-01

One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer-polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M-PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA-TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer-polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures.

A helium burst biolistic device adapted to penetrate fragile insect tissues

PubMed Central

Thomas, Jean-Luc; Bardou, Jérôme; L'hoste, Sebastien; Mauchamp, Bernard; Chavancy, Gérard

2001-01-01

To compensate for the extremely low penetration efficiency of the original PDS/1000-He Bio Rad biolistic® device and the deleterious blast effect, design modifications have been made to the launching module. These modifications were evaluated on Bombyx mori embryos and fragile tissues, such as oocytes and imaginal wing disks. The original floppy macrocarrier was replaced by a rigid macrocarrier to avoid the effects of the helium blast. The efficiency of the gene gun bombardment was reinforced by the addition of a focusing nozzle. The reduced blast effect allowed us to carry out high-pressure shootings to small organs with improved penetration. This system allowed potentially all the internal embryonic tissues to be transfected with optimal survival rates. The new module was effective on tissues that are difficult to transfect, such as the epithelial wing disk that is covered by a peripodial membrane, and the ovarian follicle cells that lie under the ovariole cell membrane. The new macrocarrier allowed both an aqueous delivery of particles and an ethanolic dry delivery. No significant differences were noted between these two modes of delivery. The major improvement is the possibility of high pressure shooting correlated with appreciable penetration and a weak blast effect. PMID:15455069

Clinical outcomes and cost-effectiveness of strategies for managing people at high risk for diabetes.

PubMed

Eddy, David M; Schlessinger, Leonard; Kahn, Richard

2005-08-16

Lifestyle modification can forestall diabetes in high-risk people, but the long-term cost-effectiveness is uncertain. To estimate the effects of the lifestyle modification program used in the Diabetes Prevention Program (DPP) on health and economic outcomes. Cost-effectiveness analysis using the Archimedes model. Published basic and epidemiologic studies, clinical trials, and Kaiser Permanente administrative data. Adults at high risk for diabetes (body mass index >24 kg/m2, fasting plasma glucose level of 5.2725 to 6.9375 mmol/L [95 to 125 mg/dL], 2-hour glucose tolerance test result of 7.77 to 11.0445 mmol/L [140 to 199 mg/dL]). 5 to 30 years. Patient, health plan, and societal. No prevention, DPP's lifestyle modification program, lifestyle modification begun after a person develops diabetes, and metformin. Diagnosis and complications of diabetes. Compared with no prevention program, the DPP lifestyle program would reduce a high-risk person's 30-year chances of getting diabetes from about 72% to 61%, the chances of a serious complication from about 38% to 30%, and the chances of dying of a complication of diabetes from about 13.5% to 11.2%. Metformin would deliver about one third the long-term health benefits achievable by immediate lifestyle modification. Compared with not implementing any prevention program, the expected 30-year cost/quality-adjusted life-year (QALY) of the DPP lifestyle intervention from the health plan's perspective would be about 143,000 dollars. From a societal perspective, the cost/QALY of the lifestyle intervention compared with doing nothing would be about 62,600 dollars. Either using metformin or delaying the lifestyle intervention until after a person develops diabetes would be more cost-effective, costing about 35,400 dollars or 24,500 dollars per QALY gained, respectively, compared with no program. Compared with delaying the lifestyle program until after diabetes is diagnosed, the marginal cost-effectiveness of beginning the DPP lifestyle program immediately would be about 201,800 dollars. Variability and uncertainty deriving from the structure of the model were tested by comparing the model's results with the results of real clinical trials of diabetes and its complications. The most critical element of uncertainty is the effectiveness of the lifestyle program, as expressed by the 95% CI of the DPP study. The most important potentially controllable factor is the cost of the lifestyle program. Compared with no program, lifestyle modification for high-risk people can be made cost-saving over 30 years if the annual cost of the intervention can be reduced to about 100 dollars. Results depend on the accuracy of the model. Lifestyle modification is likely to have important effects on the morbidity and mortality of diabetes and should be recommended to all high-risk people. The program used in the DPP study may be too expensive for health plans or a national program to implement. Less expensive methods are needed to achieve the degree of weight loss seen in the DPP.

Effects of neutral gas releases on electron beam injection from electrically tethered spacecraft

NASA Technical Reports Server (NTRS)

Winglee, R. M.

1990-01-01

The presence of high neutral densities at low altitudes and/or during thruster firings is known to modify the spacecraft potential during active electron beam injection. Two-dimensional (three velocity) particle simulations are used to investigate the ionization processes including the neutral density required, the modification of the spacecraft potential, beam profile and spatial distribution of the return current into the spacecraft. Three processes are identified: (1) beam-induced ionization, (2) vehicle-induced ionization, and (3) beam plasma discharge. Only in the first two cases does the beam propagate away with little distortion.

Effect Modification and Interaction Terms: It Takes Two to Tango.

PubMed

Jupiter, Daniel C

2016-01-01

In this Investigators' Corner I look more deeply into the previously discussed phenomenon of effect modification. I revisit an explanation and examples of the phenomenon and then examine how to account for it statistically. Specifically, I show, in detail, how to write a regression equation that includes interaction terms that account for the effect modification. Finally, I look at interpretation of regression coefficients both with and without the presence of effect modification, and the associated interaction terms. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

SPM observation of nano-dots induced by slow highly charged ions

NASA Astrophysics Data System (ADS)

Nakamura, Nobuyuki; Terada, Masashi; Nakai, Yoichi; Kanai, Yasuyuki; Ohtani, Shunsuke; Komaki, Ken-ichiro; Yamazaki, Yasunori

2005-05-01

We have observed nano-dots on a highly oriented pyrolytic graphite (HOPG) surface produced by highly charged ion impacts with a scanning probe microscope. In order to clarify the role of potential and kinetic energies in surface modification, we have measured the kinetic energy and incident ion charge dependences of the dot size. The results showed that the potential energy or the incident ion charge has strong influence on the surface modification rather than the kinetic energy.

Coating Systems for Magnesium-Based Biomaterials — State of the Art

NASA Astrophysics Data System (ADS)

Waterman, J.; Staiger, M. P.

Magnesium and its alloys have the potential to be used for biodegradable orthopedic implants. However, the corrosion rate in physiological conditions is too high for most applications. For this reason, surface modification to slow the corrosion rate is of great interest. Such modifications must remain biologically compatible as well as protective in corrosive environments. What follows is a brief review of recent research in inorganic coatings and surface modifications to create coatings for magnesium-based biomaterials.

Understanding and changing human behaviour--antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour.

PubMed

Stålsby Lundborg, Cecilia; Tamhankar, Ashok J

2014-05-01

This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the 'stages of change model', including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to 'global good', so-called 'social marketing', to improve 'welfare of the individual and society' is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement 'antibiotic mainstreaming' as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society.

Calculations of transonic boattail flow at small angle of attack

NASA Technical Reports Server (NTRS)

Nakayama, A.; Chow, W. L.

1979-01-01

A transonic flow past a boattailed afterbody under a small angle of attack was examined. It is known that the viscous effect offers significant modifications of the pressure distribution on the afterbody. Thus, the formulation for the inviscid flow was based on the consideration of a flow past a nonaxisymmetric body. The full three dimensional potential equation was solved through numerical relaxation, and quasi-axisymmetric boundary layer calculations were performed to estimate the displacement effect. It was observed again that the viscous effects were not negligible. The trend of the final results agreed well with the experimental data.

Generation of induced pluripotent stem cells from the pig

USDA-ARS?s Scientific Manuscript database

The value of stem cells has become increasingly evident in recent years with the advent of genetic engineering tools that allow site-specific modifications to the genome. The use of stem cells to induce modifications has several potential benefits for the livestock industry including improving anim...

Minimizing soil impacts from forest operations

Treesearch

Emily A. Carter

2011-01-01

Several studies were conducted by Forest Service researchers and University and Industrial collaborators that investigated the potential for lessening soil surface disturbances and compaction in forest operations through modifications of machine components or harvest systems. Specific machine modifications included change in tire size, use of dual tire systems,...

Genetic Modification in Dedicated Bioenergy Crops and Strategies for Gene Confinement

USDA-ARS?s Scientific Manuscript database

Genetic modification of dedicated bioenergy crops is in its infancy; however, there are numerous advantages to the use of these tools to improve crops used for biofuels. Potential improved traits through genetic engineering (GE) include herbicide resistance, pest, drought, cold and salt tolerance, l...

A weight modification sequential method for VSC-MTDC power system state estimation

NASA Astrophysics Data System (ADS)

Yang, Xiaonan; Zhang, Hao; Li, Qiang; Guo, Ziming; Zhao, Kun; Li, Xinpeng; Han, Feng

2017-06-01

This paper presents an effective sequential approach based on weight modification for VSC-MTDC power system state estimation, called weight modification sequential method. The proposed approach simplifies the AC/DC system state estimation algorithm through modifying the weight of state quantity to keep the matrix dimension constant. The weight modification sequential method can also make the VSC-MTDC system state estimation calculation results more ccurate and increase the speed of calculation. The effectiveness of the proposed weight modification sequential method is demonstrated and validated in modified IEEE 14 bus system.

Micro glow plasma for localized nanostructural modification of carbon nanotube forest

NASA Astrophysics Data System (ADS)

Sarwar, Mirza Saquib us; Xiao, Zhiming; Saleh, Tanveer; Nojeh, Alireza; Takahata, Kenichi

2016-08-01

This paper reports the localized selective treatment of vertically aligned carbon nanotubes, or CNT forests, for radial size modification of the nanotubes through a micro-scale glow plasma established on the material. An atmospheric-pressure DC glow plasma is shown to be stably sustained on the surface of the CNT forest in argon using micromachined tungsten electrodes with diameters down to 100 μm. Experiments reveal thinning or thickening of the nanotubes under the micro glow depending on the process conditions including discharge current and process time. These thinning and thickening effects in the treated nanotubes are measured to be up to ˜30% and ˜300% in their diameter, respectively, under the tested conditions. The elemental and Raman analyses suggest that the treated region of the CNT forest is pure carbon and maintains a degree of crystallinity. The local plasma treatment process investigated may allow modification of material characteristics in different domains for targeted regions or patterns, potentially aiding custom design of micro-electro-mechanical systems and other emerging devices enabled by the CNT forest.

Cosmological perturbations in the entangled inflationary universe

NASA Astrophysics Data System (ADS)

Robles-Pérez, Salvador J.

2018-03-01

In this paper, the model of a multiverse made up of universes that are created in entangled pairs that conserve the total momentum conjugated to the scale factor is presented. For the background spacetime, assumed is a Friedmann-Robertson-Walker metric with a scalar field with mass m minimally coupled to gravity. For the fields that propagate in the entangled spacetimes, the perturbations of the spacetime and the scalar field, whose quantum states become entangled too, are considered. They turn out to be in a quasithermal state, and the corresponding thermodynamical magnitudes are computed. Three observables are expected to be caused by the creation of the universes in entangled pairs: a modification of the Friedmann equation because of the entanglement of the spacetimes, a modification of the effective value of the potential of the scalar field by the backreaction of the perturbation modes, and a modification of the spectrum of fluctuations because the thermal distribution is induced by the entanglement of the partner universes. The later would be a distinctive feature of the creation of universes in entangled pairs.

Micro glow plasma for localized nanostructural modification of carbon nanotube forest

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

Sarwar, Mirza Saquib us; Xiao, Zhiming; Saleh, Tanveer

2016-08-22

This paper reports the localized selective treatment of vertically aligned carbon nanotubes, or CNT forests, for radial size modification of the nanotubes through a micro-scale glow plasma established on the material. An atmospheric-pressure DC glow plasma is shown to be stably sustained on the surface of the CNT forest in argon using micromachined tungsten electrodes with diameters down to 100 μm. Experiments reveal thinning or thickening of the nanotubes under the micro glow depending on the process conditions including discharge current and process time. These thinning and thickening effects in the treated nanotubes are measured to be up to ∼30% andmore » ∼300% in their diameter, respectively, under the tested conditions. The elemental and Raman analyses suggest that the treated region of the CNT forest is pure carbon and maintains a degree of crystallinity. The local plasma treatment process investigated may allow modification of material characteristics in different domains for targeted regions or patterns, potentially aiding custom design of micro-electro-mechanical systems and other emerging devices enabled by the CNT forest.« less

Profiling of Histone Post-Translational Modifications in Mouse Brain with High-Resolution Top-Down Mass Spectrometry.

PubMed

Zhou, Mowei; Paša-Tolić, Ljiljana; Stenoien, David L

2017-02-03

As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (PTMs) along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms. Here we used state-of-the-art mass spectrometry and a bioinformatics workflow for targeted data analysis and visualization. The workflow uses ProMex for intact mass deconvolution, MSPathFinder as a search engine, and LcMsSpectator as a data visualization tool. When complemented with the open-modification tool TopPIC, this workflow enabled identification of novel histone PTMs including tyrosine bromination on histone H4 and H2A, H3 glutathionylation, and mapping of conventional PTMs along the entire protein for many histone subunits.

Integrated optical-fiber capillary electrophoresis microchips with novel spin-on-glass surface modification.

PubMed

Lin, Che-Hsin; Lee, Gwo-Bin; Fu, Lung-Ming; Chen, Shu-Hui

2004-07-30

This paper presents a novel micro-capillary electrophoresis (CE) chip with embedded optical fibers for the on-line detection of DNA samples. The optical fibers are pre-etched and then inserted directly into fiber channels incorporated within low-cost soda-lime glass substrates. The embedded optical fibers are precisely aligned with the microfluidic channels such that the induced fluorescence signals from labeled bio-samples can be detected. This arrangement avoids the requirement for delicate optical alignment procedures and equipment. Surface modification of the CE channels is accomplished by means of a simple and reliable organic-based spin-on-glass (SOG) method. The zeta potential distribution and the corresponding electroosmotic mobility of the fluid are simulated numerically for the modified and non-modified channel surfaces, and then both sets of results are verified experimentally. The present results indicate that the value of the zeta potential for a surface with an SOG coating is 19.3 times smaller than that of an untreated surface. A phiX-174 DNA marker fluid is used to evaluate the injection and separation performance of the developed micro-CE device. Furthermore, the long-term stability of the SOG-coated surface is also investigated. The experimental data reveal that the microchip device is capable of providing highly efficient separations of bio-molecules, and that the SOG layer retains its low zeta potential characteristics for at least 45 days. The present results confirm the effectiveness of the proposed micro-CE chip in performing the on-line detection of DNA samples, and indicate that the SOG process represents a simple and reliable solution for the surface modification of glass-based microchannels.

Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

PubMed

Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P; Sze, Siu Kwan

2016-05-18

Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.

DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine

PubMed Central

2016-01-01

Biomarker-driven drug selection plays a central role in cancer drug discovery and development, and in diagnostic strategies to improve the use of traditional chemotherapeutic drugs. DNA-modifying anticancer drugs are still used as first line medication, but drawbacks such as resistance and side effects remain an issue. Monitoring the formation and level of DNA modifications induced by anticancer drugs is a potential strategy for stratifying patients and predicting drug efficacy. In this perspective, preclinical and clinical data concerning the relationship between drug-induced DNA adducts and biological response for platinum drugs and combination therapies, nitrogen mustards and half-mustards, hypoxia-activated drugs, reductase-activated drugs, and minor groove binding agents are presented and discussed. Aspects including measurement strategies, identification of adducts, and biological factors that influence the predictive relationship between DNA modification and biological response are addressed. A positive correlation between DNA adduct levels and response was observed for the majority of the studies, demonstrating the high potential of using DNA adducts from anticancer drugs as mechanism-based biomarkers of susceptibility, especially as bioanalysis approaches with higher sensitivity and throughput emerge. PMID:27936622

TiO2-based photocatalytic disinfection of microbes in aqueous media: A review.

PubMed

Laxma Reddy, P Venkata; Kavitha, Beluri; Kumar Reddy, Police Anil; Kim, Ki-Hyun

2017-04-01

The TiO 2 based photocatalyst has great potential for the disinfection/inactivation of harmful pathogens (such as E.coli in aqueous media) along with its well-known usefulness on various chemical pollutants. The disinfection property of TiO 2 is primarily attributed to surface generation of reactive oxygen species (ROS) as well as free metal ions formation. Furthermore, its disinfection capacity and overall performance can be significantly improved through modifications of the TiO 2 material. In this review, we provide a brief survey on the effect of various TiO 2 materials in the disinfection of a wide range of environmentally harmful microbial pathogens (e.g., bacteria, fungi, algae, and viruses) in aqueous media. The influencing factors (such as reactor design, water chemistry, and TiO 2 modifications) of such processes are discussed along with the mechanisms of such disinfection. It is believed that the combined application of disinfection and decontamination will greatly enhance the utilization of TiO 2 photocatalyst as a potential alternative to conventional methods of water purification. Copyright © 2017 Elsevier Inc. All rights reserved.

Endotoxemia: methods of detection and clinical correlates.

PubMed Central

Hurley, J C

1995-01-01

As an assay for endotoxin, the Limulus amebocyte lysate assay has several desirable properties: sensitivity, specificity, and potential for adaptation to a quantitative format. Several modifications have been developed to enhance its potential for clinical application. The modifications that allow quantitative measurement of endotoxin and also improve its application to blood samples are described in this review. In fluids other than blood, the detection of endotoxin with the Limulus amebocyte lysate assay can be used as an aid to identify the presence of gram-negative bacteria, and the assay has established utility. With blood, however, there are a range of factors that interfere with the detection of endotoxemia and there are disparate views with respect to the diagnostic and prognostic significance of the test results. In general, the clinical significance of the finding of endotoxemia broadly parallels the frequency and importance of gram-negative sepsis in the patient groups studied and a decline in endotoxin levels accompanies clinical improvement. However, with therapies designed to reduce levels of endotoxin, or to antagonize its effects, it is unclear whether clinical improvement occurs as a consequence of changes in the levels of endotoxemia. PMID:7621402

Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms

PubMed Central

Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P.; Sze, Siu Kwan

2016-01-01

Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer’s health and risk of chronic diseases. PMID:27189269

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

Kinney, William H., E-mail: whkinney@buffalo.edu

We consider observational limits on a proposed model of the string landscape in inflation. In this scenario, effects from the decoherence of entangled quantum states in long-wavelength modes in the universe result in modifications to the Friedmann Equation and a corresponding modification to inflationary dynamics. Previous work [1, 2] suggested that such effects could provide an explanation for well-known anomalies in the Cosmic Microwave Background (CMB), such as the lack of power on large scales and the ''cold spot'' seen by both the WMAP and Planck satellites. In this paper, we compute limits on these entanglement effects from the Planckmore » CMB data combined with the BICEP/Keck polarization measurement, and find no evidence for observable modulations to the power spectrum from landscape entanglement, and no sourcing of observable CMB anomalies. The originally proposed model with an exponential potential is ruled out to high significance. Assuming a Starobinsky-type R {sup 2} inflation model, which is consistent with CMB constraints, data place a 2σ lower bound of b > 6.46 × 10{sup 7} GeV on the Supersymmetry breaking scale associated with entanglement corrections.« less

Recent advances on biological production of difructose dianhydride III.

PubMed

Zhu, Yingying; Yu, Shuhuai; Zhang, Wenli; Zhang, Tao; Guang, Cuie; Mu, Wanmeng

2018-04-01

Difructose dianhydride III (DFA III) is a cyclic difructose containing two reciprocal glycosidic linkages. It is easily generated with a small amount by sucrose caramelization and thus occurs in a wide range of food-stuffs during food processing. DFA III has half sweetness but only 1/15 energy of sucrose, showing potential industrial application as low-calorie sucrose substitute. In addition, it displays many benefits including prebiotic effect, low cariogenicity property, and hypocholesterolemic effect, and improves absorption of minerals, flavonoids, and immunoglobulin G. DFA III is biologically produced from inulin by inulin fructotransferase (IFTase, EC 4.2.2.18). Plenty of DFA III-producing enzymes have been identified. The crystal structure of inulin fructotransferase has been determined, and its molecular modification has been performed to improve the catalytic activity and structural stability. Large-scale production of DFA III has been studied by various IFTases, especially using an ultrafiltration membrane bioreactor. In this article, the recent findings on physiological effects of DFA III are briefly summarized; the research progresses on identification, expression, and molecular modification of IFTase and large-scale biological production of DFA III by IFTase are reviewed in detail.

Silver Nanocoating Technology in the Prevention of Prosthetic Joint Infection

PubMed Central

Gallo, Jiri; Panacek, Ales; Prucek, Robert; Kriegova, Eva; Hradilova, Sarka; Hobza, Martin; Holinka, Martin

2016-01-01

Prosthetic joint infection (PJI) is a feared complication of total joint arthroplasty associated with increased morbidity and mortality. There is a growing body of evidence that bacterial colonization and biofilm formation are critical pathogenic events in PJI. Thus, the choice of biomaterials for implanted prostheses and their surface modifications may significantly influence the development of PJI. Currently, silver nanoparticle (AgNP) technology is receiving much interest in the field of orthopaedics for its antimicrobial properties and a strong anti-biofilm potential. The great advantage of AgNP surface modification is a minimal release of active substances into the surrounding tissue and a long period of effectiveness. As a result, a controlled release of AgNPs could ensure antibacterial protection throughout the life of the implant. Moreover, the antibacterial effect of AgNPs may be strengthened in combination with conventional antibiotics and other antimicrobial agents. Here, our main attention is devoted to general guidelines for the design of antibacterial biomaterials protected by AgNPs, its benefits, side effects and future perspectives in PJI prevention. PMID:28773461

Air pollution and mortality: effect modification by personal characteristics and specific cause of death in a case-only study.

PubMed

Qiu, Hong; Tian, Linwei; Ho, Kin-Fai; Pun, Vivian C; Wang, Xiaorong; Yu, Ignatius T S

2015-04-01

Short-term effects of air pollution on mortality have been well documented in the literature worldwide. Less is known about which subpopulations are more vulnerable to air pollution. We conducted a case-only study in Hong Kong to examine the potential effect modification by personal characteristics and specific causes of death. Individual information of 402,184 deaths of non-external causes and daily mean concentrations of air pollution were collected from 2001 to 2011. For a 10 μg/m(3) increase of pollution concentration, people aged ≥ ∇65 years (compared with younger ages) had a 0.9-1.8% additional increase in mortality related to PM, NO2, and SO2. People dying from cardiorespiratory diseases (compared with other non-external causes) had a 1.6-2.3% additional increase in PM and NO2 related mortality. Other subgroups that were particularly susceptible were females and those economically inactive. Lower socioeconomic status and causes of cardiorespiratory diseases would increase the likelihood of death associated with air pollution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Surface modification of ZSM-5 zeolite: effect of cation on selective conversion of biomass-derived oil

NASA Astrophysics Data System (ADS)

Widayatno, W. B.

2017-04-01

This paper reports the surface modification of high silica ZSM-5 zeolite, particularly emphasizing the effect of cation type on selective conversion of biomass-derived oil. XRD spectra of the NaOH-treated HZSM-5 showed notable crystallinity decrease at specific crystal plane orientation. The N2-physisorption tests confirmed mesoporosity evolution as NaOH concentration was increased. NH3-desorption tests revealed a significant change on surface acidity which involved realumination and cation replacement processes. The utilization of untreated HZSM-5 as well as hierarchical NaZSM-5 for catalytic conversion of bio-oil showed the effect of cation type and mesoporosity on chemicals distribution. The untreated HZSM-5 showed high selectivity to aromatics, which degraded gradually due to deactivation and poisoning of the acid sites. Meanwhile, hierarchical NaZSM-5 showed high selectivity to phenolic compound, which became more stable for 0.4M NaOH-treated zeolite (Na04). The current findings provide an additional insight on the potentials of NaZSM-5 for bio-oil valorization.

Surface Modification for Improved Design and Functionality of Nanostructured Materials and Devices

NASA Astrophysics Data System (ADS)

Keiper, Timothy Keiper

Progress in nanotechnology is trending towards applications which require the integration of soft (organic or biological) and hard (semiconductor or metallic) materials. Many applications for functional nanomaterials are currently being explored, including chemical and biological sensors, flexible electronics, molecular electronics, etc., with researchers aiming to develop new paradigms of nanoelectronics through manipulation of the physical properties by surface treatments. This dissertation focuses on two surface modification techniques important for integration of hard and soft materials: thermal annealing and molecular modification of semiconductors. First, the effects of thermal annealing are investigated directly for their implication in the fundamental understanding of transparent conducting oxides with respect to low resistivity contacts for electronic and optoelectronic applications and the response to environmental stimuli for sensing applications. The second focus of this dissertation covers two aspects of the importance of molecular modification on semiconductor systems. The first of these is the formation of self-assembled monolayers in patterned arrays which leads explicitly to the directed self-assembly of nanostructures. The second aspect concerns the modification of the underlying magnetic properties of the preeminent dilute magnetic semiconductor, manganese-doped gallium arsenide. Tin oxide belongs to a class of materials known as transparent conducting oxides which have received extensive interest due to their sensitivity to environmental stimuli and their potential application in transparent and flexible electronics. Nanostructures composed of SnO2 have been demonstrated as an advantageous material for high performance, point-of-care nanoelectronic sensors, capable of detecting and distinguishing gaseous or biomolecular interactions on unprecedented fast timescales. Through bottom-up fabrication techniques, binary oxide nanobelts synthesized through catalyst-free physical vapor deposition are implemented in the field-effect transistor structure. We have discovered that conductivity is absent in as-grown devices. However, utilizing a process for thermal treatment in vacuum and oxygen environments is found to be instrumental in fabricating field-effect transistors with significant conductivity, up to five orders of magnitude above the as-grown devices, for field-effect transistor application. Further investigation by photoluminescence coupled with the annealing parameters reveals that the likely cause of conductance comes from the reduction of surface defect states in the material. Importantly, the annealed material maintains its response to an applied gate potential showing orders of magnitude switching from the 'off' to the 'on' state. In order to show the practical relevance of our improvements on the SnO2 material, we show our results for implementing the annealed material in biomolecular sensing experiments to detect the presence of streptavidin and Hepatitis C virus. Surface modification was carried out on oxide-free gallium arsenide (in some cases doped with manganese or zinc) through self-assembly of thiol molecules. First, we investigate the ability to pattern via two complementary micro- and nanopatterning techniques, microcontact printing (muCP) and dip-pen nanolithography (DPN). DPN is a unique lithography tool that allows drawing of arbitrary patterns with a molecular ink on a complementary substrate. It is extremely useful in integration of molecular inks within a pre-defined structure. Here, DPN was used to investigate the diffusion of organic molecules from a point source for both a moving and stationary tip on oxide-free GaAs. The diffusion can be calibrated so that intricate patterns down to tens of nanometers can be arbitrarily drawn on the surface. muCP, a less complicated method for large-scale arrayed patterning, is utilized to investigate the deposition of different thiolated molecular inks on GaAs and (Ga,Mn)As. The patterns deposited by muCP provide the template for directed self-assembly of gold nanoparticles. The systems based on these techniques can be extended to many substrate-molecule-nanostructure systems for an incredible variety of applications. Finally, the thiol-(Ga,Mn)As system is studied to determine the effects of molecular modification on the substrates' magnetic properties via modulation of the hole concentration in the wafer. The results for two molecules, one an electron donor and one an electron acceptor, show opposite trends for modulation of both the Curie temperature and the saturation magnetization. We suggest that nanopatterning of electron donor or electron acceptor molecules could lead to the development of reconfigurable nanomagnetic systems in (Ga,Mn)As with potential applications in molecular spintronics or magnetic memory.

Effect of Carboxymethylation on the Rheological Properties of Hyaluronan

PubMed Central

Wendling, Rian J.; Christensen, Amanda M.; Quast, Arthur D.; Atzet, Sarah K.; Mann, Brenda K.

2016-01-01

Chemical modifications made to hyaluronan to enable covalent crosslinking to form a hydrogel or to attach other molecules may alter the physical properties as well, which have physiological importance. Here we created carboxymethyl hyaluronan (CMHA) with varied degree of modification and investigated the effect on the viscosity of CMHA solutions. Viscosity decreased initially as modification increased, with a minimum viscosity for about 30–40% modification. This was followed by an increase in viscosity around 45–50% modification. The pH of the solution had a variable effect on viscosity, depending on the degree of carboxymethyl modification and buffer. The presence of phosphates in the buffer led to decreased viscosity. We also compared large-scale production lots of CMHA to lab-scale and found that large-scale required extended reaction times to achieve the same degree of modification. Finally, thiolated CMHA was disulfide crosslinked to create hydrogels with increased viscosity and shear-thinning aspects compared to CMHA solutions. PMID:27611817

Pseudouridine and N6-methyladenosine modifications weaken PUF protein/RNA interactions

PubMed Central

AlSadhan, Ishraq; Merriman, Dawn K.; Al-Hashimi, Hashim M.; Herschlag, Daniel

2017-01-01

RNA modifications are ubiquitous in biology, with over 100 distinct modifications. While the vast majority were identified and characterized on abundant noncoding RNA such as tRNA and rRNA, the advent of sensitive sequencing-based approaches has led to the discovery of extensive and regulated modification of eukaryotic messenger RNAs as well. The two most abundant mRNA modifications—pseudouridine (Ψ) and N6-methyladenosine (m6A)—affect diverse cellular processes including mRNA splicing, localization, translation, and decay and modulate RNA structure. Here, we test the hypothesis that RNA modifications directly affect interactions between RNA-binding proteins and target RNA. We show that Ψ and m6A weaken the binding of the human single-stranded RNA binding protein Pumilio 2 (hPUM2) to its consensus motif, with individual modifications having effects up to approximately threefold and multiple modifications giving larger effects. While there are likely to be some cases where RNA modifications essentially fully ablate protein binding, here we see modest responses that may be more common. Such modest effects could nevertheless profoundly alter the complex landscape of RNA:protein interactions, and the quantitative rather than qualitative nature of these effects underscores the need for quantitative, systems-level accounting of RNA:protein interactions to understand post-transcriptional regulation. PMID:28138061

MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.

PubMed

Lev, Itamar; Seroussi, Uri; Gingold, Hila; Bril, Roberta; Anava, Sarit; Rechavi, Oded

2017-04-24

In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deep patch technique for landslide repair. Final report

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

Helwany, B.M.

1994-10-01

The report describes the laboratory testing of the `USFS deep patch` technique and a CTI modification of this technique for repairing landslides with geosynthetic reinforcement. The technique involves replacing sections of roadway lost due to landslides on top of a geosynthetically-reinforced embankment. The CTI modification involves replacing the reinforced slope with a geosynthetically-reinforced retaining wall with a truncated base. Both techniques rely on the cantilevering ability of the reinforced mass to limit the load on the foundation with a high slide potential. The tests with road base showed that (1) both the USFS and CTI repair reduced effectively the adversemore » effects of local landsliding on the highway pavement by preventing crack propagation; (2) the USFS repair increased the stability of the repaired slope, which was in progressive failure, by reducing the stresses exerted on it; and (3) the CTI repair produced substantially greater stresses on its foundation due to the truncated base of the reinforced mass.« less

Delayed Immunomodulatory Effect of Cow Milk-Free Diet in Ménière's Disease.

PubMed

Di Berardino, Federica; Zanetti, Diego

2018-02-01

Since 1930, dietary modification has been proposed as adjunct treatment in Ménière's disease (MD) with different and controversial results. We report the case of a 42-year-old female suffering from definite MD and intermittent seasonal allergic rhino-conjunctivitis because it highlights the importance of evaluating the different combinations of defined causative elements in an atopic patient with MD. An immunological and audiological evaluation was performed, including pure-tone, speech, and immittance audiometry; glycerol dehydration test; bithermal caloric testing; video head impulse test; cervical vestibular evoked myogenic potentials; static posturography; and Dizziness Handicap Inventory questionnaire. A milk-free diet was crucial to relief from MD symptoms and a cow's milk challenge test was able to evoke them but vestibukar symptoms persist. The effect of dietary modification was evident only after specific immunotherapies against other allergens. This highlights the importance of evaluating different combinations of defined causative elements in the allergic treatment of MD.

Effect of structural modification of α-aminoxy peptides on their intestinal absorption and transport mechanism.

PubMed

Ma, Bin; Zha, Huiyan; Li, Na; Yang, Dan; Lin, Ge

2011-08-01

A representative α-aminoxy peptide 1 has been demonstrated to have a potential for the treatment of human diseases associated with Cl(-) channel dysfunctions. However, its poor intestinal absorption was determined. The purpose of this study was to delineate the transport mechanism responsible for its poor absorption and also to prepare peptide analogues by structural modifications of 1 at its isobutyl side chains without changing the α-aminoxy core for retaining biological activity to improve the intestinal absorption. The poor intestinal absorption of 1 was proved to be due to the P-glycoprotein (P-gp) mediated efflux transport in Caco-2 cell monolayer, intestinal segments in Ussing chamber and rat single pass intestinal perfusion models. Four analogues with propionic acid (2), butanamine (3), methyl (4) and hydroxymethyl side chains (5) were synthesized and tested using the same models. Except for the permeability of 2, the absorbable permeability of the modified peptides in Caco-2 cell monolayer and their intestinal absorption in rats were significantly improved to 7-fold (3), 4-fold (4), 11-fold (5) and 36-fold (2), 42-fold (3), 55-fold (4), 102-fold (5), respectively, compared with 1 (P(app), 0.034 ± 0.003 × 10(-6) cm/s; P(blood), 1.61 ± 0.807 × 10(-6) cm/s). More interestingly, the structural modification remarkably altered transport mechanism of the peptides, leading to the conversion of the active transport via P-gp mediation (1, 2), to MRP mediation (3), MRP plus BCRP mediation (4) or a passive diffusion (5). Furthermore, P-gp mediated efflux transport of 1 and 2 was demonstrated to not alter the P-gp expression, while 1 but not 2 exhibited uncompetitive inhibitory effect on P-gp ATPase. The results demonstrated that intestinal absorption and transport mechanism of the α-aminoxy peptides varied significantly with different structures, and their absorption can be dramatically improved by structural modifications, which allow us to further design and prepare better α-aminoxy peptide candidates with appropriate pharmacokinetic fates, including intestinal absorption, for potential clinical use.

Chitosan-edible oil based materials as upgraded adsorbents for textile dyes.

PubMed

Dos Santos, Clayane Carvalho; Mouta, Rodolpho; Junior, Manoel Carvalho Castro; Santana, Sirlane Aparecida Abreu; Silva, Hildo Antonio Dos Santos; Bezerra, Cícero Wellington Brito

2018-01-15

Biopolymer chitosan is a low cost, abundant, environmentally friendly, very selective and efficient anionic dyes adsorbent, being a promising material for large-scale removal of dyes from wastewater. However, raw chitosan (CS) is an ineffective cationic dyes adsorbent and its performance is pH sensitive, thus, CS modifications that address these issues need to be developed. Here, we report the preparation and characterization of two new CS modifications using edible oils (soybean oil or babassu oil), and their adsorption performance for two dyes, one anionic (remazol red, RR) and one cationic (methylene blue, MB). Both modifications extended the pH range of RR adsorption. The babassu oil modification increased adsorption capacity of the cationic dye MB, whereas the soybean oil modification increased that of RR. Such improvements demonstrate the potential of these two new CS modifications as adsorbent candidates for controlling dyes pollution in effluents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Update: Mechanisms underlying N6-methyladenosine modification of eukaryotic mRNA

PubMed Central

Wang, Yang; Zhao, Jing Crystal

2016-01-01

Summary Eukaryotic messenger RNA (mRNA) undergoes chemical modification both at the 5′cap [1, 2] and internally [3–14]. Among internal modifications, m6A, by far the most abundant, is present in all eukaryotes examined, including mammals [3–6], flies [15], plants [16, 17] and yeast [18, 19]. m6A modification plays an essential role in diverse biological processes. Over the past few years, our knowledge relevant to establishment and function of this modification has grown rapidly. This review focuses on technologies that have facilitated m6A detection in mRNAs, identification of m6A methylation enzymes and binding proteins, and potential functions of the modification at the molecular level. Regarding m6A function at cellular or organismal levels or in disease, please refer to other recent reviews [20–23]. PMID:27793360

Modeling nanostructural surface modifications in metal cutting by an approach of thermodynamic irreversibility: Derivation and experimental validation

NASA Astrophysics Data System (ADS)

Buchkremer, S.; Klocke, F.

2017-01-01

Performance and operational safety of many metal parts in engineering depend on their surface integrity. During metal cutting, large thermomechanical loads and high gradients of the loads concerning time and location act on the surfaces and may yield significant structural material modifications, which alter the surface integrity. In this work, the derivation and validation of a model of nanostructural surface modifications in metal cutting are presented. For the first time in process modeling, initiation and kinetics of these modifications are predicted using a thermodynamic potential, which considers the interdependent developments of plastic work, dissipation, heat conduction and interface energy as well as the associated productions and flows of entropy. The potential is expressed based on the free Helmholtz energy. The irreversible thermodynamic state changes in the workpiece surface are homogenized over the volume in order to bridge the gap between discrete phenomena involved with the initiation and kinetics of dynamic recrystallization and its macroscopic implications for surface integrity. The formulation of the thermodynamic potential is implemented into a finite element model of orthogonal cutting of steel AISI 4140. Close agreement is achieved between predicted nanostructures and those obtained in transmission electron microscopical investigations of specimen produced in cutting experiments.

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...

Memantine Reverses Social Withdrawal Induced by Ketamine in Rats

PubMed Central

Landaeta, José; Wix, Richard; Eblen, Antonio

2013-01-01

The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg-1) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg-1) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia. PMID:23585718

Transcript Isoform Variation Associated with Cytosine Modification in Human Lymphoblastoid Cell Lines.

PubMed

Zhang, Xu; Zhang, Wei

2016-06-01

Cytosine modification on DNA is variable among individuals, which could correlate with gene expression variation. The effect of cytosine modification on interindividual transcript isoform variation (TIV), however, remains unclear. In this study, we assessed the extent of cytosine modification-specific TIV in lymphoblastoid cell lines (LCLs) derived from unrelated individuals of European and African descent. Our study detected cytosine modification-specific TIVs for 17% of the analyzed genes at a 5% false discovery rate. Forty-five percent of the TIV-associated cytosine modifications correlated with the overall gene expression levels as well, with the corresponding CpG sites overrepresented in transcript initiation sites, transcription factor binding sites, and distinct histone modification peaks, suggesting that alternative isoform transcription underlies the TIVs. Our analysis also revealed 33% of the TIV-associated cytosine modifications that affected specific exons, with the corresponding CpG sites overrepresented in exon/intron junctions, splicing branching points, and transcript termination sites, implying that the TIVs are attributable to alternative splicing or transcription termination. Genetic and epigenetic regulation of TIV shared target preference but exerted independent effects on 61% of the common exon targets. Cytosine modification-specific TIVs detected from LCLs were differentially enriched in those detected from various tissues in The Cancer Genome Atlas, indicating their developmental dependency. Genes containing cytosine modification-specific TIVs were enriched in pathways of cancers and metabolic disorders. Our study demonstrated a prominent effect of cytosine modification variation on the transcript isoform spectrum over gross transcript abundance and revealed epigenetic contributions to diseases that were mediated through cytosine modification-specific TIV. Copyright © 2016 by the Genetics Society of America.

Refilling the half-empty glass--Investigating the potential role of the Interpretation Modification Paradigm for Depression (IMP-D).

PubMed

Möbius, Martin; Tendolkar, Indira; Lohner, Valerie; Baltussen, Mirte; Becker, Eni S

2015-12-01

Cognitive biases are known to cause and maintain depression. However, little research has been done on techniques targeting interpretation tendencies found in depression, despite the promising findings of anxiety studies. This paper presents two experiments, investigating the suitability of an Interpretation Modification Paradigm for Depression (IMP-D) in healthy individuals, which has already proven its effectiveness in anxiety (Beard & Amir, 2008). Different from other paradigms, the IMP-D aims at modifying an interpretation bias on response- and on a more implicit reaction time-level, making this task less susceptible to demand effects. The Word-Sentence Association Paradigm for Depression (Hindash & Amir, 2011) was modified and administered in healthy volunteers (experiment I: N = 81; experiment II: N = 105). To enhance a positive interpretation bias, endorsing benign and rejecting negative interpretations of ambiguous scenarios was reinforced through feedback. This intervention was compared to the opposite training (both experiments) and a control training (experiment II only). Both experiments revealed a significant increase in bias towards benign interpretations on the level of overt decisions, while only in the first experiment a change was found on a reaction time level. These modifications are not reflected in group-differences in emotional vulnerability. Possible limitations regarding the reliability of inter-dependent response and reaction time measures are discussed. The IMP-D is able to modify interpretation biases, but adaptations are required to maximize its beneficial effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Economic Effects of Precipitation Enhancement in the Corn Belt.

NASA Astrophysics Data System (ADS)

Gapcia, Philip; Changnon, Stanley; Pinar, Musa

1990-01-01

Policy formulation in weather modification requires an understanding of the economic effects from altered weather. The focus of this study is to provide insight into the beneficiaries of a functioning weather modification technology when applied at various spatial and temporal levels. An econometric model which links the corn/scybean production to U.S. cattle, hog and poultry sectors is used to determine the effects of precipitation enhancement in the U.S. Corn Belt, a humid climatic region. A regional supply formulation permits assessment of weather modification on production, prices, revenues to producers, and savings in consumers expenditures on meat. The results provide insight into the distribution of economic effects, emphasize the importance of careful planning in the use of weather modification technology, and provide useful information on the roles of local, state, and federal governments in the support of weather modification.

Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction.

PubMed

Cribbs, Adam P; Perera, Sumeth M W

2017-12-01

Since its emergence in 2012, the genome editing technique known as CRISPR-Cas9 and its scientific use have rapidly expanded globally within a very short period of time. The technique consists of using an RNA guide molecule to bind to complementary DNA sequences, which simultaneously recruits the endonuclease Cas9 to introduce double-stranded breaks in the target DNA. The resulting double-stranded break is then repaired, allowing modification or removal of specific DNA bases. The technique has gained momentum in the laboratory because it is cheap, quick, and easy to use. Moreover, it is also being applied in vivo to generate more complex animal model systems. Such use of genome editing has proven to be highly effective and warrants a potential therapy for both genetic and non-genetic diseases. Although genome editing has the potential to be a transformative therapy for patients it is still in its infancy. Consequently, the legal and ethical frameworks are yet to be fully discussed and will be an increasingly important topic as the technology moves towards more contentious issues such as modification of the germline. Here, we review a number of scientific and ethical issues which may potentially influence the development of both the technology and its use in the clinical setting.

An injectable spheroid system with genetic modification for cell transplantation therapy.

PubMed

Uchida, Satoshi; Itaka, Keiji; Nomoto, Takahiro; Endo, Taisuke; Matsumoto, Yu; Ishii, Takehiko; Kataoka, Kazunori

2014-03-01

The new methodology to increase a therapeutic potential of cell transplantation was developed here by the use of three-dimensional spheroids of transplanting cells subsequent to the genetic modification with non-viral DNA vectors, polyplex nanomicelles. Particularly, spheroids in regulated size of 100-μm of primary hepatocytes transfected with luciferase gene were formed on the micropatterned culture plates coated with thermosensitive polymer, and were recovered in the form of injectable liquid suspension simply by cooling the plates. After subcutaneously transplanting these hepatocyte spheroids, efficient transgene expression was observed in host tissue for more than a month, whereas transplantation of a single-cell suspension from a monolayer culture resulted in an only transient expression. The spheroid system contributed to the preservation of innate functions of transplanted hepatocytes in the host tissue, such as albumin expression, thereby possessing high potential for expressing transgene. Intravital observation of transplanted cells showed that those from spheroid cultures had a tendency to localize in the vicinity of blood vessels, making a favorable microenvironment for preserving cell functionality. Furthermore, spheroids transfected with erythropoietin-expressing DNA showed a significantly higher hematopoietic effect than that of cell suspensions from monolayer cultures, demonstrating high potential of this genetically-modified spheroid transplantation system for therapeutic applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction


PubMed Central

Cribbs, Adam P.; Perera, Sumeth M. W.

2017-01-01

Since its emergence in 2012, the genome editing technique known as CRISPR-Cas9 and its scientific use have rapidly expanded globally within a very short period of time. The technique consists of using an RNA guide molecule to bind to complementary DNA sequences, which simultaneously recruits the endonuclease Cas9 to introduce double-stranded breaks in the target DNA. The resulting double-stranded break is then repaired, allowing modification or removal of specific DNA bases. The technique has gained momentum in the laboratory because it is cheap, quick, and easy to use. Moreover, it is also being applied in vivo to generate more complex animal model systems. Such use of genome editing has proven to be highly effective and warrants a potential therapy for both genetic and non-genetic diseases. Although genome editing has the potential to be a transformative therapy for patients it is still in its infancy. Consequently, the legal and ethical frameworks are yet to be fully discussed and will be an increasingly important topic as the technology moves towards more contentious issues such as modification of the germline. Here, we review a number of scientific and ethical issues which may potentially influence the development of both the technology and its use in the clinical setting. PMID:29259526

Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy

PubMed Central

Barhoumi, Aoune; Halas, Naomi J.

2013-01-01

Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics. PMID:24427449

Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy.

PubMed

Barhoumi, Aoune; Halas, Naomi J

2011-12-15

Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics.

Lorentz-violating contributions to the nuclear Schiff moment and nuclear EDM

NASA Astrophysics Data System (ADS)

Araujo, Jonas B.; Casana, Rodolfo; Ferreira, Manoel M.

2018-03-01

In the context of an atom endowed with nuclear electric dipole moments (EDM), we consider the effects on the Schiff moment of C P T -even Lorentz-violating (LV) terms that modify the Coulomb potential. First, we study the modifications on the Schiff moment when the nucleus interacts with the electronic cloud by means of a Coulomb potential altered only by the P -even LV components. Next, by supposing the existence of an additional intrinsic LV EDM generated by other LV sources, we assess the corrections to the Schiff moment when the interaction nucleus-electrons runs mediated by a Coulomb potential modified by both the P -odd and P -even LV components. We then use known estimates and EDM measurements to discuss upper bounds on the new Schiff moment components and the possibility of a nuclear EDM component ascribed to LV effects.

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

NASA Technical Reports Server (NTRS)

Barber, Peter W.; Demerdash, Nabeel A. O.; Hurysz, B.; Luo, Z.; Denny, Hugh W.; Millard, David P.; Herkert, R.; Wang, R.

1992-01-01

The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards.

Evaluation of Plume Divergence and Facility Effects on Far-Field Faraday Probe Current Density Profiles

DTIC Science & Technology

2009-09-01

elevated background pressure, compared nude Faraday probe designs, and evaluated design modifications to minimize uncertainty due to charge exchange...evaluated Faraday probe design and facility background pressure on collected ion current. A comparison of two nude Faraday probe designs concluded...140.5 Plasma potential in the region surrounding a nude Faraday probe has been measured to study the possibility of probe bias voltage acting as a

Visuo-Vestibular Interactions

NASA Technical Reports Server (NTRS)

1997-01-01

Session TA3 includes short reports covering: (1) Vestibulo-Oculomotor Interaction in Long-Term Microgravity; (2) Effects of Weightlessness on the Spatial Orientation of Visually Induced Eye Movements; (3) Adaptive Modification of the Three-Dimensional Vestibulo-Ocular Reflex during Prolonged Microgravity; (4) The Dynamic Change of Brain Potential Related to Selective Attention to Visual Signals from Left and Right Visual Fields; (5) Locomotor Errors Caused by Vestibular Suppression; and (6) A Novel, Image-Based Technique for Three-Dimensional Eye Measurement.

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.

Addition of CFCl 3 to Aromatic Aldehydes via in Situ Grignard Reaction

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

Barkakaty, Balaka; Talukdar, Bandana; Lokitz, Bradley

In the case of synthetic modification of trichlorofluoromethane (CFCl 3) to non-volatile and useful fluorinated precursors, we realized that it is a cost-effective and an environmentally benign strategy for the safe consumption/destruction of the ozone depleting potential of the reagent. In our report, we present a novel method for in situ Grignard reaction using magnesium powder and CFCl 3 for synthesis of dichlorofluoromethyl aromatic alcohols.

Addition of CFCl 3 to Aromatic Aldehydes via in Situ Grignard Reaction

DOE PAGES

Barkakaty, Balaka; Talukdar, Bandana; Lokitz, Bradley

2015-08-18

In the case of synthetic modification of trichlorofluoromethane (CFCl 3) to non-volatile and useful fluorinated precursors, we realized that it is a cost-effective and an environmentally benign strategy for the safe consumption/destruction of the ozone depleting potential of the reagent. In our report, we present a novel method for in situ Grignard reaction using magnesium powder and CFCl 3 for synthesis of dichlorofluoromethyl aromatic alcohols.

Ground cloud related weather modification effects. [heavy lift launch vehicles

NASA Technical Reports Server (NTRS)

Lee, J.

1980-01-01

The principal concerns about inadvertent weather modification by the solar power satellite system rocket effluents are discussed, namely the possibility that the ground cloud might temporarily modify local weather and the cumulative effects of nearly 500 launches per year. These issues are discussed through the consideration of (1) the possible alteration of the microphysical processes of clouds in the general area due to rocket effluents and debris and cooling water entrained during the launch and (2) the direct dynamical and thermodynamical responses to the inputs of thermal energy and moisture from the rocket exhaust for given ambient meteorological conditions. The huge amount of thermal energy contained in the exhaust of the proposed launch vehicle would in some situations induce a saturated, wet convective cloud or enhance an existing convective activity. Nevertheless, the effects would be limited to the general area of the launch site. The observed long lasting high concentrations of cloud condensation nuclei produced during and after a rocket launch may appreciably affect the frequency of occurrence and persistence of fogs and haze. In view of the high mission frequency proposed for the vehicle launches, a potential exists for a cumulative effect.

Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview.

PubMed

Mandolini, G M; Lazzaretti, M; Pigoni, A; Oldani, L; Delvecchio, G; Brambilla, P

2018-05-23

Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.

SiC JFET Transistor Circuit Model for Extreme Temperature Range

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.

2008-01-01

A technique for simulating extreme-temperature operation of integrated circuits that incorporate silicon carbide (SiC) junction field-effect transistors (JFETs) has been developed. The technique involves modification of NGSPICE, which is an open-source version of the popular Simulation Program with Integrated Circuit Emphasis (SPICE) general-purpose analog-integrated-circuit-simulating software. NGSPICE in its unmodified form is used for simulating and designing circuits made from silicon-based transistors that operate at or near room temperature. Two rapid modifications of NGSPICE source code enable SiC JFETs to be simulated to 500 C using the well-known Level 1 model for silicon metal oxide semiconductor field-effect transistors (MOSFETs). First, the default value of the MOSFET surface potential must be changed. In the unmodified source code, this parameter has a value of 0.6, which corresponds to slightly more than half the bandgap of silicon. In NGSPICE modified to simulate SiC JFETs, this parameter is changed to a value of 1.6, corresponding to slightly more than half the bandgap of SiC. The second modification consists of changing the temperature dependence of MOSFET transconductance and saturation parameters. The unmodified NGSPICE source code implements a T(sup -1.5) temperature dependence for these parameters. In order to mimic the temperature behavior of experimental SiC JFETs, a T(sup -1.3) temperature dependence must be implemented in the NGSPICE source code. Following these two simple modifications, the Level 1 MOSFET model of the NGSPICE circuit simulation program reasonably approximates the measured high-temperature behavior of experimental SiC JFETs properly operated with zero or reverse bias applied to the gate terminal. Modification of additional silicon parameters in the NGSPICE source code was not necessary to model experimental SiC JFET current-voltage performance across the entire temperature range from 25 to 500 C.

Transgenerational Inheritance of Modified DNA Methylation Patterns and Enhanced Tolerance Induced by Heavy Metal Stress in Rice (Oryza sativa L.)

PubMed Central

Xu, Chunming; Lin, Xiuyun; Zang, Qi; Zhuang, Tingting; Jiang, Lili; von Wettstein, Diter; Liu, Bao

2012-01-01

Background DNA methylation is sensitive and responsive to stressful environmental conditions. Nonetheless, the extent to which condition-induced somatic methylation modifications can impose transgenerational effects remains to be fully understood. Even less is known about the biological relevance of the induced epigenetic changes for potentially altered well-being of the organismal progenies regarding adaptation to the specific condition their progenitors experienced. Methodology/Principal Findings We analyzed DNA methylation pattern by gel-blotting at genomic loci representing transposable elements and protein-coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants (S0), and its three successive organismal generations. We assessed expression of putative genes involved in establishing and/or maintaining DNA methylation patterns by reverse transcription (RT)-PCR. We measured growth of the stressed plants and their unstressed progenies vs. the control plants. We found (1) relative to control, DNA methylation patterns were modified in leaf-tissue of the immediately treated plants, and the modifications were exclusively confined to CHG hypomethylation; (2) the CHG-demethylated states were heritable via both maternal and paternal germline, albeit often accompanying further hypomethylation; (3) altered expression of genes encoding for DNA methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited enhanced tolerance to the same stress their progenitor experienced, and this transgenerational inheritance of the effect of condition accompanying heritability of modified methylation patterns. Conclusions/Significance Our findings suggest that stressful environmental condition can produce transgenerational epigenetic modifications. Progenies of stressed plants may develop enhanced adaptability to the condition, and this acquired trait is inheritable and accord with transmission of the epigenetic modifications. We suggest that environmental induction of heritable modifications in DNA methylation provides a plausible molecular underpinning for the still contentious paradigm of inheritance of acquired traits originally put forward by Jean-Baptiste Lamarck more than 200 years ago. PMID:22984395

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.

Transgenerational inheritance of modified DNA methylation patterns and enhanced tolerance induced by heavy metal stress in rice (Oryza sativa L.).

PubMed

Ou, Xiufang; Zhang, Yunhong; Xu, Chunming; Lin, Xiuyun; Zang, Qi; Zhuang, Tingting; Jiang, Lili; von Wettstein, Diter; Liu, Bao

2012-01-01

DNA methylation is sensitive and responsive to stressful environmental conditions. Nonetheless, the extent to which condition-induced somatic methylation modifications can impose transgenerational effects remains to be fully understood. Even less is known about the biological relevance of the induced epigenetic changes for potentially altered well-being of the organismal progenies regarding adaptation to the specific condition their progenitors experienced. We analyzed DNA methylation pattern by gel-blotting at genomic loci representing transposable elements and protein-coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants (S0), and its three successive organismal generations. We assessed expression of putative genes involved in establishing and/or maintaining DNA methylation patterns by reverse transcription (RT)-PCR. We measured growth of the stressed plants and their unstressed progenies vs. the control plants. We found (1) relative to control, DNA methylation patterns were modified in leaf-tissue of the immediately treated plants, and the modifications were exclusively confined to CHG hypomethylation; (2) the CHG-demethylated states were heritable via both maternal and paternal germline, albeit often accompanying further hypomethylation; (3) altered expression of genes encoding for DNA methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited enhanced tolerance to the same stress their progenitor experienced, and this transgenerational inheritance of the effect of condition accompanying heritability of modified methylation patterns. Our findings suggest that stressful environmental condition can produce transgenerational epigenetic modifications. Progenies of stressed plants may develop enhanced adaptability to the condition, and this acquired trait is inheritable and accord with transmission of the epigenetic modifications. We suggest that environmental induction of heritable modifications in DNA methylation provides a plausible molecular underpinning for the still contentious paradigm of inheritance of acquired traits originally put forward by Jean-Baptiste Lamarck more than 200 years ago.

Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

PubMed

Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong

2016-07-01

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. © The Author 2016. Published by Oxford University Press.

Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy

PubMed Central

Dai, Hanren; Wang, Yao; Lu, Xuechun

2016-01-01

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

Hydrophilic/hydrophobic surface modification impact on colloid lithography: Schottky-like defects, dislocation, and ideal distribution

NASA Astrophysics Data System (ADS)

Burtsev, Vasilii; Marchuk, Valentina; Kugaevskiy, Artem; Guselnikova, Olga; Elashnikov, Roman; Miliutina, Elena; Postnikov, Pavel; Svorcik, Vaclav; Lyutakov, Oleksiy

2018-03-01

Nano-spheres lithography is actually considered as a powerful tool to manufacture various periodic structures with a wide potential in the field of nano- and micro-fabrication. However, during self-assembling of colloid microspheres, various defects and mismatches can appear. In this work the size and quality of single-domains of closed-packed polystyrene (PS), grown up on thin Au layers modified by hydrophilic or hydrophobic functional groups via diazonium chemistry was studied. The effects of the surface modification on the quality and single-domain size of polystyrene (PS) microspheres array were investigated and discussed. Modified surfaces were characterized using the AFM and wettability tests. PS colloidal suspension was deposited using the drop evaporation method. Resulted PS microspheres array was characterized using the SEM, AFM and confocal microscopy technique.

Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo.

PubMed

Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

2015-05-07

The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.

Chemical diversity of microbial volatiles and their potential for plant growth and productivity

PubMed Central

Kanchiswamy, Chidananda Nagamangala; Malnoy, Mickael; Maffei, Massimo E.

2015-01-01

Microbial volatile organic compounds (MVOCs) are produced by a wide array of microorganisms ranging from bacteria to fungi. A growing body of evidence indicates that MVOCs are ecofriendly and can be exploited as a cost-effective sustainable strategy for use in agricultural practice as agents that enhance plant growth, productivity, and disease resistance. As naturally occurring chemicals, MVOCs have potential as possible alternatives to harmful pesticides, fungicides, and bactericides as well as genetic modification. Recent studies performed under open field conditions demonstrate that efficiently adopting MVOCs may contribute to sustainable crop protection and production. We review here the chemical diversity of MVOCs by describing microbial–plants and microbial–microbial interactions. Furthermore, we discuss MVOCs role in inducing phenotypic plant responses and their potential physiological effects on crops. Finally, we analyze potential and actual limitations for MVOC use and deployment in field conditions as a sustainable strategy for improving productivity and reducing pesticide use. PMID:25821453

Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.

PubMed Central

McClelland, M; Nelson, M; Raschke, E

1994-01-01

Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes. PMID:7937074

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats.

PubMed

Jiang, Nan; Du, Pinggong; Qu, Weidong; Li, Lin; Liu, Zhonghao; Zhu, Songsong

For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP) treatment and TiO 2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM), atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO 2 -modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO 2 -modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and suppressed osteoclastogenesis with increased expression of OPG and decreased levels of RANKL. These promising results show that PRP treatment combined with a TiO 2 -nanomodified surface can improve titanium-implant biomechanical stability in ovariectomized rats, suggesting a beneficial effect to support the success of implants in osteoporotic bone.

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats

PubMed Central

Jiang, Nan; Du, Pinggong; Qu, Weidong; Li, Lin; Liu, Zhonghao; Zhu, Songsong

2016-01-01

For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP) treatment and TiO2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM), atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO2-modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO2-modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and suppressed osteoclastogenesis with increased expression of OPG and decreased levels of RANKL. These promising results show that PRP treatment combined with a TiO2-nanomodified surface can improve titanium-implant biomechanical stability in ovariectomized rats, suggesting a beneficial effect to support the success of implants in osteoporotic bone. PMID:27695328

Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection.

PubMed

Teo, Pei Yun; Yang, Chuan; Hedrick, James L; Engler, Amanda C; Coady, Daniel J; Ghaem-Maghami, Sadaf; George, Andrew J T; Yang, Yi Yan

2013-10-01

Hydrophobic modification of low molecular weight (LMW) polyethylenimine (PEI) is known to increase gene transfection efficiency of LMW PEI. However, few studies have explored how the conjugated hydrophobic groups influence the properties of the modified LMW PEI mainly due to difficulties in obtaining well defined final product compositions and limitations in current chemical synthesis routes. The aim of this study was to modify LMW PEI (Mn 1.8 kDa, PEI-1.8) judiciously with different hydrophobic functional groups and to investigate how hydrophobicity, molecular structure and inclusion of hydrogen bonding properties in the conjugated side groups as well as the conjugation degree (number of primary amine groups of PEI-1.8 modified with hydrophobic groups) influence PEI-1.8 gene transfection efficiency. The modified polymers were characterized for DNA binding ability, particle size, zeta potential, in vitro gene transfection efficiency and cytotoxicity in SKOV-3 human ovarian cancer and HepG2 human liver carcinoma cell lines. The study shows that modified PEI-1.8 polymers are able to condense plasmid DNA into cationic nanoparticles, of sizes ~100 nm, whereas unmodified polymer/DNA complexes display larger particle sizes of 2 μm. Hydrophobic modification also increases the zeta potential of polymer/DNA complexes. Importantly, modified PEI-1.8 shows enhanced transfection efficiency over the unmodified counterpart. Higher transfection efficiency is obtained when PEI-1.8 is modified with shorter hydrophobic groups (MTC-ethyl) as opposed to longer ones (MTC-octyl and MTC-deodecyl). An aromatic structured functional group (MTC-benzyl) also enhances transfection efficiency more than an alkyl functional group (MTC-octyl). An added hydrogen-bonding urea group in the conjugated functional group (MTC-urea) does not enhance transfection efficiency over one without urea (MTC-benzyl). The study also demonstrates that modification degree greatly influences gene transfection, and ~100% substitution of primary amine groups leads to significantly lower gene transfection efficiency. These findings provide insights to modification of PEI for development of effective and non-cytotoxic non-viral vectors. Copyright © 2013 Elsevier Ltd. All rights reserved.

A modified theoretical framework to assess implementation fidelity of adaptive public health interventions.

PubMed

Pérez, Dennis; Van der Stuyft, Patrick; Zabala, Maríadel Carmen; Castro, Marta; Lefèvre, Pierre

2016-07-08

One of the major debates in implementation research turns around fidelity and adaptation. Fidelity is the degree to which an intervention is implemented as intended by its developers. It is meant to ensure that the intervention maintains its intended effects. Adaptation is the process of implementers or users bringing changes to the original design of an intervention. Depending on the nature of the modifications brought, adaptation could either be potentially positive or could carry the risk of threatening the theoretical basis of the intervention, resulting in a negative effect on expected outcomes. Adaptive interventions are those for which adaptation is allowed or even encouraged. Classical fidelity dimensions and conceptual frameworks do not address the issue of how to adapt an intervention while still maintaining its effectiveness. We support the idea that fidelity and adaptation co-exist and that adaptations can impact either positively or negatively on the intervention's effectiveness. For adaptive interventions, research should answer the question how an adequate fidelity-adaptation balance can be reached. One way to address this issue is by looking systematically at the aspects of an intervention that are being adapted. We conducted fidelity research on the implementation of an empowerment strategy for dengue prevention in Cuba. In view of the adaptive nature of the strategy, we anticipated that the classical fidelity dimensions would be of limited use for assessing adaptations. The typology we used in the assessment-implemented, not-implemented, modified, or added components of the strategy-also had limitations. It did not allow us to answer the question which of the modifications introduced in the strategy contributed to or distracted from outcomes. We confronted our empirical research with existing literature on fidelity, and as a result, considered that the framework for implementation fidelity proposed by Carroll et al. in 2007 could potentially meet our concerns. We propose modifications to the framework to assess both fidelity and adaptation. The modified Carroll et al.'s framework we propose may permit a comprehensive assessment of the implementation fidelity-adaptation balance required when implementing adaptive interventions, but more empirical research is needed to validate it.

The Potential of Clear Sky Carbon Dioxide Satellite Retrievals

NASA Astrophysics Data System (ADS)

Nelson, R.; O'Dell, C.

2013-12-01

It has been shown that neglecting scattering and absorption by aerosols and thin clouds can lead to significant errors in retrievals of the column-averaged dry-air mole fraction of carbon dioxide (XCO2) from space-based measurements of near-infrared reflected sunlight. These clear sky retrievals, which assume no aerosol effects, are desirable because of their high computational efficiency relative to common full physics retrievals. Further, clear sky retrievals may be able to make higher quality measurements relative to the full physics approach because they may introduce fewer potential biases under certain circumstances. These biases can appear when we try to retrieve clouds and aerosols in the full physics methods when there are none actually present. Recent work has shown that intelligent pre-screening can remove soundings with large light-path modifications over ocean surfaces. In this work, we test the hypothesis that intelligent pre-screening of soundings may be successfully used over land surfaces as well as oceans, which would allow clear sky retrievals to be applicable over all surfaces. We also test the hypothesis that major light path modification effects associated with aerosols can be identified based on spectral tests at 0.76, 1.6, and 2 microns. This presentation summarizes our study of both simulated data and satellite observations from the GOSAT instrument in order to assess the effectiveness of using a clear sky retrieval algorithm coupled with intelligent pre-screening to accurately measure carbon dioxide from space-borne instruments.

Microscopic mechanism of amino silicone oil modification and modification effect with different amino group contents based on molecular dynamics simulation

NASA Astrophysics Data System (ADS)

He, Liping; Li, Wenjun; Chen, Dachuan; Yuan, Jianmin; Lu, Gang; Zhou, Dianwu

2018-05-01

The microscopic mechanism of amino silicone oil (ASO) modification of natural fiber was investigated for the first time using molecular dynamics (MD) simulation at the atomic and molecular levels. The MD simulation results indicated that the ASO molecular interacted with the cellulose molecular within the natural fiber, mainly by intermolecular forces of Nsbnd Hsbnd O and Osbnd Hsbnd N hydrogen bonds and the molecular chain of ASO absorbed onto the natural fiber in a selective orientation, i.e., the hydrophobic alkyl groups (sbnd CnH2n+1) project outward and the polar amino groups (sbnd NH2) point to the surface of natural fiber. Consequently, the ASO modification changed the surface characteristic of natural fiber from hydrophilic to hydrophobic. Furthermore, the modification effects of the ASO modification layer with different amino group contents (m:n ratio) were also evaluated in this study by calculating the binding energy between the ASO modifier and natural fiber, and the cohesive energy density and free volume of the ASO modification layer. The results showed that the binding energy reached a maximum when the m:n ratio of ASO was of 8:4, suggesting that a good bonding strength was achieved at this m:n ratio. It was also found that the cohesive energy density enhanced with the increase in the amino group content, and the higher the cohesive energy density, the easier the formation of the ASO modification layer. However, the fraction free volume decreased with the increase in the amino group content. This is good for improving the water-proof property of natural fiber. The present work can provide an effective method for predicting the modification effects and designing the optimized m:n ratio of ASO modification.

Metabolic memory and chronic diabetes complications: potential role for epigenetic mechanisms.

PubMed

Intine, Robert V; Sarras, Michael P

2012-10-01

Recent estimates indicate that diabetes mellitus currently affects more than 10 % of the world's population. Evidence from both the laboratory and large scale clinical trials has revealed that prolonged hyperglycemia induces chronic complications which persist and progress unimpeded even when glycemic control is pharmaceutically achieved via the phenomenon of metabolic memory. The epigenome is comprised of all chromatin modifications including post translational histone modification, expression control via miRNAs and the methylation of cytosine within DNA. Modifications of these epigenetic marks not only allow cells and organisms to quickly respond to changing environmental stimuli but also confer the ability of the cell to "memorize" these encounters. As such, these processes have gained much attention as potential molecular mechanisms underlying metabolic memory and chronic diabetic complications. Here we present a review of the very recent literature published pertaining to this subject.

Lifestyle modification in the management of the metabolic syndrome: achievements and challenges

PubMed Central

Grave, Riccardo Dalle; Calugi, Simona; Centis, Elena; Marzocchi, Rebecca; Ghoch, Marwan El; Marchesini, Giulio

2010-01-01

Lifestyle modification based on behavior therapy is the most important and effective strategy to manage the metabolic syndrome. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioral and cognitive strategies. The intervention may be delivered face-to-face or in groups, or in groups combined with individual sessions. The main challenge of treatment is helping patients maintain healthy behavior changes in the long term. In the last few years, several strategies have been evaluated to improve the long-term effect of lifestyle modification. Promising results have been achieved by combining lifestyle modification with pharmacotherapy, using meals replacement, setting higher physical activity goals, and long-term care. The key role of cognitive processes in the success/failure of weight loss and maintenance suggests that new cognitive procedures and strategies should be included in the traditional lifestyle modification interventions, in order to help patients build a mind-set favoring long-term lifestyle changes. These new strategies raise optimistic expectations for an effective treatment of metabolic syndrome with lifestyle modifications, provided public health programs to change the environment where patients live support them. PMID:21437107

Activated Dual Specificity Lymphocytes and Their Methods of Use | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of using genetic modifications to generate leukocytes with multiple specificities. This technology represents a potential therapy for a wide variety of malignancies, and because of the genetic modification used, this therapy will be applicable to patients of any MHC type.

Research Review: Attention Bias Modification (ABM)--A Novel Treatment for Anxiety Disorders

ERIC Educational Resources Information Center

Bar-Haim, Yair

2010-01-01

Attention bias modification (ABM) is a newly emerging therapy for anxiety disorders that is rooted in current cognitive models of anxiety and in established experimental data on threat-related attentional biases in anxiety. This review describes the evidence indicating that ABM has the potential to become an enhancing tool for current…

Beyond Transcription Factors: The Role of Chromatin Modifying Enzymes in Regulating Transcription Required for Memory

ERIC Educational Resources Information Center

Barrett, Ruth M.; Wood, Marcelo A.

2008-01-01

One of the alluring aspects of examining chromatin modifications in the role of modulating transcription required for long-term memory processes is that these modifications may provide transient and potentially stable epigenetic marks in the service of activating and/or maintaining transcriptional processes. These, in turn, may ultimately…

Post-translational modifications of transthyretin affect the triiodonine-binding potential

PubMed Central

Henze, Andrea; Homann, Thomas; Serteser, Mustafa; Can, Ozge; Sezgin, Ozlem; Coskun, Abdurrahman; Unsal, Ibrahim; Schweigert, Florian J; Ozpinar, Aysel

2015-01-01

Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10), which is frequently affected by oxidative post-translational modifications. As Cys10 is part of the thyroid hormone-binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype- and site-specific manner with S-glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function-specific patterns of TTR with a substantial decrease in S-sulphonated, S-cysteinylglycinated and S-glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability. PMID:25311081

Biopharmaceuticals from plants: a multitude of options for posttranslational modifications.

PubMed

Warzecha, Heribert

2008-01-01

In 1982 the first recombinant therapeutic, human insulin, was introduced into the market and started a new branch of pharmaceutical development, manufacture, and therapy options. To date, more than 130 recombinant protein therapeutics have been approved by the US Food and Drug Administration (FDA) and many more are being developed world wide. With the increasing number of protein therapeutics the number of potential production organisms is also expanding, and posttranslational modification of proteins has become a topic of special focus. One major difference between small-molecule drugs and protein therapeutics is that the latter are reliant on a host organism for their production and this can have a large influence on the final structure and can ultimately affect the pharmacokinetics, immunogenicity, and the function of the protein depending on the production process. Plants can be efficiently used as production systems for recombinant proteins thereby offering a variety of options for transgene targeting and modification. This review is intended to give an overview about the potential of plants to serve as a production system for therapeutic and prophylactic biopharmaceuticals with respect to posttranslational modifications.

Sulfonamido tripods: tuning redox potentials via ligand modifications

PubMed Central

Lau, Nathanael; Ziller, Joseph W.

2014-01-01

A series of FeII–OH2 complexes were synthesized with ligands based on the tetradentate sulfonamido tripod N,N',N"-[2,2',2"-nitrilotris(ethane-2,1-diyl)]-tris-({R-Ph}-sulfonamido). These complexes differ by the substituent on the aryl rings and were fully characterized, including their molecular structures via X-ray diffraction methods. All the complexes were five-coordinate with trigonal bipyramidal geometry. A linear correlation was observed between the electronic effects of each ligand, given by the Hammett constants of the para-substituents, and the potential of the FeII/FeIII redox couple, which were determined using cyclic voltammetry. It was found that the range of redox potentials for the complexes spanned approximately 160 mV. PMID:25419035

Sulfonamido tripods: tuning redox potentials via ligand modifications.

PubMed

Lau, Nathanael; Ziller, Joseph W; Borovik, A S

2015-01-08

A series of Fe II -OH 2 complexes were synthesized with ligands based on the tetradentate sulfonamido tripod N , N ', N "-[2,2',2"-nitrilotris(ethane-2,1-diyl)]-tris-({R-Ph}-sulfonamido). These complexes differ by the substituent on the aryl rings and were fully characterized, including their molecular structures via X-ray diffraction methods. All the complexes were five-coordinate with trigonal bipyramidal geometry. A linear correlation was observed between the electronic effects of each ligand, given by the Hammett constants of the para -substituents, and the potential of the Fe II /Fe III redox couple, which were determined using cyclic voltammetry. It was found that the range of redox potentials for the complexes spanned approximately 160 mV.

The Tuning of Optical Properties of Nanoscale MOFs-Based Thin Film through Post-Modification.

PubMed

Yin, Wenchang; Tao, Cheng-An; Zou, Xiaorong; Wang, Fang; Qu, Tianlian; Wang, Jianfang

2017-08-29

Optical properties, which determine the application of optical devices in different fields, are the most significant properties of optical thin films. In recent years, Metal-organic framework (MOF)-based optical thin films have attracted increasing attention because of their novel optical properties and important potential applications in optical and photoelectric devices, especially optical thin films with tunable optical properties. This study reports the first example of tuning the optical properties of a MOF-based optical thin film via post-modification. The MOF-based optical thin film was composed of NH₂-MIL-53(Al) nanorods (NRs) (MIL: Materials from Institute Lavoisier), and was constructed via a spin-coating method. Three aldehydes with different lengths of carbon chains were chosen to modify the MOF optical thin film to tune their optical properties. After post-modification, the structural color of the NH₂-MIL-53(Al) thin film showed an obvious change from purple to bluish violet and cyan. The reflection spectrum and the reflectivity also altered in different degrees. The effective refractive index ( n eff ) of MOFs thin film can also be tuned from 1.292 to 1.424 at a wavelength of 750 nm. The success of tuning of the optical properties of MOFs thin films through post-modification will make MOFs optical thin films meet different needs of optical properties in various optical and optoelectronic devices.

The Tuning of Optical Properties of Nanoscale MOFs-Based Thin Film through Post-Modification

PubMed Central

Zou, Xiaorong; Wang, Fang; Qu, Tianlian; Wang, Jianfang

2017-01-01

Optical properties, which determine the application of optical devices in different fields, are the most significant properties of optical thin films. In recent years, Metal-organic framework (MOF)-based optical thin films have attracted increasing attention because of their novel optical properties and important potential applications in optical and photoelectric devices, especially optical thin films with tunable optical properties. This study reports the first example of tuning the optical properties of a MOF-based optical thin film via post-modification. The MOF-based optical thin film was composed of NH2-MIL-53(Al) nanorods (NRs) (MIL: Materials from Institute Lavoisier), and was constructed via a spin-coating method. Three aldehydes with different lengths of carbon chains were chosen to modify the MOF optical thin film to tune their optical properties. After post-modification, the structural color of the NH2-MIL-53(Al) thin film showed an obvious change from purple to bluish violet and cyan. The reflection spectrum and the reflectivity also altered in different degrees. The effective refractive index (neff) of MOFs thin film can also be tuned from 1.292 to 1.424 at a wavelength of 750 nm. The success of tuning of the optical properties of MOFs thin films through post-modification will make MOFs optical thin films meet different needs of optical properties in various optical and optoelectronic devices. PMID:28850057

Modification of carbon nanotube's dispersion using cetyltrimethyl ammonium bromide (CTAB) as cancer drug delivery

NASA Astrophysics Data System (ADS)

Wulan, Praswati PDK.; Wulandari, Hanifia; Ulwan, Sekar H.; Purwanto, Widodo W.; Mulia, Kamarza

2018-02-01

Cancer is a disease that causes many deaths globally. Cancer treatments have side effects that can danger the human body. Carbon nanotube (CNT) becomes drug (anti-cancer) delivery towards cancer cells that have been targeted. Yet, CNT tends to aggregate. It could be overcome by functionalization (modification) of CNT using Cetyltrimethyl Ammonium Bromide (CTAB). The variations we use were CNT-CTAB with a dose of CNT 100 mg and CTAB varied between 80, 90, 100, 110, and 120 mg. There were several stages of CNT modification process: dispersion, filtration, washing, and drying. The optimum condition obtained was on CNT-110 mg CTAB because it could be dispersed up to 70 hours better than pure CNT, Zeta Potential (ZP) ≥16 mV, and absorbance Uv-vis 1.05. Both the ZP value and the absorbance of Uv-vis showed the CNT dispersion modified to be better than the pure CNT. Furthermore, SEM-EDX did not produce structural damage to CNT modified surfaces, the percentage of the mass of Oxygen (O) elements as characteristic of increased hydrophilic properties, and Ni elements as toxic impurities become reduced. FTIR spectrum results showed the highest intensity occurred at CTAB CNT-110mg at 1221 m-1. This strong C-N vibration interaction suggests that CNTs CNT modification become readily dispersed in water.

Hierarchical layered double hydroxides with Ag nanoparticle modification for ethanol sensing

NASA Astrophysics Data System (ADS)

Qin, Yuxiang; Wang, Liping; Wang, Xiaofei

2018-07-01

Layered double hydroxides (LDHs) have recently been revealed to be promising in gas sensor applications due to their compositional flexibility and unique 2D-interlayer channel for gas diffusion and adsorption. This work demonstrates highly porous hierarchical LDHs containing Mg2+ and Al3+ (MgAl-LDHs) for ethanol sensing at room temperature. These MgAl-LDHs, with unique flower-like hierarchical structure and mesoporous interlayer, were synthesized hydrothermally using sodium dodecyl sulfate as soft template as well as intercalating agent. Further modification by discrete Ag nanoparticles (NPs) was achieved via an environmentally friendly glucose-reduction method to improve the gas-sensing response of the LDH-based sensor. It is found that the hierarchical MgAl-LDHs show potential in sensing ethanol gas with rapid dynamic characteristics at room temperature; their response magnitude towards ethanol can be enhanced significantly by Ag NP modification. The gas-response value of the Ag-modified MgAl-LDH sensor is about twice that of pristine MgAl-LDH sensors, towards 5–200 ppm ethanol at room temperature. Meanwhile, rapid response-recovery characteristics are achieved, with response and recovery times shorter than 10 and 50 s, respectively. The satisfactory sensing performance and remarkable response enhancement by Ag NP modification are demonstrated in terms of the unique microstructure of the hierarchical MgAl-LDHs and a constructed conductive effect model of Ag functionalized LDHs.

Application of the Trend Filtering Algorithm for Photometric Time Series Data

NASA Astrophysics Data System (ADS)

Gopalan, Giri; Plavchan, Peter; van Eyken, Julian; Ciardi, David; von Braun, Kaspar; Kane, Stephen R.

2016-08-01

Detecting transient light curves (e.g., transiting planets) requires high-precision data, and thus it is important to effectively filter systematic trends affecting ground-based wide-field surveys. We apply an implementation of the Trend Filtering Algorithm (TFA) to the 2MASS calibration catalog and select Palomar Transient Factory (PTF) photometric time series data. TFA is successful at reducing the overall dispersion of light curves, however, it may over-filter intrinsic variables and increase “instantaneous” dispersion when a template set is not judiciously chosen. In an attempt to rectify these issues we modify the original TFA from the literature by including measurement uncertainties in its computation, including ancillary data correlated with noise, and algorithmically selecting a template set using clustering algorithms as suggested by various authors. This approach may be particularly useful for appropriately accounting for variable photometric precision surveys and/or combined data sets. In summary, our contributions are to provide a MATLAB software implementation of TFA and a number of modifications tested on synthetics and real data, summarize the performance of TFA and various modifications on real ground-based data sets (2MASS and PTF), and assess the efficacy of TFA and modifications using synthetic light curve tests consisting of transiting and sinusoidal variables. While the transiting variables test indicates that these modifications confer no advantage to transit detection, the sinusoidal variables test indicates potential improvements in detection accuracy.

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.

PubMed

Liu, Jiqin; Ren, Dangli; Du, Zhenhua; Wang, Hekong; Zhang, Hua; Jin, Ying

2018-08-25

N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m 6 A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m 6 A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m 6 A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m 6 A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m 6 A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical assessment of dietary interventions and lifestyle modifications in Madhumeha (type- 2 Diabetes Mellitus)

PubMed Central

Gupta, Archana; Agarwal, Neeraj Kumar; Byadgi, Parameswarappa S.

2014-01-01

Background: India leads the world with maximum number of diabetes patients being termed as the “diabetes capital of the world.” Certain risk factors including unsatisfactory diet, overweight, and a sedentary lifestyle are potentially reversible. Acharayas have widely described the role of diet and activities to control Madhumeha (type 2 diabetes mellitus [T2DM]) along with medications. Habitual consumption of roasted or dry Barley (Hordeum vulgare L.) flour, Mudga (Phaseolus aureus Roxb.) and Amalaki (Emblica officinalis Gaertn.) prevents the manifestation of Prameha. Aim: To assess the clinical effects of dietary interventions and life style modifications in Madhumeha patients. Materials and Methods: Present study was carried out on 56 patients of Madhumeha from S.S. Hospital, Banaras Hindu University, Varanasi. Dietary interventions and life style modifications schedule was prepared based on Ayurvedic principles and patients were advised to follow this regimen. Three consecutive follow-ups were done for 3 months at the interval of one month each. Results: Significant improvement was observed in clinical signs and symptoms along with plasma glucose and glycosylated hemoglobin (HbA1c) in Madhumeha patients after these interventions (P < 0.001). Conclusion: Dietary interventions and life style modifications are two important tools by which adequate glycemic control can be obtained, especially in newly diagnosed T2DM patients and in patients who are on antidiabetic medication, but not properly controlled. PMID:26195901

REDOX REGULATION OF SIRT1 IN INFLAMMATION AND CELLULAR SENESCENCE

PubMed Central

Hwang, Jae-woong; Yao, Hongwei; Caito, Samuel; Sundar, Isaac K.; Rahman, Irfan

2013-01-01

Sirtuin1 (SIRT1) regulates inflammation, aging (lifespan and healthspan), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. SIRT1 is regulated by a NAD+-dependent DNA repair enzyme poly(ADP-ribose)-polymerase-1 (PARP-1), and subsequent NAD+ depletion by oxidative stresses may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to post-translational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65 and FOXO3, thereby enhancing the inflammatory, pro-senescent and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox post-translational modifications of SIRT1 and its role in PARP1, NF-κB activation, FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging are discussed. Furthermore, we also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases. PMID:23542362

Hierarchical layered double hydroxides with Ag nanoparticle modification for ethanol sensing.

PubMed

Qin, Yuxiang; Wang, Liping; Wang, Xiaofei

2018-07-06

Layered double hydroxides (LDHs) have recently been revealed to be promising in gas sensor applications due to their compositional flexibility and unique 2D-interlayer channel for gas diffusion and adsorption. This work demonstrates highly porous hierarchical LDHs containing Mg 2+ and Al 3+ (MgAl-LDHs) for ethanol sensing at room temperature. These MgAl-LDHs, with unique flower-like hierarchical structure and mesoporous interlayer, were synthesized hydrothermally using sodium dodecyl sulfate as soft template as well as intercalating agent. Further modification by discrete Ag nanoparticles (NPs) was achieved via an environmentally friendly glucose-reduction method to improve the gas-sensing response of the LDH-based sensor. It is found that the hierarchical MgAl-LDHs show potential in sensing ethanol gas with rapid dynamic characteristics at room temperature; their response magnitude towards ethanol can be enhanced significantly by Ag NP modification. The gas-response value of the Ag-modified MgAl-LDH sensor is about twice that of pristine MgAl-LDH sensors, towards 5-200 ppm ethanol at room temperature. Meanwhile, rapid response-recovery characteristics are achieved, with response and recovery times shorter than 10 and 50 s, respectively. The satisfactory sensing performance and remarkable response enhancement by Ag NP modification are demonstrated in terms of the unique microstructure of the hierarchical MgAl-LDHs and a constructed conductive effect model of Ag functionalized LDHs.

Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations

PubMed Central

Jiang, Jun; Aduri, Raviprasad; Chow, Christine S.; SantaLucia, John

2014-01-01

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson–Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity. PMID:24371282

Applied Self-Statement Modification and Applied Modified Desensitization in the Treatment of Speech Anxiety: The Synergy Hypothesis.

ERIC Educational Resources Information Center

Melanson, Diane C.

A study examined the relative effectiveness and synergistic effect of two treatments for reducing speech anxiety--Self-Statement Modification (SSM), a therapy focused on modification of cognitive behavior; and Modified Desensitization (MD), a therapy focused on physiological variables, utilizing relaxation training, group hierarchy construction,…

Effects of wing modification on an aircraft's aerodynamic parameters as determined from flight data

NASA Technical Reports Server (NTRS)

Hess, R. A.

1986-01-01

A study of the effects of four wing-leading-edge modifications on a general aviation aircraft's stability and control parameters is presented. Flight data from the basic aircraft configuration and configurations with wing modifications are analyzed to determine each wing geometry's stability and control parameters. The parameter estimates and aerodynamic model forms are obtained using the stepwise regression and maximum likelihood techniques. The resulting parameter estimates and aerodynamic models are verified using vortex-lattice theory and by analysis of each model's ability to predict aircraft behavior. Comparisons of the stability and control derivative estimates from the basic wing and the four leading-edge modifications are accomplished so that the effects of each modification on aircraft stability and control derivatives can be determined.

Modification of Sr on 4004 Aluminum Alloy

NASA Astrophysics Data System (ADS)

Guo, Erjun; Cao, Guojian; Feng, Yicheng; Wang, Liping; Wang, Guojun; Lv, Xinyu

2013-05-01

As a brazing foil, 4004 Al alloy has good welding performance. However, the high Si content decreases the plasticity of the alloy. To improve the plasticity of 4004 Al alloy and subsequently improve the productivity of 4004 Al foil or 434 composite foil, 4004 Al alloy was modified by Al-10%Sr master alloy. Modification effects of an additional amount of Sr, modification temperature, and holding time on 4004 aluminum alloy were studied by orthogonal design. The results showed that the greatest impact parameter of 4004 aluminum alloy modification was the additional amount of Sr, followed by holding time and modification temperature. The optimum modification parameters obtained by orthogonal design were as follows: Sr addition of 0.04%, holding time of 60 min, and modification temperature of 760°C. The effect of Sr addition on modification was analyzed in detail based on orthogonal results. With increasing of Sr addition, elongation of 4004 alloy increased at first, and decreased after reaching the maximum value.

Modification of surface properties of cellulosic substrates by quaternized silicone emulsions.

PubMed

Purohit, Parag S; Somasundaran, P

2014-07-15

The present work describes the effect of quaternization of silicones as well as the relevant treatment parameter pH on the frictional, morphological and relaxation properties of fabric substrates. Due to their unique surface properties, silicone polymers are extensively used to modify surface properties of various materials, although the effects of functionalization of silicones and relevant process conditions on modification of substrates are not well understood. Specifically we show a considerable reduction in fabric friction, roughness and waviness upon treatment with quaternized silicones. The treatment at acidic pH results in better deposition of silicone polymers onto the fabric as confirmed through streaming potential measurements which show charge reversal of the fabric. Interestingly, Raman spectroscopy studies show the band of C-O ring stretching mode at ∼1095 cm(-1) shift towards higher wavenumber indicating lowering of stress in fibers upon appropriate silicone treatment. Thus along with the morphological and frictional properties being altered, silicone treatment can lead to a reduction in fabric strain. It is concluded that the electrostatic interactions play an initial role in modification of the fiber substrate followed by multilayer deposition of polymer. This multi-technique approach to study fiber properties upon treatment by combining macro to molecular level methods has helped in understanding of new functional coating materials. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantification of the effect of surface heating on shock wave modification by a plasma actuator in a low-density supersonic flow over a flat plate

NASA Astrophysics Data System (ADS)

Joussot, Romain; Lago, Viviana; Parisse, Jean-Denis

2015-05-01

This paper describes experimental and numerical investigations focused on the shock wave modification induced by a dc glow discharge. The model is a flat plate in a Mach 2 air flow, equipped with a plasma actuator composed of two electrodes. A weakly ionized plasma was created above the plate by generating a glow discharge with a negative dc potential applied to the upstream electrode. The natural flow exhibited a shock wave with a hyperbolic shape. Pitot measurements and ICCD images of the modified flow revealed that when the discharge was ignited, the shock wave angle increased with the discharge current. The spatial distribution of the surface temperature was measured with an IR camera. The surface temperature increased with the current and decreased along the model. The temperature distribution was reproduced experimentally by placing a heating element instead of the active electrode, and numerically by modifying the boundary condition at the model surface. For the same surface temperature, experimental investigations showed that the shock wave angle was lower with the heating element than for the case with the discharge switched on. The results show that surface heating is responsible for roughly 50 % of the shock wave angle increase, meaning that purely plasma effects must also be considered to fully explain the flow modifications observed.

Testing the relative contribution of positive and negative interactions in rocky intertidal communities

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

Bertness, M.D.; Leonard, G.H.; Levine, J.M.

In contrast to many other biotic forces, such as competition and predation, the role played by habitat modification by plants and sessile animals in natural communities has not been given the experimental attention it deserves. To test the hypothesis that habitat modification by seaweed canopies can have direct positive effects on rocky intertidal communities, the authors quantified habitat amelioration by Ascophyllum nodosum canopies and its consequences on understory organisms in the Gulf of Maine, USA. At the upper and lower elevational borders of the algal canopy, the authors examined the recruitment, growth, and survivorship of common benthic organisms in canopymore » removal, and shaded canopy removal plots intended to mimic canopy habitat modifications. The algal canopy greatly reduced potential physical stresses, particularly at high tidal heights. Maximum daily rock temperatures were 5--10 C lower and evaporative water loss was in order of magnitude less under the canopy than in canopy removal plots. The response of understory organisms to canopy removal, however, was species specific and somewhat idiosyncratic. Nonetheless, in general, at the high intertidal border of the canopy the recruitment, growth, and survival of understory organisms were enhanced by the canopy, whereas at the low intertidal border canopy effects were negative or neutral. nearly half of the interactions the authors studied were positive in the high zone.« less

Improvements to the strength and corrosion resistance of aluminum-magnesium-manganese alloys of near-AA5083 chemistry

NASA Astrophysics Data System (ADS)

Carroll, Mark Christopher

Aluminum alloys of the 5000 series (AI-Mg-Mn) are extremely popular in a wide range of applications that call for a balance of moderately high strength, good corrosion resistance, and light weight, all at a moderate cost. One of the most popular 5000 series alloys is designated A1-5083, containing, in addition to aluminum, approximately 4 wt% magnesium and 0.7 wt% manganese. In order to increase the range of versatility of this particular alloy, a number of modifications have been examined that will potentially improve the strength and corrosion resistance characteristics while maintaining a chemical composition that is very close to the proven 5083 alloy. The strength of the 5083-based alloys under study are investigated with two goals in mind---to maximize the potential strength characteristics in a "standard" 5083 form through changes in minor processing parameters or through minor alloying additions. Increasing the standard alloy's potential is possible through improved efficiency of "preprocessing" heat treatments that maximize the homogeneous dispersion of secondary manganese-based particles. For the modified alloy study, additions of scandium and zirconium are shown to improve strength not only by forming secondary particles in the alloy, but also through substitutional solid solution strengthening, even when added at very small levels. Corrosion resistance of these 5083-based alloys is investigated once again through minor alloying additions; specifically zinc, copper, and silver. Zinc is particularly effective in that it changes the corrosion-susceptible binary aluminum-magnesium phase that would otherwise form on grain boundaries following exposure to moderately elevated temperatures for extended periods of time to a ternary aluminum-magnesium-zinc phase. This chemical composition of this ternary phase that forms following zinc additions can be further altered through minor additions of copper and silver. By determining threshold levels for these modifications while maintaining a chemical composition that is very near that of standard Al-5083, it can be shown that even minor modifications to processing and alloying parameters can have a favorable effect on the final bulk properties of the alloy. The increased range of strength and corrosion resistance of these lightly modified alloys make them more attractive in a broadened range of potential applications.

Noncompound nucleus decay contribution in the 12C+93Nb reaction using various formulations of nuclear proximity potential

NASA Astrophysics Data System (ADS)

Chopra, Sahila; Kaur, Arshdeep; Gupta, Raj K.

2015-01-01

The earlier study of excitation functions of *105Ag, formed in the 12C+93Nb reaction, based on the dynamical cluster-decay model (DCM), using the pocket formula for nuclear proximity potential is extended to the use of other nuclear interaction potentials derived from the Skyrme energy density functional (SEDF) based on the semiclassical extended Thomas Fermi (ETF) approach and to the use of the extended-Wong model of Gupta and collaborators. The Skyrme forces used are the old SIII and SIV and the new SSk, GSkI, and KDE0(v1) given for both normal and isospin-rich nuclei, with densities added in the frozen-density approximation. Taking advantage of the fact that different Skyrme forces provide different barrier characteristics, we look for the "barrier modification" effects in terms of choosing an appropriate force and hence for the existence or nonexistence of noncompound nucleus (nCN) effects in this reaction. Interestingly, independent of the choice of Skyrme or proximity force, the extended-Wong model fits the experimental data nicely, without any barrier modification and hence no nCN component in the measured fusion cross section, which consists of light-particle evaporation residue (ER) and intermediate-mass fragments (IMFs) up to mass 13, i.e., σfusionExpt .=σER+σIMFs . However, the predicted fusion cross section due to the extended-Wong model is much larger, possibly because of the so-far missing fusion-fission (ff) component in the data. On the other hand, in agreement with the earlier work using the pocket proximity potential, the DCM fits only some data (mainly IMFs) for only some Skyrme forces, and hence it presents the chosen reaction as a case of a large nCN component, whose empirically estimated content is fitted for use of the DCM with a fragment preformation factor taken equal to one, i.e., using DCM (P0=1 ), by introducing "barrier modification" through changing the neck-length parameter Δ R for a best fit to the empirical nCN data in each (ER and IMF) decay channel. Also, the ff component of the DCM is predicted to lie around the symmetric mass A /2 ±16 . All calculations are made for deformed and oriented coplanar nuclei.

Optimizing empiric therapy for Gram-negative bloodstream infections in children.

PubMed

Chao, Y; Reuter, C; Kociolek, L K; Patel, R; Zheng, X; Patel, S J

2018-06-01

Antimicrobial stewardship can be challenging in children with bloodstream infections (BSIs) caused by Gram-negative bacilli (GNB). This retrospective cohort study explored how data elements in the electronic health record could potentially optimize empiric antibiotic therapy for BSIs caused by GNB, via the construction of customized antibiograms for categorical GNB infections and identification of opportunities to minimize organism-drug mismatch and decrease time to effective therapy. Our results suggest potential strategies that could be implemented at key decision points in prescribing at initiation, modification, and targeting of therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Surface modification effects on defect-related photoluminescence in colloidal CdS quantum dots.

PubMed

Lee, TaeGi; Shimura, Kunio; Kim, DaeGwi

2018-05-03

We investigated the effects of surface modification on the defect-related photoluminescence (PL) band in colloidal CdS quantum dots (QDs). A size-selective photoetching process and a surface modification technique with a Cd(OH)2 layer enabled the preparation of size-controlled CdS QDs with high PL efficiency. The Stokes shift of the defect-related PL band before and after the surface modification was ∼1.0 eV and ∼0.63 eV, respectively. This difference in the Stokes shifts suggests that the origin of the defect-related PL band was changed by the surface modification. Analysis by X-ray photoelectron spectroscopy revealed that the surface of the CdS QDs before and after the surface modification was S rich and Cd rich, respectively. These results suggest that Cd-vacancy acceptors and S-vacancy donors affect PL processes in CdS QDs before and after the surface modification, respectively.

Impact of acid and oxidative modifications, single or dual, of sorghum starch on biodegradable films.

PubMed

Biduski, Bárbara; Silva, Francine Tavares da; Silva, Wyller Max da; Halal, Shanise Lisie de Mello El; Pinto, Vania Zanella; Dias, Alvaro Renato Guerra; Zavareze, Elessandra da Rosa

2017-01-01

The objective of this study was to evaluate the effects of acid and oxidation modifications on sorghum starch, as well as the effect of dual modification of starch on the physical, morphological, mechanical, and barrier properties of biodegradable films. The acid modification was performed with 3% lactic acid and the oxidation was performed with 1.5% active chlorine. For dual modification, the acid modification was performed first, followed by oxidation under the same conditions as above. Both films of the oxidized starches, single and dual, had increased stiffness, providing a higher tensile strength and lower elongation when compared to films based on native and single acid modified starches. However, the dual modification increased the water vapor permeability of the films without changing their solubility. The increase in sorghum starch concentration in the filmogenic solution increased the thickness, water vapor permeability, and elongation of the films. Copyright © 2016. Published by Elsevier Ltd.

Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions.

PubMed

McCarty, Kathleen M; Smith, Thomas J; Zhou, Wei; Gonzalez, Ernesto; Quamruzzaman, Quazzi; Rahman, Mahmuder; Mahiuddin, Golam; Ryan, Louise; Su, Li; Christiani, David C

2007-08-01

Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions.

Antioxidants in dermatology*

PubMed Central

Addor, Flavia Alvim Sant'anna

2017-01-01

The skin cells continuously produce, through cellular respiration, metabolic processes or under external aggressions, highly reactive molecules oxidation products, generally called free radicals. These molecules are immediately neutralized by enzymatic and non-enzymatic systems in a physiological and dynamic balance. In situations where this balance is broken, various cellular structures, such as the cell membrane, nuclear or mitochondrial DNA may suffer structural modifications, triggering or worsening skin diseases. several substances with alleged antioxidant effects has been offered for topical or oral use, but little is known about their safety, possible associations and especially their mechanism of action. The management of topical and oral antioxidants can help dermatologist to intervene in the oxidative processes safely and effectively, since they know the mechanisms, limitations and potential risks of using these molecules as well as the potential benefits of available associations. PMID:29186248

Stabilization of lower hybrid drift modes by finite parallel wavenumber and electron temperature gradients in field-reversed configurations

NASA Astrophysics Data System (ADS)

Farengo, R.; Guzdar, P. N.; Lee, Y. C.

1989-08-01

The effect of finite parallel wavenumber and electron temperature gradients on the lower hybrid drift instability is studied in the parameter regime corresponding to the TRX-2 device [Fusion Technol. 9, 48 (1986)]. Perturbations in the electrostatic potential and all three components of the vector potential are considered and finite beta electron orbit modifications are included. The electron temperature gradient decreases the growth rate of the instability but, for kz=0, unstable modes exist for ηe(=T'en0/Ten0)>6. Since finite kz effects completely stabilize the mode at small values of kz/ky(≂5×10-3), magnetic shear could be responsible for stabilizing the lower hybrid drift instability in field-reversed configurations.

Mechanisms of transient receptor potential vanilloid 1 activation and sensitization by allyl isothiocyanate.

PubMed

Gees, Maarten; Alpizar, Yeranddy A; Boonen, Brett; Sanchez, Alicia; Everaerts, Wouter; Segal, Andrei; Xue, Fenqin; Janssens, Annelies; Owsianik, Grzegorz; Nilius, Bernd; Voets, Thomas; Talavera, Karel

2013-09-01

Allyl isothiocyanate (AITC; aka, mustard oil) is a powerful irritant produced by Brassica plants as a defensive trait against herbivores and confers pungency to mustard and wasabi. AITC is widely used experimentally as an inducer of acute pain and neurogenic inflammation, which are largely mediated by the activation of nociceptive cation channels transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 (TRPV1). Although it is generally accepted that electrophilic agents activate these channels through covalent modification of cytosolic cysteine residues, the mechanism underlying TRPV1 activation by AITC remains unknown. Here we show that, surprisingly, AITC-induced activation of TRPV1 does not require interaction with cysteine residues, but is largely dependent on S513, a residue that is involved in capsaicin binding. Furthermore, AITC acts in a membrane-delimited manner and induces a shift of the voltage dependence of activation toward negative voltages, which is reminiscent of capsaicin effects. These data indicate that AITC acts through reversible interactions with the capsaicin binding site. In addition, we show that TRPV1 is a locus for cross-sensitization between AITC and acidosis in nociceptive neurons. Furthermore, we show that residue F660, which is known to determine the stimulation by low pH in human TRPV1, is also essential for the cross-sensitization of the effects of AITC and low pH. Taken together, these findings demonstrate that not all reactive electrophiles stimulate TRPV1 via cysteine modification and help understanding the molecular bases underlying the surprisingly large role of this channel as mediator of the algesic properties of AITC.

Understanding and changing human behaviour—antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour

PubMed Central

Tamhankar, Ashok J.

2014-01-01

This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the ‘stages of change model’, including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to ‘global good’, so-called ‘social marketing’, to improve ‘welfare of the individual and society’ is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement ‘antibiotic mainstreaming’ as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society. PMID:24735112

Hydrologic conditions in the Chicod Creek basin, North Carolina, before and during channel modifications, 1975-81

USGS Publications Warehouse

Watkins, S.A.; Simmons, C.E.

1984-01-01

Beginning in late 1978, stream channels throughout the 60-square mile Chicod Creek basin underwent extensive modification to increase drainage efficiency and reduce flooding potential. Drainage modifications in this Coastal Plain basin, consisting primarily of channel excavation and clearing of channel blockages, were completed in December 1981. The hydrologic condition of the basin before and during modification was determined from observed data. Observed data indicate hydrologic changes occurred in selected basin characteristics. For example, water levels in the surficial aquifer within 250 feet of Juniper Branch declined as much as 0.4 feet during modifications; at distances greater than 250 feet from the stream, ground-water levels did not change. Base flows increased, and suspended-sediment concentrations for high flows were several times greater than before channel modifications. Increases in selected chemical constituent concentrations in stream water during modifications were as follows: calcium, 12 percent; sodium, 18 percent; bicarbonate, 84 percent; and phosphorous, 80 percent. Significant changes were not found in either pesticide concentrations or coliform bacteria counts.

Controlled levels of protein modification through a chromatography-mediated bioconjugation

DOE PAGES

Kwant, Richard L.; Jaffe, Jake; Palmere, Peter J.; ...

2015-02-27

Synthetically modified proteins are increasingly finding applications as well-defined scaffolds for materials. In practice it remains difficult to construct bioconjugates with precise levels of modification because of the limited number of repeated functional groups on proteins. This article describes a method to control the level of protein modification in cases where there exist multiple potential modification sites. A protein is first tagged with a handle using any of a variety of modification chemistries. This handle is used to isolate proteins with a particular number of modifications via affinity chromatography, and then the handle is elaborated with a desired moiety usingmore » an oxidative coupling reaction. This method results in a sample of protein with a well-defined number of modifications, and we find it particularly applicable to systems like protein homomultimers in which there is no way to discern between chemically identical subunits. We demonstrate the use of this method in the construction of a protein-templated light-harvesting mimic, a type of system which has historically been difficult to make in a well-defined manner.« less

2D Hexagonal Boron Nitride (2D-hBN) Explored for the Electrochemical Sensing of Dopamine.

PubMed

Khan, Aamar F; Brownson, Dale A C; Randviir, Edward P; Smith, Graham C; Banks, Craig E

2016-10-04

Crystalline 2D hexagonal boron nitride (2D-hBN) nanosheets are explored as a potential electrocatalyst toward the electroanalytical sensing of dopamine (DA). The 2D-hBN nanosheets are electrically wired via a drop-casting modification process onto a range of commercially available carbon supporting electrodes, including glassy carbon (GC), boron-doped diamond (BDD), and screen-printed graphitic electrodes (SPEs). 2D-hBN has not previously been explored toward the electrochemical detection/electrochemical sensing of DA. We critically evaluate the potential electrocatalytic performance of 2D-hBN modified electrodes, the effect of supporting carbon electrode platforms, and the effect of "mass coverage" (which is commonly neglected in the 2D material literature) toward the detection of DA. The response of 2D-hBN modified electrodes is found to be largely dependent upon the interaction between 2D-hBN and the underlying supporting electrode material. For example, in the case of SPEs, modification with 2D-hBN (324 ng) improves the electrochemical response, decreasing the electrochemical oxidation potential of DA by ∼90 mV compared to an unmodified SPE. Conversely, modification of a GC electrode with 2D-hBN (324 ng) resulted in an increased oxidation potential of DA by ∼80 mV when compared to the unmodified electrode. We explore the underlying mechanisms of the aforementioned examples and infer that electrode surface interactions and roughness factors are critical considerations. 2D-hBN is utilized toward the sensing of DA in the presence of the common interferents ascorbic acid (AA) and uric acid (UA). 2D-hBN is found to be an effective electrocatalyst in the simultaneous detection of DA and UA at both pH 5.0 and 7.4. The peak separations/resolution between DA and UA increases by ∼70 and 50 mV (at pH 5.0 and 7.4, respectively, when utilizing 108 ng of 2D-hBN) compared to unmodified SPEs, with a particularly favorable response evident in pH 5.0, giving rise to a significant increase in the peak current of DA. The limit of detection (3σ) is found to correspond to 0.65 μM for DA in the presence of UA. However, it is not possible to deconvolute the simultaneous detection of DA and AA. The observed electrocatalytic effect at 2D-hBN has not previously been reported in the literature when supported upon carbon or any other electrode. We provide valuable insights into the modifier-substrate interactions of this material, essential for those designing, fabricating, and consequently performing electrochemical experiments utilizing 2D-hBN and related 2D materials.

Small nucleolar RNAs that guide modification in trypanosomatids: repertoire, targets, genome organisation, and unique functions.

PubMed

Uliel, Shai; Liang, Xue-hai; Unger, Ron; Michaeli, Shulamit

2004-03-29

Small nucleolar RNAs constitute a family of newly discovered non-coding small RNAs, most of which function in guiding RNA modifications. Two prevalent types of modifications are 2'-O-methylation and pseudouridylation. The modification is directed by the formation of a canonical small nucleolar RNA-target duplex. Initially, RNA-guided modification was shown to take place on rRNA, but recent studies suggest that small nuclear RNA, mRNA, tRNA, and the trypanosome spliced leader RNA also undergo guided modifications. Trypanosomes contain more modifications and potentially more small nucleolar RNAs than yeast, and the increased number of modifications may help to preserve ribosome function under adverse environmental conditions during the cycling between the insect and mammalian host. The genome organisation in clusters carrying the two types of small nucleolar RNAs, C/D and H/ACA-like RNAs, resembles that in plants. However, the trypanosomatid H/ACA RNAs are similar to those found in Archaea and are composed of a single hairpin that may represent the primordial H/ACA RNA. In this review we summarise this new field of trypanosome small nucleolar RNAs, emphasising the open questions regarding the number of small nucleolar RNAs, the repertoire, genome organisation, and the unique function of guided modifications in these protozoan parasites.

Adverse Effects of Electroconvulsive Therapy.

PubMed

Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

2016-09-01

Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. Copyright © 2016 Elsevier Inc. All rights reserved.

Methodological guidelines for developing accident modification functions.

PubMed

Elvik, Rune

2015-07-01

This paper proposes methodological guidelines for developing accident modification functions. An accident modification function is a mathematical function describing systematic variation in the effects of road safety measures. The paper describes ten guidelines. An example is given of how to use the guidelines. The importance of exploratory analysis and an iterative approach in developing accident modification functions is stressed. The example shows that strict compliance with all the guidelines may be difficult, but represents a level of stringency that should be strived for. Currently the main limitations in developing accident modification functions are the small number of good evaluation studies and the often huge variation in estimates of effect. It is therefore still not possible to develop accident modification functions for very many road safety measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Investigation of the Aerodynamic Characteristics of an 0.08-Scale Model of the Chance Vought XF7U-1 Airplane in the Langley High-Speed 7- by 10-Foot Tunnel. Part V - Wing-Alone Tests and Effect of Modifications to the Vertical Fins, Speed Brakes, and Fuselage TED No. NACA DE308. Part V; Wing-Alone Tests and Effect of Modifications to the Vertical Fins, Speed Brakes, and Fuselage, TED No. NACA DE308

NASA Technical Reports Server (NTRS)

Kuhri, Richard E.; Myers, Boyd C., II

1947-01-01

Tests have been conducted in the Langley high-speed 7- by 10-foot tunnel over a Mach number range from 0.40 to 0.91 to determine the stability and control characteristics of an 0.08-scale model of the Chance Vought XF7U-1 airplane. The wing-alone tests and the effect of the various vertical-fin modifications, speed-brake modifications, and fuselage modifications on the aerodynamic characteristics in pitch and yaw are presented in the present paper with a limited analysis of the results. Also included are tuft studies of the flow for some of the modifications tested.

Infections and sepsis in disasters.

PubMed

Steinberg, S M; Nichols, R L

1991-04-01

It seems reasonable to expect that infections will occur after certain types of disasters. There are some data to support this conjecture in studies of tornadoes, hurricanes, and mass trauma situations. We have tried to extrapolate from these data what we believe will be the infectious effects of different types of disasters, taking into account the potential for alteration in the host secondary to injury, the modification of living conditions, and the possibility of the disruption of medical care.

An Analysis of the Effectiveness of the Air Force Drug Testing Program and Four Potential Modifications

DTIC Science & Technology

1993-09-01

attempted to control substance abuse. In the 1920’s and 30’s, marijuana was commonly used as a substitute for alcohol during prohibition (1:4-7). In...discovered D-lysergic acia tiiethylamide (LSD), methaqualone (quaalude), and phencyclidine (PCP) joined heroin, amphetamines, and marijuana as drugs abused...themselves in Southeast Asia where drugs were plentiful and cheap. The most commonly used drugs were heroin and marijuana . Initially, the DOD policy

Modification of BRCA1 Breast Cancer Risk by Coffee Consumption: Potential Mechanisms for Biologic Effect

DTIC Science & Technology

2007-08-01

engineered mice for the animal study to determine whether coffee, decaffeinated coffee, or caffeine prevents BRCA1 hereditary breast cancer. We...have bred the necessary genetically engineered mice for the animal study to determine whether coffee, decaffeinated coffee, or caffeine prevents BRCA1...participates in the regulation of DNA repair. As the repair process concludes, gamma H2AX is removed from the surrounding region. We were interested in

Benefits and risks associated with genetically modified food products.

PubMed

Kramkowska, Marta; Grzelak, Teresa; Czyżewska, Krystyna

2013-01-01

Scientists employing methods of genetic engineering have developed a new group of living organisms, termed 'modified organisms', which found application in, among others, medicine, the pharmaceutical industry and food distribution. The introduction of transgenic products to the food market resulted in them becoming a controversial topic, with their proponents and contestants. The presented study aims to systematize objective data on the potential benefits and risks resulting from the consumption of transgenic food. Genetic modifications of plants and animals are justified by the potential for improvement of the food situation worldwide, an increase in yield crops, an increase in the nutritional value of food, and the development of pharmaceutical preparations of proven clinical significance. In the opinions of critics, however, transgenic food may unfavourably affect the health of consumers. Therefore, particular attention was devoted to the short- and long-lasting undesirable effects, such as alimentary allergies, synthesis of toxic agents or resistance to antibiotics. Examples arguing for the justified character of genetic modifications and cases proving that their use can be dangerous are innumerable. In view of the presented facts, however, complex studies are indispensable which, in a reliable way, evaluate effects linked to the consumption of food produced with the application of genetic engineering techniques. Whether one backs up or negates transgenic products, the choice between traditional and non-conventional food remains to be decided exclusively by the consumers.

Environmentally friendly surface modification of silk fiber: Chitosan grafting and dyeing

NASA Astrophysics Data System (ADS)

Davarpanah, Saideh; Mahmoodi, Niyaz Mohammad; Arami, Mokhtar; Bahrami, Hajir; Mazaheri, Firoozmehr

2009-01-01

In this paper, the surface modification of silk fiber using anhydrides to graft the polysaccharide chitosan and dyeing ability of the grafted silk were studied. Silk fiber was degummed and acylated with two anhydrides, succinic anhydride (SA) and phthalic anhydride (PA), in different solvents (dimethyl sulfoxide (DMSO) and N, N-dimethyl formamide (DMF)). The effects of anhydrides, solvents, anhydride concentration, liquor ratio (L:R) and reaction time on acylation of silk were studied. The polysaccharide chitosan was grafted to the acylated silk fiber and dyed by acid dye (Acid Black NB.B). The effects of pH, chitosan concentration, and reaction time on chitosan grafting of acylated silk were investigated. The physical properties show sensible changes regardless of weight gain. Scanning electron microscopy (SEM) analysis showed the presence of foreign materials firmly attached to the surface of silk. FTIR spectroscopy provided evidence that chitosan was grafted onto the acylated silk through the formation of new covalent bonds. The dyeing of the chitosan grafted-acylated silk fiber indicated the higher dye ability in comparison to the acylated and degummed silk samples. The mechanism of chitosan grafting over degummed silk through anhydride linkage was proposed. The findings of this research support the potential production of new environmentally friendly textile fibers. It is worthwhile to mention that the grafted samples have antibacterial potential due to the antibacterial property of chitosan molecules.

Public perceptions of hurricane modification.

PubMed

Klima, Kelly; Bruine de Bruin, Wändi; Morgan, M Granger; Grossmann, Iris

2012-07-01

If hurricane modification were to become a feasible strategy for potentially reducing hurricane damages, it would likely generate public discourse about whether to support its implementation. To facilitate an informed and constructive discourse, policymakers need to understand how people perceive hurricane modification. Here, we examine Florida residents' perceptions of hurricane modification techniques that aim to alter path and wind speed. Following the mental models approach, we conducted a survey study about public perceptions of hurricane modification that was guided by formative interviews on the topic. We report a set of four primary findings. First, hurricane modification was perceived as a relatively ineffective strategy for damage reduction, compared to other strategies for damage reduction. Second, hurricane modification was expected to lead to changes in projected hurricane path, but not necessarily to the successful reduction of projected hurricane strength. Third, more anger was evoked when a hurricane was described as having changed from the initially forecasted path or strength after an attempted modification. Fourth, unlike what we expected, participants who more strongly agreed with statements that recognized the uncertainty inherent in forecasts reported more rather than less anger at scientists across hurricane modification scenarios. If the efficacy of intensity-reduction techniques can be increased, people may be willing to support hurricane modification. However, such an effort would need to be combined with open and honest communications to members of the general public. © 2011 Society for Risk Analysis.

Behavior modification therapy in hyperactive children. Research and clinical implications.

PubMed

Wolraich, M L

1979-09-01

One hundred fifty-seven studies employing behavior modification in the management of hyperactive and disruptive children were reviewed. The studies were analyzed against standards of scientific validity. The review found: (1) behavior modification was effective in alleviating problem behaviors; (2) token programs were the most commonly used; (3) both positive reinforcement and punishment were effective; positive reinforcement, however, had the advantage of improving self-esteem; (4) behavioral problems occurring in the home most likely require a home-based program; (5) behavior modification and stimulant medication can be used simultaneously, often with additive effects; and (6) long-term benefits beyond one year have not been assessed.

Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome.

PubMed

Brouwer, Jesca Gm; Makama, Maureen; van Woudenbergh, Geertruida J; Vasen, Hans Fa; Nagengast, Fokko M; Kleibeuker, Jan H; Kampman, Ellen; van Duijnhoven, Fränzel Jb

2017-11-01

Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet. Objective: We aimed to investigate the association between the inflammatory potential of the diet and the risk of CRTs in persons with LS. Design: We used the dietary intake of 457 persons with LS from a prospective cohort study to calculate the adapted dietary inflammatory index (ADII). The ADII was split into tertiles in which the highest tertile reflects the most proinflammatory potential of the diet. Cox proportional hazard models, with robust sandwich variance estimates to adjust for dependency within families, were used to calculate HRs and 95% CIs of CRTs by ADII tertile. HRs were adjusted for age, smoking status, and education level, and number of colonoscopies as a time-dependent variable. A potential effect measure modification was explored by stratifying the results by mutated MMR gene, sex, and a history of CRTs. We performed sensitivity analyses by repeating the analyses in non-nonsteroidal anti-inflammatory drug (NSAID) users ( n = 315). Results: During a median follow-up time of 59 mo, 200 participants (43.8%) developed CRTs. No significant association was shown between highest compared with lowest ADII tertiles (HR for highest compared with lowest tertiles: 1.37; 95% CI: 0.80, 2.34). Stratification by mutated MMR gene, sex, and CRT history did not show significantly differential associations ( P -interactions ≥ 0.64). In non-NSAID users, an HR of 1.60 (95% CI: 0.88, 2.93) for highest compared with lowest tertiles was shown. No significant effect modification was shown in this group either ( P -interactions ≥ 0.24). Conclusion: A proinflammatory potential of the diet does not seem to be significantly associated with CRT risk in persons with LS. © 2017 American Society for Nutrition.

Garlic and onions: Their cancer prevention properties

PubMed Central

Nicastro, Holly L.; Ross, Sharon A.; Milner, John A.

2015-01-01

The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiological studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biological processes that modify cancer risk. This review discusses the cancer preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps. PMID:25586902

General Astrophysics and Comparative Planetology with the Terrestrial Planet Finder Missions

NASA Technical Reports Server (NTRS)

Kuchner, Marc J. (Editor)

2005-01-01

This document discusses the potential of the Terrestrial Planet Finder (TPF) for general astrophysics beyond its base mission, focusing on science obtainable with no or minimal modifications to the mission design, but also exploring possible modifications of TPF with high scientific merit and no impact on the basic search for extrasolar Earth analogs.

78 FR 65570 - Modification of Significant New Uses of 1-Propene, 2,3,3,3-tetrafluoro-

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... include, but are not limited to: Manufacturers or processors of the subject chemical substance (NAICS... by this action. Other types of entities not listed in this unit could also be affected. The North... modification. One of the commenters also noted a potential ambiguity in the proposed regulatory text. Part of...

Modification of the Fosberg fire weather index to include drought

Treesearch

Scott L. Goodrick

2002-01-01

The Fosberg fire weather index is a simple tool for evaluating the potential influence of weather on a wildland fire based on temperature, relative humidity and wind speed. A modification to this index that includes the impact of precipitation is proposed. The Keetch-Byram drought index is used to formulate a 'fuel availability' factor that modifies the...

Fast Learning with Weak Synaptic Plasticity.

PubMed

Yger, Pierre; Stimberg, Marcel; Brette, Romain

2015-09-30

New sensory stimuli can be learned with a single or a few presentations. Similarly, the responses of cortical neurons to a stimulus have been shown to increase reliably after just a few repetitions. Long-term memory is thought to be mediated by synaptic plasticity, but in vitro experiments in cortical cells typically show very small changes in synaptic strength after a pair of presynaptic and postsynaptic spikes. Thus, it is traditionally thought that fast learning requires stronger synaptic changes, possibly because of neuromodulation. Here we show theoretically that weak synaptic plasticity can, in fact, support fast learning, because of the large number of synapses N onto a cortical neuron. In the fluctuation-driven regime characteristic of cortical neurons in vivo, the size of membrane potential fluctuations grows only as √N, whereas a single output spike leads to potentiation of a number of synapses proportional to N. Therefore, the relative effect of a single spike on synaptic potentiation grows as √N. This leverage effect requires precise spike timing. Thus, the large number of synapses onto cortical neurons allows fast learning with very small synaptic changes. Significance statement: Long-term memory is thought to rely on the strengthening of coactive synapses. This physiological mechanism is generally considered to be very gradual, and yet new sensory stimuli can be learned with just a few presentations. Here we show theoretically that this apparent paradox can be solved when there is a tight balance between excitatory and inhibitory input. In this case, small synaptic modifications applied to the many synapses onto a given neuron disrupt that balance and produce a large effect even for modifications induced by a single stimulus. This effect makes fast learning possible with small synaptic changes and reconciles physiological and behavioral observations. Copyright © 2015 the authors 0270-6474/15/3513351-12$15.00/0.

Effects of Plants and Isolates of Celastraceae Family on Cancer Pathways.

PubMed

Bukhari, Syed Nasir Abbas; Jantan, Ibrahim; Seyed, Mohamed Ali

2015-01-01

The evaluation of crude drugs of natural origin as sources of new effective anticancer agents continues to be important due to the lack of effective anticancer drugs currently used in practice which are generally accompanied with adverse effects at different levels of severity. The aim of this concise review is to gather existing literature on anticancer potential of extracts and compounds isolated from Celastraceae species. This review covers six genera (Maytenus, Tripterygium, Hippocratea, Gymnosporia, Celastrus and Austroplenckia) belonging to this family and their 33 isolates. Studies carried out by using different cell lines have shown remarkable indication of anticancer activity, however, only a restricted number of studies have been reported using in vivo tumor models. Some of the compounds, such as triptolide, celastrol and demethylzeylasteral from T. wilfordii, have been extensively studied on their mechanisms of action due to their potent activity on various cancer cell lines. Such promising lead compounds should generate considerable interest among scientists to improve their therapeutic potential with fewer side effects by molecular modification.

Wildlife conservation and solar energy development in the Desert Southwest, United States

USGS Publications Warehouse

Lovich, Jeffrey E.; Ennen, Josua R.

2011-01-01

Large areas of public land are currently being permitted or evaluated for utility-scale solar energy development (USSED) in the southwestern United States, including areas with high biodiversity and protected species. However, peer-reviewed studies of the effects of USSED on wildlife are lacking. The potential effects of the construction and the eventual decommissioning of solar energy facilities include the direct mortality of wildlife; environmental impacts of fugitive dust and dust suppressants; destruction and modification of habitat, including the impacts of roads; and off-site impacts related to construction material acquisition, processing, and transportation. The potential effects of the operation and maintenance of the facilities include habitat fragmentation and barriers to gene flow, increased noise, electromagnetic field generation, microclimate alteration, pollution, water consumption, and fire. Facility design effects, the efficacy of site-selection criteria, and the cumulative effects of USSED on regional wildlife populations are unknown. Currently available peer-reviewed data are insufficient to allow a rigorous assessment of the impact of USSED on wildlife.

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

PubMed Central

2013-01-01

Background Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy. PMID:23866721

The zoogeomorphic characteristics of burrows and burrowing by nine-banded armadillos (Dasypus novemcinctus)

NASA Astrophysics Data System (ADS)

Sawyer, Carol F.; Brinkman, Donald C.; Walker, Vincent D.; Covington, Tyler D.; Stienstraw, Elizabeth A.

2012-07-01

Burrowing animals act like a geomorphic disturbance, changing the environment through soil excavation, landform creation and bioturbation. The potential zoogeomorphic effects of these actions include modification of surficial features, increased soil erosion, changes in the growth and distribution of vegetation, and modifications to soil fertility. The burrowing ninebanded armadillo (Dasypus novemcinctus) migrated to North America prior to the 1850s and has since continued to expand its habitat to the American Southeast and parts of the Midwest. Little data are available on the zoogeomorphic impact of the burrowing nature of this species, making it difficult to predict future implications of this animal as it continues to migrate into new regions. On the University of South Alabama campus, in Mobile, Alabama, armadillos are present on a 35-hectare unprotected forested preserve used by the university community for outdoor activities and research. To understand the potential zoogeomorphic impact of armadillo burrows on the local environment, morphometric measurements were recorded on 187 burrows located in the study area. Using dimensions of burrow entrances and minimum lengths of tunnels in calculations, armadillos excavated approximately 0.029 m3 to 0.04 m3 of soil from each burrow. The entrances to burrows averaged 33.5° in slope and tended to be located in a microhabitat of a fallen tree, exposed tree roots, or a sideslope. Persistent fall of forest litter and anthropogenic modifications makes positive identification of spoil mounds possible in approximately half of the burrow sites. Surface modification by armadillos is ongoing in the study area with over half of the burrows classified as active during the four-month project. We concluded that, for southern Alabama, armadillos prefer to excavate burrows into sideslopes, and that given the lack of ground cover, sandy soil, and humid climate, armadillos are an important zoogeomorphic agent in the region.

Novel and nonpharmacologic approaches to cardio-protection in hypertension.

PubMed

Donazzan, Luca; Mahfoud, Felix; Linz, Dominik; Ewen, Sebastian; Ukena, Christian; Böhm, Michael

2014-05-01

Hypertension has wide (30-45 %) prevalence in the general population and is related to important increases in overall cardiovascular morbidity and mortality. Despite lifestyle modifications and optimal medical therapy (three drugs, one being diuretic), about 5-20 % of hypertensives are affected by resistant hypertension. Chronic high blood pressure has adverse effects on the heart and other organs such as the kidneys and vasculature. Renal sympathetic denervation and baroreceptor stimulation are invasive approaches initially investigated to treat resistant hypertension. Their pleiotropic effects appear promising in cardiovascular remodeling, heart failure and arrhythmias and could potentially affect cardiovascular morbidity and mortality.

Body piercing with fatal consequences.

PubMed

Ranga, N; Jeffery, A J

2011-01-25

Body modifications such as piercings, tattoos and surgery have increased in popularity in recent times and have become more socially acceptable. The common complications of piercing different parts of the human anatomy are well-documented, including sepsis, allergic reactions and, more rarely, endocarditis and ischaemia. Deaths related to piercing complications are primarily septic in origin. In this case, a man in his 50s died due to complications of his multiple umbilical piercings. The cause of death was unusually linked to body modification; the umbilical piercings had ultimately led to a mesenteric infarction. Cases such as these are forensically important due to potential manslaughter charges that could be brought against a piercing establishment. More importantly, this case highlights another extreme complication of body modification. Fashion statements are always changing and impact upon many lives. It is important to highlight to people the potentially life-threatening complications of common piercing practices.

Improved sensitivity of a graphene FET biosensor using porphyrin linkers

NASA Astrophysics Data System (ADS)

Kawata, Takuya; Ono, Takao; Kanai, Yasushi; Ohno, Yasuhide; Maehashi, Kenzo; Inoue, Koichi; Matsumoto, Kazuhiko

2018-06-01

Graphene FET (G-FET) biosensors have considerable potential due to the superior characteristics of graphene. Realizing this potential requires judicious choice of the linker molecule connecting the target-specific receptor molecule to the graphene surface, yet there are few reports comparing linker molecules for G-FET biosensors. In this study, tetrakis(4-carboxyphenyl)porphyrin (TCPP) was used as a linker for surface modification of a G-FET and the properties of the device were compared to those of a G-FET device modified with the conventional linker 1-pyrenebutanoic acid succinimidyl ester (PBASE). TCPP modification resulted in a higher density of receptor immunoglobulin E (IgE) aptamer molecules on the G-FET. The detection limit of the target IgE was enhanced from 13 nM for the PBASE-modified G-FET to 2.2 nM for the TCPP-modified G-FET, suggesting that the TCPP linker is a powerful candidate for G-FET modification.

Mapping of ribosomal 23S ribosomal RNA modifications in Clostridium sporogenes.

PubMed

Kirpekar, Finn; Hansen, Lykke H; Mundus, Julie; Tryggedsson, Stine; Teixeira Dos Santos, Patrícia; Ntokou, Eleni; Vester, Birte

2018-06-27

All organisms contain RNA modifications in their ribosomal RNA (rRNA), but the importance, positions and exact function of these are still not fully elucidated. Various functions such as stabilising structures, controlling ribosome assembly and facilitating interactions have been suggested and in some cases substantiated. Bacterial rRNA contains much fewer modifications than eukaryotic rRNA. The rRNA modification patterns in bacteria differ from each other, but too few organisms have been mapped to draw general conclusions. This study maps 23S ribosomal RNA modifications in Clostridium sporogenes that can be characterised as a non-toxin producing Clostridium botulinum. Clostridia are able to sporulate and thereby survive harsh conditions, and are in general considered to be resilient to antibiotics. Selected regions of the 23S rRNA were investigated by mass spectrometry and by primer extension analysis to pinpoint modified sites and the nature of the modifications. Apparently, C. sporogenes 23S rRNA contains few modifications compared to other investigated bacteria. No modifications were identified in domain II and III of 23S rRNA. Three modifications were identified in domain IV, all of which have also been found in other organisms. Two unusual modifications were identified in domain V, methylated dihydrouridine at position U2449 and dihydrouridine at position U2500 (Escherichia coli numbering), in addition to four previously known modified positions. The enzymes responsible for the modifications were searched for in the C. sporogenes genome using BLAST with characterised enzymes as query. The search identified genes potentially coding for RNA modifying enzymes responsible for most of the found modifications.

Undermining and Strengthening Social Networks through Network Modification

PubMed Central

Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

2016-01-01

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention. PMID:27703198

Artificial specific binders directly recovered from chemically modified nucleic acid libraries.

PubMed

Kasahara, Yuuya; Kuwahara, Masayasu

2012-01-01

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

A Scoping Review of Behavioral Economic Interventions for Prevention and Treatment of Type 2 Diabetes Mellitus.

PubMed

Kullgren, Jeffrey T; Hafez, Dina; Fedewa, Allison; Heisler, Michele

2017-09-01

The purpose of this paper was to review studies of behavioral economic interventions (financial incentives, choice architecture modifications, or commitment devices) to prevent type 2 diabetes mellitus (T2DM) among at-risk patients or improve self-management among patients with T2DM. We found 15 studies that used varied study designs and outcomes to test behavioral economic interventions in clinical, workplace, or health plan settings. Of four studies that focused on prevention of T2DM, two found that financial incentives increased weight loss and completion of a fasting blood glucose test, and two choice architecture modifications had mixed effects in encouraging completion of tests to screen for T2DM. Of 11 studies that focused on improving self-management of T2DM, four of six tests of financial incentives demonstrated increased engagement in recommended care processes or improved biometric measures, and three of five tests of choice architecture modifications found improvements in self-management behaviors. Though few studies have tested behavioral economic interventions for prevention or treatment of T2DM, those that have suggested such approaches have the potential to improve patient behaviors and such approaches should be tested more broadly.

Gene modification therapies: views of parents of people with Down syndrome.

PubMed

Michie, Marsha; Allyse, Megan

2018-06-21

In considering gene modification technologies, the priorities of patient communities must be a central consideration. The purpose of this study is to assess views of families with Down syndrome (DS) regarding potential genome-based interventions. We constructed an anonymous online survey for family members of people with DS. Participants were asked to agree or disagree with scenarios describing hypothetical interventions to silence or significantly alter the physical and cognitive effects of a trisomy 21, and also with scenarios depicting currently available physical interventions. All 532 respondents were parents of people with DS. For each of the five scenarios, over half said they would approve the intervention or would advise their children with DS to do so. Responses to hypothetical prenatal and pediatric cognitive interventions were significantly affected by participants' assessments of the impact of DS on their children's and their families' lives, while physical and adult cognitive scenarios were not. Future interventions to address genetic conditions will impact patient communities and cannot succeed without their input and support. While many parents of people with DS indicated approval for hypothetical genetic therapies, these results indicate a need for continuing dialogue about benefits and drawbacks of gene modification technologies.

Biodegradable magnesium alloys for orthopaedic applications: A review on corrosion, biocompatibility and surface modifications.

PubMed

Agarwal, Sankalp; Curtin, James; Duffy, Brendan; Jaiswal, Swarna

2016-11-01

Magnesium (Mg) and its alloys have been extensively explored as potential biodegradable implant materials for orthopaedic applications (e.g. Fracture fixation). However, the rapid corrosion of Mg based alloys in physiological conditions has delayed their introduction for therapeutic applications to date. The present review focuses on corrosion, biocompatibility and surface modifications of biodegradable Mg alloys for orthopaedic applications. Initially, the corrosion behaviour of Mg alloys and the effect of alloying elements on corrosion and biocompatibility is discussed. Furthermore, the influence of polymeric deposit coatings, namely sol-gel, synthetic aliphatic polyesters and natural polymers on corrosion and biological performance of Mg and its alloy for orthopaedic applications are presented. It was found that inclusion of alloying elements such as Al, Mn, Ca, Zn and rare earth elements provides improved corrosion resistance to Mg alloys. It has been also observed that sol-gel and synthetic aliphatic polyesters based coatings exhibit improved corrosion resistance as compared to natural polymers, which has higher biocompatibility due to their biomimetic nature. It is concluded that, surface modification is a promising approach to improve the performance of Mg-based biomaterials for orthopaedic applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Undermining and Strengthening Social Networks through Network Modification.

PubMed

Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

2016-10-05

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention.

Undermining and Strengthening Social Networks through Network Modification

NASA Astrophysics Data System (ADS)

Mellon, Jonathan; Yoder, Jordan; Evans, Daniel

2016-10-01

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention.

A Scoping Review of Behavioral Economic Interventions for Prevention and Treatment of Type 2 Diabetes Mellitus

PubMed Central

Kullgren, Jeffrey T.; Hafez, Dina; Fedewa, Allison; Heisler, Michele

2017-01-01

Purpose of review To review studies of behavioral economic interventions (financial incentives, choice architecture modifications, or commitment devices) to prevent type 2 diabetes mellitus (T2DM) among at-risk patients or improve self-management among patients with T2DM. Recent findings We found 15 studies that used varied study designs and outcomes to test behavioral economic interventions in clinical, workplace, or health plan settings. Of four studies that focused on prevention of T2DM, two found that financial incentives increased weight loss and completion of a fasting blood glucose test, and two choice architecture modifications had mixed effects in encouraging completion of tests to screen for T2DM. Of 11 studies that focused on improving self-management of T2DM, four of six tests of financial incentives demonstrated increased engagement in recommended care processes or improved biometric measures, and three of five tests of choice architecture modifications found improvements in self-management behaviors. Summary Though few studies have tested behavioral economic interventions for prevention or treatment of T2DM, those that have suggest such approaches have potential to improve patient behaviors and should be tested more broadly. PMID:28755061

Surface modification of paclitaxel-loaded tri-block copolymer PLGA- b-PEG- b-PLGA nanoparticles with protamine for liver cancer therapy

NASA Astrophysics Data System (ADS)

Gao, Nansha; Chen, Zhihong; Xiao, Xiaojun; Ruan, Changshun; Mei, Lin; Liu, Zhigang; Zeng, Xiaowei

2015-08-01

In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide- co-glycolide)- b-poly(ethylene glycol)- b-poly(lactide- co-glycolide) (PLGA- b-PEG- b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA- b-PEG- b-PLGA was synthesized by ring-opening polymerization and characterized by 1H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol® as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol® did. All the results suggested that surface modification of PTX-loaded PLGA- b-PEG- b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

The short-term effect of heat waves on mortality and its modifiers in China: an analysis from 66 communities.

PubMed

Ma, Wenjun; Zeng, Weilin; Zhou, Maigeng; Wang, Lijun; Rutherford, Shannon; Lin, Hualiang; Liu, Tao; Zhang, Yonghui; Xiao, Jianpeng; Zhang, Yewu; Wang, Xiaofeng; Gu, Xin; Chu, Cordia

2015-02-01

Many studies have reported increased mortality risk associated with heat waves. However, few have assessed the health impacts at a nation scale in a developing country. This study examines the mortality effects of heat waves in China and explores whether the effects are modified by individual-level and community-level characteristics. Daily mortality and meteorological variables from 66 Chinese communities were collected for the period 2006-2011. Heat waves were defined as ≥2 consecutive days with mean temperature ≥95th percentile of the year-round community-specific distribution. The community-specific mortality effects of heat waves were first estimated using a Distributed Lag Non-linear Model (DLNM), adjusting for potential confounders. To investigate effect modification by individual characteristics (age, gender, cause of death, education level or place of death), separate DLNM models were further fitted. Potential effect modification by community characteristics was examined using a meta-regression analysis. A total of 5.0% (95% confidence intervals (CI): 2.9%-7.2%) excess deaths were associated with heat waves in 66 Chinese communities, with the highest excess deaths in north China (6.0%, 95% CI: 1%-11.3%), followed by east China (5.2%, 95% CI: 0.4%-10.2%) and south China (4.5%, 95% CI: 1.4%-7.6%). Our results indicate that individual characteristics significantly modified heat waves effects in China, with greater effects on cardiovascular mortality, cerebrovascular mortality, respiratory mortality, the elderly, females, the population dying outside of a hospital and those with a higher education attainment. Heat wave mortality effects were also more pronounced for those living in urban cities or densely populated communities. Heat waves significantly increased mortality risk in China with apparent spatial heterogeneity, which was modified by some individual-level and community-level factors. Our findings suggest adaptation plans that target vulnerable populations in susceptible communities during heat wave events should be developed to reduce health risks. Copyright © 2014 Elsevier Ltd. All rights reserved.

Longitudinal changes in everyday life after home modifications for people aging with disabilities.

PubMed

Petersson, Ingela; Kottorp, Anders; Bergström, Jakob; Lilja, Margareta

2009-05-01

To investigate longitudinal impacts of home modifications on the difficulty of performing everyday life tasks for people aging with disabilities, and to investigate whether other factors had any additional impacts on difficulty in everyday life tasks for people receiving home modifications. The sample consisted of 103 persons aging with disabilities and in need of home modifications, divided into an intervention group and a comparison group. The data were first subjected to Rasch analysis and a random coefficient model was used. Participants in the intervention group reported a significantly lower level of difficulty in everyday life tasks compared with those in the comparison group. One confounding factor, number of months waiting for home modification, had an impact on difficulty in everyday life. Home modifications are effective in decreasing difficulty in performing everyday life tasks up to six months after the installation. Furthermore, to be effective home modifications need to be installed in a timely fashion. For each consecutive month the person waited for their home modification the difficulty of performing everyday life tasks increased. Therefore, it is important that home modifications be installed as soon as possible after the need has been identified.

Selectively starving cancer cells through dietary manipulation: methods and clinical implications.

PubMed

Simone, Brittany A; Champ, Colin E; Rosenberg, Anne L; Berger, Adam C; Monti, Daniel A; Dicker, Adam P; Simone, Nicole L

2013-07-01

As the link between obesity and metabolic syndrome and cancer becomes clearer, the need to determine the optimal way to incorporate dietary manipulation in the treatment of cancer patients becomes increasingly important. Metabolic-based therapies, such as caloric restriction, intermittent fasting and a ketogenic diet, have the ability to decrease the incidence of spontaneous tumors and slow the growth of primary tumors, and may have an effect on distant metastases in animal models. Despite the abundance of preclinical data demonstrating the benefit of dietary modification for cancer, to date there are few clinical trials targeting diet as an intervention for cancer patients. We hypothesize that this may be due, in part, to the fact that several different types of diet modification exist with no clear recommendations regarding the optimal method. This article will delineate three commonly used methods of dietary manipulation to assess the potential of each as a regimen for cancer therapy.

The transfer function method for gear system dynamics applied to conventional and minimum excitation gearing designs

NASA Technical Reports Server (NTRS)

Mark, W. D.

1982-01-01

A transfer function method for predicting the dynamic responses of gear systems with more than one gear mesh is developed and applied to the NASA Lewis four-square gear fatigue test apparatus. Methods for computing bearing-support force spectra and temporal histories of the total force transmitted by a gear mesh, the force transmitted by a single pair of teeth, and the maximum root stress in a single tooth are developed. Dynamic effects arising from other gear meshes in the system are included. A profile modification design method to minimize the vibration excitation arising from a pair of meshing gears is reviewed and extended. Families of tooth loading functions required for such designs are developed and examined for potential excitation of individual tooth vibrations. The profile modification design method is applied to a pair of test gears.

Mechanisms of CaMKII Activation in the Heart.

PubMed

Erickson, Jeffrey R

2014-01-01

Calcium/calmodulin (Ca(2+)/CaM) dependent protein kinase II (CaMKII) has emerged as a key nodal protein in the regulation of cardiac physiology and pathology. Due to the particularly elegant relationship between the structure and function of the kinase, CaMKII is able to translate a diverse set of signaling events into downstream physiological effects. While CaMKII is typically autoinhibited at basal conditions, prolonged rapid Ca(2+) cycling can activate the kinase and allow post-translational modifications that depend critically on the biochemical environment of the heart. These modifications result in sustained, autonomous CaMKII activation and have been associated with pathological cardiac signaling. Indeed, improved understanding of CaMKII activation mechanisms could potentially lead to new clinical therapies for the treatment or prevention of cardiovascular disease. Here we review the known mechanisms of CaMKII activation and discuss some of the pathological signaling pathways in which they play a role.

Recent structural and mechanistic insights into post-translational enzymatic glycosylation.

PubMed

Hurtado-Guerrero, Ramon; Davies, Gideon J

2012-12-01

Enzymatic glycosylation of proteins, a post-transitional modification of great significance, is carried out by diverse glycosyltransferases (GTs) that harness activated sugar donors, typically nucleotide or lipid-phosphate linked species. Recent work has seen a major increase in the study of the 3D structure and reaction mechanism of these enzymes. Key advances include the dissection of the classical O-glycosylating and N-glycosylating apparatus, revealing unusual folds and hitherto unconsidered chemical mechanisms for acceptor activation. There has been considerable success in the application of kinetic isotope effects and quantum simulations to address the controversial issue of the reaction mechanism of retaining GTs. New roles for old modifications, exemplified by potential epigenetic roles for glycosylation, have been discovered and there has also been a plethora of studies into important mammalian glycosylations that play key roles in cellular biology, opening up new targets for chemical intervention approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Beam orbit simulation in the central region of the RIKEN AVF cyclotron

NASA Astrophysics Data System (ADS)

Toprek, Dragan; Goto, Akira; Yano, Yasushige

1999-04-01

This paper describes the modification design of the central region for h=2 mode of acceleration in the RIKEN AVF cyclotron. we made a small modification to the electrode shape in the central region for optimization of the beam transmission. The central region is equipped with an axial injection system. The spiral type inflector is used for axial injection. The electric field distribution in the inflector and in four acceleration gaps has been numerically calculated from an electric potential map produced by the program RELAX3D. The magnetic field is measured. The geometry of the central region has been tested with the computations of orbits carried out by means of the computer code CYCLONE. The optical properties of the spiral inflector and the central region are studied by using the program CASINO and CYCLONE, respectively. We have also made an effort to minimize the inflector fringe field effects using the RELAX3D program.

Tuning electronic and magnetic properties of GaN nanosheets by surface modifications and nanosheet thickness.

PubMed

Xiao, Meixia; Yao, Tingzhen; Ao, Zhimin; Wei, Peng; Wang, Danghui; Song, Haiyang

2015-04-14

Density-functional theory calculations are performed to investigate the effects of surface modifications and nanosheet thickness on the electronic and magnetic properties of gallium nitride (GaN) nanosheets (NSs). Unlike the bare GaN NSs terminating with polar surfaces, the systems with hydrogenated Ga (H-GaN), fluorinated Ga (F-GaN), and chlorinated Ga (Cl-GaN) preserve their initial wurtzite structures and exhibit ferromagnetic states. The abovementioned three different decorations on Ga atoms are energetically more favorable for thicker GaN NSs. Moreover, as the thickness increases, H-GaN and F-GaN NSs undergo semiconductor to metal and half-metal to metal transition, respectively, while Cl-GaN NSs remain completely metallic. The predicted diverse and tunable electronic and magnetic properties highlight the potential of GaN NSs for novel electronic and spintronic nanodevices.

Plasma modification of starch.

PubMed

Zhu, Fan

2017-10-01

Plasma is a medium of unbound negative and positive particles with the overall electrical charge being roughly zero. Non-thermal plasma processing is an emerging green technology with great potential to improve the quality and microbial safety of various food materials. Starch is a major component of many food products and is an important ingredient for food and other industries. There has been increasing interest in utilizing plasma to modify the functionalities of starch through interactions with reactive species. This mini-review summarises the impact of plasma on composition, chemical and granular structures, physicochemical properties, and uses of starch. Structure-function relationships of starch components as affected by plasma modifications are discussed. Effect of plasma on the properties of wheat flour, which is a typical example of starch based complex food systems, is also reviewed. Future research directions on how to better utilise plasma to improve the functionalities of starch are suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

The relevance of epigenetics to PTSD: implications for the DSM-V.

PubMed

Yehuda, Rachel; Bierer, Linda M

2009-10-01

Epigenetic modifications, such as DNA methylation, can occur in response to environmental influences to alter the functional expression of genes in an enduring and potentially, intergenerationally transmissible manner. As such, they may explain interindividual variation, as well as the long-lasting effects of trauma exposure. Although there are currently no findings that suggest epigenetic modifications that are specific to posttraumatic stress disorder (PTSD) or PTSD risk, many recent observations are compatible with epigenetic explanations. These include recent findings of stress-related gene expression, in utero contributions to infant biology, the association of PTSD risk with maternal PTSD, and the relevance of childhood adversity to the development of PTSD. The relevance of epigenetic mechanisms to formulations of PTSD for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is described. Copyright © 2009 International Society for Traumatic Stress Studies.

Adhesion of perfume-filled microcapsules to model fabric surfaces.

PubMed

He, Yanping; Bowen, James; Andrews, James W; Liu, Min; Smets, Johan; Zhang, Zhibing

2014-01-01

The retention and adhesion of melamine formaldehyde (MF) microcapsules on a model fabric surface in aqueous solution were investigated using a customised flow chamber technique and atomic force microscopy (AFM). A cellulose film was employed as a model fabric surface. Modification of the cellulose with chitosan was found to increase the retention and adhesion of microcapsules on the model fabric surface. The AFM force-displacement data reveal that bridging forces resulting from the extension of cellulose chains dominate the adhesion between the microcapsule and the unmodified cellulose film, whereas electrostatic attraction helps the microcapsules adhere to the chitosan-modified cellulose film. The correlation between results obtained using these two complementary techniques suggests that the flow chamber device can be potentially used for rapid screening of the effect of chemical modification on the adhesion of microparticles to surfaces, reducing the time required to achieve an optimal formulation.

Influence of nucleotide modifications at the C2’ position on the Hoogsteen base-paired parallel-stranded duplex of poly(A) RNA

PubMed Central

Copp, William; Denisov, Alexey Y.; Xie, Jingwei; Noronha, Anne M.; Liczner, Christopher; Safaee, Nozhat

2017-01-01

Abstract Polyadenylate (poly(A)) has the ability to form a parallel duplex with Hoogsteen adenine:adenine base pairs at low pH or in the presence of ammonium ions. In order to evaluate the potential of this structural motif for nucleic acid-based nanodevices, we characterized the effects on duplex stability of substitutions of the ribose sugar with 2′-deoxyribose, 2′-O-methyl-ribose, 2′-deoxy-2′-fluoro-ribose, arabinose and 2′-deoxy-2′-fluoro-arabinose. Deoxyribose substitutions destabilized the poly(A) duplex both at low pH and in the presence of ammonium ions: no duplex formation could be detected with poly(A) DNA oligomers. Other sugar C2’ modifications gave a variety of effects. Arabinose and 2′-deoxy-2′-fluoro-arabinose nucleotides strongly destabilized poly(A) duplex formation. In contrast, 2′-O-methyl and 2′-deoxy-2′-fluoro-ribo modifications were stabilizing either at pH 4 or in the presence of ammonium ions. The differential effect suggests they could be used to design molecules selectively responsive to pH or ammonium ions. To understand the destabilization by deoxyribose, we determined the structures of poly(A) duplexes with a single DNA residue by nuclear magnetic resonance spectroscopy and X-ray crystallography. The structures revealed minor structural perturbations suggesting that the combination of sugar pucker propensity, hydrogen bonding, pKa shifts and changes in hydration determine duplex stability. PMID:28973475

Influence of nucleotide modifications at the C2' position on the Hoogsteen base-paired parallel-stranded duplex of poly(A) RNA.

PubMed

Copp, William; Denisov, Alexey Y; Xie, Jingwei; Noronha, Anne M; Liczner, Christopher; Safaee, Nozhat; Wilds, Christopher J; Gehring, Kalle

2017-09-29

Polyadenylate (poly(A)) has the ability to form a parallel duplex with Hoogsteen adenine:adenine base pairs at low pH or in the presence of ammonium ions. In order to evaluate the potential of this structural motif for nucleic acid-based nanodevices, we characterized the effects on duplex stability of substitutions of the ribose sugar with 2'-deoxyribose, 2'-O-methyl-ribose, 2'-deoxy-2'-fluoro-ribose, arabinose and 2'-deoxy-2'-fluoro-arabinose. Deoxyribose substitutions destabilized the poly(A) duplex both at low pH and in the presence of ammonium ions: no duplex formation could be detected with poly(A) DNA oligomers. Other sugar C2' modifications gave a variety of effects. Arabinose and 2'-deoxy-2'-fluoro-arabinose nucleotides strongly destabilized poly(A) duplex formation. In contrast, 2'-O-methyl and 2'-deoxy-2'-fluoro-ribo modifications were stabilizing either at pH 4 or in the presence of ammonium ions. The differential effect suggests they could be used to design molecules selectively responsive to pH or ammonium ions. To understand the destabilization by deoxyribose, we determined the structures of poly(A) duplexes with a single DNA residue by nuclear magnetic resonance spectroscopy and X-ray crystallography. The structures revealed minor structural perturbations suggesting that the combination of sugar pucker propensity, hydrogen bonding, pKa shifts and changes in hydration determine duplex stability. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Targeting Cancer using Polymeric Nanoparticle mediated Combination Chemotherapy

PubMed Central

Gad, Aniket; Kydd, Janel; Piel, Brandon; Rai, Prakash

2016-01-01

Cancer forms exhibiting poor prognosis have been extensively researched for therapeutic solutions. One of the conventional modes of treatment, chemotherapy shows inadequacy in its methodology due to imminent side-effects and acquired drug-resistance by cancer cells. However, advancements in nanotechnology have opened new frontiers to significantly alleviate collateral damage caused by current treatments via innovative delivery techniques, eliminating pitfalls encountered in conventional treatments. Properties like reduced drug-clearance and increased dose efficacy by the enhanced permeability and retention effect deem nanoparticles suitable for this application. Optimization of size, surface charge and surface modifications have provided nanoparticles with stealth properties capable of evading immune responses, thus deeming them as excellent carriers of chemotherapeutic agents. Biocompatible and biodegradable forms of polymers enhance the bioavailability of chemotherapeutic agents, and permit a sustained and time-dependent release of drugs which is a characteristic of their composition, thereby providing a controlled therapeutic approach. Studies conducted in vitro and animal models have also demonstrated a synergism in cytotoxicity given the mechanism of action of anticancer drugs when administered in combination providing promising results. Combination therapy has also shown implications in overcoming multiple-drug resistance, which can however be subdued by the adaptable nature of tumor microenvironment. Surface modifications with targeting moieties can therefore feasibly increase nanoparticle uptake by specific receptor-ligand interactions, increasing dose efficacy which can seemingly overcome drug-resistance. This article reviews recent trends and investigations in employing polymeric nanoparticles for effectively delivering combination chemotherapy, and modifications in delivery parameters enhancing dose efficacy, thus validating the potential in this approach for anticancer treatment. PMID:28042613

40 CFR 52.736 - Review of new sources and modifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sources and modifications. (a) [Reserved] (b) The rules submitted by the State on March 24, 1988, to... Sources Construction and Modification as effective March 22, 1991. The moratorium on construction and...

Epigenetic and chromatin-based mechanisms in environmental stress adaptation and stress memory in plants.

PubMed

Lämke, Jörn; Bäurle, Isabel

2017-06-27

Plants frequently have to weather both biotic and abiotic stressors, and have evolved sophisticated adaptation and defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, and DNA methylation have been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for a stress memory, enabling plants to respond more efficiently to recurring stress or even to prepare their offspring for potential future assaults. In this review, we discuss both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory.

Effects of preparation relief and flow channels on seating full coverage castings during cementation.

PubMed

Webb, E L; Murray, H V; Holland, G A; Taylor, D F

1983-06-01

Machined steel dies were used to study the effects of three die modifications on seating full coverage castings during cementation. The die modifications consisted of occlusal channels, occlusal surface relief, and axial channels. Fourteen specimens having one or more forms of die modification were compared with two control specimens having no die modifications. Statistical analysis of the data revealed that the addition of four axial channels to the simulated preparation on the steel die produced a significant reduction in the mean marginal discrepancy during cementation. Occlusal modifications alone failed to produce significant reductions in marginal discrepancies when compared with the control specimens. Occlusal modifications in conjunction with axial channels failed to produce further significant reductions in marginal discrepancies when compared with those reductions observed in specimens having only axial channels.

Bioactive Coating with Two-Layer Hierarchy of Relief Obtained by Sol-Gel Method with Shock Drying and Osteoblast Response of Its Structure.

PubMed

Zemtsova, Elena G; Arbenin, Andrei Y; Yudintceva, Natalia M; Valiev, Ruslan Z; Orekhov, Evgeniy V; Smirnov, Vladimir M

2017-10-13

In this work, we analyze the efficiency of the modification of the implant surface. This modification was reached by the formation of a two-level relief hierarchy by means of a sol-gel approach that included dip coating with subsequent shock drying. Using this method, we fabricated a nanoporous layer with micron-sized defects on the nanotitanium surface. The present work continues an earlier study by our group, wherein the effect of osteoblast-like cell adhesion acceleration was found. In the present paper, we give the results of more detailed evaluation of coating efficiency. Specifically, cytological analysis was performed that included the study of the marker levels of osteoblast-like cell differentiation. We found a significant increase in the activity of alkaline phosphatase at the initial incubation stage. This is very important for implantation, since such an effect assists the decrease in the induction time of implant engraftment. Moreover, osteopontin expression remains high for long expositions. This indicates a prolonged osteogenic effect in the coating. The results suggest the acceleration of the pre-implant area mineralization and, correspondingly, the potential use of the developed coatings for bone implantation.

Effects of sea lamprey substrate modification and carcass nutrients on macroinvertebrate assemblages in a small Atlantic coastal stream

USGS Publications Warehouse

Weaver, Daniel M.; Coghlan, Stephen M.; Zydlewski, Joseph D.

2018-01-01

Aquatic macroinvertebrates respond to patch dynamics arising from interactions of physical and chemical disturbances across space and time. Anadromous fish, such as sea lamprey, Petromyzon marinus, migrate from the ocean and alter physical and chemical properties of recipient spawning streams. Sea lamprey disturb stream benthos physically through nest construction and spawning, and enrich food webs through nutrient deposition from decomposing carcasses. Sea lamprey spawning nests support greater macroinvertebrate abundance than adjacent reference areas, but concurrent effects of stream bed modification and nutrient supplementation have not been examined sequentially. We added carcasses and cleared substrate experimentally to mimic the physical disturbance and nutrient enrichment associated with lamprey spawning, and characterized effects on macroinvertebrate assemblage structure. We found that areas receiving cleared substrate and carcass nutrients were colonized largely by Simuliidae compared to upstream and downstream control areas that were colonized largely by Hydropsychidae, Philopotamidae, and Chironomidae. Environmental factors such as stream flow likely shape assemblages by physically constraining macroinvertebrate establishment and feeding. Our results indicate potential changes in macroinvertebrate assemblages from the physical and chemical changes to streams brought by spawning populations of sea lamprey.

Photo-pharmaceutical therapy: features and prospects

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Potapenko, Alexander Y.; Minenkov, Alexander A.

2001-07-01

This article is an attempt to analyze the concept, distinguishing features and possible application of photo- pharmaceutical therapy (PPT). Besides photopheresis, PUVA, and photodynamic therapy, PPT also embraces a broad spectrum of various combinations of light and drugs. PPT techniques can be classified according to the role of light in drug therapy into several groups: 1) Light activation of drugs before, during or after their administration, 2) light activation of cells of biotissue to potentiate the pharmaceutical effect of drugs, 3) light assisted drug delivery, 4) optical sensing of drug action at cellular and subcellular levels, and 5) selective photochemistry of drugs during their manufacturing. PPT seeks to describe the mechanisms of light-drug interaction, to time and sequence light-drug action, and to verify their synergetic effect. This article yields the results of developing new PPT modifications created in collaboration with some Russian scientific institutes and medical centers. The developed modifications are as follows: 1) drug pre-administration photoactivation, 2) antibody-photoconformation photoimmunotherapy, 3) photophonophoresis with a blend of photosensitizers and antibiotics, 4) photoelectrophoresis, 5) drug effect enhancement due to laser-induced blood circulation activation, 6) photoimmunization with alpha- fetoprotein, 7) photo-pharmaceutical dosimetry, and 8) a rapid drug toxicity photoassay.

Bioactive Coating with Two-Layer Hierarchy of Relief Obtained by Sol-Gel Method with Shock Drying and Osteoblast Response of Its Structure

PubMed Central

Zemtsova, Elena G.; Arbenin, Andrei Y.; Valiev, Ruslan Z.; Orekhov, Evgeniy V.; Smirnov, Vladimir M.

2017-01-01

In this work, we analyze the efficiency of the modification of the implant surface. This modification was reached by the formation of a two-level relief hierarchy by means of a sol-gel approach that included dip coating with subsequent shock drying. Using this method, we fabricated a nanoporous layer with micron-sized defects on the nanotitanium surface. The present work continues an earlier study by our group, wherein the effect of osteoblast-like cell adhesion acceleration was found. In the present paper, we give the results of more detailed evaluation of coating efficiency. Specifically, cytological analysis was performed that included the study of the marker levels of osteoblast-like cell differentiation. We found a significant increase in the activity of alkaline phosphatase at the initial incubation stage. This is very important for implantation, since such an effect assists the decrease in the induction time of implant engraftment. Moreover, osteopontin expression remains high for long expositions. This indicates a prolonged osteogenic effect in the coating. The results suggest the acceleration of the pre-implant area mineralization and, correspondingly, the potential use of the developed coatings for bone implantation. PMID:29027930

Effects of repeated potassium iodide administration on genes involved in synthesis and secretion of thyroid hormone in adult male rat.

PubMed

Lebsir, Dalila; Manens, Line; Grison, Stephane; Lestaevel, Philippe; Ebrahimian, Teni; Suhard, David; Phan, Guillaume; Dublineau, Isabelle; Tack, Karine; Benderitter, Marc; Pech, Annick; Jourdain, Jean-Rene; Souidi, Maâmar

2018-02-26

A single dose of potassium iodide (KI) is recommended to reduce the risk of thyroid cancer during nuclear accidents. However in case of prolonged radioiodine exposure, more than one dose of KI may be necessary. This work aims to evaluate the potential toxic effect of repeated administration of KI. Adult Wistar rats received an optimal dose of KI 1 mg/kg over a period of 1, 4 or 8 days. hormonal status (TSH, FT4) of treated rats was unaffected. Contrariwise, a sequential Wolff-Chaikoff effect was observed, resulting in a prompt decrease of NIS and MCT8 mRNA expression (-58% and -26% respectively), followed by a delayed decrease of TPO mRNA expression (-33%) in conjunction with a stimulation of PDS mRNA expression (+62%). we show for the first time that repeated administration of KI at 1 mg/kg/24h doesn't cause modification of thyroid hormones level, but leads to a reversible modification of the expression of genes involved in the synthesis and secretion of thyroid hormones. Copyright © 2018 Elsevier B.V. All rights reserved.

Multifunctional substrate of Al alloy based on general hierarchical micro/nanostructures: superamphiphobicity and enhanced corrosion resistance.

PubMed

Li, Xuewu; Shi, Tian; Liu, Cong; Zhang, Qiaoxin; Huang, Xingjiu

2016-10-24

Aluminum alloys are vulnerable to penetrating and peeling failures in seawater and preparing a barrier coating to isolate the substrate from corrosive medium is an effective anticorrosion method. Inspired by the lotus leaves effect, a wetting alloy surface with enhanced anticorrosion behavior has been prepared via etch, deposition, and low-surface-energy modification. Results indicate that excellent superamphiphobicity has been achieved after the modification of the constructed hierarchical labyrinth-like microstructures and dendritic nanostructures. The as-prepared surface is also found with good chemical stability and mechanical durability. Furthermore, superior anticorrosion behaviors of the resultant samples in seawater are investigated by electrochemical measurements. Due to trapped air in micro/nanostructures, the newly presented solid-air-liquid contacting interface can help to resist the seawater penetration by greatly reducing the interface interaction between corrosive ions and the superamphiphobic surface. Finally, an optimized two-layer perceptron artificial neural network is set up to model and predict the cause-and-effect relationship between preparation conditions and the anticorrosion parameters. This work provides a great potential to extend the applications of aluminum alloys especially in marine engineering fields.

Multifunctional substrate of Al alloy based on general hierarchical micro/nanostructures: superamphiphobicity and enhanced corrosion resistance

PubMed Central

Li, Xuewu; Shi, Tian; Liu, Cong; Zhang, Qiaoxin; Huang, Xingjiu

2016-01-01

Aluminum alloys are vulnerable to penetrating and peeling failures in seawater and preparing a barrier coating to isolate the substrate from corrosive medium is an effective anticorrosion method. Inspired by the lotus leaves effect, a wetting alloy surface with enhanced anticorrosion behavior has been prepared via etch, deposition, and low-surface-energy modification. Results indicate that excellent superamphiphobicity has been achieved after the modification of the constructed hierarchical labyrinth-like microstructures and dendritic nanostructures. The as-prepared surface is also found with good chemical stability and mechanical durability. Furthermore, superior anticorrosion behaviors of the resultant samples in seawater are investigated by electrochemical measurements. Due to trapped air in micro/nanostructures, the newly presented solid-air-liquid contacting interface can help to resist the seawater penetration by greatly reducing the interface interaction between corrosive ions and the superamphiphobic surface. Finally, an optimized two-layer perceptron artificial neural network is set up to model and predict the cause-and-effect relationship between preparation conditions and the anticorrosion parameters. This work provides a great potential to extend the applications of aluminum alloys especially in marine engineering fields. PMID:27775053

Multifunctional substrate of Al alloy based on general hierarchical micro/nanostructures: superamphiphobicity and enhanced corrosion resistance

NASA Astrophysics Data System (ADS)

Li, Xuewu; Shi, Tian; Liu, Cong; Zhang, Qiaoxin; Huang, Xingjiu

2016-10-01

Aluminum alloys are vulnerable to penetrating and peeling failures in seawater and preparing a barrier coating to isolate the substrate from corrosive medium is an effective anticorrosion method. Inspired by the lotus leaves effect, a wetting alloy surface with enhanced anticorrosion behavior has been prepared via etch, deposition, and low-surface-energy modification. Results indicate that excellent superamphiphobicity has been achieved after the modification of the constructed hierarchical labyrinth-like microstructures and dendritic nanostructures. The as-prepared surface is also found with good chemical stability and mechanical durability. Furthermore, superior anticorrosion behaviors of the resultant samples in seawater are investigated by electrochemical measurements. Due to trapped air in micro/nanostructures, the newly presented solid-air-liquid contacting interface can help to resist the seawater penetration by greatly reducing the interface interaction between corrosive ions and the superamphiphobic surface. Finally, an optimized two-layer perceptron artificial neural network is set up to model and predict the cause-and-effect relationship between preparation conditions and the anticorrosion parameters. This work provides a great potential to extend the applications of aluminum alloys especially in marine engineering fields.

A plasma modified cellulose-chitosan porous membrane allows efficient DNA binding and provides antibacterial properties: A step towards developing a new DNA collecting card.

PubMed

Chumwangwapee, Sasiwimon; Chingsungnoen, Artit; Siri, Sineenat

2016-11-01

In forensic DNA analyses, biological specimens are collected and stored for subsequent recovery and analysis of DNA. A cost-effective and efficient DNA recovery approach is therefore a need. This study aims to produce a plasma modified cellulose-chitosan membrane (pCE-CS) that efficiently binds and retains DNA as a potential DNA collecting card. The pCE-CS membrane was produced by a phase separation of ionic liquid dissolving CE and CS in water with subsequent surface-modification by a two-step exposure of argon plasma and nitrogen gas. Through plasma modification, the pCE-CS membrane demonstrated better DNA retention after a washing process and higher rate of DNA recovery as compared with the original CE-CS membrane and the commercial FTA card. In addition, the pCE-CS membrane exhibited anti-bacterial properties against both Escherichia coli and Staphylococcus aureus. The results of this work suggest a potential function of the pCE-CS membrane as a DNA collecting card with a high recovery rate of captured DNA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Potential influence of birds on soil testate amoebae in the Arctic

NASA Astrophysics Data System (ADS)

Mazei, Yuri A.; Lebedeva, Natalia V.; Taskaeva, Anastasia A.; Ivanovsky, Alexander A.; Chernyshov, Viktor A.; Tsyganov, Andrey N.; Payne, Richard J.

2018-06-01

Birds can be an important agent of environmental change in High Arctic ecosystems, particularly due to the role of seabirds as a vector transferring nutrients from the marine to terrestrial realms. The soils of bird nesting sites are known to host distinct plant communities but the consequences of bird modification for microorganisms are much less clear. Our focus here is testate amoebae: a widely-distributed group of protists with significant roles in many aspects of ecosystem functioning. We compared the testate amoeba assemblages of a site on Spitsbergen (Svalbard archipelago) affected by nesting birds, with nearby control sites. We found differences in assemblage between sites, typified by reduced relative abundance of Phryganella acropodia and Centropyxis aerophila in bird-modified soils. These changes may reflect a reduced availability of fungal food sources. We found no evidence for differences in assemblage diversity or test concentration between bird-modified and control soils. Our dataset is small but results provide the first evidence for the potential effect of bird modification of soils on testate amoebae in the Arctic. Results show only limited similarity to experimental studies of nutrient addition, implying that response mechanisms may be more complicated than simply additional nutrient supply.

Intestine, immunity, and parenteral nutrition in an era of preferred enteral feeding.

PubMed

Barrett, Meredith; Demehri, Farokh R; Teitelbaum, Daniel H

2015-09-01

To review the benefits of enteral nutrition in contrast to the inflammatory consequences of administration of parenteral nutrition and enteral deprivation. To present the most recent evidence for the mechanisms of these immunologic changes and discuss potential areas for modification to decrease infectious complications of its administration. There is significant data supporting the early initiation of enteral nutrition in both medical and surgical patients unable to meet their caloric goals via oral intake alone. Despite the preference for enteral nutrition, some patients are unable to utilize their gut for nutritious gain and therefore require parenteral nutrition administration, along with its infectious complications. The mechanisms behind these complications are multifactorial and have yet to be fully elucidated. Recent study utilizing both animal and human models has provided further information regarding parenteral nutrition's deleterious effect on intestinal epithelial barrier function along with the complications associated with enterocyte deprivation. Changes associated with parenteral nutrition administration and enteral deprivation are complex with multiple potential areas for modification to allow for safer administration. Recent discovery of the mechanisms behind these changes present exciting areas for future study as to make parenteral nutrition administration in the enterally deprived patient safer.

Novel small molecule epithelial sodium channel inhibitors as potential therapeutics in cystic fibrosis - a patent evaluation.

PubMed

Schoenberger, Matthias; Althaus, Mike

2013-10-01

Novel molecular platforms for epithelial sodium channel (ENaC) modulators are claimed in the following six patents: WO2012035158(A1); WO2009074575(A2); WO2011028740(A1); WO2009150137(A2); WO2011079087(A1); WO2008135557(A1). These ENaC inhibitors may be used in blocking transepithelial sodium and consequently water absorption across airway epithelia. This may result in airway rehydration and enhanced mucociliary clearance in patients with cystic fibrosis (CF) lung disease. All inhibitors resemble the classical ENaC blocker amiloride but follow different strategies to increase structural diversity in a sterically tolerant region. These substitutions can be modified to i) enhance potency of ENaC inhibition; ii) reduce epithelial permeability; and iii) broaden applicability in order to be used as potential drugs for CF therapy. Most of the claims and patent data are supported by the currently available literature. The patents deliver a solid chemical basis for a variety of chemical modifications of the ENaC inhibitor amiloride. These modifications may result in the development of a novel, applicable ENaC inhibitors which may have lasting effects on diseased airways and may achieve airway rehydration and enhanced mucociliary clearance in CF lung disease.

Residential Modifications and Decline in Physical Function among Community-Dwelling Older Adults

ERIC Educational Resources Information Center

Liu, Sze Y.; Lapane, Kate L.

2009-01-01

Purpose: The purpose of this study is to quantify the effect of residential modification on decreasing risk of physical function decline in 2 years. Design: Cohort study using propensity scores method to control for baseline differences between individuals with residential modifications and those without residential modifications. Participants:…

Effects of Combining Na and Sr additions on Eutectic Modification in Al-Si alloy

NASA Astrophysics Data System (ADS)

Zhu, G. L.; Gu, N. J.; Zhou, B. J.

2017-09-01

Experiments were designed to investigate the effects of strontium and sodium modified on the eutectic silicon for Al-Si alloy. It was found that combining addition of Na and Sr did not appear to cause deleterious interactions of modification, at at the same time, Sr-Na was fairly constant with holding time and without obvious modification fading. Addition of Na-Sr modifier could take effect quickly and decrease incubation period.

Modification, characterization and investigations of key factors controlling the transport of modified nano zero-valent iron (nZVI) in porous media.

PubMed

Saha, Amal Krishna; Sinha, Alok; Pasupuleti, Srinivas

2018-01-25

Enhancement of nano zero-valent iron (nZVI) stability and transport in the subsurface environment is important for in situ degradation of contaminants. Various biodegradable dispersants (poly (acrylic acid) (PAA), Tween 20 and Reetha Extracts) have been tested to evaluate their effectiveness in this regard. Application of dispersants during the synthesis of nZVI have positively affected the reduction in particle size. The transport capacity in terms of fraction elution at different pore water velocities and collector grain size (filter media) was analyzed using correlation equation for the filtration model by Rajagopalan and Tien (RT model). At a surfactant concentration of 5% for PAA, Tween 20 and Reetha (Sapindus trifoliata) extracts, the lowest particle size and the highest zeta potential achieved are 8.67 nm and -55.29 mV, 75.24 nm and -62.68 mV, 61.6 nm and -37.82 mV, respectively. The trend of colloidal stability by The Derjaguin-Landau-Verwey-Overbeek (DLVO) Theory model for PAA and Reetha applied concentration was 3% > 4% > 5% > 2% > 1% > 0%. For Tween 20, modified nZVI particle shows a higher repulsive force with increasing Tween 20 concentration. Results indicated that some mechanisms such as aggregation, ripening and surface modification with different carrier pore water velocities had a considerable impact on nZVI retention in porous media. The results indicate that natural surfactant like Reetha extracts exhibits an alternative potential capacity for nZVI modification in comparison with synthetic surfactants (PAA and Tween 20).

Evaluation of the material and tablet formation properties of modified forms of Dioscorea starches.

PubMed

Odeku, Oluwatoyin A; Picker-Freyer, Katharina M

2009-11-01

Starches obtained from four different Dioscorea species-namely, White yam (Dioscorea rotundata), Bitter yam (Dioscorea dumetorum), Chinese yam (Dioscorea oppositifolia), and Water yam (Dioscorea alata)-were modified by cross-linking, hydroxypropylation, and dual modification-cross-linking followed by hydroxypropylation. The physicochemical, material, and tablet properties of the modified starches were investigated with the aim of understanding their properties to determine their potential use for different applications. The tablet formation properties were assessed using 3D modeling, the Heckel equation, and force-displacement profiles. The analyzed tablet properties were elastic recovery, compactibility, and disintegration. The result indicates that the modifications generally increased the swelling power for all the starches in the rank order hydroxypropyl > hydroxypropylated cross-linked > cross-linked (CL) while the solubility did not show a clear-cut pattern. This indicates that hydroxypropylation generally showed the strongest effects on swelling. Furthermore, hydroxypropylation improved the hot water swelling of the CL starches. The modifications did not cause any detectable morphological change in the starch granules shape or size although slight rupture was observed in some granules. CL starch had the lowest water sorption capacity and hydroxypropylation increased the sorption capacity of the CL starches. The material property results indicate that hydroxypropylation and cross-linking did not significantly improve the flowability and compressibility but improved bonding, which resulted in an increased compaction and higher tablet crushing force even though they all disintegrated rapidly. Thus, the modified Dioscorea starches showed potentials for development as new excipients in solid dosage form design, and they could be useful as disintegrants or for Soft tableting.

Highly Modified Cellulose Nanocrystals and Formation of Epoxy-CNC Nanocomposites.

PubMed

Abraham, Eldho; Kam, Doron; Nevo, Yuval; Slattegard, Rikard; Rivkin, Amit; Lapidot, Shaul; Shoseyov, Oded

2016-10-05

This work presents an environmentally friendly, iodine-catalysed chemical modification method to generate highly hydrophobic, optically active cellulose nanocrystals (CNC). The high degree of ester substitution (DS=2.18), hydrophobicity, crystalline behaviour and optical activity of the generated acetylated CNC (Ac-CNC) were quantified by TEM, FTIR, solid 13C NMR, contact angle, XRD and POM analyses. Ac-CNC possessing substantial enhancement in thermal stability (16.8%) and forms thin films with interlayer distance of 50-150 nm, presenting cavities suitable for entrapping nano and micro particles. Generated Ac-CNC proved as an effective reinforcing agent in hydrophobic polymer matrices for fabricating high performance nanocomposites. When integrated at a very low weight percentage (0.5%) in an epoxy matrix, Ac-CNC provided for a 73% increase in tensile strength and a 98% increase in modulus, demonstrating its remarkable reinforcing potential and effective stress transfer behaviour. The method of modification and the unique properties of the modified CNC (hydrophobicity, crystallinity, reinforcing ability and optical activity) render them a novel bionanomaterial for a range of multipurpose applications.

A review about the effect of life style modification on diabetes and quality of life.

PubMed

Shrestha, Prabha; Ghimire, Laxmi

2012-10-10

The aim of this review is to examine diabetes and quality of life improvements through modifying life style. The data was collected by reviewing published articles from PubMed, Medline, Web of Science, and Google open access publications. The review identified prevention strategies can reduce the risk and complications of diabetes. Life style modification in relation to obesity, eating habit, and physical exercise can play a major role in the prevention of diabetes. Nowadays, there has been progress in the development of behavioural strategies to modify these life style habits and it is not easy to accept for long term basis. If people maintain a balanced diet and physical exercise this can have real and potential benefits for their prevention and control of complications from chronic diseases particularly for cardiovascular risk and diabetes. Healthy life style may best be achieved through public private partnerships involving government, partners organizations, health services providers, community and people living with diabetes. Effective strategies to reduce the incidence of diabetes globally and assist in managing the disease are urgently required.

Structural and antioxidant modification of wheat peptides modified by the heat and lipid peroxidation product malondialdehyde.

PubMed

Tang, Xue; Wu, Qiuping; Le, Guowei; Wang, Jiao; Yin, Kaijian; Shi, Yonghui

2012-01-01

Wheat peptides, the biological active peptides derived from foods, has an array of biological actions, including antiobesity, antimicrobial, and angiotensin I-converting enzyme inhibitory effects in mammalian species. Recent studies showed that some wheat peptides may show the noteworthy antioxidant potency against the peroxidation of lipids or fatty acids, but the effect of oxidation on its antioxidant activities is unclear. In the present study, we demonstrate that heat and malandialdehyde (MDA)-oxidized wheat peptides lose its surface hydrophobicity and reducing power, and show a relatively lower free radical-scavenging activitiy in vitro. Those modifications also lead to gradual formation of aggregates in wheat peptides and induce more reactive oxygen species (ROS) production in vivo. These findings indicate that oxidation may influence the functional properties and directly alter the structure of wheat peptides, and lead to the loss of its antioxidant potency both in vitro and in vivo, thereby providing a novel explanation for some of the potential health risks proposed for oxidized food in human. © 2011 Institute of Food Technologists®

A Review about the Effect of Life style Modification on Diabetes and Quality of Life

PubMed Central

Shrestha, Prabha; Ghimire, Laxmi

2012-01-01

The aim of this review is to examine diabetes and quality of life improvements through modifying life style. The data was collected by reviewing published articles from PubMed, Medline, Web of Science, and Google open access publications. The review identified prevention strategies can reduce the risk and complications of diabetes. Life style modification in relation to obesity, eating habit, and physical exercise can play a major role in the prevention of diabetes. Nowadays, there has been progress in the development of behavioural strategies to modify these life style habits and it is not easy to accept for long term basis. If people maintain a balanced diet and physical exercise this can have real and potential benefits for their prevention and control of complications from chronic diseases particularly for cardiovascular risk and diabetes. Healthy life style may best be achieved through public private partnerships involving government, partners organizations, health services providers, community and people living with diabetes. Effective strategies to reduce the incidence of diabetes globally and assist in managing the disease are urgently required. PMID:23121755

Effect of ultrasound pre-treatment on the physicochemical composition of Agave durangensis leaves and potential enzyme production.

PubMed

Contreras-Hernández, M G; Ochoa-Martínez, L A; Rutiaga-Quiñones, J G; Rocha-Guzmán, N E; Lara-Ceniceros, T E; Contreras-Esquivel, J C; Prado Barragán, L A; Rutiaga-Quiñones, O M

2018-02-01

Approximately 1 million tons of agave plants are processed annually by the Mexican tequila and mezcal industry, generating vast amounts of agroindustrial solid waste. This type of lignocellulosic biomass is considered to be agroindustrial residue, which can be used to produce enzymes, giving it added value. However, the structure of lignocellulosic biomass makes it highly recalcitrant, and results in relatively low yield when used in its native form. The aim of this study was to investigate an effective pre-treatment method for the production of commercially important hydrolytic enzymes. In this work, the physical and chemical modification of Agave durangensis leaves was analysed using ultrasound and high temperature as pre-treatments, and production of enzymes was evaluated. The pre-treatments resulted in modification of the lignocellulosic structure and composition; the ultrasound pre-treatment improved the production of inulinase by 4 U/mg and cellulase by 0.297 U/mg, and thermal pre-treatment improved β-fructofuranosidase by 30 U/mg. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

PubMed

Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

2017-10-01

Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hyperpolarization of the plasma membrane potential provokes reorganization of the actin cytoskeleton and increases the stability of adherens junctions in bovine corneal endothelial cells in culture.

PubMed

Nin, Verónica; Hernández, Julio A; Chifflet, Silvia

2009-12-01

In previous works we showed that the depolarization of the plasma membrane potential (PMP) determines a reorganization of the cytoskeleton of diverse epithelia in culture, consisting mainly of a reallocation of peripheral actin toward the cell center, ultimately provoking intercellular disruption. In view of this evidence, we explored in this study the possible effects of membrane potential hyperpolarization on the cytoskeletal organization and adherens junction (AJ) morphology and the stability of confluent bovine corneal endothelial cells in culture. For this purpose, hyperpolarization was achieved by substitution of extracellular sodium by nondiffusible cations or via the incorporation of valinomycin to the control solution. Actin compactness at the cell periphery was assessed by quantitative analysis of fluorescence microscopy images. The stability of the AJ was challenged by calcium deprivation or temperature decrease. Our results showed that plasma membrane hyperpolarization provokes a compaction of AJ-associated actin filaments toward the plasma membrane and an increase in the stability of the AJs. We also observed that the hyperpolarizing procedures determined similar modifications in the actin cytoskeleton of endothelial cells in whole bovine corneas. Together with our previous work, the results of this study contribute to the idea that modifications in the PMP of nonexcitable cells participate in cellular adaptive responses involving reorganization of cytoskeletal components. (c) 2009 Wiley-Liss, Inc.

Laser-induced modification of graphene in the presence of ethanol on a graphene - substrate interface

NASA Astrophysics Data System (ADS)

Pivovarov, P. A.; Frolov, V. D.; Zavedeev, E. V.; Konov, V. I.

2017-12-01

We have studied the effect that the substitution of an organic substance (ethanol) for water adsorbate on a CVD graphene-SiO2/Si interface has on the laser-induced modification of graphene and graphene structures on the SiO2 film. Scanning probe microscopy has been used to analyse changes in the electronic properties of graphene structures on a hydrophilic substrate in the presence of ethanol and as a result of a laser-induced spatial redistribution of a water-alcohol adsorbate on the interface. It has been demonstrated experimentally that ethanol substitution for water adsorbate leads to an increase in the surface potential of the graphene, which is equivalent to a reduction in its work function with respect to the original level under normal conditions at a relative humidity of air from 30% to 60%. In the laser irradiation zone, we observe an additional increase in surface potential by 30-50 mV. Thus, ethanol makes it possible to tune the laser-induced electronic properties of graphene on a substrate. In addition, it has been shown that the intercalation of ethanol molecules leads to severe temporal instability of the physical properties of graphene structures produced by local laser irradiation. We have demonstrated the possibility of information ‘rewriting’ by low-intensity laser pulses in microregions with a changed surface potential in the presence of ethanol.

Mathematical Modeling of Herpes Simplex Virus Distribution in Solid Tumors: Implications for Cancer Gene Therapy

PubMed Central

Mok, Wilson; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.

2010-01-01

Purpose Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site. Experimental Design The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus. Results This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more. An increase in the effective diffusion coefficient can result in similar gains. Conclusions This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy. PMID:19318482

[Genome editing of industrial microorganism].

PubMed

Zhu, Linjiang; Li, Qi

2015-03-01

Genome editing is defined as highly-effective and precise modification of cellular genome in a large scale. In recent years, such genome-editing methods have been rapidly developed in the field of industrial strain improvement. The quickly-updating methods thoroughly change the old mode of inefficient genetic modification, which is "one modification, one selection marker, and one target site". Highly-effective modification mode in genome editing have been developed including simultaneous modification of multiplex genes, highly-effective insertion, replacement, and deletion of target genes in the genome scale, cut-paste of a large DNA fragment. These new tools for microbial genome editing will certainly be applied widely, and increase the efficiency of industrial strain improvement, and promote the revolution of traditional fermentation industry and rapid development of novel industrial biotechnology like production of biofuel and biomaterial. The technological principle of these genome-editing methods and their applications were summarized in this review, which can benefit engineering and construction of industrial microorganism.

Crash Modification Factors for Chevrons in Iowa

DOT National Transportation Integrated Search

2018-02-02

Although chevron alignment signs have been utilized for some time along horizontal curves, their effectiveness is not well documented. The Crash Modification Factors Clearinghouse includes crash modification factors (CMFs) for chevrons from 0.41 to 1...

Oxidative stress and mitochondria-mediated cell death mechanisms triggered by the familial Danish dementia ADan amyloid.

PubMed

Todd, Krysti; Ghiso, Jorge; Rostagno, Agueda

2016-01-01

Familial Danish Dementia (FDD), an early-onset non-amyloid-β (Aβ) cerebral amyloidosis, is neuropathologically characterized by widespread cerebral amyloid angiopathy, parenchymal amyloid and preamyloid deposits, as well as neurofibrillary degeneration indistinguishable to that seen in Alzheimer's disease (AD). The main amyloid subunit composing FDD lesions, a 34-amino acid de-novo generated peptide ADan, is the direct result of a genetic defect at the 3'-end of the BRI2 gene and the physiologic action of furin-like proteolytic processing at the C-terminal region of the ADan precursor protein. We aimed to study the impact of the FDD mutation, the additional formation of the pyroglutamate (pE) posttranslational modification as well as the relevance of C-terminal truncations -all major components of the heterogeneous FDD deposits- on the structural and neurotoxic properties of the molecule. Our data indicates that whereas the mutation generated a β-sheet-rich hydrophobic ADan subunit of high oligomerization/fibrillization propensity and the pE modification further enhanced these properties, C-terminal truncations had the opposite effect mostly abolishing these features. The potentiation of pro-amyloidogenic properties correlated with the initiation of neuronal cell death mechanisms involving oxidative stress, perturbation of mitochondrial membrane potential, release of mitochondrial cytochrome c, and downstream activation of caspase-mediated apoptotic pathways. The amyloid-induced toxicity was inhibited by targeting specific components of these detrimental cellular pathways, using reactive oxygen scavengers and monoclonal antibodies recognizing the pathological amyloid subunit. Taken together, the data indicate that the FDD mutation and the pE posttranslational modification are both primary elements driving intact ADan into an amyloidogenic/neurotoxic pathway while truncations at the C-terminus eliminate the pro-amyloidogenic characteristics of the molecule, likely reflecting effect of physiologic clearance mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength.

PubMed

Manickam, Nandini; Joshi, Kartikeya; Bhatt, Monika J; Farabaugh, Philip J

2016-02-29

Cellular health and growth requires protein synthesis to be both efficient to ensure sufficient production, and accurate to avoid producing defective or unstable proteins. The background of misreading error frequency by individual tRNAs is as low as 2 × 10(-6) per codon but is codon-specific with some error frequencies above 10(-3) per codon. Here we test the effect on error frequency of blocking post-transcriptional modifications of the anticodon loops of four tRNAs in Escherichia coli. We find two types of responses to removing modification. Blocking modification of tRNA(UUC)(Glu) and tRNA(QUC)(Asp) increases errors, suggesting that the modifications act at least in part to maintain accuracy. Blocking even identical modifications of tRNA(UUU)(Lys) and tRNA(QUA)(Tyr) has the opposite effect of decreasing errors. One explanation could be that the modifications play opposite roles in modulating misreading by the two classes of tRNAs. Given available evidence that modifications help preorder the anticodon to allow it to recognize the codons, however, the simpler explanation is that unmodified 'weak' tRNAs decode too inefficiently to compete against cognate tRNAs that normally decode target codons, which would reduce the frequency of misreading. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Immediate effects of a distal gait modification during stair descent in individuals with patellofemoral pain.

PubMed

Aliberti, Sandra; Mezêncio, Bruno; Amadio, Alberto Carlos; Serrão, Julio Cerca; Mochizuki, Luis

2018-05-23

Knee pain during stair managing is a common complaint among individuals with PFP and can negatively affect their activities of daily living. Gait modification programs can be used to decrease patellofemoral pain. Immediate effects of a stair descent distal gait modification session that intended to emphasize forefoot landing during stair descent are described in this study. To analyze the immediate effects of a distal gait modification session on lower extremity movements and intensity of pain in women with patellofemoral pain during stair descent. Nonrandomized controlled trial. Sixteen women with patellofemoral pain were allocated into two groups: (1) Gait Modification Group (n = 8); and 2) Control Group (n = 8). The intensity of pain (visual analog scale) and kinematics of knee, ankle, and forefoot (multi-segmental foot model) during stair descent were assessed before and after the intervention. After the gait modification session, there was an increase of forefoot eversion and ankle plantarflexion as well as a decrease of knee flexion. An immediate decrease in patellofemoral pain intensity during stair descent was also observed. The distal gait modification session changed the lower extremity kinetic chain strategy of movement, increasing foot and ankle movement contribution and decreasing knee contribution to the task. An immediate decrease in patellofemoral pain intensity during stair descent was also observed. To emphasize forefoot landing may be a useful intervention to immediately relieve pain in patients with patellofemoral pain during stair descent. Clinical studies are needed to verify the gait modification session effects in medium and long terms.

Repairing a critical-sized bone defect with highly porous modified and unmodified baghdadite scaffolds.

PubMed

Roohani-Esfahani, S I; Dunstan, C R; Davies, B; Pearce, S; Williams, R; Zreiqat, H

2012-11-01

This is the first reported study to prepare highly porous baghdadite (Ca₃ZrSi₂O₉) scaffolds with and without surface modification and investigate their ability to repair critical-sized bone defects in a rabbit radius under normal load. The modification was carried out to improve the mechanical properties of the baghdadite scaffolds (particularly to address their brittleness) by coating their surfaces with a thin layer (∼400 nm) of polycaprolactone (PCL)/bioactive glass nanoparticles (nBGs). The β-tricalcium phosphate/hydroxyapatite (TCP/HA) scaffolds with and without modification were used as the control groups. All of the tested scaffolds had an open and interconnected porous structure with a porosity of ∼85% and average pore size of 500 μm. The scaffolds (six per scaffold type and size of 4 mm × 4 mm × 15 mm) were implanted (press-fit) into the rabbit radial segmental defects for 12 weeks. Micro-computed tomography and histological evaluations were used to determine bone ingrowth, bone quality, and implant integration after 12 weeks of healing. Extensive new bone formation with complete bridging of the radial defect was evident with the baghdadite scaffolds (modified/unmodified) at the periphery and in close proximity to the ceramics within the pores, in contrast to TCP/HA scaffolds (modified/unmodified), where bone tended to grow between the ulna adjacent to the implant edge. Although the modification of the baghdadite scaffolds significantly improved their mechanical properties, it did not show any significant effect on in vivo bone formation. Our findings suggest that baghdadite scaffolds with and without modification can serve as a potential material to repair critical sized bone defects. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Current nutritional treatments of obesity.

PubMed

Greenwald, Ashli

2006-01-01

Obesity in our country is a growing concern. There are several different options for weight loss; however, individuals must be self-motivated and amendable to change in order to achieve success with their weight loss goals. Several strategies used by professionals in the US today to treat overweight and obesity, include diet therapy, exercise, behavior modification, pharmacotherapy, and surgery. The focus of the American Dietetic Association (ADA) Weight Management Position Statement is no longer just on weight loss but now on weight management. Reaching one's ideal body weight is recommended but not often realistic. Frequently, the goal of treatment shifts to maintenance of ones current weight or attempts at moderate weight loss. Lifestyle modification or behavioral modification interventions rely on analyzing behavior to identify events that are associated with appropriate vs. inappropriate eating, exercise, or thinking habits. Certain primary strategies that have been found to be useful for helping people change their behaviors so that they can lose weight and maintain their weight loss, include self-monitoring, stimulus control, cognitive restructuring, stress management, social support, physical activity, and relapse prevention. Weight loss programs should strive to combine a nutritionally balanced dietary regimen with exercise and lifestyle modifications at the lowest possible cost. There are several different methods used for dietary modifications; low calorie diets, very low calorie diets, fasting, formula diets and meal replacement programs, and popular diets. Bariatric surgery is gaining popularity as it has been an effective way to treat obesity. Following gastric bypass surgery, the patients must be prepared to modify their eating behaviors and dietary selections to assist with weight loss and prevent potential complications. Patients should be educated on the dietary guidelines extensively prior to surgery and again post-operatively.

76 FR 27910 - Modification of the Significant New Uses of 2-Propen-1-one, 1-(4-morpholinyl)-

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... Modification of the Significant New Uses of 2-Propen-1-one, 1-(4- morpholinyl)- AGENCY: Environmental... use rule (SNUR) under the Toxic Substances Control Act (TSCA) for 2-Propen-1- one, 1-(4-morpholinyl..., or use 2-Propen-1-one, 1-(4-morpholinyl)-(CAS No. 5117-12-4). Potentially affected entities may...

Effect of gaming on absenteeism rate.

PubMed

Vassar, M L; Gines, D J

1985-05-01

Gaming, a behavior modification technique, was used in an attempt to decrease absenteeism in a dietary department of a 426-bed medical center. A lottery reward system was used to reinforce the appropriate behavior (as identified by management) of perfect attendance. The intervention strategy did lower the absenteeism rate from 2.46% to 2.03%, not significant when tested by one-way analysis of variance at the 0.05 level. However, from an administrative standpoint, the decline in absenteeism was important because of the potential monetary savings.

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

Carpenter, Alberta; Mann, Margaret; Gelman, Rachel

In evaluating next-generation materials and processes, the supply chain can have a large impact on the life cycle energy impacts. The Materials Flow through Industry (MFI) tool was developed for the Department of Energy's Advanced Manufacturing Office to be able to evaluate the energy impacts of the U.S. supply chain. The tool allows users to perform process comparisons, material substitutions, and grid modifications, and to see the effects of implementing sector efficiency potentials (Masanet, et al. 2009). This paper reviews the methodology of the tool and provides results around specific scenarios.

Isolation and confinement - Considerations for colonization

NASA Technical Reports Server (NTRS)

Akins, F. R.

1978-01-01

This paper discusses three types of isolation (sensory/perceptual, temporal, and social) that could adversely affect mankind in space. The literature dealing with laboratory and field experiments relevant to these areas is summarized and suggestions are given for dealing with these problems within the space colony community. Also, consideration is given to the potential effects of physical confinement and the need for usable space. Finally, a modification of Maslow's hierarchy of needs is proposed as a theoretical framework to understand and investigate mankind's psychological needs in space.

Hydrodynamic fluctuations, nonequilibrium equations of state, and the shift of the spinodal line in polymer solutions under flow

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

Criado-Sancho, M.; Casas-Vazquez, J.; Jou, D.

1997-08-01

In the literature, the shift of the spinodal line of polymer solutions under flow is attributed either to an actual shift of the spinodal due to a nonequilibrium modification of the equation of state for the chemical potential, or to an apparent shift due to an increase of hydrodynamic fluctuations owing to the flow. Here we see that both approaches are compatible and that both effects add up. {copyright} {ital 1997} {ital The American Physical Society}

Charging and heat collection by a positively charged dust grain in a plasma.

PubMed

Delzanno, Gian Luca; Tang, Xian-Zhu

2014-07-18

Dust particulates immersed in a quasineutral plasma can emit electrons in several important applications. Once electron emission becomes strong enough, the dust enters the positively charged regime where the conventional orbital-motion-limited (OML) theory can break down due to potential-well effects on trapped electrons. A minimal modification of the trapped-passing boundary approximation in the so-called OML(+) approach is shown to accurately predict the dust charge and heat collection flux for a wide range of dust size and temperature.

The food choice at work study: effectiveness of complex workplace dietary interventions on dietary behaviours and diet-related disease risk - study protocol for a clustered controlled trial

PubMed Central

2013-01-01

Background Dietary behaviour interventions have the potential to reduce diet-related disease. Ample opportunity exists to implement these interventions in the workplace. The overall aim is to assess the effectiveness and cost-effectiveness of complex dietary interventions focused on environmental dietary modification alone or in combination with nutrition education in large manufacturing workplace settings. Methods/design A clustered controlled trial involving four large multinational manufacturing workplaces in Cork will be conducted. The complex intervention design has been developed using the Medical Research Council’s framework and the National Institute for Health and Clinical Excellence (NICE) guidelines and will be reported using the TREND statement for the transparent reporting of evaluations with non-randomized designs. It will draw on a soft paternalistic “nudge” theoretical perspective. Nutrition education will include three elements: group presentations, individual nutrition consultations and detailed nutrition information. Environmental dietary modification will consist of five elements: (a) restriction of fat, saturated fat, sugar and salt, (b) increase in fibre, fruit and vegetables, (c) price discounts for whole fresh fruit, (d) strategic positioning of healthier alternatives and (e) portion size control. No intervention will be offered in workplace A (control). Workplace B will receive nutrition education. Workplace C will receive nutrition education and environmental dietary modification. Workplace D will receive environmental dietary modification alone. A total of 448 participants aged 18 to 64 years will be selected randomly. All permanent, full-time employees, purchasing at least one main meal in the workplace daily, will be eligible. Changes in dietary behaviours, nutrition knowledge, health status with measurements obtained at baseline and at intervals of 3 to 4 months, 7 to 9 months and 13 to 16 months will be recorded. A process evaluation and cost-effectiveness economic evaluation will be undertaken. Discussion A 'Food Choice at Work’ toolbox (concise teaching kit to replicate the intervention) will be developed to inform and guide future researchers, workplace stakeholders, policy makers and the food industry. Trial registration Current Controlled Trials, ISRCTN35108237 PMID:24192134

The food choice at work study: effectiveness of complex workplace dietary interventions on dietary behaviours and diet-related disease risk - study protocol for a clustered controlled trial.

PubMed

Geaney, Fiona; Scotto Di Marrazzo, Jessica; Kelly, Clare; Fitzgerald, Anthony P; Harrington, Janas M; Kirby, Ann; McKenzie, Ken; Greiner, Birgit; Perry, Ivan J

2013-11-06

Dietary behaviour interventions have the potential to reduce diet-related disease. Ample opportunity exists to implement these interventions in the workplace. The overall aim is to assess the effectiveness and cost-effectiveness of complex dietary interventions focused on environmental dietary modification alone or in combination with nutrition education in large manufacturing workplace settings. A clustered controlled trial involving four large multinational manufacturing workplaces in Cork will be conducted. The complex intervention design has been developed using the Medical Research Council's framework and the National Institute for Health and Clinical Excellence (NICE) guidelines and will be reported using the TREND statement for the transparent reporting of evaluations with non-randomized designs. It will draw on a soft paternalistic 'nudge' theoretical perspective. It will draw on a soft paternalistic "nudge" theoretical perspective. Nutrition education will include three elements: group presentations, individual nutrition consultations and detailed nutrition information. Environmental dietary modification will consist of five elements: (a) restriction of fat, saturated fat, sugar and salt, (b) increase in fibre, fruit and vegetables, (c) price discounts for whole fresh fruit, (d) strategic positioning of healthier alternatives and (e) portion size control. No intervention will be offered in workplace A (control). Workplace B will receive nutrition education. Workplace C will receive nutrition education and environmental dietary modification. Workplace D will receive environmental dietary modification alone. A total of 448 participants aged 18 to 64 years will be selected randomly. All permanent, full-time employees, purchasing at least one main meal in the workplace daily, will be eligible. Changes in dietary behaviours, nutrition knowledge, health status with measurements obtained at baseline and at intervals of 3 to 4 months, 7 to 9 months and 13 to 16 months will be recorded. A process evaluation and cost-effectiveness economic evaluation will be undertaken. A 'Food Choice at Work' toolbox (concise teaching kit to replicate the intervention) will be developed to inform and guide future researchers, workplace stakeholders, policy makers and the food industry. Current Controlled Trials, ISRCTN35108237.

Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity

PubMed Central

Rudolph, Andreas; Teske, Michael; Illner, Sabine; Kiefel, Volker; Sternberg, Katrin; Grabow, Niels; Wree, Andreas; Hovakimyan, Marina

2015-01-01

Purpose Drug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents. Materials and Methods Five different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test. Results Both endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces. Conclusion Surface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo. PMID:26641662

Contrasting Taxonomic and Phylogenetic Diversity Responses to Forest Modifications: Comparisons of Taxa and Successive Plant Life Stages in South African Scarp Forest

PubMed Central

Grass, Ingo; Brandl, Roland; Botzat, Alexandra; Neuschulz, Eike Lena; Farwig, Nina

2015-01-01

The degradation of natural forests to modified forests threatens subtropical and tropical biodiversity worldwide. Yet, species responses to forest modification vary considerably. Furthermore, effects of forest modification can differ, whether with respect to diversity components (taxonomic or phylogenetic) or to local (α-diversity) and regional (β-diversity) spatial scales. This real-world complexity has so far hampered our understanding of subtropical and tropical biodiversity patterns in human-modified forest landscapes. In a subtropical South African forest landscape, we studied the responses of three successive plant life stages (adult trees, saplings, seedlings) and of birds to five different types of forest modification distinguished by the degree of within-forest disturbance and forest loss. Responses of the two taxa differed markedly. Thus, the taxonomic α-diversity of birds was negatively correlated with the diversity of all plant life stages and, contrary to plant diversity, increased with forest disturbance. Conversely, forest disturbance reduced the phylogenetic α-diversity of all plant life stages but not that of birds. Forest loss neither affected taxonomic nor phylogenetic diversity of any taxon. On the regional scale, taxonomic but not phylogenetic β-diversity of both taxa was well predicted by variation in forest disturbance and forest loss. In contrast to adult trees, the phylogenetic diversity of saplings and seedlings showed signs of contemporary environmental filtering. In conclusion, forest modification in this subtropical landscape strongly shaped both local and regional biodiversity but with contrasting outcomes. Phylogenetic diversity of plants may be more threatened than that of mobile species such as birds. The reduced phylogenetic diversity of saplings and seedlings suggests losses in biodiversity that are not visible in adult trees, potentially indicating time-lags and contemporary shifts in forest regeneration. The different responses of taxonomic and phylogenetic diversity to forest modifications imply that biodiversity conservation in this subtropical landscape requires the preservation of natural and modified forests. PMID:25719204

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

PubMed

Zhu, Kuiyu; Zhang, Ye; Li, Zengyao; Zhou, Fan; Feng, Kang; Dou, Huiqiang; Wang, Tong

2015-08-05

Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

Surface modification of biomaterials by pulsed laser ablation deposition and plasma/gamma polymerization

NASA Astrophysics Data System (ADS)

Rau, Kaustubh R.

Surface modification of stainless-steel was carried out by two different methods: pulsed laser ablation deposition (PLAD) and a combined plasma/gamma process. A potential application was the surface modification of endovascular stents, to enhance biocompatibility. The pulsed laser ablation deposition process, had not been previously reported for modifying stents and represented a unique and potentially important method for surface modification of biomaterials. Polydimethylsiloxane (PDMS) elatomer was studied using the PLAD technique. Cross- linked PDMS was deemed important because of its general use for biomedical implants and devices as well as in other fields. Furthermore, PDMS deposition using PLAD had not been previously studied and any information gained on its ablation characteristics could be important scientifically and technologically. The studies reported here showed that the deposited silicone film properties had a dependence on the laser energy density incident on the target. Smooth, hydrophobic, silicone-like films were deposited at low energy densities (100-150 mJ/cm2). At high energy densities (>200 mJ/cm2), the films had an higher oxygen content than PDMS, were hydrophilic and tended to show a more particulate morphology. It was also determined that (1)the deposited films were stable and extremely adherent to the substrate, (2)silicone deposition exhibited an `incubation effect' which led to the film properties changing with laser pulse number and (3)films deposited under high vacuum were similar to films deposited at low vacuum levels. The mechanical properties of the PLAD films were determined by nanomechanical measurements which are based on the Atomic Force Microscope (AFM). From these measurements, it was possible to determine the modulus of the films and also study their scratch resistance. Such measurement techniques represent a significant advance over current state-of-the-art thin film characterization methods. An empirical model for ablation was developed for the 248 nm laser irradiation of silicone. The model demonstrated a good fit to the experimental data and showed that silicone underwent ablation by a thermal mechanism. In addition to PLAD studies, functionalization of stainless steel was carried out by a combined plasma/gamma method involving deposition of a hexane plasma polymer by RF plasma polymerization, followed by gamma radiation graft polymerization of methacrylic acid. The hydrograft modified surfaces were further modified by chemisorption reactions with poly(ethylene imine) to produce amine-rich surfaces. Bovine serum albumin was then bound via amino groups using glutaraldehyde coupling. A streaming potential cell was also built and used to measure the zeta potential of these ionic surfaces.

Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation

PubMed Central

CHANG, H.; YANACHKOV, I. B.; DIX, E. J.; LI, Y. F.; BARNARD, M. R.; WRIGHT, G. E.; MICHELSON, A. D.; FRELINGER, A. L.

2017-01-01

Summary Background Diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A), a natural compound stored in platelet dense granules, inhibits ADP-induced platelet aggregation. Ap4A inhibits the platelet ADP receptors P2Y1 and P2Y12, is a partial agonist of P2Y12, and is a full agonist of the platelet ATP-gated ion channel P2X1. Modification of the Ap4A tetraphosphate backbone enhances inhibition of ADP-induced platelet aggregation. However, the effects of these Ap4A analogs on human platelet P2Y1, P2Y12 and P2X1 are unclear. Objective To determine the agonist and antagonist activities of diadenosine tetraphosphate analogs towards P2Y1, P2Y12, and P2X1. Methods We synthesized the following Ap4A analogs: P1,P4-dithiotetraphosphate; P2,P3-chloromethylenetetraphosphate; P1-thio-P2,P3-chloromethylenetetraphosphate; and P1,P4-dithio-P2,P3-chloromethylenetetraphosphate. We then measured the effects of these analogs on: (i) ADP-induced platelet aggregation; (ii) P2Y1-mediated changes in cytosolic Ca2+; (iii) P2Y12-mediated changes in vasodilator-stimulated phosphoprotein phosphorylation; and (iv) P2X1-mediated entry of extracellular Ca2+. Results Ap4A analogs with modifications in the phosphate backbone inhibited both P2Y1 and P2Y12, and showed no agonist activity towards these receptors. The dithio modification increased inhibition of P2Y1, P2Y12, and platelet aggregation, whereas the chloromethylene modification increased inhibition of P2Y12 and platelet aggregation, but decreased P2Y1 inhibition. Combining the dithio and chloromethylene modifications increased P2Y1 and P2Y12 inhibition. As compared with Ap4A, each modification decreased agonist activity towards P2X1, and the dual modification completely eliminated P2X1 agonist activity. Conclusions As compared with Ap4A, tetraphosphate backbone analogs of Ap4A have diminished activity towards P2X1 but inhibit both P2Y1 and P2Y12 and, with greater potency, inhibit ADP-induced platelet aggregation. Thus, diadenosine tetraphosphate analogs with dual receptor selectivity may have potential as antiplatelet drugs. PMID:23083103

A study of dietary modification: Perceptions and attitudes of patients with multiple sclerosis.

PubMed

Brenton, J Nicholas; Goldman, Myla D

2016-07-01

Modifiable risk factors for multiple sclerosis (MS), including obesity and the gut microbiome, have been studied and have been found to be potentially relevant. Given this, there is a growing interest in diet modification as a means of impacting MS risk and disease course. The aim of this study was to determine the current behaviors, level of interest, and relevant factors surrounding modification of diet in MS patients. A total of 601 MS patients were mailed a dietary modification survey containing questions regarding subject demographics, disease course, and diet-related questions. Of the 199 survey responders, 17% admitted to currently attempting a diet for their MS and 91.5% were interested in diet modification as a means of benefiting their disease. Willingness to attempt diet therapy was not affected by demographic features or an individual's disease course. Over 85% of these patients were willing to attempt diet therapy for 3 months or longer. The majority of survey responders expressed interest in diet modification in attempts to improve or treat their MS. Our data demonstrate the feasibility of patient recruitment for future studies assessing therapeutic intervention by way of diet modification for MS disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia

PubMed Central

Kim, Wan Jung; Korthals, Keith A.; Li, Suhua; Le, Christine; Kalisiak, Jarosław; Sharpless, K. Barry; Fokin, Valery V.; Miyamoto, Yukiko

2017-01-01

ABSTRACT Giardia lamblia is an important and ubiquitous cause of diarrheal disease. The primary agents in the treatment of giardiasis are nitroheterocyclic drugs, particularly the imidazoles metronidazole and tinidazole and the thiazole nitazoxanide. Although these drugs are generally effective, treatment failures occur in up to 20% of cases, and resistance has been demonstrated in vivo and in vitro. Prior work had suggested that side chain modifications of the imidazole core can lead to new effective 5-nitroimidazole drugs that can combat nitro drug resistance, but the full potential of nitroheterocycles other than imidazole to yield effective new antigiardial agents has not been explored. Here, we generated derivatives of two clinically utilized nitroheterocycles, nitrothiazole and nitrofuran, as well as a third heterocycle, nitropyrrole, which is related to nitroimidazole but has not been systematically investigated as an antimicrobial drug scaffold. Click chemistry was employed to synthesize 442 novel nitroheterocyclic compounds with extensive side chain modifications. Screening of this library against representative G. lamblia strains showed a wide spectrum of in vitro activities, with many of the compounds exhibiting superior activity relative to reference drugs and several showing >100-fold increase in potency and the ability to overcome existing forms of metronidazole resistance. The majority of new compounds displayed no cytotoxicity against human cells, and several compounds were orally active against murine giardiasis in vivo. These findings provide additional impetus for the systematic development of nitroheterocyclic compounds with nonimidazole cores as alternative and improved agents for the treatment of giardiasis and potentially other infectious agents. PMID:28396548

The Effects of Hsp90α1 Mutations on Myosin Thick Filament Organization.

PubMed

He, Qiuxia; Liu, Kechun; Tian, Zhenjun; Du, Shao Jun

2015-01-01

Heat shock protein 90α plays a key role in myosin folding and thick filament assembly in muscle cells. To assess the structure and function of Hsp90α and its potential regulation by post-translational modification, we developed a combined knockdown and rescue assay in zebrafish embryos to systematically analyze the effects of various mutations on Hsp90α function in myosin thick filament organization. DNA constructs expressing the Hsp90α1 mutants with altered putative ATP binding, phosphorylation, acetylation or methylation sites were co-injected with Hsp90α1 specific morpholino into zebrafish embryos. Myosin thick filament organization was analyzed in skeletal muscles of the injected embryos by immunostaining. The results showed that mutating the conserved D90 residue in the Hsp90α1 ATP binding domain abolished its function in thick filament organization. In addition, phosphorylation mimicking mutations of T33D, T33E and T87E compromised Hsp90α1 function in myosin thick filament organization. Similarly, K287Q acetylation mimicking mutation repressed Hsp90α1 function in myosin thick filament organization. In contrast, K206R and K608R hypomethylation mimicking mutations had not effect on Hsp90α1 function in thick filament organization. Given that T33 and T87 are highly conserved residues involved post-translational modification (PTM) in yeast, mouse and human Hsp90 proteins, data from this study could indicate that Hsp90α1 function in myosin thick filament organization is potentially regulated by PTMs involving phosphorylation and acetylation.

The Effects of Hsp90α1 Mutations on Myosin Thick Filament Organization

PubMed Central

He, Qiuxia; Liu, Kechun; Tian, Zhenjun; Du, Shao Jun

2015-01-01

Heat shock protein 90α plays a key role in myosin folding and thick filament assembly in muscle cells. To assess the structure and function of Hsp90α and its potential regulation by post-translational modification, we developed a combined knockdown and rescue assay in zebrafish embryos to systematically analyze the effects of various mutations on Hsp90α function in myosin thick filament organization. DNA constructs expressing the Hsp90α1 mutants with altered putative ATP binding, phosphorylation, acetylation or methylation sites were co-injected with Hsp90α1 specific morpholino into zebrafish embryos. Myosin thick filament organization was analyzed in skeletal muscles of the injected embryos by immunostaining. The results showed that mutating the conserved D90 residue in the Hsp90α1 ATP binding domain abolished its function in thick filament organization. In addition, phosphorylation mimicking mutations of T33D, T33E and T87E compromised Hsp90α1 function in myosin thick filament organization. Similarly, K287Q acetylation mimicking mutation repressed Hsp90α1 function in myosin thick filament organization. In contrast, K206R and K608R hypomethylation mimicking mutations had not effect on Hsp90α1 function in thick filament organization. Given that T33 and T87 are highly conserved residues involved post-translational modification (PTM) in yeast, mouse and human Hsp90 proteins, data from this study could indicate that Hsp90α1 function in myosin thick filament organization is potentially regulated by PTMs involving phosphorylation and acetylation. PMID:26562659

Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia.

PubMed

Kim, Wan Jung; Korthals, Keith A; Li, Suhua; Le, Christine; Kalisiak, Jarosław; Sharpless, K Barry; Fokin, Valery V; Miyamoto, Yukiko; Eckmann, Lars

2017-06-01

Giardia lamblia is an important and ubiquitous cause of diarrheal disease. The primary agents in the treatment of giardiasis are nitroheterocyclic drugs, particularly the imidazoles metronidazole and tinidazole and the thiazole nitazoxanide. Although these drugs are generally effective, treatment failures occur in up to 20% of cases, and resistance has been demonstrated in vivo and in vitro Prior work had suggested that side chain modifications of the imidazole core can lead to new effective 5-nitroimidazole drugs that can combat nitro drug resistance, but the full potential of nitroheterocycles other than imidazole to yield effective new antigiardial agents has not been explored. Here, we generated derivatives of two clinically utilized nitroheterocycles, nitrothiazole and nitrofuran, as well as a third heterocycle, nitropyrrole, which is related to nitroimidazole but has not been systematically investigated as an antimicrobial drug scaffold. Click chemistry was employed to synthesize 442 novel nitroheterocyclic compounds with extensive side chain modifications. Screening of this library against representative G. lamblia strains showed a wide spectrum of in vitro activities, with many of the compounds exhibiting superior activity relative to reference drugs and several showing >100-fold increase in potency and the ability to overcome existing forms of metronidazole resistance. The majority of new compounds displayed no cytotoxicity against human cells, and several compounds were orally active against murine giardiasis in vivo These findings provide additional impetus for the systematic development of nitroheterocyclic compounds with nonimidazole cores as alternative and improved agents for the treatment of giardiasis and potentially other infectious agents. Copyright © 2017 American Society for Microbiology.

Modification of the effects of guanethidine on cardiac catechol amines by various agents

PubMed Central

Bhagat, B.

1964-01-01

A study has been made of the effect of injections of guanethidine in rats, in depleting catechol amines from the whole cardiac ventricles and from various subcellular fractions. Unlike reserpine, guanethidine first affected the concentration of the amines in the soluble fraction of the cell. Neither [2-(2,6-dimethylphenoxy)-propyl]trimethylammonium chloride monohydrate (β-methyl xylocholine) nor hemicholinium affected the endogenous catechol amines or the uptake of injected noradrenaline, but each significantly reduced the action of guanethidine in depleting catechol amines. Administration of choline chloride after hemicholinium reversed its influence on guanethidine depletion. In cats, cocaine potentiated the pressor response to noradrenaline, but antagonized the response to tyramine and guanethidine, while bretylium and N-o-chlorobenzyl-N'N”-dimethylguanidine sulphate (BW392C60) potentiated the responses to noradrenaline, tyramine and guanethidine. PMID:14190459

Nanotechnology-Based Strategies for siRNA Brain Delivery for Disease Therapy.

PubMed

Zheng, Meng; Tao, Wei; Zou, Yan; Farokhzad, Omid C; Shi, Bingyang

2018-05-01

Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies. In this review, we outline the challenges of systemic delivery of siRNA-based therapy for brain diseases, highlight recent advances in the development and engineering of siRNA nanomedicines for various brain diseases, and discuss our perspectives on this exciting research field for siRNA-based therapy towards more effective brain disease therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optimal Control Modification Adaptive Law for Time-Scale Separated Systems

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2010-01-01

Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. A model matching conditions in the transformed time coordinate results in an increase in the actuator command that effectively compensate for the slow actuator dynamics. Simulations demonstrate effectiveness of the method.

Optimal Control Modification for Time-Scale Separated Systems

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2012-01-01

Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. A model matching conditions in the transformed time coordinate results in an increase in the actuator command that effectively compensate for the slow actuator dynamics. Simulations demonstrate effectiveness of the method.

A scanning probe mounted on a field-effect transistor: Characterization of ion damage in Si.

PubMed

Shin, Kumjae; Lee, Hoontaek; Sung, Min; Lee, Sang Hoon; Shin, Hyunjung; Moon, Wonkyu

2017-10-01

We have examined the capabilities of a Tip-On-Gate of Field-Effect Transistor (ToGoFET) probe for characterization of FIB-induced damage in Si surface. A ToGoFET probe is the SPM probe which the Field Effect Transistor(FET) is embedded at the end of a cantilever and a Pt tip was mounted at the gate of FET. The ToGoFET probe can detect the surface electrical properties by measuring source-drain current directly modulated by the charge on the tip. In this study, a Si specimen whose surface was processed with Ga+ ion beam was prepared. Irradiation and implantation with Ga+ ions induce highly localized modifications to the contact potential. The FET embedded on ToGoFET probe detected the surface electric field profile generated by schottky contact between the Pt tip and the sample surface. Experimentally, it was shown that significant differences of electric field due to the contact potential barrier in differently processed specimens were observed using ToGOFET probe. This result shows the potential that the local contact potential difference can be measured by simple working principle with high sensitivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anomalous transport of charged dust grains in a magnetized collisional plasma: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Bezbaruah, Pratikshya; Das, Nilakshi

2018-05-01

Anomalous diffusion of charged dust grains immersed in a plasma in the presence of strong ion-neutral collision, flowing ions, and a magnetic field has been observed. Molecular Dynamics simulation confirms the deviation from normal diffusion in an ensemble of dust grains probed in laboratory plasma chambers. Collisional effects are significant in governing the nature of diffusion. In order to have a clear idea on the transport of particles in a real experimental situation, the contribution of streaming ions and the magnetic field along with collision is considered through the relevant interaction potential. The nonlinear evolution of Mean Square Displacement is an indication of the modification in particle trajectories due to several effects as mentioned above. It is found that strong collision and ion flow significantly affect the interparticle interaction potential in the presence of the magnetic field and lead to the appearance of the asymmetric type of Debye Hückel (D H) potential. Due to the combined effect of the magnetic field, ion flow, and collision, dusty plasma exhibits a completely novel behavior. The coupling parameter Γ enhances the asymmetric D H type potential arising due to ion flow, and this may drive the system to a disordered state.

Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

PubMed

Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

2017-05-08

Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and activates B cells.