Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs.

PubMed

Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara; Lüning, Ulrich

2016-01-01

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO 2 , NH 2 , OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine "cores" ( 3a , 3b ) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO 2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19 . Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers.

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

PubMed Central

Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara

2016-01-01

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO2, NH2, OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine “cores” (3a,3b) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19. Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers. PMID:28144293

46 CFR 58.60-2 - Alternatives and substitutions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... substitute provides an equivalent level of safety. (b) In any case where it is shown to the satisfaction of..., or test to such an extent and upon such condition as will insure, to his satisfaction, a degree of...

Protein substitute dosage in PKU: how much do young patients need?

PubMed

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-07-01

The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Initial glenoid fixation using two different reverse shoulder designs with an equivalent center of rotation in a low-density and high-density bone substitute.

PubMed

Stroud, Nicholas J; DiPaola, Matthew J; Martin, Brian L; Steiler, Cindy A; Flurin, Pierre-Henri; Wright, Thomas W; Zuckerman, Joseph D; Roche, Christopher P

2013-11-01

Numerous glenoid implant designs have been introduced into the global marketplace in recent years; however, little comparative biomechanical data exist to substantiate one design consideration over another. This study dynamically evaluated reverse shoulder glenoid baseplate fixation and compared the initial fixation associated with 2 reverse shoulder designs having an equivalent center of rotation in low-density and high-density bone substitute substrates. Significant differences in fixation were observed between implant designs, where the circular-porous reverse shoulder was associated with approximately twice the micromotion per equivalent test than the oblong-grit-blasted design. Additionally, 6 of the 7 circular-porous reverse shoulders failed catastrophically in the low-density bone model at an average of 2603 ± 981 cycles. None of the oblong-grit-blasted designs failed in the low-or high-density bone models and none of the circular-porous designs failed in the high-density bone models after 10,000 cycles of loading. These results demonstrate that significant differences in initial fixation exist between reverse shoulder implants having an equivalent center of rotation and suggest that design parameters, other than the position of the center of rotation, significantly affect fixation in low-density and high-density polyurethane bone substitutes. Subtle changes in glenoid baseplate design can dramatically affect fixation, particularly in low-density bone substitutes that are intended to simulate the bone quality of the recipient population for reverse shoulders. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Generic substitution of antihypertensive drugs: does it affect adherence?

PubMed

Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius

2006-01-01

Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. To assess the association between generic substitution and nonadherence to antihypertensive drugs. We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

Equivalent-Continuum Modeling of Nano-Structured Materials

NASA Technical Reports Server (NTRS)

Odegard, Gregory M.; Gates, Thomas S.; Nicholson, Lee M.; Wise, Kristopher E.

2001-01-01

A method has been developed for modeling structure-property relationships of nano-structured materials. This method serves as a link between computational chemistry and solid mechanics by substituting discrete molecular structures with an equivalent-continuum model. It has been shown that this substitution may be accomplished by equating the vibrational potential energy of a nano-structured material with the strain energy of representative truss and continuum models. As an important example with direct application to the development and characterization of single-walled carbon nanotubes, the model has been applied to determine the effective continuum geometry of a graphene sheet. A representative volume element of the equivalent-continuum model has been developed with an effective thickness. This effective thickness has been shown to be similar to, but slightly smaller than, the interatomic spacing of graphite.

Generic and therapeutic substitutions in the UK: are they a good thing?

PubMed Central

Duerden, Martin G; Hughes, Dyfrig A

2010-01-01

There is considerable interest and debate concerning the place of generic substitution (switching from a brand to generic product); and on therapeutic substitution, that is, switching to a cheaper, but apparently equivalent, product, usually within the drug class. Generic substitution by pharmacists is standard practice in UK hospital settings, and is being proposed for implementation in primary care. Although most prescriptions are already written generically (83% in the community in England in 2008), there are still cost savings that could be made if generic medicines are substituted against prescriptions written by branded name or by getting prescribers to adhere to advice to prescribe generically. Therapeutic substitution is more contentious, as direct evidence to support equivalence is normally lacking. However, the price differential between established drugs whose patents have expired and for which generics are available and newer, branded medicines within the same therapeutic class, makes therapeutic substitution an attractive application of cost-minimization analysis for the more efficient use of healthcare resources. Here we explore the tension that exists between the clinical appropriateness and safety of switching from an individual patient perspective and the consideration of value for money which is required to maximize population health from a health service perspective. Although substitution may affect individual patients (such as, for instance, reduced adherence, increased potential for medication error), it might be a price worth paying given the opportunity cost associated with the use of medicines that are clinically no better than cheaper alternatives. PMID:20716231

On the use of Lineal Energy Measurements to Estimate Linear Energy Transfer Spectra

NASA Technical Reports Server (NTRS)

Adams, David A.; Howell, Leonard W., Jr.; Adam, James H., Jr.

2007-01-01

This paper examines the error resulting from using a lineal energy spectrum to represent a linear energy transfer spectrum for applications in the space radiation environment. Lineal energy and linear energy transfer spectra are compared in three diverse but typical space radiation environments. Different detector geometries are also studied to determine how they affect the error. LET spectra are typically used to compute dose equivalent for radiation hazard estimation and single event effect rates to estimate radiation effects on electronics. The errors in the estimations of dose equivalent and single event rates that result from substituting lineal energy spectra for linear energy spectra are examined. It is found that this substitution has little effect on dose equivalent estimates in interplanetary quiet-time environment regardless of detector shape. The substitution has more of an effect when the environment is dominated by solar energetic particles or trapped radiation, but even then the errors are minor especially if a spherical detector is used. For single event estimation, the effect of the substitution can be large if the threshold for the single event effect is near where the linear energy spectrum drops suddenly. It is judged that single event rate estimates made from lineal energy spectra are unreliable and the use of lineal energy spectra for single event rate estimation should be avoided.

Protein substitute dosage in PKU: how much do young patients need?

PubMed Central

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-01-01

Background The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). Aim To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.1 Methods In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2–10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre‐breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8–14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5–3.1 g/kg/day). Results When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre‐breakfast by 301 μmol/l (95% CI 215 to 386) and in the evening by 337 μmol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. Conclusions A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/− fat) content of the protein substitute. PMID:16547085

Scope of claim coverage in patents of fufang Chinese herbal drugs: Substitution of ingredients

PubMed Central

2011-01-01

Herbal ingredients in a Chinese fufang prescription are often replaced by one or several other herbal combinations. As there have been very few Chinese herbal patent infringement cases, it is still unclear how the Doctrine of Equivalents should be applied to determine the scope of 'equivalents' in Chinese fufang prescriptions. Case law principles from cases in other technical areas such as chemical patents and biological drug patents can be borrowed to ascertain a precise scope of a fufang patent. This article summarizes and discusses several chemical and biopharmaceutical patent cases. In cases where a certain herbal ingredient is substituted by another herb or a combination of herbs, accused infringers are likely to relate herbal drug patents to chemical drug patents with strict interpretation whereas patent owners may take advantage of the liberal application of Doctrine of Equivalence in biopharmaceutical patents by analogizing the complex nature of herbal drugs with biological drugs. Therefore, consideration should be given to the purpose of an ingredient in a patent, the qualities when combined with the other ingredients and the intended function. The scope of equivalents also depends on the stage of the prior art. Moreover, it is desirable to disclose any potential substitutes when drafting the application. Claims should be drafted in such a way that all foreseeable modifications are encompassed for the protection of the patent owner's intellectual property. PMID:21854570

Scope of claim coverage in patents of fufang Chinese herbal drugs: Substitution of ingredients.

PubMed

Wang, Xinsheng; Tian, Jiaher; Chan, Albert Wai-Kit

2011-08-19

Herbal ingredients in a Chinese fufang prescription are often replaced by one or several other herbal combinations. As there have been very few Chinese herbal patent infringement cases, it is still unclear how the Doctrine of Equivalents should be applied to determine the scope of 'equivalents' in Chinese fufang prescriptions. Case law principles from cases in other technical areas such as chemical patents and biological drug patents can be borrowed to ascertain a precise scope of a fufang patent. This article summarizes and discusses several chemical and biopharmaceutical patent cases. In cases where a certain herbal ingredient is substituted by another herb or a combination of herbs, accused infringers are likely to relate herbal drug patents to chemical drug patents with strict interpretation whereas patent owners may take advantage of the liberal application of Doctrine of Equivalence in biopharmaceutical patents by analogizing the complex nature of herbal drugs with biological drugs. Therefore, consideration should be given to the purpose of an ingredient in a patent, the qualities when combined with the other ingredients and the intended function. The scope of equivalents also depends on the stage of the prior art. Moreover, it is desirable to disclose any potential substitutes when drafting the application. Claims should be drafted in such a way that all foreseeable modifications are encompassed for the protection of the patent owner's intellectual property.

Numerical investigation of exhaust gas emissions for a dual fuel engine configuration using diesel and pongamia oil.

PubMed

Mohamed Ibrahim, N H; Udayakumar, M

2016-12-01

The investigation presented in this paper focuses on determination of gaseous exhaust emissions by computational simulation during combustion in compression ignition engine with pongamia oil substitution. Combustion is modeled using Equilibrium Constants Method (ECM) with MATLAB program to calculate the mole fraction of 10 combustion products when pongamia oil is burnt along with diesel at variable equivalence ratio and blend ratio. It had been observed that pongamia oil substitution causes decrease in the CO emission and increase in the NO x emission as the blend ratio as well as equivalence ratio increases. Copyright © 2015 Elsevier Inc. All rights reserved.

Polymeric medium

DOEpatents

Klaehn, John R [Idaho Falls, ID; Peterson, Eric S [Idaho Falls, ID; Orme, Christopher J [Shelley, ID; Jones, Michael G [Chubbuck, ID; Wertsching, Alan K [Idaho Falls, ID; Luther, Thomas A [Idaho Falls, ID; Trowbridge, Tammy L [Idaho Falls, ID

2012-03-06

A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

Polybenzimidazole compounds

DOEpatents

Klaehn, John R [Idaho Falls, ID; Peterson, Eric S [Idaho Falls, ID; Orme, Christopher J [Shelley, ID; Jones, Michael G [Chubbuck, ID; Wertsching, Alan K [Idaho Falls, ID; Luther, Thomas A [Idaho Falls, ID; Trowbridge, Tammy L [Idaho Falls, ID

2011-11-22

A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

Salt equivalence and temporal dominance of sensations of different sodium chloride substitutes in butter.

PubMed

de Souza, Vanessa Rios; Freire, Tassyana Vieira Marques; Saraiva, Carla Gonçalves; de Deus Souza Carneiro, João; Pinheiro, Ana Carla Marques; Nunes, Cleiton Antônio

2013-08-01

Studies indicate a positive association between dietary salt intake and some diseases, which has promoted the tendency to reduce the sodium in foods. The objective of this study was to determine the equivalent amount of different sodium chloride replacements required to promote the same degree of ideal saltiness in butter and to study the sensory profile of sodium chloride and the substitutes using the analysis of Temporal Dominance of Sensations (TDS). Using the magnitude estimation method, it was determined that the potencies of potassium chloride, monosodium glutamate and potassium phosphate relative to the 1% sodium chloride in butter are 83·33, 31·59 and 33·32, respectively. Regarding the sensory profile of the tested salt substitutes, a bitter taste was perceived in the butter with potassium chloride, a sour taste was perceived in the butter with potassium phosphate and sweet and umami tastes were dominant in the butter with monosodium glutamate. Of all the salt substitutes tested calcium lactate, potassium lactate, calcium chloride and magnesium chloride were impractical to use in butter.

A survey to determine the views of renal transplant patients on generic substitution in the UK.

PubMed

Al Ameri, Mubarak N; Whittaker, Clare; Tucker, Arthur; Yaqoob, Magdi; Johnston, Atholl

2011-08-01

Rising healthcare costs promote the generic substitution among patients because it is identifiable costs. A key concern is that patients should be involved in the decision of switching. The aim of this study was to examine renal transplant patients' views on generic substitution in the UK. A total of 163 renal patients were surveyed using 36 multiple-choice questions at Barts and The London Renal Transplant Clinic, in the UK. Transplant recipients over 18 years, able to read and write English and willing to fill in the questionnaire were targeted; 84% of patients were conscious of the availability of generic medicines, 70% understood the terms "generic" and "branded" in relation to medicines and 54% were aware of generic substitution practice. However, 75% did not know if they were taking generics and 84% felt that generics are not equivalent or only equivalent sometimes and they were uncertain that generics had the same quality as branded medicines. Moreover, many patients admitted that they would not accept the generic substitution of ciclosporin when become available in the UK. A number of factors such as patients' education, knowledge, severity of the disease, efficacy of generic medicines and patients' involvement in decisions regarding their health appear to drive patients' attitudes towards generic substitution. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

PubMed Central

Johnston, Atholl

2013-01-01

The calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are the mainstay of immunosuppression in solid organ transplantation. Generic formulations of these drugs are now available. With increasing pressure on healthcare budgets and the consequent need to match health expectations to available resources, substitution with a generic product appears an attractive option to reduce costs. Approval of generic products differs from innovator drugs, and narrow therapeutic index drugs (NTIs; including CNIs) bring their own particular considerations. With NTIs, small variations in drug exposure could result in reduced immunosuppression or drug toxicity with potentially adverse effects on patient outcomes. NTIs are subject to stricter regulatory approval versus many other generic drugs. However, different generic formulations may still not necessarily be therapeutically equivalent in individuals, raising the possibility of significant differences in exposure between products. Although regional recommendations vary, many guidelines emphasise the need for NTI drug substitution to be initiated by the transplant physician, thus ensuring careful therapeutic monitoring and reduced negative patient impact. The need for therapeutic monitoring during generic substitution has important implications for the overall costs of generic treatment as these costs have to be factored in to the potential savings made from using generic formulations. The reduced acquisition costs of generic products may not necessarily translate into lower overall healthcare costs. This article examines the issue of equivalence and interchangeability of NTI drugs used in organ transplantation, the implications of the approval process for generic drugs on treatment efficacy and safety, and the effective management of substitutions between products. PMID:24089632

More Similar but Less Satisfying: Comparing Preferences for and the Efficacy of Within- and Cross-Category Substitutes for Food.

PubMed

Huh, Young Eun; Vosgerau, Joachim; Morewedge, Carey K

2016-06-01

When people cannot get what they want, they often satisfy their desire by consuming a substitute. Substitutes can originate from within the taxonomic category of the desired stimulus (i.e., within-category substitutes) or from a different taxonomic category that serves the same basic goal (i.e., cross-category substitutes). Both a store-brand chocolate (within-category substitute) and a granola bar (cross-category substitute), for example, can serve as substitutes for gourmet chocolate. Here, we found that people believe that within-category substitutes, which are more similar to desired stimuli, will more effectively satisfy their cravings than will cross-category substitutes (Experiments 1, 2a, and 2b). However, because within-category substitutes are more similar than cross-category substitutes to desired stimuli, they are more likely to evoke an unanticipated negative contrast effect. As a result, unless substitutes are equivalent in quality to the desired stimulus, cross-category substitutes more effectively satisfy cravings for the desired stimulus (Experiments 3 and 4). © The Author(s) 2016.

Polybenzimidazole compounds, polymeric media, and methods of post-polymerization modifications

DOEpatents

Klaehn, John R.; Peterson, Eric S.; Orme, Christopher J.; Jones, Michael G.; Wertsching, Alan K.; Luther, Thomas A.; Trowbridge, Tammy L.

2007-12-18

A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

Antimalarial Activity of C-10 Substituted Triazolyl Artemisinin.

PubMed

Park, Gab-Man; Park, Hyun; Oh, Sangtae; Lee, Seokjoon

2017-12-01

We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate.

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

17 CFR 240.17i-7 - Calculations of allowable capital and risk allowances or alternative capital assessment.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Cumulative and non-cumulative preferred stock, except that the amount of cumulative preferred stock may not..., and credit substitutes in as follows: (1) By multiplying the credit equivalent amount of the... accordance with the following: (i) Credit equivalent amount: (A) Certain loans and loan commitments...

Sensory Substitution: The Spatial Updating of Auditory Scenes "Mimics" the Spatial Updating of Visual Scenes.

PubMed

Pasqualotto, Achille; Esenkaya, Tayfun

2016-01-01

Visual-to-auditory sensory substitution is used to convey visual information through audition, and it was initially created to compensate for blindness; it consists of software converting the visual images captured by a video-camera into the equivalent auditory images, or "soundscapes". Here, it was used by blindfolded sighted participants to learn the spatial position of simple shapes depicted in images arranged on the floor. Very few studies have used sensory substitution to investigate spatial representation, while it has been widely used to investigate object recognition. Additionally, with sensory substitution we could study the performance of participants actively exploring the environment through audition, rather than passively localizing sound sources. Blindfolded participants egocentrically learnt the position of six images by using sensory substitution and then a judgment of relative direction task (JRD) was used to determine how this scene was represented. This task consists of imagining being in a given location, oriented in a given direction, and pointing towards the required image. Before performing the JRD task, participants explored a map that provided allocentric information about the scene. Although spatial exploration was egocentric, surprisingly we found that performance in the JRD task was better for allocentric perspectives. This suggests that the egocentric representation of the scene was updated. This result is in line with previous studies using visual and somatosensory scenes, thus supporting the notion that different sensory modalities produce equivalent spatial representation(s). Moreover, our results have practical implications to improve training methods with sensory substitution devices (SSD).

Comparison of the x-ray attenuation properties of breast calcifications, aluminium, hydroxyapatite and calcium oxalate.

PubMed

Warren, L M; Mackenzie, A; Dance, D R; Young, K C

2013-04-07

Aluminium is often used as a substitute material for calcifications in phantom measurements in mammography. Additionally, calcium oxalate, hydroxyapatite and aluminium are used in simulation studies. This assumes that these materials have similar attenuation properties to calcification, and this assumption is examined in this work. Sliced mastectomy samples containing calcification were imaged at ×5 magnification using a digital specimen cabinet. Images of the individual calcifications were extracted, and the diameter and contrast of each calculated. The thicknesses of aluminium required to achieve the same contrast as each calcification when imaged under the same conditions were calculated using measurements of the contrast of aluminium foils. As hydroxyapatite and calcium oxalate are also used to simulate calcifications, the equivalent aluminium thicknesses of these materials were also calculated using tabulated attenuation coefficients. On average the equivalent aluminium thickness was 0.85 times the calcification diameter. For calcium oxalate and hydroxyapatite, the equivalent aluminium thicknesses were 1.01 and 2.19 times the thickness of these materials respectively. Aluminium and calcium oxalate are suitable substitute materials for calcifications. Hydroxyapatite is much more attenuating than the calcifications and aluminium. Using solid hydroxyapatite as a substitute for calcification of the same size would lead to excessive contrast in the mammographic image.

Synthesis of Aromatic Polyhedral Oligomeric Silsesquioxane (POSS) Dianilines for Use in High-Temperature Polyimides

DTIC Science & Technology

2012-05-01

In all cases, a Grignard reagent of a para- or meta- substituted, protected aniline was reacted with a chlorosilane. Control of the reaction is...one equivalent of Grignard reagent with a small excess of tetrachlorosilane generates a good yield of monosubstituted trichlorosilane (6a). It must...methyltrichlorosilane. It is possible to add either 1 equivalent (to make 4a and 4b) or 2 equivalents of the protected aniline Grignard reagent (to make 5a

Ecological equivalency as a tool for endangered species management.

PubMed

Searcy, Christopher A; Rollins, Hilary B; Shaffer, H Bradley

2016-01-01

The use of taxon substitutes for extinct or endangered species is a controversial conservation measure. We use the example of the endangered California tiger salamander (Ambystoma californiense; CTS), which is being replaced by hybrids with the invasive barred tiger salamander (Ambystoma mavortium), to illustrate a strategy for evaluating taxon substitutes based on their position in a multivariate community space. Approximately one-quarter of CTS's range is currently occupied by "full hybrids" with 70% nonnative genes, while another one-quarter is occupied by "superinvasives" where a specific set of 3/68 genes comprising 4% of the surveyed genome is nonnative. Based on previous surveys of natural CTS breeding ponds, we stocked experimental mesocosms with field-verified, realistic densities of tiger salamander larvae and their prey, and used these mesocosms to evaluate ecological equivalency between pure CTS, full hybrids, and superinvasives in experimental pond communities. We also included a fourth treatment with no salamanders present to evaluate the community effects of eliminating Ambystoma larvae altogether. We found that pure CTS and superinvasive larvae were ecologically equivalent, because their positions in the multivariate community space were statistically indistinguishable and they did not differ significantly along any univariate community axes. Full hybrids were ecologically similar, but not equivalent, to the other two genotypes, and the no-Ambystoma treatment was by far the most divergent. We conclude that, at least for the larval stage, superinvasives are adequate taxon substitutes for pure CTS and should probably be afforded protection under the Endangered Species Act. The proper conservation status for full hybrids remains debatable.

Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.

PubMed

Alonso, Beatriz; Ocejo, Marta; Carrillo, Luisa; Vicario, Jose L; Reyes, Efraim; Uria, Uxue

2013-01-18

We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.

Sensory Substitution: The Spatial Updating of Auditory Scenes “Mimics” the Spatial Updating of Visual Scenes

PubMed Central

Pasqualotto, Achille; Esenkaya, Tayfun

2016-01-01

Visual-to-auditory sensory substitution is used to convey visual information through audition, and it was initially created to compensate for blindness; it consists of software converting the visual images captured by a video-camera into the equivalent auditory images, or “soundscapes”. Here, it was used by blindfolded sighted participants to learn the spatial position of simple shapes depicted in images arranged on the floor. Very few studies have used sensory substitution to investigate spatial representation, while it has been widely used to investigate object recognition. Additionally, with sensory substitution we could study the performance of participants actively exploring the environment through audition, rather than passively localizing sound sources. Blindfolded participants egocentrically learnt the position of six images by using sensory substitution and then a judgment of relative direction task (JRD) was used to determine how this scene was represented. This task consists of imagining being in a given location, oriented in a given direction, and pointing towards the required image. Before performing the JRD task, participants explored a map that provided allocentric information about the scene. Although spatial exploration was egocentric, surprisingly we found that performance in the JRD task was better for allocentric perspectives. This suggests that the egocentric representation of the scene was updated. This result is in line with previous studies using visual and somatosensory scenes, thus supporting the notion that different sensory modalities produce equivalent spatial representation(s). Moreover, our results have practical implications to improve training methods with sensory substitution devices (SSD). PMID:27148000

Polybenzimidazole compounds, polymeric media, and methods of post-polymerization modifications

DOEpatents

Klaehn, John R [Idaho Falls, ID; Peterson, Eric S [Idaho Falls, ID; Wertsching, Alan K [Idaho Falls, ID; Orme, Christopher J [Shelley, ID; Luther, Thomas A [Idaho Falls, ID; Jones, Michael G [Pocatello, ID

2007-08-21

A PBI compound includes imidazole nitrogens at least a portion of which are substituted with an organic-inorganic hybrid moiety. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2-- where R is selected from among methyl, phenyl, vinyl, and allyl. The PBI compound may exhibit similar thermal properties in comparison to the unsubstituted PBI. The PBI compound may exhibit a solubility in an organic solvent greater than the solubility of the unsubstituted PBI. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may occur at about room temperature and/or at about atmospheric pressure. Substituting may use at least 5 equivalents in relation to the imidazole nitrogens to be substituted or, preferably, about 15.

X-ray phase contrast imaging of the breast: Analysis of tissue simulating materials

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

Vedantham, Srinivasan; Karellas, Andrew

Purpose: Phase contrast imaging, particularly of the breast, is being actively investigated. The purpose of this work is to investigate the x-ray phase contrast properties of breast tissues and commonly used breast tissue substitutes or phantom materials with an aim of determining the phantom materials best representative of breast tissues. Methods: Elemental compositions of breast tissues including adipose, fibroglandular, and skin were used to determine the refractive index, n= 1 -{delta}+i {beta}. The real part of the refractive index, specifically the refractive index decrement ({delta}), over the energy range of 5-50 keV were determined using XOP software (version 2.3, Europeanmore » Synchrotron Radiation Facility, France). Calcium oxalate and calcium hydroxyapatite were considered to represent the material compositions of microcalcifications in vivo. Nineteen tissue substitutes were considered as possible candidates to represent adipose tissue, fibroglandular tissue and skin, and four phantom materials were considered as possible candidates to represent microcalcifications. For each material, either the molecular formula, if available, or the elemental composition based on weight fraction, was used to determine {delta}. At each x-ray photon energy, the absolute percent difference in {delta} between the breast tissue and the substitute material was determined, from which three candidates were selected. From these candidate tissue substitutes, the material that minimized the absolute percent difference in linear attenuation coefficient {mu}, and hence {beta}, was considered to be best representative of that breast tissue. Results: Over the energy range of 5-50 keV, while the {delta} of CB3 and fibroglandular tissue-equivalent material were within 1% of that of fibroglandular tissue, the {mu} of fibroglandular tissue-equivalent material better approximated the fibroglandular tissue. While the {delta} of BR10 and adipose tissue-equivalent material were within 1% of that of adipose tissue, the tissue-equivalent material better approximated the adipose tissue in terms of {mu}. Polymethyl methacrylate, a commonly used tissue substitute, exhibited {delta} greater than fibroglandular tissue by {approx}12%. The A-150 plastic closely approximated the skin. Several materials exhibited {delta} between that of adipose and fibroglandular tissue. However, there was an energy-dependent mismatch in terms of equivalent fibroglandular weight fraction between {delta} and {mu} for these materials. For microcalcifications, aluminum and calcium carbonate were observed to straddle the {delta} and {mu} of calcium oxalate and calcium hydroxyapatite. Aluminum oxide, commonly used to represent microcalcifications in the American College of Radiology recommended phantoms for accreditation exhibited {delta} greater than calcium hydroxyapatite by {approx}23%. Conclusions: A breast phantom comprising A-150 plastic to represent the skin, commercially available adipose and fibroglandular tissue-equivalent formulations to represent adipose and fibroglandular tissue, respectively, was found to be best suited for x-ray phase-sensitive imaging of the breast. Calcium carbonate or aluminum can be used to represent microcalcifications.« less

X-ray phase contrast imaging of the breast: Analysis of tissue simulating materials1

PubMed Central

Vedantham, Srinivasan; Karellas, Andrew

2013-01-01

Purpose: Phase contrast imaging, particularly of the breast, is being actively investigated. The purpose of this work is to investigate the x-ray phase contrast properties of breast tissues and commonly used breast tissue substitutes or phantom materials with an aim of determining the phantom materials best representative of breast tissues. Methods: Elemental compositions of breast tissues including adipose, fibroglandular, and skin were used to determine the refractive index, n = 1 − δ + i β. The real part of the refractive index, specifically the refractive index decrement (δ), over the energy range of 5–50 keV were determined using XOP software (version 2.3, European Synchrotron Radiation Facility, France). Calcium oxalate and calcium hydroxyapatite were considered to represent the material compositions of microcalcifications in vivo. Nineteen tissue substitutes were considered as possible candidates to represent adipose tissue, fibroglandular tissue and skin, and four phantom materials were considered as possible candidates to represent microcalcifications. For each material, either the molecular formula, if available, or the elemental composition based on weight fraction, was used to determine δ. At each x-ray photon energy, the absolute percent difference in δ between the breast tissue and the substitute material was determined, from which three candidates were selected. From these candidate tissue substitutes, the material that minimized the absolute percent difference in linear attenuation coefficient μ, and hence β, was considered to be best representative of that breast tissue. Results: Over the energy range of 5–50 keV, while the δ of CB3 and fibroglandular tissue-equivalent material were within 1% of that of fibroglandular tissue, the μ of fibroglandular tissue-equivalent material better approximated the fibroglandular tissue. While the δ of BR10 and adipose tissue-equivalent material were within 1% of that of adipose tissue, the tissue-equivalent material better approximated the adipose tissue in terms of μ. Polymethyl methacrylate, a commonly used tissue substitute, exhibited δ greater than fibroglandular tissue by ∼12%. The A-150 plastic closely approximated the skin. Several materials exhibited δ between that of adipose and fibroglandular tissue. However, there was an energy-dependent mismatch in terms of equivalent fibroglandular weight fraction between δ and μ for these materials. For microcalcifications, aluminum and calcium carbonate were observed to straddle the δ and μ of calcium oxalate and calcium hydroxyapatite. Aluminum oxide, commonly used to represent microcalcifications in the American College of Radiology recommended phantoms for accreditation exhibited δ greater than calcium hydroxyapatite by ∼23%. Conclusions: A breast phantom comprising A-150 plastic to represent the skin, commercially available adipose and fibroglandular tissue-equivalent formulations to represent adipose and fibroglandular tissue, respectively, was found to be best suited for x-ray phase-sensitive imaging of the breast. Calcium carbonate or aluminum can be used to represent microcalcifications. PMID:23556900

Chemoselective ratiometric imaging of protein S-sulfenylation.

PubMed

Tom, Christopher T M B; Crellin, John E; Motiwala, Hashim F; Stone, Matthew B; Davda, Dahvid; Walker, William; Kuo, Yu-Hsuan; Hernandez, Jeannie L; Labby, Kristin J; Gomez-Rodriguez, Lyanne; Jenkins, Paul M; Veatch, Sarah L; Martin, Brent R

2017-06-29

Here we report a ratiometric fluorescent probe for chemoselective conjugation to sulfenic acids in living cells. Our approach couples an α-fluoro-substituted dimedone to an aminonaphthalene fluorophore (F-DiNap), which upon sulfenic acid conjugation is locked as the 1,3-diketone, changing the fluorophore excitation. F-DiNap reacts with S-sulfenylated proteins at equivalent rates to current probes, but the α-fluorine substitution blocks side-reactions with biological aldehydes.

[Special considerations in generic substitution of immunosuppressive drugs in transplantation].

PubMed

Remport, Adám; Dankó, Dávid; Gerlei, Zsuzsa; Czebe, Krisztina; Kiss, István

2012-08-26

Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payer's presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers.

State generic substitution laws can lower drug outlays under Medicaid.

PubMed

Shrank, William H; Choudhry, Niteesh K; Agnew-Blais, Jessica; Federman, Alex D; Liberman, Joshua N; Liu, Jun; Kesselheim, Aaron S; Brookhart, M Alan; Fischer, Michael A

2010-07-01

To stem the rising costs of medications provided to patients enrolled in Medicaid, states have implemented varying policies about generic substitution. These policies differ in the extent to which pharmacists or patients can influence which medications they choose. Using national Medicaid data, we evaluated the relationship between different generic substitution policies and the use of generic simvastatin, a cholesterol-lowering drug, after the patent for the brand-name equivalent, Zocor, expired. States that implemented policies requiring patients' consent prior to generic substitution experienced rates of substitution that were 25 percent lower than those of states that did not require patient consent. By eliminating patient consent requirements, state Medicaid programs could expect to save more than $100 million in coverage for three top-selling medications that are nearing patent expiration. Although these consent requirements are probably intended to increase patient autonomy, policy makers should consider the sizable opportunity costs.

Lanthanide-Substituted Magnetite Nanoparticles Using a New Mixed Precursor Method by Thermoanaerobacter ethanolicus

NASA Astrophysics Data System (ADS)

Moon, J.; Roh, Y.; Yeary, L. W.; Lauf, R. J.; Phelps, T. J.

2006-12-01

A metal reducing bacterium, Thermoanaerobacter ethanolicus successfully converted the precursor of L (lanthanide)-mixed akaganeite (LxFe1-xOOH) phase to L-substituted magnetite (LyFe3-yO4) while avoiding the potentially toxic effects of soluble L-ions. Antibiotic elements, lanthanide (Nd, Gd, Tb, Ho, and Er)-substituted magnetites were produced by microbial fermentation using LxFe1-xOOH, where x was up to 0.02 which is equivalent to 0.72 mM. Combining lanthanides into the akaganeite precursor phase mitigated some of the toxicity when compared to the traditional method by using pure akaganeite and the dissolved L-salt form. This new technique showed that an upper limit of L-concentrations between 0.02 and 0.1 mM might suppress bacterial activity. At the equivalent L-cation mole fraction, the traditional method increased the concentration of soluble toxic L ions in the final media. The precursor method enabled production of microbially synthesized L- substituted magnetite with an L-concentration 36-fold greater than could be obtained when the lanthanides were added as soluble salts. These results were confirmed by protein assay. The increase of L-concentration in the magnetite evidently manipulates its physical properties such as decreasing Curie temperature and decreasing saturation magnetism of L-substituted magnetite. This mixed precursor method can therefore be used to extend the application for nanofermentation and other bacterial synthesis fields where there is a need for economically low-energy consumable microbial production of nanoscale materials that should involve toxic or inhibitory elements to bacterial growth.

Levels of non-ortho-substituted (coplanar), mono- and di-ortho-substituted polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans in human serum and adipose tissue.

PubMed Central

Patterson, D G; Todd, G D; Turner, W E; Maggio, V; Alexander, L R; Needham, L L

1994-01-01

We have measured non-ortho-substituted (coplanar) polychlorinated biphenyl (PCB) levels as well as polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in human adipose tissue and serum collected in Atlanta, Georgia. The results show that the concentrations of the coplanar PCBs can be more than an order of magnitude higher than the concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Our measurements in pooled serum collected in 1982, 1988, and 1989 show a decrease in coplanar PCB levels from 1982 to 1989. We found that the pattern of relative amounts of coplanar PCBs in adipose tissue varied greatly from person to person unlike the PCDD and PCDF patterns, which were more nearly the same. Age was significantly correlated with the concentrations of 2,3,7,8-TCDD,3,3'4,4'-PCB, 3,3',4,4',5-PCB, and 3,3'4,4',5,5'-PCB in adipose tissue. We also measured levels of the mono- and di-ortho chlorine-substituted PCBs in human serum. The levels for some of these PCB congeners were three orders of magnitude higher than the coplanar PCBs, PCDDs, and PCDFs. We used the international toxicity equivalency factors (TEFs) for PCDDs and PCDFs and the TEFs proposed by Safe for PCBs to calculate the 2,3,7,8-TCDD equivalents. Four PCBs (3,3',4,4',5-; 2,3',4,4',5-;2,3,3',4,4'-;2,3,3',4,4',5-) make a larger contribution than 2,3,7,8-TCDD, while four other PCBs (3,3',4,4'5,5'-; 2,2',3,4,4',5'-;2,2',4,4',5,5'-;2,2',3,4,4',5,5'-) make nearly the same contribution as 2,3,7,8-TCDD. The mono-ortho-chlorine-substituted 2,3',4,4',5-PCB, however, is the major contributor to the total 2,3,7,8-TCDD equivalents in general population samples from the United States, Sweden, and Japan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8187709

Synthesis of (Silylamino)phosphines by the Wilburn Method.

DTIC Science & Technology

1982-08-01

by the addi- tion of two equivalents of an alkyl Grignard reagent at 0 0C affords the [bis(trimethylsilyl)aminoldialkylphosphines 1 -3 (eq 1). Simi...larly, the use of dichlorophenylphosphine and one equivalent of Grignard reagent permits the convenient preparation of the corres- ponding alkyl(phenyl...Received The importance of (silylamino)phosphines, e.g. (Me3Si)2NPMe2, as reagents for the synthesis of organo-substituted phosphazene 1 2,3 polymers

A Guide for Emergency Evacuation Management and Operations

DTIC Science & Technology

1981-02-01

such as scrambled eggs (A.M. meal) and hash or stew (P.M. meal). Frequent cold meals are possible. Some relocation guidance indicates that...cheese; and nuts) 4 lbs. with bone Eggs 6 eggs Milk (fresh) 7 pints (If fresh fluid milk is not available, see Exhibit 20.2 for acceptable substitutes...Unit Equivalent Unit Substitute Foods Meat and Meat 1/2 lb. Cereal and cereal products Alternates 1/4 lb. Food fats and oils 12 Eggs 1 lb. boneless 2-3

Iron-rich clay minerals on Mars - Potential sources or sinks for hydrogen and indicators of hydrogen loss over time

NASA Technical Reports Server (NTRS)

Burt, D. M.

1989-01-01

Although direct evidence is lacking, indirect evidence suggests that iron-rich clay minerals or poorly-ordered chemical equivalents are widespread on the Martian surface. Such clays can act as sources or sinks for hydrogen ('hydrogen sponges'). Ferrous clays can lose hydrogen and ferric clays gain it by the coupled substitution Fe(3+)O(Fe(2+)OH)-1, equivalent to minus atomic H. This 'oxy-clay' substitution involves only proton and electron migration through the crystal structure, and therefore occurs nondestructively and reversibly, at relatively low temperatures. The reversible, low-temperature nature of this reaction contrasts with the irreversible nature of destructive dehydroxylation (H2O loss) suffered by clays heated to high temperatures. In theory, metastable ferric oxy-clays formed by dehydrogenation of ferrous clays over geologic time could, if exposed to water vapor, extract the hydrogen from it, releasing oxygen.

Micropore-free surface-activated carbon for the analysis of polychlorinated dibenzo-p-dioxins-dibenzofurans and non-ortho-substituted polychlorinated biphenyls in environmental samples.

PubMed

Kemmochi, Yukio; Tsutsumi, Kaori; Arikawa, Akihiro; Nakazawa, Hiroyuki

2002-11-22

2,3,7,8-Substituted polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) and non-ortho-substituted polychlorinated biphenyls (PCBs) account for almost all of the total toxic equivalents (TEQ) in environmental samples. Activated carbon columns are used to fractionate the samples for GC-MS analysis or bioassay. Micropore-free surface-activated carbon is highly selective for PCDD/Fs and non-ortho-PCBs and can improve the conventional activated carbon column clean-up. Along with sulfuric acid-coated diatomaceous earth columns, micropore-free surface-activated carbon provides a rapid, robust, and high-throughput sample preparation method for PCDD/Fs and non-ortho-PCBs analysis.

The 2.5-diacyl-1,4-dimethylbenzenes: Examples of bisphotoenol equivalents

NASA Technical Reports Server (NTRS)

Meador, Michael A.

1987-01-01

The photochemistry of 2,5-dibenzoyl(DBX)-and 2,5-diacetyl-1,4-dimethylbenzene (DAX) has been investigated. Both compounds readily undergo photoenolization similar to 0-alkylphenyl ketones. However, unlike 0-alkylphenyl ketones DAX and DBX are each capable of undergoing two tandem photoenolizations. Photoenols derived from o-alkylphenyl ketones have been successfully trapped with Diels-Alder dienophiles to provide a convenient synthesis of substituted tetralins. Similarly, Diels-Alder trapping of DBX photoenils afforded substituted tetra- and octahydro anthracenes. Further mainpulation of these photadducts provided the corresponding anthracenes in good yield. The photochemistry of DAX and DBX will be discussed, in particular their use in the synthesis of substituted anthracenes.

[Oral mucosa analog allografts in non-consanguineous rats].

PubMed

González, Luis; Padrón, Karla; Salmen, Siham; Jerez, Elsy; Dávila, Lorena; Solórzano, Eduvigis

2017-01-24

Although there are therapeutic options for the treatment of oral mucosa defects, the need for functional, anatomical and aesthetically similar substitutes persists, as well as for solutions to reduce autologous grafts morbidity. To determine clinical and histological compatibility of equivalent oral mucosa allografts generated through tissue engineering in non-consanguineous rats. We used a sample of oral mucosa from Sprague Dawley rats to obtain a fibroblast culture and a keratinocytes and fibroblasts co-culture. In both cases, we used a commercial collagen membrane as "scaffold". After ten weeks of culture, we grafted the resulting membranes into four Wistar rats. The first phase of the study was the development of the oral mucosa equivalents generated by tissue engineering. Then, we implanted them in immunocompetent Wistar rats, and finallywe evaluated the clinical and histological features of the allografts. In vivo evaluation of mucosal substitutes showed a correct integration of artificial oral mucosa in immunocompetent hosts, with an increase in periodontal biotype and the creation of a zone with increased keratinization. Histologically, the tissue was similar to the control oral mucosa sample with no inflammatory reaction nor clinical or histological rejection signs. The equivalent oral mucosa allografts generated by tissue engineering showed clinical and histological compatibility.

Determination of tissue equivalent materials of a physical 8-year-old phantom for use in computed tomography

NASA Astrophysics Data System (ADS)

Akhlaghi, Parisa; Miri Hakimabad, Hashem; Rafat Motavalli, Laleh

2015-07-01

This paper reports on the methodology applied to select suitable tissue equivalent materials of an 8-year phantom for use in computed tomography (CT) examinations. To find the appropriate tissue substitutes, first physical properties (physical density, electronic density, effective atomic number, mass attenuation coefficient and CT number) of different materials were studied. Results showed that, the physical properties of water and polyurethane (as soft tissue), B-100 and polyvinyl chloride (PVC) (as bone) and polyurethane foam (as lung) agree more with those of original tissues. Then in the next step, the absorbed doses in the location of 25 thermoluminescent dosimeters (TLDs) as well as dose distribution in one slice of phantom were calculated for original and these proposed materials by Monte Carlo simulation at different tube voltages. The comparisons suggested that at tube voltages of 80 and 100 kVp using B-100 as bone, water as soft tissue and polyurethane foam as lung is suitable for dosimetric study in pediatric CT examinations. In addition, it was concluded that by considering just the mass attenuation coefficient of different materials, the appropriate tissue equivalent substitutes in each desired X-ray energy range could be found.

Quantum-chemical modeling of smectite clays

NASA Technical Reports Server (NTRS)

Aronowitz, S.; Coyne, L.; Lawless, J.; Rishpon, J.

1982-01-01

A self-consistent charge extended Hueckel program is used in modeling isomorphic substitution of Al(3+) by Na(+), K(+), Mg(2+), Fe(2+), and Fe(3+) in the octahedral layer of a dioctahedral smectite clay, such as montmorillonite. Upon comparison of the energies involved in the isomorphic substitution, it is found that the order for successful substitution is as follows: Al(3+), Fe(3+), Mg(2+), Fe(2+), Na(+), which is equivalent to Ca(2+), and then K(+). This ordering is found to be consistent with experimental observation. The calculations also make it possible to determine the possible penetration of metal ions into the clay's 2:1 crystalline layer. For the cases studied, this type of penetration can occur at elevated temperatures into regions where isomorphic substitution has occurred with metal ions that bear a formal charge of less than 3+. The computed behavior of the electronic structure in the presence of isomorphic substitution is found to be similar to behavior associated with semiconductors.

A study of a tissue equivalent gelatine based tissue substitute

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

Spence, J.L.

1992-11-01

A study of several tissue substitutes for use as volumetric dosimeters was performed. The tissue substitutes studied included tissue substitutes from previous studies and from ICRU 44. The substitutes were evaluated for an overall match to Reference Man which was used as a basis for this study. The evaluation was based on the electron stopping power, the mass attenuation coefficient, the electron density, and the specific gravity. The tissue substitute chosen also had to be capable of changing from a liquid into a solid form to maintain an even distribution of thermoluminesent dosimetry (TLD) powder and then back to amore » liquid for recovery of the TLD powder without adversely effecting the TLD powder. The gelatine mixture provided the closest match to the data from Reference Man tissue. The gelatine mixture was put through a series of test to determine it's usefulness as a reliable tissue substitute. The TLD powder was cast in the gelatine mixture and recovered to determine if the TLD powder was adversely effected. The distribution of the TLD powder after being cast into the gelatin mixture was tested in insure an even was maintained.« less

A study of a tissue equivalent gelatine based tissue substitute

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

Spence, Jody L.

1992-11-01

A study of several tissue substitutes for use as volumetric dosimeters was performed. The tissue substitutes studied included tissue substitutes from previous studies and from ICRU 44. The substitutes were evaluated for an overall match to Reference Man which was used as a basis for this study. The evaluation was based on the electron stopping power, the mass attenuation coefficient, the electron density, and the specific gravity. The tissue substitute chosen also had to be capable of changing from a liquid into a solid form to maintain an even distribution of thermoluminesent dosimetry (TLD) powder and then back to amore » liquid for recovery of the TLD powder without adversely effecting the TLD powder. The gelatine mixture provided the closest match to the data from Reference Man tissue. The gelatine mixture was put through a series of test to determine it`s usefulness as a reliable tissue substitute. The TLD powder was cast in the gelatine mixture and recovered to determine if the TLD powder was adversely effected. The distribution of the TLD powder after being cast into the gelatin mixture was tested in insure an even was maintained.« less

Rotational characterization of methyl methacrylate: Internal dynamics and structure determination

NASA Astrophysics Data System (ADS)

Herbers, Sven; Wachsmuth, Dennis; Obenchain, Daniel A.; Grabow, Jens-Uwe

2018-01-01

Rotational constants, Watson's S centrifugal distortion coefficients, and internal rotation parameters of the two most stable conformers of methyl methacrylate were retrieved from the microwave spectrum. Splittings of rotational energy levels were caused by two non equivalent methyl tops. Constraining the centrifugal distortion coefficients and internal rotation parameters to the values of the main isotopologues, the rotational constants of all single substituted 13C and 18O isotopologues were determined. From these rotational constants the substitution structures and semi-empirical zero point structures of both conformers were precisely determined.

Is sensorimotor BCI performance influenced differently by mono, stereo, or 3-D auditory feedback?

PubMed

McCreadie, Karl A; Coyle, Damien H; Prasad, Girijesh

2014-05-01

Imagination of movement can be used as a control method for a brain-computer interface (BCI) allowing communication for the physically impaired. Visual feedback within such a closed loop system excludes those with visual problems and hence there is a need for alternative sensory feedback pathways. In the context of substituting the visual channel for the auditory channel, this study aims to add to the limited evidence that it is possible to substitute visual feedback for its auditory equivalent and assess the impact this has on BCI performance. Secondly, the study aims to determine for the first time if the type of auditory feedback method influences motor imagery performance significantly. Auditory feedback is presented using a stepped approach of single (mono), double (stereo), and multiple (vector base amplitude panning as an audio game) loudspeaker arrangements. Visual feedback involves a ball-basket paradigm and a spaceship game. Each session consists of either auditory or visual feedback only with runs of each type of feedback presentation method applied in each session. Results from seven subjects across five sessions of each feedback type (visual, auditory) (10 sessions in total) show that auditory feedback is a suitable substitute for the visual equivalent and that there are no statistical differences in the type of auditory feedback presented across five sessions.

Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies

PubMed Central

2012-01-01

Background For millennia, iron-tannate dyes have been used to colour ceremonial and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed objects are part of our cultural heritage but their existence is threatened by the dye itself which can accelerate oxidation and acid hydrolysis of the substrate. This causes many iron-tannate dyed textiles to discolour and decrease in tensile strength and flexibility at a faster rate than equivalent undyed textiles. The current lack of suitable stabilisation treatments means that many historic iron-tannate dyed objects are rapidly crumbling to dust with the knowledge and value they hold being lost forever. This paper describes the production, characterisation, and validation of model iron-tannate dyed textiles as substitutes for historic iron-tannate dyed textiles in the development of stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM-EDX, and XRF have been used to characterise the model textiles. Results On application to textiles, the model dyes imparted mid to dark blue-grey colouration, an immediate tensile strength loss of the textiles and an increase in surface acidity. The dyes introduced significant quantities of iron into the textiles which was distributed in the exterior and interior of the cotton, abaca, and silk fibres but only in the exterior of the wool fibres. As seen with historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles lost tensile strength faster and more significantly than undyed equivalents during accelerated thermal ageing and all of the dyed model textiles, most notably the cotton, discoloured more than the undyed equivalents on ageing. Conclusions The abaca, cotton, and silk model textiles are judged to be suitable for use as substitutes for cultural heritage materials in the testing of stabilisation treatments. PMID:22616934

Tocopherols and tocotrienols in Finnish foods: human milk and infant formulas.

PubMed

Syväoja, E L; Piironen, V; Varo, P; Koivistoinen, P; Salminen, K

1985-01-01

Individual tocopherols and tocotrienols in human milk, mother's milk substitutes and other infant formulas have been determined by an HPLC method. 107 human milk samples (23 colostral, 22 transitional and 62 mature) obtained from six healthy mothers throughout the lactation were found to contain all the tocopherols, although delta-tocopherol occurred only in traces. A high content of alpha-tocopherol was found in colostrum (average 1.90 +/- 1.62 (SD) mg/100 g), as compared with transitional (0.65 +/- 0.22 mg/100 g) and mature milk (0.47 +/- 0.16 mg/100 g). The content of beta-tocopherol averaged 0.05 +/- 0.03, 0.02 +/- 0.01 and 0.02 +/- 0.01 and gamma-tocopherol 0.11 +/- 0.09, 0.07 +/- 0.04 and 0.07 +/- 0.04 mg/100 g in colostral, transitional and mature milk respectively. The alpha-tocopherol equivalents thus were 1.93, 0.66 and 0.49 mg/100 g; their ratios to the contents of polyunsaturated fatty acids meet the nutritional need of the newborn and young infant: 5.7, 2.1 and 1.4 mg/g in colostral, transitional and mature milk. Mother's milk substitutes and gruel and porridge powders are enriched with tocopherol acetate to vitamin E levels similar to or higher than those in human milk: substitutes contained on average 1.4 mg alpha-tocopherol equivalents/100 g and reconstituted powders 1.1 mg/100 g. The ratio of vitamin E to polyunsaturated fatty acids of these infant formulas was higher than the recommended value of 0.6 mg/g. The average values for alpha-tocopherol equivalents in fruit-berry and meat-vegetable infant formulas were 0.46 and 0.38 mg/100 g.

Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers

PubMed Central

O’Connell, Grant; Graff, Donald W.; D’Ruiz, Carl D.

2016-01-01

Abstract Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes of compounds reported by FDA to be significant contributors to smoking-associated disease risks were measured in 105 clinical-confined subjects following randomization and a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use of commercial e-cigarettes and the subject’s usual cigarette brand; or (iii) discontinued use of all tobacco or nicotine products. Levels of urinary biomarkers in subjects that completely substituted their usual cigarette with e-cigarettes were significantly lower (29–95%) after 5 days. Percent reductions in eight of nine urinary BoEs were indistinguishable to smokers who had quit smoking, except for nicotine equivalents, which declined by 25–40%. Dual users who halved self-reported daily cigarette consumption with e-cigarettes exhibited reductions (7–38%) in eight of nine urinary biomarkers, but had increase (1–20%) in nicotine equivalents. Reductions were broadly proportional to the reduced numbers of cigarettes smoked. Dual user urinary nicotine equivalents were slightly higher, but not statistically significant. After 5 days, blood nicotine biomarker levels were lower in the cessation (75–96%) and exclusive use groups (11–83%); with dual users experiencing no significant reductions. All subjects experienced significant decreases in exhaled CO. Decreases in the cessation and exclusive groups ranged from 88–89% and 27–32% in dual users. Exhaled NO increased in the cessation and exclusive groups (46–63% respectively), whereas the dual users experienced minimal changes. Overall, smokers who completely or partially substituted conventional cigarettes with e-cigarettes over five days, experienced reductions in HPHCs. PMID:27401591

Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers.

PubMed

O'Connell, Grant; Graff, Donald W; D'Ruiz, Carl D

2016-07-01

Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes of compounds reported by FDA to be significant contributors to smoking-associated disease risks were measured in 105 clinical-confined subjects following randomization and a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use of commercial e-cigarettes and the subject's usual cigarette brand; or (iii) discontinued use of all tobacco or nicotine products. Levels of urinary biomarkers in subjects that completely substituted their usual cigarette with e-cigarettes were significantly lower (29-95%) after 5 days. Percent reductions in eight of nine urinary BoEs were indistinguishable to smokers who had quit smoking, except for nicotine equivalents, which declined by 25-40%. Dual users who halved self-reported daily cigarette consumption with e-cigarettes exhibited reductions (7-38%) in eight of nine urinary biomarkers, but had increase (1-20%) in nicotine equivalents. Reductions were broadly proportional to the reduced numbers of cigarettes smoked. Dual user urinary nicotine equivalents were slightly higher, but not statistically significant. After 5 days, blood nicotine biomarker levels were lower in the cessation (75-96%) and exclusive use groups (11-83%); with dual users experiencing no significant reductions. All subjects experienced significant decreases in exhaled CO. Decreases in the cessation and exclusive groups ranged from 88-89% and 27-32% in dual users. Exhaled NO increased in the cessation and exclusive groups (46-63% respectively), whereas the dual users experienced minimal changes. Overall, smokers who completely or partially substituted conventional cigarettes with e-cigarettes over five days, experienced reductions in HPHCs.

Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies.

PubMed

Wilson, Helen; Carr, Chris; Hacke, Marei

2012-05-22

For millennia, iron-tannate dyes have been used to colour ceremonial and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed objects are part of our cultural heritage but their existence is threatened by the dye itself which can accelerate oxidation and acid hydrolysis of the substrate. This causes many iron-tannate dyed textiles to discolour and decrease in tensile strength and flexibility at a faster rate than equivalent undyed textiles. The current lack of suitable stabilisation treatments means that many historic iron-tannate dyed objects are rapidly crumbling to dust with the knowledge and value they hold being lost forever.This paper describes the production, characterisation, and validation of model iron-tannate dyed textiles as substitutes for historic iron-tannate dyed textiles in the development of stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM-EDX, and XRF have been used to characterise the model textiles. On application to textiles, the model dyes imparted mid to dark blue-grey colouration, an immediate tensile strength loss of the textiles and an increase in surface acidity. The dyes introduced significant quantities of iron into the textiles which was distributed in the exterior and interior of the cotton, abaca, and silk fibres but only in the exterior of the wool fibres. As seen with historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles lost tensile strength faster and more significantly than undyed equivalents during accelerated thermal ageing and all of the dyed model textiles, most notably the cotton, discoloured more than the undyed equivalents on ageing. The abaca, cotton, and silk model textiles are judged to be suitable for use as substitutes for cultural heritage materials in the testing of stabilisation treatments.

Novel three-dimensional autologous tissue-engineered vaginal tissues using the self-assembly technique.

PubMed

Orabi, Hazem; Saba, Ingrid; Rousseau, Alexandre; Bolduc, Stéphane

2017-02-01

Many diseases necessitate the substitution of vaginal tissues. Current replacement therapies are associated with many complications. In this study, we aimed to create bioengineered neovaginas with the self-assembly technique using autologous vaginal epithelial (VE) and vaginal stromal (VS) cells without the use of exogenous materials and to document the survival and incorporation of these grafts into the tissues of nude female mice. Epithelial and stromal cells were isolated from vaginal biopsies. Stromal cells were driven to form collagen sheets, 3 of which were superimposed to form vaginal stromas. VE cells were seeded on top of these stromas and allowed to mature in an air-liquid interface. The vaginal equivalents were implanted subcutaneously in female nude mice, which were sacrificed after 1 and 2 weeks after surgery. The in vitro and animal-retrieved equivalents were assessed using histologic, functional, and mechanical evaluations. Vaginal equivalents could be handled easily. VE cells formed a well-differentiated epithelial layer with a continuous basement membrane. The equivalent matrix was composed of collagen I and III and elastin. The epithelium, basement membrane, and stroma were comparable to those of native vaginal tissues. The implanted equivalents formed mature vaginal epithelium and matrix that were integrated into the mice tissues. Using the self-assembly technique, in vitro vaginal tissues were created with many functional and biological similarities to native vagina without any foreign material. They formed functional vaginal tissues after in vivo animal implantation. It is appropriate for vaginal substitution and disease modeling for infectious studies, vaginal applicants, and drug testing. Copyright © 2016 Elsevier Inc. All rights reserved.

Computer-Based Linguistic Analysis.

ERIC Educational Resources Information Center

Wright, James R.

Noam Chomsky's transformational-generative grammar model may effectively be translated into an equivalent computer model. Phrase-structure rules and transformations are tested as to their validity and ordering by the computer via the process of random lexical substitution. Errors appearing in the grammar are detected and rectified, and formal…

A literature review of international implementation of opioid substitution treatment in prisons: equivalence of care?

PubMed

Larney, Sarah; Dolan, Kate

2009-01-01

Opioid substitution treatment (OST) is an effective treatment for heroin dependence. The World Health Organization has recommended that OST be implemented in prisons because of its role in reducing drug injection and associated problems such as HIV transmission. The aim of this paper was to examine the extent to which OST has been implemented in prisons internationally. Literature review. As of January 2008, OST had been implemented in prisons in at least 29 countries or territories. For 20 of those countries, the proportion of all prisoners in OST could be calculated, with results ranging from less than 1% to over 14%. At least 37 countries offer OST in community settings, but not prisons. This study has identified an increase in the international implementation of OST in prisons. However, there remain large numbers of prisoners who are unable to access OST, even in countries that provide such programs. This raises issues of equivalence of care for prisoners and HIV prevention in prisons. 2009 S. Karger AG, Basel.

The two gap transitions in Ge1 -xSnx : Effect of non-substitutional complex defects

NASA Astrophysics Data System (ADS)

Querales-Flores, J. D.; Ventura, C. I.; Fuhr, J. D.; Barrio, R. A.

2016-09-01

The existence of non-substitutional β-Sn defects in Ge1 -xSnx alloys was confirmed by emission channeling experiments [Decoster et al., Phys. Rev. B 81, 155204 (2010)], which established that, although most Sn enters substitutionally (α-Sn) in the Ge lattice, a second significant fraction corresponds to the Sn-vacancy defect complex in the split-vacancy configuration (β-Sn), in agreement with our previous theoretical study [Ventura et al., Phys. Rev. B 79, 155202 (2009)]. Here, we present the electronic structure calculations for Ge1 -xSnx , including the substitutional α-Sn as well as the non-substitutional β-Sn defects. To include the presence of the non-substitutional complex defects in the electronic structure calculation for this multi-orbital alloy problem, we extended the approach for the purely substitutional alloy by Jenkins and Dow [Phys. Rev. B 36, 7994 (1987)]. We employed an effective substitutional two-site cluster equivalent to the real non-substitutional β-Sn defect, which was determined by a Green's functions calculation. We then calculated the electronic structure of the effective alloy purely in terms of substitutional defects, embedding the effective substitutional clusters in the lattice. Our results describe the two transitions of the fundamental gap of Ge1 -xSnx as a function of the total Sn-concentration: namely, from an indirect to a direct gap, first, and the metallization transition at a higher x. They also highlight the role of β-Sn in the reduction of the concentration range, which corresponds to the direct-gap phase of this alloy of interest for the optoelectronics applications.

Artificial Neural Networks Equivalent to Fuzzy Algebra T-Norm Conjunction Operators

NASA Astrophysics Data System (ADS)

Iliadis, L. S.; Spartalis, S. I.

2007-12-01

This paper describes the construction of three Artificial Neural Networks with fuzzy input and output, imitating the performance of fuzzy algebra conjunction operators. More specifically, it is applied over the results of a previous research effort that used T-Norms in order to produce a characteristic torrential risk index that unified the partial risk indices for the area of Xanthi. Each one of the three networks substitutes a T-Norm and consequently they can be used as equivalent operators. This means that ANN performing Fuzzy Algebra operations can be designed and developed.

40 CFR 52.1488 - Visibility protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... substituting equivalent or superior control technology, provided such technology meets applicable emission... operator shall meet the following deadlines for design and construction of the emission control equipment... binding contract to design the SO2, opacity and NOX control systems for Unit 1 and Unit 2 by March 1, 2003...

40 CFR 52.1488 - Visibility protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... substituting equivalent or superior control technology, provided such technology meets applicable emission... operator shall meet the following deadlines for design and construction of the emission control equipment... binding contract to design the SO2, opacity and NOX control systems for Unit 1 and Unit 2 by March 1, 2003...

40 CFR 52.1488 - Visibility protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... substituting equivalent or superior control technology, provided such technology meets applicable emission... operator shall meet the following deadlines for design and construction of the emission control equipment... binding contract to design the SO2, opacity and NOX control systems for Unit 1 and Unit 2 by March 1, 2003...

40 CFR 52.1488 - Visibility protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... substituting equivalent or superior control technology, provided such technology meets applicable emission... operator shall meet the following deadlines for design and construction of the emission control equipment... binding contract to design the SO2, opacity and NOX control systems for Unit 1 and Unit 2 by March 1, 2003...

Electronic regioselectivity of diarylalkynes in cobalt-mediated Pauson-Khand reaction: an experimental and computational study with para- and meta-substituted diarylalkynes and norbornene.

PubMed

Fager-Jokela, Erika; Muuronen, Mikko; Patzschke, Michael; Helaja, Juho

2012-10-19

Both steric and electronic factors of substituted alkynes are known to guide α/β-cyclopentenone regioselectivity in the cobalt-mediated Pauson-Khand reaction (PKR). In synthetic applications of the PKR, the steric factors can often override or render possible electronic effects. This study examined alkyne-dependent electronic regioselectivity of cyclopentenone formation in PKR with norbornene and sterically equivalent, but electronically unsymmetrical, meta- and para-substituted diarylethynyls to unveil the role of electronic effects alone. In agreement with the literature reports, EDG para-substituted aryls, to some extent, favored the cyclopentenone α-regioisomer, while the EWG-substituted aryls correspondingly preferred the β-regioisomer. The cooperation of EGW and EDG in diaryl-substituted alkynes did not lead to any increased regioselectivities that could be expected by a "push-pull" effect. Both EWG and EDG meta-substituted aryls preferred the β-regioisomer, which was demonstrated by 3,5-dimethoxy- and 3,5-bis(trifluoromethyl)-1-phenylethynyls that yielded 1/1.6 and 1/2.0 α/β-regioselectivities, respectively. Theoretically, inspection of Hammett values of α-alkyne carbons gave qualitatively satisfactory prediction for para-substituted aryls but correlated only weakly with meta-substituted effects. Computational investigations at the DFT level revealed a correlation between NBO charges and the regioselectivity. Overall, the results suggest that the polarity of an alkyne, also designated by the relative polarization of aryl α-carbons, dictates the regioselectivity in the absence of steric effects.

40 CFR 721.1765 - 2-Substituted benzotriazole.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (l) and (q). (iv) Release to water. Requirements as specified in § 721.90 (a)(4), (b)(4), (c)(4), -(where N = 80 ). However, contrary to § 721.91(a)(4), if the waste stream containing the PMN substance will be treated using biological treatment (activated sludge or equivalent) plus clarification, then...

Composting and compost utilization: accounting of greenhouse gases and global warming contributions.

PubMed

Boldrin, Alessio; Andersen, Jacob K; Møller, Jacob; Christensen, Thomas H; Favoino, Enzo

2009-11-01

Greenhouse gas (GHG) emissions related to composting of organic waste and the use of compost were assessed from a waste management perspective. The GHG accounting for composting includes use of electricity and fuels, emissions of methane and nitrous oxide from the composting process, and savings obtained by the use of the compost. The GHG account depends on waste type and composition (kitchen organics, garden waste), technology type (open systems, closed systems, home composting), the efficiency of off-gas cleaning at enclosed composting systems, and the use of the compost. The latter is an important issue and is related to the long-term binding of carbon in the soil, to related effects in terms of soil improvement and to what the compost substitutes; this could be fertilizer and peat for soil improvement or for growth media production. The overall global warming factor (GWF) for composting therefore varies between significant savings (-900 kg CO(2)-equivalents tonne(-1) wet waste (ww)) and a net load (300 kg CO(2)-equivalents tonne( -1) ww). The major savings are obtained by use of compost as a substitute for peat in the production of growth media. However, it may be difficult for a specific composting plant to document how the compost is used and what it actually substitutes for. Two cases representing various technologies were assessed showing how GHG accounting can be done when specific information and data are available.

The Rotational Spectrum of Singly and Doubly 13C-SUBSTITUTED Dimethylether

NASA Astrophysics Data System (ADS)

Koerber, Monika; Endres, Christian P.; Lewen, Frank; Giesen, Thomas F.; Schlemmer, Stephan; Pohl, Roland; Klein, Axel

2010-06-01

Dimethylether (DME) is a nearly prolate asymmetric top with two internal rotors (methyl groups) which undergo periodic large amplitude motions and show a complicated torsional splitting of each rotational energy level. Due to its complex spectrum and its high abundance in hot cores such as Orion KL or Sagittarius B2 at temperatures exceeding 100 K, DME is very prominent in astronomical line surveys and contributes to spectral line confusion of such sources. The interpretation of astronomical observations therefore depends on the knowledge of accurate rest frequencies and reliable intensities. Precise predictions for the ground state of DME's main isotopologue are now available up to 2.1 THz In contrast, very little is known about 13C-substituted DME. Only a few data are available on singly 13C-substituted DME, 12CH_3O13CH_3. However, no data are available on doubly 13C-substituted DME, (13CH_3)_2O, yet. While in (13CH_3)_2O the two internal rotating methyl groups are equivalent and the splitting of rotational energy levels into four substates is comparable to the main isotopologue, singly 13C-substituted DME has two non-equivalent internal rotors resulting in torsional splitting of rotational energy levels into five substates. The purpose of our new laboratory measurements is to extend the knowledge on the astrophysically relevant species 12CH_3O13CH_3. To analyze the complicated spectrum resulting from a 13C-enriched sample of DME, containing all different 13C-substituted species as well as the main isotopologue, also precise data on doubly 13C-substituted DME are inevitable. We performed measurements in the frequency region 35-120 GHz using an all solid state spectrometer. Rotational as well as torsional parameters have been obtained for (13CH_3)_2O as well as 12CH_3O13CH_3 by fitting the assigned transitions to an effective rotational Hamiltonian introduced by Peter Groner. C. Comito et al., Astrophys. J. Suppl. Ser. 156, 127-167 (2005) C. P. Endres et al., Astronomy & Astrophysics 504, 635-640 (2009) Y. Niide and M. Hayashi, J. Mol. Spectrosc. 220, 65-79 (2003) P. Groner, J. Chem. Phys. 107, 4483-4498 (1997).

Adipose-derived stromal cells for the reconstruction of a human vesical equivalent.

PubMed

Rousseau, Alexandre; Fradette, Julie; Bernard, Geneviève; Gauvin, Robert; Laterreur, Véronique; Bolduc, Stéphane

2015-11-01

Despite a wide panel of tissue-engineering models available for vesical reconstruction, the lack of a differentiated urothelium remains their main common limitation. For the first time to our knowledge, an entirely human vesical equivalent, free of exogenous matrix, has been reconstructed using the self-assembly method. Moreover, we tested the contribution of adipose-derived stromal cells, an easily available source of mesenchymal cells featuring many potential advantages, by reconstructing three types of equivalent, named fibroblast vesical equivalent, adipose-derived stromal cell vesical equivalent and hybrid vesical equivalent--the latter containing both adipose-derived stromal cells and fibroblasts. The new substitutes have been compared and characterized for matrix composition and organization, functionality and mechanical behaviour. Although all three vesical equivalents displayed adequate collagen type I and III expression, only two of them, fibroblast vesical equivalent and hybrid vesical equivalent, sustained the development of a differentiated and functional urothelium. The presence of uroplakins Ib, II and III and the tight junction marker ZO-1 was detected and correlated with impermeability. The mechanical resistance of these tissues was sufficient for use by surgeons. We present here in vitro tissue-engineered vesical equivalents, built without the use of any exogenous matrix, able to sustain mechanical stress and to support the formation of a functional urothelium, i.e. able to display a barrier function similar to that of native tissue. Copyright © 2013 John Wiley & Sons, Ltd.

Triazine-Substituted and Acyl Hydrazones: Experiment and Computation Reveal a Stability Inversion at Low pH.

PubMed

Ji, Kun; Lee, Changsuk; Janesko, Benjamin G; Simanek, Eric E

2015-08-03

Condensation of a hydrazine-substituted s-triazine with an aldehyde or ketone yields an equivalent to the widely used, acid-labile acyl hydrazone. Hydrolysis of these hydrazones using a formaldehyde trap as monitored using HPLC reveals that triazine-substituted hydrazones are more labile than acetyl hydrazones at pH>5. The reactivity trends mirror that of the corresponding acetyl hydrazones, with hydrolysis rates increasing along the series (aromatic aldehyde

ortho- and meta-substituted aromatic thiols are efficient redox buffers that increase the folding rate of a disulfide-containing protein.

PubMed

Gough, Jonathan D; Barrett, Elvis J; Silva, Yenia; Lees, Watson J

2006-08-20

Thiol based redox buffers are used to enhance the folding rates of disulfide-containing proteins in vitro. Traditionally, small molecule aliphatic thiols such as glutathione are employed. Recently, we have demonstrated that aromatic thiols can further enhance protein-folding rates. In the presence of para-substituted aromatic thiols the folding rate of a disulfide-containing protein was increased by 4-23 times over that measured for glutathione. However, several important practical issues remain to be addressed. Aromatic thiols have never been tested in the presence of denaturants such as guanidine hydrochloride. Only two of the para-substituted aromatic thiols previously examined are commercially available. To expand the number of aromatic thiols for protein folding, several commercially available meta- and ortho-substituted aromatic thiols were studied. Furthermore, an ortho-substituted aromatic thiol, easily obtained from inexpensive starting materials, was investigated. Folding rates of scrambled ribonuclease A at pH 6.0, 7.0 and 7.7, with ortho- and meta-substituted aromatic thiols, were up to 10 times greater than those with glutathione. In the presence of the common denaturant guanidine hydrochloride (0.5M) aromatic thiols provided 100% yield of active protein while maintaining equivalent folding rates.

Editorial Commentary: "Knot" Less Strength at Half the Cost-Is It Time to Abandon Medial Row Anchors in Shoulder Double-Row Rotator Cuff Repair?

PubMed

Sherman, Seth L

2018-01-01

Transosseous equivalent rotator cuff repair is an expensive construct that has demonstrated biomechanical superiority when compared with other rotator cuff repair techniques. A novel transosseous knotless repair that substitutes medial row anchors for a transosseous tunnel rivals the biomechanical advantages of transosseous equivalent rotator cuff repair at half the cost and with reduced dependence on bone quality. Surgeons should carefully consider if "knotless transosseous is more." Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Climate change mitigation effect of harvested wood products in regions of Japan.

PubMed

Kayo, Chihiro; Tsunetsugu, Yuko; Tonosaki, Mario

2015-12-01

Harvested wood products (HWPs) mitigate climate change through carbon storage, material substitution, and energy substitution. We construct a model to assess the overall climate change mitigation effect (comprising the carbon storage, material substitution, and energy substitution effects) resulting from HWPs in regions of Japan. The model allows for projections to 2050 based on future scenarios relating to the domestic forestry industry, HWP use, and energy use. Using the production approach, a nationwide maximum figure of 2.9 MtC year -1 for the HWP carbon storage effect is determined for 2030. The maximum nationwide material substitution effect is 2.9 MtC year -1 in 2050. For the energy substitution effect, a nationwide maximum projection of 4.3 MtC year -1 in 2050 is established, with at least 50 % of this figure derived from east and west Japan, where a large volume of logging residue is generated. For the overall climate change mitigation effect, a nationwide maximum projection of 8.4 MtC year -1 in 2050 is established, equivalent to 2.4 % of Japan's current carbon dioxide emissions. When domestic roundwood production and HWP usage is promoted, an overall climate change mitigation effect is consistently expected to be attributable to HWPs until 2050. A significant factor in obtaining the material substitution effect will be substituting non-wooden buildings with wooden ones. The policy of promoting the use of logging residue will have a significant impact on the energy substitution effect. An important future study is an integrated investigation of the climate change mitigation effect for both HWPs and forests.

77 FR 66388 - Approval and Promulgation of Air Quality Implementation Plans; New Hampshire; Reasonably...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-05

... facilities in the state. Additionally, the state removed a section regarding an equivalent substitute control... a selective non-catalytic reducing (SNCR) control device to meet an emission limit of 0.975 lbs NO X... and Promulgation of Air Quality Implementation Plans; New Hampshire; Reasonably Available Control...

75 FR 67047 - Standard for the Flammability of Mattresses and Mattress Pads

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

.... Response: The new SRM cigarette is designed to be equivalent to the original test cigarette. In its report... confirmatory test consumes about two packs, and a ticking substitution test consumes about one pack. Assuming... specified in the standard for use in the mattress standard's performance tests is no longer being produced...

21 CFR 180.37 - Saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... additive, calculated as saccharin, for each expressed teaspoonful of sugar sweetening equivalency. (3) In... safely used as sweetening agents in food in accordance with the following conditions, if the substitution... additives are used or intended for use as a sweetening agent only in special dietary foods, as follows: (1...

21 CFR 180.37 - Saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... additive, calculated as saccharin, for each expressed teaspoonful of sugar sweetening equivalency. (3) In... safely used as sweetening agents in food in accordance with the following conditions, if the substitution... additives are used or intended for use as a sweetening agent only in special dietary foods, as follows: (1...

21 CFR 180.37 - Saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... additive, calculated as saccharin, for each expressed teaspoonful of sugar sweetening equivalency. (3) In... safely used as sweetening agents in food in accordance with the following conditions, if the substitution... additives are used or intended for use as a sweetening agent only in special dietary foods, as follows: (1...

21 CFR 180.37 - Saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... additive, calculated as saccharin, for each expressed teaspoonful of sugar sweetening equivalency. (3) In... safely used as sweetening agents in food in accordance with the following conditions, if the substitution... additives are used or intended for use as a sweetening agent only in special dietary foods, as follows: (1...

42 CFR 422.308 - Adjustments to capitation rates, benchmarks, bids, and payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... equivalence. CMS may add to, modify, or substitute for risk adjustment factors if those changes will improve... adjust for health status, CMS applies a risk factor based on data obtained in accordance with § 422.310. (ii) Implementation. CMS applies a risk factor that incorporates inpatient hospital and ambulatory...

Global warming potential of manure amended soils under rice-wheat system in the Indo-Gangetic plains

NASA Astrophysics Data System (ADS)

Bhatia, A.; Pathak, H.; Jain, N.; Singh, P. K.; Singh, A. K.

Use of organic amendments such as farmyard manure (FYM), green manure (GM) and crop residues is important to improve soil health and reduce the dependence on synthetic chemical fertilizer. However, these organic amendments also effect the emissions of greenhouse gas (GHG) from soil. Influence of different organic amendments on emissions of GHG from soil and their global warming potential (GWP) was studied in a field experiment in rice-wheat cropping system of Indo-Gangetic plains (IGP). There was 28% increase in CH 4 emissions on addition of 25% N through Sesbania GM along with urea compared to urea alone. Substitution of 100% inorganic N by organic sources lead to a 60% increase in CH 4 emissions. The carbon equivalent emission from rice-wheat systems varied between 3816 and 4886 kg C equivalent ha -1 depending upon fertilizer and organic amendment. GWP of rice-wheat system increased by 28% on full substitution of organic N by chemical N. However, the C efficiency ratios of the GM and crop residue treatments were at par with the recommended inorganic fertilizer treatment. Thus use of organic amendments along with inorganic fertilizer increases the GWP of the rice-wheat system but may improve the soil fertility status without adversely affecting the C efficiency ratio. However, the trade-off between improved yield and soil health versus GHG emissions should be taken into account while promoting the practice of farming with organic residues substitution for mineral fertilizer.

Trypanocidal 1,3-arylene diketone bis(guanylhydrazone)s. Structure-activity relationships among substituted and heterocyclic analogues.

PubMed

Ulrich, P; Cerami, A

1984-01-01

Based on the antitrypanosomal activity of 1,3-diacetylbenzene bis(guanylhydrazone) (4) and 2,6-diacetylpyridine bis(guanylhydrazone) (17), a number of substituted and heterocyclic 1,3-arylene diketone bis(guanylhydrazone)s were prepared and tested against Trypanosoma brucei infections in mice. A wide range of ED50 values was observed among 5-substituted derivatives of 4. The 5-amino analogue 5 and 5-acetamido analogue 6 were about twice as active as 4. 1,3,5-Triacetylbenzene tris(guanylhydrazone) (12) was about 9 times as active as 4 and was approximately one-half as active as the currently used trypanocide diminazene aceturate in this test system. Other 5-derivatives had activity equivalent to or less than that of the parent compound 4. Three new heterocyclic analogues were all less active than 2,6-diacetylpyridine derivative 17 and benzene derivative 4. Ring substitution ortho to the guanylhydrazone side chains was invariably detrimental to activity. Side-chain homologues 1,3-dipentanoylbenzene bis(guanylhydrazone) and 1,3-diacetylbenzene bis(2-imidazolin-2-ylhydrazone) were essentially inactive.

Diels-Alder Trapping of Photochemically Generated o-Xylenols: Application in the Synthesis of Novel Organic Molecules and Polymers

NASA Technical Reports Server (NTRS)

Meador, Michael A.

2003-01-01

Bis(o-xylenol) equivalents are useful synthetic intermediates in the construction of polymers and hydroxyl substituted organic molecules which can organize by hydrogen bonded self-assembly into unique supramolecular structures. These polymers and supramolecular materials have potential use as coatings and thin films in aerospace, electronic and biomedical applications.

40 CFR 63.94 - Approval of State permit terms and conditions that substitute for a section 112 rule.

Code of Federal Regulations, 2010 CFR

2010-07-01

... approval of a State program under this section and making a preliminary determination of equivalence, the... the Regional Office's decision, the State shall limit the number of sources for which it submits.... The Administrator will follow the process outlined in paragraph (a) of this section for up-front...

Insights into Casual Relief Teaching: Casual Relief Teachers' Perceptions of Their Knowledge and Skills

ERIC Educational Resources Information Center

Nicholas, Maria; Wells, Muriel

2017-01-01

Research into the experiences of casual relief teachers (CRTs) (substitute or supply teachers) across Australia and internationally has reported feelings of marginalisation among participants. These findings are concerning when one considers that students might be in the care of CRTs for an equivalent of 1 year or more throughout their schooling.…

New Fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species.

PubMed

Johnson, Michael E; Katiyar, Santosh K; Edlind, Thomas D

2011-08-01

Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two "hot spot" regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new "hot spot 3" in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES.

Differences in chemical doping matter: Superconductivity in Ti 1-xTa xSe 2 but not in Ti 1-xNb xSe 2

DOE PAGES

Luo, Huixia; Zhu, Yimei; Xie, Weiwei; ...

2016-02-21

We report that 1T-TiSe 2, an archetypical layered transition metal dichalcogenide, becomes superconducting when Ta is substituted for Ti but not when Nb is substituted for Ti. This is unexpected because Nb and Ta should be chemically equivalent electron donors. Superconductivity emerges near x = 0.02 for Ti 1–xTa xSe 2, while, for Ti 1–xNb xSe 2, no superconducting transitions are observed above 0.4 K. The equivalent chemical nature of the dopants is confirmed by X-ray photoelectron spectroscopy. ARPES and Raman scattering studies show similarities and differences between the two systems, but the fundamental reasons why the Nb and Tamore » dopants yield such different behavior are unknown. We present a comparison of the electronic phase diagrams of many electron-doped 1T-TiSe 2 systems, showing that they behave quite differently, which may have broad implications in the search for new superconductors. Here, we propose that superconducting Ti 0.8Ta 0.2Se 2 will be suitable for devices and other studies based on exfoliated crystal flakes.« less

Sequential Auctions with Partially Substitutable Goods

NASA Astrophysics Data System (ADS)

Vetsikas, Ioannis A.; Jennings, Nicholas R.

In this paper, we examine a setting in which a number of partially substitutable goods are sold in sequential single unit auctions. Each bidder needs to buy exactly one of these goods. In previous work, this setting has been simplified by assuming that bidders do not know their valuations for all items a priori, but rather are informed of their true valuation for each item right before the corresponding auction takes place. This assumption simplifies the strategies of bidders, as the expected revenue from future auctions is the same for all bidders due to the complete lack of private information. In our analysis we don't make this assumption. This complicates the computation of the equilibrium strategies significantly. We examine this setting both for first and second-price auction variants, initially when the closing prices are not announced, for which we prove that sequential first and second-price auctions are revenue equivalent. Then we assume that the prices are announced; because of the asymmetry in the announced prices between the two auction variants, revenue equivalence does not hold in this case. We finish the paper, by giving some initial results about the case when free disposal is allowed, and therefore a bidder can purchase more than one item.

EXPERIMENTAL RICKETS IN RATS

PubMed Central

Pappenheimer, A. M.; McCann, G. F.; Zucker, T. F.

1922-01-01

1. Casein phosphorus does not completely prevent the development of rickets when substituted in Diet 84 in amount equivalent to a protective dose of basic potassium phosphate. 2. The protection given by lecithin is equivalent to its phosphorus content. 3. The protection given by yeast is at least proportional to its phosphorus content. An amount carrying sufficient vitamine B to promote growth, but insufficient to provide adequate phosphorus, does not prevent rickets. 4. Vitamine A, in the form of butter or butter fat to the amount of 10 per cent of the diet, neither prevents nor cures rickets. 5. The substitution of 10 per cent of egg albumin in Diet 84 improves the nutrition, but does not prevent rickets. 6. The addition of meat to Diet 84, thereby supplying an abundance of phosphorus, promotes normal growth and normal bone formation. A diet consisting solely of meat and flour is inadequate for proper growth, and leads to changes in the bones comparable with those observed on a diet low in calcium, but rich in phosphorus. 7. A diet has been found which contains the necessary food elements for approximately normal growth, and in which the only known deficiency is phosphorus. This leads regularly to the production of rickets. PMID:19868618

Evaluation of 2,3,7,8 specific congener and toxic potency of persistent polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in cetaceans from the Mediterranean Sea, Italy

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

Jimenez, B.; Gonzalez, M.J.; Jimenez, O.

2000-03-01

The present study investigates individual 2,3,7,8-substituted polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) concentrations in cetaceans and assesses the PCDD and PCDF contributions to the total TCDD equivalent concentration. Liver samples of a variety of cetaceans species found stranded along the Italian coasts during the period of 1987--1992 were analyzed for PCDDs and PCDFs. The main aims were to scrutinize levels and patterns of PCDDs and PCDFs for the first time in cetaceans from the Mediterranean Sea and to estimate whether chlorinated compounds mentioned are implicated in the exceptionally high mortality of dolphins that occurred in the Mediterranean sea duringmore » 1990--1992. PCDD and PCDF profiles were dominated by congeners OCCD and OCDF. The new toxic equivalency factors recommended by WHO in 1997 were used for calculation of dioxin-like toxicity. On the basis of their previous study of PCBs, the overall TEQ calculated from the 2,3,7,8-substituted PCDDs and PCDFs do not contribute as much dioxin-like toxicity as PCBs.« less

Substitution determination of Fmoc‐substituted resins at different wavelengths

PubMed Central

Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

2017-01-01

In solid‐phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc‐substituted resins, substitution determination is often performed by suspending the Fmoc‐protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene–piperidine adduct that is quantified by ultraviolet–visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene–piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert–Beer's law, together with the substance‐specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol−1 cm−1 and 8100 l mol−1 cm−1 have been reported for the dibenzofulvene–piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. PMID:28635051

[Uncertainty evaluation of the determination of toxic equivalent quantity of polychlorinated dibenzo-p-dioxins and dibenzofurans in soil by isotope dilution high resolution gas chromatography and high resolution mass spectrometry].

PubMed

Du, Bing; Liu Aimin; Huang, Yeru

2014-09-01

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in soil samples were analyzed by isotope dilution method with high resolution gas chromatography and high resolution mass spectrometry (ID-HRGC/HRMS), and the toxic equivalent quantity (TEQ) were calculated. The impacts of major source of measurement uncertainty are discussed, and the combined relative standard uncertainties were calculated for each 2, 3, 7, 8 substituted con- gener. Furthermore, the concentration, combined uncertainty and expanded uncertainty for TEQ of PCDD/Fs in a soil sample in I-TEF, WHO-1998-TEF and WHO-2005-TEF schemes are provided as an example. I-TEF, WHO-1998-TEF and WHO-2005-TEF are the evaluation schemes of toxic equivalent factor (TEF), and are all currently used to describe 2,3,7,8 sub- stituted relative potencies.

The Farnsworth Flashlight is not equivalent to the Farnsworth Lantern.

PubMed

Dain, Stephen

2012-02-01

The Farnsworth Lantern has been accepted in many occupational applications. Modern instruments purporting to be equivalent were inevitable given the ubiquity of its use. The OPTEC900® (Stereo Optical) has been validated and adopted as an acceptable substitute, although the fail rate is slightly higher. The Farnsworth Flashlight (Gulden Ophthalmics) has been marketed without validation. The color and luminous intensities of the three lanterns' stimuli were measured using a Topcon SR-3 telespectroradiometer and compared with Farnsworth's recommendations. The OPTEC900® chromaticities comply with Farnsworth's recommendations, but the luminous intensities are rather different. The Farnsworth Flashlight differs from the Farnsworth Lantern in both chromaticity and luminous intensities. A cheap and portable equivalent to the Farnsworth Lantern is a highly attractive product. However, the Farnsworth Flashlight is significantly different in construction from the Farnsworth Lantern. © 2012 Optical Society of America

Amino acid substitution equivalent to human chorea-acanthocytosis I2771R in yeast Vps13 protein affects its binding to phosphatidylinositol 3-phosphate

PubMed Central

Rzepnikowska, Weronika; Flis, Krzysztof; Kaminska, Joanna; Grynberg, Marcin; Urbanek, Agnieszka; Ayscough, Kathryn R.

2017-01-01

Abstract The rare human disorder chorea-acanthocytosis (ChAc) is caused by mutations in hVPS13A gene. The hVps13A protein interacts with actin and regulates the level of phosphatidylinositol 4-phosphate (PI4P) in the membranes of neuronal cells. Yeast Vps13 is involved in vacuolar protein transport and, like hVps13A, participates in PI4P metabolism. Vps13 proteins are conserved in eukaryotes, but their molecular function remains unknown. One of the mutations found in ChAc patients causes amino acids substitution I2771R which affects the localization of hVps13A in skeletal muscles. To dissect the mechanism of pathogenesis of I2771R, we created and analyzed a yeast strain carrying the equivalent mutation. Here we show that in yeast, substitution I2749R causes dysfunction of Vps13 protein in endocytosis and vacuolar transport, although the level of the protein is not affected, suggesting loss of function. We also show that Vps13, like hVps13A, influences actin cytoskeleton organization and binds actin in immunoprecipitation experiments. Vps13-I2749R binds actin, but does not function in the actin cytoskeleton organization. Moreover, we show that Vps13 binds phospholipids, especially phosphatidylinositol 3-phosphate (PI3P), via its SHR_BD and APT1 domains. Substitution I2749R attenuates this ability. Finally, the localization of Vps13-GFP is altered when cellular levels of PI3P are decreased indicating its trafficking within the endosomal membrane system. These results suggest that PI3P regulates the functioning of Vps13, both in protein trafficking and actin cytoskeleton organization. Attenuation of PI3P-binding ability in the mutant hVps13A protein may be one of the reasons for its mislocalization and disrupted function in cells of patients suffering from ChAc. PMID:28334785

Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PubMed

Le Calvez-Kelm, Florence; Lesueur, Fabienne; Damiola, Francesca; Vallée, Maxime; Voegele, Catherine; Babikyan, Davit; Durand, Geoffroy; Forey, Nathalie; McKay-Chopin, Sandrine; Robinot, Nivonirina; Nguyen-Dumont, Tù; Thomas, Alun; Byrnes, Graham B; Hopper, John L; Southey, Melissa C; Andrulis, Irene L; John, Esther M; Tavtigian, Sean V

2011-01-18

Both protein-truncating variants and some missense substitutions in CHEK2 confer increased risk of breast cancer. However, no large-scale study has used full open reading frame mutation screening to assess the contribution of rare missense substitutions in CHEK2 to breast cancer risk. This absence has been due in part to a lack of validated statistical methods for summarizing risk attributable to large numbers of individually rare missense substitutions. Previously, we adapted an in silico assessment of missense substitutions used for analysis of unclassified missense substitutions in BRCA1 and BRCA2 to the problem of assessing candidate genes using rare missense substitution data observed in case-control mutation-screening studies. The method involves stratifying rare missense substitutions observed in cases and/or controls into a series of grades ordered a priori from least to most likely to be evolutionarily deleterious, followed by a logistic regression test for trends to compare the frequency distributions of the graded missense substitutions in cases versus controls. Here we used this approach to analyze CHEK2 mutation-screening data from a population-based series of 1,303 female breast cancer patients and 1,109 unaffected female controls. We found evidence of risk associated with rare, evolutionarily unlikely CHEK2 missense substitutions. Additional findings were that (1) the risk estimate for the most severe grade of CHEK2 missense substitutions (denoted C65) is approximately equivalent to that of CHEK2 protein-truncating variants; (2) the population attributable fraction and the familial relative risk explained by the pool of rare missense substitutions were similar to those explained by the pool of protein-truncating variants; and (3) post hoc power calculations implied that scaling up case-control mutation screening to examine entire biochemical pathways would require roughly 2,000 cases and controls to achieve acceptable statistical power. This study shows that CHEK2 harbors many rare sequence variants that confer increased risk of breast cancer and that a substantial proportion of these are missense substitutions. The study validates our analytic approach to rare missense substitutions and provides a method to combine data from protein-truncating variants and rare missense substitutions into a one degree of freedom per gene test.

Combined LC/MS-platform for analysis of all major stratum corneum lipids, and the profiling of skin substitutes.

PubMed

van Smeden, Jeroen; Boiten, Walter A; Hankemeier, Thomas; Rissmann, Robert; Bouwstra, Joke A; Vreeken, Rob J

2014-01-01

Ceramides (CERs), cholesterol, and free fatty acids (FFAs) are the main lipid classes in human stratum corneum (SC, outermost skin layer), but no studies report on the detailed analysis of these classes in a single platform. The primary aims of this study were to 1) develop an LC/MS method for (semi-)quantitative analysis of all main lipid classes present in human SC; and 2) use this method to study in detail the lipid profiles of human skin substitutes and compare them to human SC lipids. By applying two injections of 10μl, the developed method detects all major SC lipids using RPLC and negative ion mode APCI-MS for detection of FFAs, and NPLC using positive ion mode APCI-MS to analyze CERs and cholesterol. Validation showed this lipid platform to be robust, reproducible, sensitive, and fast. The method was successfully applied on ex vivo human SC, human SC obtained from tape strips and human skin substitutes (porcine SC and human skin equivalents). In conjunction with FFA profiles, clear differences in CER profiles were observed between these different SC sources. Human skin equivalents more closely mimic the lipid composition of human stratum corneum than porcine skin does, although noticeable differences are still present. These differences gave biologically relevant information on some of the enzymes that are probably involved in SC lipid processing. For future research, this provides an excellent method for (semi-)quantitative, 'high-throughput' profiling of SC lipids and can be used to advance the understanding of skin lipids and the biological processes involved. © 2013.

A Healthy Reduction in Oil Dependence and Carbon Emissions

NASA Astrophysics Data System (ADS)

Higgins, P. A.; Higgins, M.

2003-12-01

Societal dependence on oil as an energy source for personal transportation leads to increasingly negative social consequences including climate change, air pollution, political and economic instability and habitat degradation. Our heavy reliance on the automobile for transportation, determined in part by urban sprawl, also contributes to the population's increasingly sedentary lifestyle and to a concomitant degradation in health. We have shown that widespread substitution of exercise, commensurate with previously recommended levels, through biking or walking instead of driving can substantially reduce oil consumption and carbon emissions. For example, if all individuals between the ages of 10 and 64 substituted one hour of cycling for driving the reduction in gasoline demand would be equivalent to the gas produced from 34.9 percent of current oil consumption. Relative to 1990 net US emissions, this constitutes a 10.9 percent reduction in carbon emissions. Therefore, substitution of exercise for driving could improve health, reduce carbon emissions and save more oil than even upper estimates of that contained in the Arctic National Wildlife Refuge.

Advanced therapies of skin injuries.

PubMed

Maver, Tina; Maver, Uroš; Kleinschek, Karin Stana; Raščan, Irena Mlinarič; Smrke, Dragica Maja

2015-12-01

The loss of tissue is still one of the most challenging problems in healthcare. Efficient laboratory expansion of skin tissue to reproduce the skins barrier function can make the difference between life and death for patients with extensive full-thickness burns, chronic wounds, or genetic disorders such as bullous conditions. This engineering has been initiated based on the acute need in the 1980s and today, tissue-engineered skin is the reality. The human skin equivalents are available not only as models for permeation and toxicity screening, but are frequently applied in vivo as clinical skin substitutes. This review aims to introduce the most important recent development in the extensive field of tissue engineering and to describe already approved, commercially available skin substitutes in clinical use.

New Fks Hot Spot for Acquired Echinocandin Resistance in Saccharomyces cerevisiae and Its Contribution to Intrinsic Resistance of Scedosporium Species▿

PubMed Central

Johnson, Michael E.; Katiyar, Santosh K.; Edlind, Thomas D.

2011-01-01

Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two “hot spot” regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new “hot spot 3” in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES. PMID:21576441

Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease

PubMed Central

Kesselheim, Aaron S.; Misono, Alexander S.; Lee, Joy L.; Stedman, Margaret R.; Brookhart, M. Alan; Choudhry, Niteesh K.; Shrank, William H.

2009-01-01

Context Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. Objectives To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Data Sources Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Study Selection Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. Data Extraction We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors’ positions on generic substitution as negative, positive, or neutral. Results We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of β-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of α-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was −0.03 (95% confidence interval, −0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. Conclusions Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs. PMID:19050195

Factors associated with the acceptance of sugar and sugar substitutes by the public.

PubMed

Mackay, D A

1985-09-01

Acceptance is described in both market and sensory research terminology and recent developments in the fields of applied psychology and physiology are examined for their pertinence to public acceptance of sucrose and its substitutes. Information on the function of sucrose in foods other than beverages is presented with emphasis on salivation as an acceptance factor and attention is drawn to its possible dental significance. Distinctions are made between the sweetening and bulking properties of sucrose and sugar substitutes. Factors having a bearing on the acceptance of sweet foods and the determination of their optimal sugar content are described in detail. While major decreases in sucrose intake in the US resulted from high-fructose corn-sweetener usage in soft drinks, no evidence is yet available to suggest that the use of sugar substitutes of the intense artificial sweetener type has caused any decrease in ordinary sugar consumption. Neither is the consumption of polyols (sorbitol, mannitol, xylitol) high enough in confectionery categories to cause any discernible decrease in sugar usage. The evidence suggests not so much that sugar substitutes may have stopped the growth in sucrose usage, but that new product categories such as diet foods and "sugarless' confections may have been created. These categories were never available to fermentable carbohydrate sweeteners and equivalence in acceptance to sucrose-sweetened products was not an important factor in their growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Substitution determination of Fmoc-substituted resins at different wavelengths.

PubMed

Eissler, Stefan; Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

2017-10-01

In solid-phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc-substituted resins, substitution determination is often performed by suspending the Fmoc-protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene-piperidine adduct that is quantified by ultraviolet-visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene-piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert-Beer's law, together with the substance-specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol -1  cm -1 and 8100 l mol -1  cm -1 have been reported for the dibenzofulvene-piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

Red light accelerates the formation of a human dermal equivalent.

PubMed

Oliveira, Anna Cb; Morais, Thayz Fl; Bernal, Claudia; Martins, Virginia Ca; Plepis, Ana Mg; Menezes, Priscila Fc; Perussi, Janice R

2018-04-01

Development of biomaterials' substitutes and/or equivalents to mimic normal tissue is a current challenge in tissue engineering. Thus, three-dimensional cell culture using type I collagen as a polymeric matrix cell support designed to promote cell proliferation and differentiation was employed to create a dermal equivalent in vitro, as well to evaluate the photobiomodulation using red light. Polymeric matrix cell support was prepared from porcine serous collagen (1.1%) hydrolyzed for 96 h. The biomaterial exhibited porosity of 95%, a median pore of 44 µm and channels with an average distance between the walls of 78 ± 14 µm. The absorption of culture medium was 95%, and the sponge showed no cytotoxicity to Vero cells, a non-tumor cell line. Additionally, it was observed that irradiation with light at 630 nm (fluency 30 J cm -2 ) leads to the cellular photobiomodulation in both monolayer and human dermal equivalent (three-dimensional cell culture system). It was also verified that the cells cultured in the presence of the polymeric matrix cell support, allows differentiation and extracellular matrix secretion. Therefore, the results showed that the collagen sponge used as polymeric matrix cell support and the photobiomodulation at 630 nm are efficient for the production of a reconstructed human dermal equivalent in vitro.

Black-footed ferrets and Siberian polecats as ecological surrogates and ecological equivalents

USGS Publications Warehouse

Biggins, D.E.; Hanebury, L.R.; Miller, B.J.; Powell, R.A.

2011-01-01

Ecologically equivalent species serve similar functions in different communities, and an ecological surrogate species can be used as a substitute for an equivalent species in a community. Siberian polecats (Mustela eversmanii) and black-footed ferrets (M. nigripes) have long been considered ecological equivalents. Polecats also have been used as investigational surrogates for black-footed ferrets, yet the similarities and differences between the 2 species are poorly understood. We contrasted activity patterns of radiotagged polecats and ferrets released onto ferret habitat. Ferrets tended to be nocturnal and most active after midnight. Polecats were not highly selective for any period of the day or night. Ferrets and polecats moved most during brightly moonlit nights. The diel activity pattern of ferrets was consistent with avoidance of coyotes (Canis latrans) and diurnal birds of prey. Similarly, polecat activity was consistent with avoidance of red foxes (Vulpes vulpes) in their natural range. Intraguild predation (including interference competition) is inferred as a selective force influencing behaviors of these mustelines. Examination of our data suggests that black-footed ferrets and Siberian polecats might be ecological equivalents but are not perfect surrogates. Nonetheless, polecats as surrogates for black-footed ferrets have provided critical insight needed, especially related to predation, to improve the success of ferret reintroductions. ?? 2011 American Society of Mammalogists.

Considerable contribution of the Montreal Protocol to declining greenhouse gas emissions from the United States

NASA Astrophysics Data System (ADS)

Hu, Lei; Montzka, Stephen A.; Lehman, Scott J.; Godwin, David S.; Miller, Benjamin R.; Andrews, Arlyn E.; Thoning, Kirk; Miller, John B.; Sweeney, Colm; Siso, Caroline; Elkins, James W.; Hall, Bradley D.; Mondeel, Debra J.; Nance, David; Nehrkorn, Thomas; Mountain, Marikate; Fischer, Marc L.; Biraud, Sébastien C.; Chen, Huilin; Tans, Pieter P.

2017-08-01

Ozone depleting substances (ODSs) controlled by the Montreal Protocol are potent greenhouse gases (GHGs), as are their substitutes, the hydrofluorocarbons (HFCs). Here we provide for the first time a comprehensive estimate of U.S. emissions of ODSs and HFCs based on precise measurements in discrete air samples from across North America and in the remote atmosphere. Derived emissions show spatial and seasonal variations qualitatively consistent with known uses and largely confirm U.S. Environmental Protection Agency (EPA) national emissions inventories for most gases. The measurement-based results further indicate a substantial decline of ODS emissions from 2008 to 2014, equivalent to 50% of the CO2-equivalent decline in combined emissions of CO2 and all other long-lived GHGs inventoried by the EPA for the same period. Total estimated CO2-equivalent emissions of HFCs were comparable to the sum of ODS emissions in 2014, but can be expected to decline in the future in response to recent policy measures.

Effects of Stoichiometry on Transformation Temperatures and Actuator-Type Performance of NiTiPd and NiTiPdX High-Temperature Shape Memory Alloys

NASA Technical Reports Server (NTRS)

Bigelow, Glen S.; Gaydosh, Darrell; Garg, Anita; Padula, Santo A., II; Noebe, Ronald D.

2007-01-01

High-temperature shape memory NiTiPd and NiTiPdX (X=Au, Pt, Hf) alloys were produced with titanium equivalent (Ti+Hf) compositions of 50.5, 50.0, 49.5, and 49.0 at.%. Thermo-mechanical testing in compression was used to evaluate the transformation temperatures, transformation strain, work output, and permanent deformation behavior of each alloy to study the effects of quaternary alloying and stoichiometry on high-temperature shape memory alloy behavior. Microstructural evaluation showed the presence of second phases for all alloy compositions. No load transformation temperatures in the stoichiometric alloys were relatively unchanged by Au and Pt substitutions, while the substitution of Hf for Ti causes a drop in transformation temperatures. The NiTiPd, NiTiPdAu and NiTiPdHf alloys exhibited transformation temperatures that were highest in the Ti-rich compositions, slightly lower at stoichiometry, and significantly reduced when the Ti equivalent composition was less than 50 at.%. For the NiTiPdPt alloy, transformation temperatures were highest for the Ti-rich compositions, lowest at stoichiometry, and slightly higher in the Ni-rich composition. When thermally cycled under constant stresses of up to 300 MPa, all of the alloys had transformation strains, and therefore work outputs, which increased with increasing stress. In each series of alloys, the transformation strain and thus work output was highest for stoichiometric or Ti-rich compositions while permanent strain associated with the constant-load thermal cycling was lowest for alloys with Ni-equivalent-rich compositions. Based on these results, basic rules for optimizing the composition of NiTiPd alloys for actuator performance will be discussed.

Greenhouse gas emissions of different waste treatment options for sector-specific commercial and industrial waste in Germany.

PubMed

Helftewes, Markus; Flamme, Sabine; Nelles, Michael

2012-04-01

This article investigates greenhouse gas (GHG) emissions from commercial and industrial (C&I) waste treatment considering five sector-specific waste compositions and four different treatment scenarios in Germany. Results show that the highest share of CO₂-equivalent emissions can be avoided in each of the analysed industrial sectors if solid recovered fuel (SRF) is produced for co-incineration in cement kilns. Across all industries, emissions of approximately 680 kg CO₂-eq. Mg⁻¹ C&I waste can be avoided on average under this scenario. The combustion of C&I waste in waste incineration plants without any previous mechanical treatment generates the lowest potential to avoid GHG emissions with a value of approximately 50 kg CO₂-eq. Mg⁻¹ C&I waste on average in all industries. If recyclables are sorted, this can save emissions of approximately 280 kg CO₂-eq. Mg⁻¹ C&I waste while the treatment in SRF power plants amounts to savings of approximately 210 kg CO₂-eq. Mg⁻¹ C&I waste. A comparison of the treatment scenarios of the waste from these five sectors shows that waste treatment of the craft sector leads to the lowest CO₂-equivalent reduction rates of all scenarios. In contrast, the treatment of waste from catering sector leads to the highest CO₂-equivalent reduction rates except for direct incineration in waste incineration plants. The sensitivity analysis of the different scenarios for this paper shows that the efficiency and the substitution factor of energy have a relevant influence on the result. Changes in the substitution factor of 10% can result in changes in emissions of approximately 55 to 75 kg CO₂-eq. Mg⁻¹ in waste incineration plants and approximately 90 kg CO₂-eq. Mg⁻¹ in the case of cement kilns.

Cervi cornus Colla (deer antler glue) induce epidermal differentiation in the reconstruction of skin equivalents.

PubMed

Choi, H-R; Nam, K-M; Kim, D-S; Huh, C-H; Na, J-I; Park, K-C

2013-06-01

In the reconstruction of skin equivalents (SEs), keratinocyte differentiation is important because epidermal differentiation is closely related with barrier function. The aim of this study was to investigate the effects of Cervi cornus Colla (CCC) on the stem cell activity and epidermal differentiation in the reconstruction of skin equivalent. Four different models were constructed according to different composition of dermal substitute. Results showed similar morphologic findings when hyaluronic acid (HA) and/or CCC was added. But, immunohistochemical staining showed that p63 was significantly increased by addition of HA and/or CCC. Increased staining of integrin α6 and β1 was variably observed when HA and/or CCC was added to make dermal substitute. These finding showed that addition of HA and/or CCC may affect the stem cell activity in the reconstruction of skin. Furthermore, filaggrin expression was much increased when CCC was added. It showed that epidermal differentiation was significantly improved by addition of CCC. In conclusion, simultaneous presence of HA and CCC contributed to the stem cell activity and epidermal differentiation in the reconstruction of SE. Legislation in the EU prohibits marketing cosmetics and personal care products that contain constituents that have been examined through animal experiments. To avoid these limitations, SEs can be used for testing the safety or the efficacy of cosmetic ingredients. Therefore, our results showed that combined use of HA and CCC can be helpful for the reconstruction of SE with good stem cell activity and epidermal differentiation. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Engineering Upper Hinge Improves Stability and Effector Function of a Human IgG1

PubMed Central

Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y.; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf

2012-01-01

Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys231 directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His229-mediated hinge cleavage. On the other hand, the substitution of His229 with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2–3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed. PMID:22203673

Engineering upper hinge improves stability and effector function of a human IgG1.

PubMed

Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf

2012-02-17

Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys(231) directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His(229)-mediated hinge cleavage. On the other hand, the substitution of His(229) with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2-3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed.

Equivalence between short-time biphasic and incompressible elastic material responses.

PubMed

Ateshian, Gerard A; Ellis, Benjamin J; Weiss, Jeffrey A

2007-06-01

Porous-permeable tissues have often been modeled using porous media theories such as the biphasic theory. This study examines the equivalence of the short-time biphasic and incompressible elastic responses for arbitrary deformations and constitutive relations from first principles. This equivalence is illustrated in problems of unconfined compression of a disk, and of articular contact under finite deformation, using two different constitutive relations for the solid matrix of cartilage, one of which accounts for the large disparity observed between the tensile and compressive moduli in this tissue. Demonstrating this equivalence under general conditions provides a rationale for using available finite element codes for incompressible elastic materials as a practical substitute for biphasic analyses, so long as only the short-time biphasic response is sought. In practice, an incompressible elastic analysis is representative of a biphasic analysis over the short-term response deltat

Equivalent Sensor Radiance Generation and Remote Sensing from Model Parameters. Part 1; Equivalent Sensor Radiance Formulation

NASA Technical Reports Server (NTRS)

Wind, Galina; DaSilva, Arlindo M.; Norris, Peter M.; Platnick, Steven E.

2013-01-01

In this paper we describe a general procedure for calculating equivalent sensor radiances from variables output from a global atmospheric forecast model. In order to take proper account of the discrepancies between model resolution and sensor footprint the algorithm takes explicit account of the model subgrid variability, in particular its description of the probably density function of total water (vapor and cloud condensate.) The equivalent sensor radiances are then substituted into an operational remote sensing algorithm processing chain to produce a variety of remote sensing products that would normally be produced from actual sensor output. This output can then be used for a wide variety of purposes such as model parameter verification, remote sensing algorithm validation, testing of new retrieval methods and future sensor studies. We show a specific implementation using the GEOS-5 model, the MODIS instrument and the MODIS Adaptive Processing System (MODAPS) Data Collection 5.1 operational remote sensing cloud algorithm processing chain (including the cloud mask, cloud top properties and cloud optical and microphysical properties products.) We focus on clouds and cloud/aerosol interactions, because they are very important to model development and improvement.

Particle Density Substitution Method for Trafficability of Soil in Different Gravity Environments

NASA Astrophysics Data System (ADS)

Huang, Chuan; Gao, Feng; Xie, Xiaolin; Jiang, Hui; Zeng, Wen

2017-12-01

By selecting metal powders with comparable particle size class, similar shape and material and almost the same void ratio but different particle densities, the influence of different gravity on the trafficability of soil under different states of gravitational fields is found to be equivalent to the change in particle density. This method is named particle density substitution. The shearing and bearing characteristics of simulated soil were studied. An influence of different factors on the experimental results was achieved, and a minimal influence of factors other than particle density on experimental results was obtained. Regression of shearing and bearing characteristics of the simulated soil was designed. The relationship between particle density and mechanical parameters of soil was fitted with curves. The formulation between particle density and maximal static thrust was established. By analyzing these data, the maximal static thrust slowly decreased with increasing particle density, reached the minimum when particle density was 3 g/cm3, and then sharply increased. This trend is consistent with the theoretical result. It can also certify that the particle density substitution method established here is reasonable.

[The skin substitute center--a need in the treatment of patients with severe burns].

PubMed

Pieptu, D; Luchian, S

1999-01-01

The treatment of the severe burned patient has two main dimensions acting in an interdependent manner. First it is the life keeping and the second is skin resurfacing in a fair period of time. The failure of one of these two components leads to the patient's death. In the absence of the autografts the skin resurfacing has to be made by permanent skin substitutes--cultured epithelium, dermal equivalents or reconstructed skin, developed by a special unit, a Skin Substitute Center. The paper is setting the utility of such a center in our area, and the possible developing directions. It is our firm opinion that in case of failure to develop such a center, despite all the financial efforts directed toward the infrastructure of a modern Burn Unit affiliated to an University Accident Hospital, all the surgical experience cumulated during the past 13 years by a very motivated team, good quality results are still to be expected. Any patient with a deep second degree burn on more than 50% TBSA will be a potentially victim as in early 60s.

Equivalent model construction for a non-linear dynamic system based on an element-wise stiffness evaluation procedure and reduced analysis of the equivalent system

NASA Astrophysics Data System (ADS)

Kim, Euiyoung; Cho, Maenghyo

2017-11-01

In most non-linear analyses, the construction of a system matrix uses a large amount of computation time, comparable to the computation time required by the solving process. If the process for computing non-linear internal force matrices is substituted with an effective equivalent model that enables the bypass of numerical integrations and assembly processes used in matrix construction, efficiency can be greatly enhanced. A stiffness evaluation procedure (STEP) establishes non-linear internal force models using polynomial formulations of displacements. To efficiently identify an equivalent model, the method has evolved such that it is based on a reduced-order system. The reduction process, however, makes the equivalent model difficult to parameterize, which significantly affects the efficiency of the optimization process. In this paper, therefore, a new STEP, E-STEP, is proposed. Based on the element-wise nature of the finite element model, the stiffness evaluation is carried out element-by-element in the full domain. Since the unit of computation for the stiffness evaluation is restricted by element size, and since the computation is independent, the equivalent model can be constructed efficiently in parallel, even in the full domain. Due to the element-wise nature of the construction procedure, the equivalent E-STEP model is easily characterized by design parameters. Various reduced-order modeling techniques can be applied to the equivalent system in a manner similar to how they are applied in the original system. The reduced-order model based on E-STEP is successfully demonstrated for the dynamic analyses of non-linear structural finite element systems under varying design parameters.

Design and Synthesis of Candidate Prophylactic and Therapeutic Compounds for Use in the Management of Organophosphorus Poisoning.

DTIC Science & Technology

1985-01-01

resynthesis. The Grignard reagent , prepared from 4- chlorobromobenzene and magnesium metal, was treated with NN-diethyl-P- methylphosphonamidic chloride and the...ref. 26-28). Thus, diethylaminodichlorophosphine was treated with two equivalents of butyl Grignard reagent to give phosphinous amide 1 in 63% yield...compound following a general method developed by Ash Stevens Inc. for the synthesis of substituted aryl methylphosphinates. Thus, the Grignard reagent

Pharmacists' views and reported practices in relation to a new generic drug substitution policy in Lebanon: a mixed methods study.

PubMed

El-Jardali, Fadi; Fadlallah, Racha; Morsi, Rami Z; Hemadi, Nour; Al-Gibbawi, Mounir; Haj, Magda; Khalil, Suzan; Saklawi, Youssef; Jamal, Diana; Akl, Elie A

2017-02-17

Governments in both developed and developing countries have adopted generic drug substitution policies to decrease pharmaceutical expenditures and improve access to medicine. In August 2015, the Ministry of Public Health (MOPH) in Lebanon introduced generic drug substitution and a unified medical prescription form as policy instruments to promote generic drug use. The objective of this exploratory study was to examine the attitudes of community pharmacists and the reported practices in relation to the implementation of the new generic drug substitution policy. We used a cross-sectional mixed methods approach composed of self-administered questionnaires and semi-structured interviews. The study population consisted of community pharmacists in Lebanon. We randomly approached one pharmacy personnel from each selected community pharmacy. We conducted descriptive analyses to assess responses to questionnaire and regression analyses to understand associations between responses and respondent demographics. We analyzed qualitative data thematically. Out of 204 invited community pharmacies, 153 pharmacies participated (75% response rate). The majority of respondents (64%) were in favor of generic drug substitution; however, less than half (40%) indicated they have substituted brand drugs for generic equivalents. Moreover, 57% indicated that the existing pricing system discourages them from performing generic drug substitution. Most respondents indicated that physicians are overusing the "non-substitutable" option (84%) and that there are technical problems with processing the new prescription form (78%). Less than half (47%) reported that the MOPH is performing regular audits on the forms collected by the pharmacy. While 45% of the respondents indicated that consumers have accepted most of the generic substitutions, 21% perceived the increase in generic drug dispensing to be significant. Findings suggested a potentially significant association between being informed about generic drugs and respondents' support of the policy. Suggested strategies to address implementation challenges included strengthening stewardship function of MOPH, securing full commitment of health care providers, conducting educational and awareness campaigns about generic drugs and generic drug substitution, and aligning incentive systems of the key stakeholders. The majority of community pharmacists were supportive of generic drug substitution in general but not of the current implementation of the policy in Lebanon. Findings revealed implementation challenges at the provider, patient, and system level which are hindering attainment of the policy objectives. The key lessons derived from this study can be used for continuous improvement of the policy and its implementation.

Using equivalence-based instruction to teach piano skills to college students.

PubMed

Griffith, Kristin R; Ramos, Amber L; Hill, Kelli E; Miguel, Caio F

2018-04-01

The purpose of the current study was to evaluate the effects of equivalence-based instruction (EBI) on the emergence of basic music reading and piano playing skills. Six female college students learned to identify three musical chord notations given their respective dictated names. Participants also learned to play chords on the piano following the dictated name of the chord, and to play the chords to a song on a keyboard. Results are consistent with past research, in that stimuli became substitutable for each other and acquired a common behavioral function. Data suggest that EBI was an effective and efficient procedure to teach adults to read musical notation, as well as play chords and a song on a piano keyboard. © 2018 Society for the Experimental Analysis of Behavior.

Optimized alumina coagulants for water treatment

DOEpatents

Nyman, May D [Albuquerque, NM; Stewart, Thomas A [Albuquerque, NM

2012-02-21

Substitution of a single Ga-atom or single Ge-atom (GaAl.sub.12 and GeAl.sub.12 respectively) into the center of an aluminum Keggin polycation (Al.sub.13) produces an optimal water-treatment product for neutralization and coagulation of anionic contaminants in water. GaAl.sub.12 consistently shows .about.1 order of magnitude increase in pathogen reduction, compared to Al.sub.13. At a concentration of 2 ppm, GaAl.sub.12 performs equivalently to 40 ppm alum, removing .about.90% of the dissolved organic material. The substituted GaAl.sub.12 product also offers extended shelf-life and consistent performance. We also synthesized a related polyaluminum chloride compound made of pre-hydrolyzed dissolved alumina clusters of [GaO.sub.4Al.sub.12(OH).sub.24(H.sub.2O).sub.12].sup.7+.

Vinylcyclopropylacyl and polyeneacyl radicals. Intramolecular ketene alkyl radical additions in ring synthesis.

PubMed

De Boeck, Benoit; Herbert, Nicola M A; Harrington-Frost, Nicole M; Pattenden, Gerald

2005-01-21

Treatment of a variety of substituted vinylcyclopropyl selenyl esters, e.g. 11, with Bu(3)SnH-AIBN in refluxing benzene leads to the corresponding acyl radical intermediates, which undergo rearrangement and intramolecular cyclisations via their ketene alkyl radical equivalents producing cyclohexenones in 50-60% yield. By contrast, treatment of conjugated triene selenyl esters, e.g. 32, with Bu(3)SnH-AIBN produces substituted 2-cyclopentenones via intramolecular cyclisations of their ketene alkyl radical intermediates. Under the same radical-initiating conditions the selenyl esters derived from o-vinylbenzoic acid and o-vinylcinnamic acid undergo intramolecular cyclisations producing 1-indanone and 5,6-dihydrobenzocyclohepten-7-one respectively in 60-70% yields. A tandem radical cyclisation from the alpha,beta,gamma,delta-diene selenyl ester 31 provides an expeditious synthesis of the diquinane 35 in 69% yield.

Potential to curb the environmental burdens of American beef consumption using a novel plant-based beef substitute

PubMed Central

Moses, Rebekah; Sammons, Norman; Birkved, Morten

2017-01-01

The food demands of the United States (US) impart significant environmental pressures. The high rate of consumption of beef has been shown to be the largest driver of food-borne greenhouse gas emissions, water use and land occupation in the US diet. The environmental benefits of substituting animal products with vegetal foods are well documented, but significant psychological barriers persist in reducing meat consumption. Here we use life cycle assessment to appraise the environmental performance of a novel vegetal protein source in the mean US diet where it replaces ground beef, and in vegetarian and vegan diets where it substitutes for legumes, tofu and other protein sources. We find that relative to the mean US diet, vegetarian and vegan diets significantly reduce per-capita food-borne greenhouse gas emission (32% and 67%, respectively), blue water use (70% and 75%, respectively) and land occupation (70% and 79%, respectively), primarily in the form of rangeland. The substitution of 10%, 25% and 50% of ground beef with plant-based burger (PBB) at the national scale results in substantial reductions in annual US dietary greenhouse gas emissions (4.55–45.42 Mt CO2 equivalents), water consumption (1.30–12.00 km3) and land occupation (22300–190100 km2). Despite PBB’s elevated environmental pressures compared to other vegetal protein sources, we demonstrate that minimal risk exists for the disservices of PBB substitution in non-meat diets to outweigh the benefits of ground-beef substitution in the omnivorous American diet. Demand for plant-based oils in PBB production has the potential to increase land use pressures in biodiversity hotspots, though these could be obviated through responsible land stewardship. Although the apparent environmental benefits of the PBB are contingent on actual uptake of the product, this study demonstrates the potential for non-traditional protein substitutes to play a role in a transition towards more sustainable consumption regimes in the US and potentially abroad. PMID:29211775

A case study in generic drug use: should there be risk adjustment in incentive payments for the use of generic medications?

PubMed

Walton, Surrey M; Rash, Christine; Lambert, Bruce L; Galanter, William L

2014-11-01

Encouraging generic drug use has reduced health care costs for payers and consumers, but the availability of therapeutically interchangeable medications or generic medications of choice is not equal across disease states. The extent to which systems of care are able to substitute with generics is not well understood.  To (a) define and measure the maximum generic rate (MGR) of currently prescribed drugs within an academic medical group in and (b) illustrate differences across drugs associated with selected underlying diseases.   Prescription claims data were examined from an academic medical group in Chicago, Illinois. Based on pharmacologic and therapeutic criteria, drugs were classified into 2 categories-potentially substitutable and not potentially substitutable-based on whether the drugs are branded forms of the same chemical entities that are available as generics or are therapeutically interchangeable with other medications that have different chemical compositions but the same mechanisms of action and potential efficacy. A medication was considered potentially substitutable if it (a) did not have a narrow therapeutic index as defined by the FDA; (b) did not belong to 1 of 6 protected classes of drugs in the Medicare D provisions; (c) was substitutable with a generic medication containing the same chemical entity; or (d) was therapeutically interchangeable with a therapeutically equivalent medication. MGR was defined as the percentage of prescriptions that could potentially be prescribed in generic form. This rate was examined overall and across drugs known to be associated with illustrative diseases including hypertension, diabetes mellitus, and obstructive lung diseases.   The MGR ranged from 100% for drugs used in hypertension to 26.7% for drugs used in obstructive lung diseases. The MGR was 83.6%.  Payers wishing to promote generic substitution should incorporate the potential for substitution of clinically appropriate generic medications as part of incentives for generic utilization to avoid unintended consequences of using a fixed target rate. A practical methodology for determining an MGR is offered.

Potential to curb the environmental burdens of American beef consumption using a novel plant-based beef substitute.

PubMed

Goldstein, Benjamin; Moses, Rebekah; Sammons, Norman; Birkved, Morten

2017-01-01

The food demands of the United States (US) impart significant environmental pressures. The high rate of consumption of beef has been shown to be the largest driver of food-borne greenhouse gas emissions, water use and land occupation in the US diet. The environmental benefits of substituting animal products with vegetal foods are well documented, but significant psychological barriers persist in reducing meat consumption. Here we use life cycle assessment to appraise the environmental performance of a novel vegetal protein source in the mean US diet where it replaces ground beef, and in vegetarian and vegan diets where it substitutes for legumes, tofu and other protein sources. We find that relative to the mean US diet, vegetarian and vegan diets significantly reduce per-capita food-borne greenhouse gas emission (32% and 67%, respectively), blue water use (70% and 75%, respectively) and land occupation (70% and 79%, respectively), primarily in the form of rangeland. The substitution of 10%, 25% and 50% of ground beef with plant-based burger (PBB) at the national scale results in substantial reductions in annual US dietary greenhouse gas emissions (4.55-45.42 Mt CO2 equivalents), water consumption (1.30-12.00 km3) and land occupation (22300-190100 km2). Despite PBB's elevated environmental pressures compared to other vegetal protein sources, we demonstrate that minimal risk exists for the disservices of PBB substitution in non-meat diets to outweigh the benefits of ground-beef substitution in the omnivorous American diet. Demand for plant-based oils in PBB production has the potential to increase land use pressures in biodiversity hotspots, though these could be obviated through responsible land stewardship. Although the apparent environmental benefits of the PBB are contingent on actual uptake of the product, this study demonstrates the potential for non-traditional protein substitutes to play a role in a transition towards more sustainable consumption regimes in the US and potentially abroad.

Dietary Fat, Fiber, and Carbohydrate Intake and Endogenous Hormone Levels in Premenopausal Women

PubMed Central

Cui, Xiaohui; Rosner, Bernard; Willett, Walter C; Hankinson, Susan E

2011-01-01

The authors conducted a cross-sectional study to investigate the associations of fat, fiber and carbohydrate intake with endogenous estrogen, androgen, and insulin-like growth factor (IGF) levels among 595 premenopausal women. Overall, no significant associations were found between dietary intake of these macronutrients and plasma sex steroid hormone levels. Dietary fat intake was inversely associated with IGF-I and IGF-binding protein 3 (IGFBP-3) levels. When substituting 5% of energy from total fat for the equivalent amount of energy from carbohydrate or protein intake, the plasma levels of IGF-I and IGFBP-3 were 2.8% (95% confidence interval [CI] 0.3, 5.3) and 1.6% (95% CI 0.4, 2.8) lower, respectively. Animal fat, saturated fat and monounsaturated fat intakes also were inversely associated with IGFBP-3 levels (P < 0.05). Carbohydrates were positively associated with plasma IGF-I level. When substituting 5% of energy from carbohydrates for the equivalent amount of energy from fat or protein intake, the plasma IGF-I level was 2.0% (95% CI 0.1, 3.9%) higher. No independent associations between fiber intake and hormone levels were observed. The results suggest that a low-fat/high-fiber or carbohydrate diet is not associated with endogenous levels of sex steroid hormones, but it may modestly increase IGF-I and IGFBP-3 levels among premenopausal women. PMID:21761370

Comparison of sliced lungs with whole lung sets for a torso phantom measured with Ge detectors using Monte Carlo simulations (MCNP).

PubMed

Kramer, Gary H; Guerriere, Steven

2003-02-01

Lung counters are generally used to measure low energy photons (<100 keV). They are usually calibrated with lung sets that are manufactured from a lung tissue substitute material that contains homogeneously distributed activity; however, it is difficult to verify either the activity in the phantom or the homogeneity of the activity distribution without destructive testing. Lung sets can have activities that are as much as 25% different from the expected value. An alternative method to using whole lungs to calibrate a lung counter is to use a sliced lung with planar inserts. Experimental work has already indicated that this alternative method of calibration can be a satisfactory substitute. This work has extended the experimental study by the use of Monte Carlo simulation to validate that sliced and whole lungs are equivalent. It also has determined the optimum slice thicknesses that separate the planar sources in the sliced lung. Slice thicknesses have been investigated in the range of 0.5 cm to 9.0 cm and at photon energies from 17 keV to 1,000 keV. Results have shown that there is little difference between sliced and whole lungs at low energies providing that the slice thickness is 2.0 cm or less. As the photon energy rises the slice thickness can increase substantially with no degradation on equivalence.

Altered Gag Polyprotein Cleavage Specificity of Feline Immunodeficiency Virus/Human Immunodeficiency Virus Mutant Proteases as Demonstrated in a Cell-Based Expression System

PubMed Central

Lin, Ying-Chuan; Brik, Ashraf; de Parseval, Aymeric; Tam, Karen; Torbett, Bruce E.; Wong, Chi-Huey; Elder, John H.

2006-01-01

We have used feline immunodeficiency virus (FIV) protease (PR) as a mutational system to study the molecular basis of substrate-inhibitor specificity for lentivirus PRs, with a focus on human immunodeficiency virus type 1 (HIV-1) PR. Our previous mutagenesis studies demonstrated that discrete substitutions in the active site of FIV PR with structurally equivalent residues of HIV-1 PR dramatically altered the specificity of the mutant PRs in in vitro analyses. Here, we have expanded these studies to analyze the specificity changes in each mutant FIV PR expressed in the context of the natural Gag-Pol polyprotein ex vivo. Expression mutants were prepared in which 4 to 12 HIV-1-equivalent substitutions were made in FIV PR, and cleavage of each Gag-Pol polyprotein was then assessed in pseudovirions from transduced cells. The findings demonstrated that, as with in vitro analyses, inhibitor specificities of the mutants showed increased HIV-1 PR character when analyzed against the natural substrate. In addition, all of the mutant PRs still processed the FIV polyprotein but the apparent order of processing was altered relative to that observed with wild-type FIV PR. Given the importance of the order in which Gag-Pol is processed, these findings likely explain the failure to produce infectious FIVs bearing these mutations. PMID:16873240

Virtually complete control of simple and face diastereoselectivity in the Michael addition reactions between achiral equivalents of a nucleophilic glycine and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: practical method for preparation of beta-substituted pyroglutamic acids and prolines.

PubMed

Soloshonok, Vadim A; Ueki, Hisanori; Tiwari, Rohit; Cai, Chaozhong; Hruby, Victor J

2004-07-23

This study demonstrates a new strategy for controlling the stereochemical outcome of the Michael addition reactions between nucleophilic glycine equivalents and alpha,beta-unsaturated carboxylic acid derivatives: The addition reactions between achiral Ni(II)-complex of the Schiff base of glycine with o-[N-alpha-pycolylamino]acetophenone and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones were shown to occur at room temperature in the presence of nonchelating organic bases and, most notably, with very high stereoselectivity at both newly formed stereogenic centers. Thus, the chiral 4-phenyl-1,3-oxazolidin-2-one moiety was found to control efficiently both face diastereoselectivities of the glycine derived enolate and the C,C double bond of the Michael acceptor. The new strategy developed in this work is methodologically superior to previous methods, most notably in terms of generality and synthetic efficiency. Excellent chemical yields and diastereoselectivities, combined with the simplicity of the experimental procedures, render the present method of immediate use for preparing various 3-substituted pyroglutamic acids and related amino acids (glutamic acids, glutamines, prolines, etc.) available via conventional transformations of the former.

Effect of Fe and Co substitution on the martensitic stability and the elastic, electronic, and magnetic properties of Mn2NiGa : Insights from ab initio calculations

NASA Astrophysics Data System (ADS)

Kundu, Ashis; Ghosh, Sheuly; Ghosh, Subhradip

2017-11-01

We investigate the effects of Fe and Co substitutions on the phase stability of the martensitic phase and mechanical, electronic, and magnetic properties of the magnetic shape memory system Mn2NiGa by first-principles density functional theory calculations. The evolution of these aspects upon substitution of Fe and Co at different crystallographic sites is investigated by computing the electronic structure, mechanical properties (tetragonal shear constant, Pugh ratio, and Cauchy pressure), and magnetic exchange parameters. We find that the austenite phase of Mn2NiGa gradually stabilizes with increase in concentration of Fe/Co due to the weakening of the minority spin hybridization of Ni and Mn atoms occupying crystallographically equivalent sites. The interplay between relative structural stability and the compositional changes is understood from the variations in the elastic moduli and electronic structures. We find that like in the Ni2MnGa -based systems, the elastic shear modulus C' can be considered as a predictor of composition dependence of martensitic transformation temperature Tm in substituted Mn2NiGa , thus singling it out as the universally acceptable predictor for martensitic transformation in Ni-Mn-Ga compounds over a wide composition range. The magnetic properties of Mn2NiGa are found to be greatly improved by the substitutions due to stronger ferromagnetic interactions in the compounds. The gradually weaker (stronger) Jahn-Teller distortion (covalent bonding) in the minority spin densities of states due to substitutions leads to a half-metallic-like gap in these compounds resulting in materials with high spin polarization when the substitutions are complete. The substitutions at the Ga site result in the two compounds Mn2NiFe and Mn2NiCo with very high magnetic moments and Curie temperatures. Thus, our work indicates that although the substitutions destroy the martensitic transformation and thus the possibility of realization of shape memory properties in Mn2NiGa , magnetic materials with very good magnetic parameters that are potentially useful for novel magnetic applications can be obtained. This can trigger interest in the experimental community in further research on substituted Mn2NiGa .

Generic maintenance immunosuppression in solid organ transplant recipients.

PubMed

Ensor, Christopher R; Trofe-Clark, Jennifer; Gabardi, Steven; McDevitt-Potter, Lisa M; Shullo, Michael A

2011-11-01

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

[Follow-up of a cohort of patients after substitution of phenytoin for phenytoin sodium in an epilepsy center].

PubMed

Lavandier, N; Tourniaire, D

2015-02-01

In March 2012, the French Health Products Safety Agency interrupted the commercialization of di-hydan (phenytoin). It was replaced by diphantoïne (phenytoin sodium) and prescribers were informed that posology was equivalent for both products. We conducted a retrospective study of phenytoinemia and clinical effects comparatively for these two drugs in a population of adult patients with epilepsy admitted in La TEPPE. Forty-four patients were included. Mean age was 47.6 years. Phenytoinemia significantly decreased after substitution (17.14mg/L with di-hydan versus 12.17mg/L with diphantoïne, P<8 10(-6)). Moreover an increase in post substitution posology of diphantoïne was noticed (264.77mg/L with di-hydan versus 274.73mg/L with diphantoïne), although not significant (P=0.11). Increase of seizures was non-significant (P = 0.09). The decrease of phenytoinemia was probably due to the difference of composition between the drugs: a 100mg di-hydan tablet contains 100mg of phenytoin whereas a 100mg diphantoïne tablet contains 92mg. The specific non-linear kinetics of phenytoin reinforces this difference. A prospective study could better evaluate the risk of substituting di-hydan with diphantoïne. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Amino Acid Substitution in Trichophyton rubrum Squalene Epoxidase Associated with Resistance to Terbinafine

PubMed Central

Osborne, Colin S.; Leitner, Ingrid; Favre, Bertrand; Ryder, Neil S.

2005-01-01

There has only been one clinically confirmed case of terbinafine resistance in dermatophytes, where six sequential Trichophyton rubrum isolates from the same patient were found to be resistant to terbinafine and cross-resistant to other squalene epoxidase (SE) inhibitors. Microsomal SE activity from these resistant isolates was insensitive to terbinafine, suggesting a target-based mechanism of resistance (B. Favre, M. Ghannoum, and N. S. Ryder, Med. Mycol. 42:525-529, 2004). In this study, we have characterized at the molecular level the cause of the resistant phenotype of these clinical isolates. Cloning and sequencing of the SE gene and cDNA from T. rubrum revealed the presence of an intron in the gene and an open reading frame encoding a protein of 489 residues, with an equivalent similarity (57%) to both yeast and mammalian SEs. The nucleotide sequences of SE from two terbinafine-susceptible strains were identical whereas those of terbinafine-resistant strains, serially isolated from the same patient, each contained the same single missense introducing the amino acid substitution L393F. Introduction of the corresponding substitution in the Candida albicans SE gene (L398F) and expression of this gene in Saccharomyces cerevisiae conferred a resistant phenotype to the transformants when compared to those expressing the wild-type sequence. Terbinafine resistance in these T. rubrum clinical isolates appears to be due to a single amino acid substitution in SE. PMID:15980358

A point mutation in the acetylcholinesterase-1 gene is associated with chlorpyrifos resistance in the plant bug Apolygus lucorum.

PubMed

Wu, Shuwen; Zuo, Kairan; Kang, Zhaokui; Yang, Yihua; Oakeshott, John G; Wu, Yidong

2015-10-01

Control of Chinese Apolygus lucorum relies heavily on organophosphate insecticides. Here we describe resistance to the organophosphate chlorpyrifos in an A. lucorum strain, BZ-R, which was developed from a field-collected strain (BZ) by selection with chlorpyrifos in the laboratory. BZ-R showed 21-58 fold resistance to chlorpyrifos compared with the laboratory reference strain LSF and another susceptible strain, BZ-S, derived from BZ. BZ-R also showed several fold resistance to two other organophosphates and a carbamate. No synergism of chlorpyrifos by metabolic enzyme inhibitors nor any increase in detoxifying enzyme activities were observed in BZ-R. No sequence differences in acetylcholinesterase-2 were found to be associated with the resistance but the frequency of an alanine to serine substitution at position 216 of acetylcholinesterase-1 was 100% in BZ-R, ∼21-23% in SLF and BZ, and 0% in BZ-S. A single generation treatment of chlorpyrifos on the BZ strain also increased its frequency of the serine substitution to 64%. Recombinantly expressed acetylcholinesterase-1 carrying the serine substitution was about five fold less sensitive to inhibition by chlorpyrifos oxon than the wild-type enzyme. Quantitative real-time PCR found no differences in ace1 or ace2 expression levels among the strains tested. Thus the chlorpyrifos resistance is strongly associated with the serine substituted acetylcholinesterase-1. An equivalent substitution has been found to confer resistance to many organophosphate and carbamate insecticides in four other insect species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kernel Equating Under the Non-Equivalent Groups With Covariates Design

PubMed Central

Bränberg, Kenny

2015-01-01

When equating two tests, the traditional approach is to use common test takers and/or common items. Here, the idea is to use variables correlated with the test scores (e.g., school grades and other test scores) as a substitute for common items in a non-equivalent groups with covariates (NEC) design. This is performed in the framework of kernel equating and with an extension of the method developed for post-stratification equating in the non-equivalent groups with anchor test design. Real data from a college admissions test were used to illustrate the use of the design. The equated scores from the NEC design were compared with equated scores from the equivalent group (EG) design, that is, equating with no covariates as well as with equated scores when a constructed anchor test was used. The results indicate that the NEC design can produce lower standard errors compared with an EG design. When covariates were used together with an anchor test, the smallest standard errors were obtained over a large range of test scores. The results obtained, that an EG design equating can be improved by adjusting for differences in test score distributions caused by differences in the distribution of covariates, are useful in practice because not all standardized tests have anchor tests. PMID:29881012

EQUIVALENCE BETWEEN SHORT-TIME BIPHASIC AND INCOMPRESSIBLE ELASTIC MATERIAL RESPONSES

PubMed Central

Ateshian, Gerard A.; Ellis, Benjamin J.; Weiss, Jeffrey A.

2009-01-01

Porous-permeable tissues have often been modeled using porous media theories such as the biphasic theory. This study examines the equivalence of the short-time biphasic and incompressible elastic responses for arbitrary deformations and constitutive relations from first principles. This equivalence is illustrated in problems of unconfined compression of a disk, and of articular contact under finite deformation, using two different constitutive relations for the solid matrix of cartilage, one of which accounts for the large disparity observed between the tensile and compressive moduli in this tissue. Demonstrating this equivalence under general conditions provides a rationale for using available finite element codes for incompressible elastic materials as a practical substitute for biphasic analyses, so long as only the short-time biphasic response is sought. In practice, an incompressible elastic analysis is representative of a biphasic analysis over the short-term response δt≪Δ2/‖C4‖||K||, where Δ is a characteristic dimension, C4 is the elasticity tensor and K is the hydraulic permeability tensor of the solid matrix. Certain notes of caution are provided with regard to implementation issues, particularly when finite element formulations of incompressible elasticity employ an uncoupled strain energy function consisting of additive deviatoric and volumetric components. PMID:17536908

Kernel Equating Under the Non-Equivalent Groups With Covariates Design.

PubMed

Wiberg, Marie; Bränberg, Kenny

2015-07-01

When equating two tests, the traditional approach is to use common test takers and/or common items. Here, the idea is to use variables correlated with the test scores (e.g., school grades and other test scores) as a substitute for common items in a non-equivalent groups with covariates (NEC) design. This is performed in the framework of kernel equating and with an extension of the method developed for post-stratification equating in the non-equivalent groups with anchor test design. Real data from a college admissions test were used to illustrate the use of the design. The equated scores from the NEC design were compared with equated scores from the equivalent group (EG) design, that is, equating with no covariates as well as with equated scores when a constructed anchor test was used. The results indicate that the NEC design can produce lower standard errors compared with an EG design. When covariates were used together with an anchor test, the smallest standard errors were obtained over a large range of test scores. The results obtained, that an EG design equating can be improved by adjusting for differences in test score distributions caused by differences in the distribution of covariates, are useful in practice because not all standardized tests have anchor tests.

Thermal actuation of extinguishing systems

NASA Astrophysics Data System (ADS)

Evans, D. D.

1984-03-01

A brief review of the Response Time Index (RTI) method of characterizing the thermal response of commercial sprinklers and heat detectors is presented. Measured ceiling layer flow temperature and velocity histories from a bedroom fire test are used to illustrate the use of RTI in calculating sprinkler operation times. In small enclosure fires, a quiescent warm gas layer confined by the room walls may accumulate below the ceiling before sprinkler operation. The effects of this warm gas layer on the fire plume and ceiling jet flows are accounted for by substitution of an equivalent point source fire. Encouraging agreement was found between measured ceiling jet temperatures from steady fires in a laboratory scale cylindrical enclosure put into dimensionless form based on parameters of the substitute fire source, and existing empirical correlations from fire tests in large enclosures in which a quiescent warm upper gas layer does not accumulate.

Possibilities of vaccine manufacture in human diploid cell strains with a serum replacement factor.

PubMed

Candal, F J; George, V G; Ades, E W

1991-07-01

Cell lines MDCK (canine kidney), BGM (Buffalo green monkey kidney) and human embryonic lung fibroblast will support viral growth efficiently in medium without serum. Both MRC-5 and WI-38 cell strains have been approved by the Food and Drug Administration for manufacturing viral vaccines against cytomegalovirus and varicella-zoster virus. In this study we examine these two cell lines and viruses for their ability to grow in medium containing a serum replacement. The serum substitute used is LPSR-1 (low protein serum replacement). Using LPSR-1 in defined medium, we demonstrate multipassage cell growth and viral cultivation and replication equivalent to those obtained in medium containing fetal bovine serum (FBS). Viral growth after complete elimination of FBS varies and depends on cell line and virus. Serum substitutes can eliminate FBS in the viral growth phase of vaccine production and reduce costs.

Fractal Tomlinson model for mesoscopic friction: from microscopic velocity-dependent damping to macroscopic Coulomb friction.

PubMed

Filippov, A E; Popov, V L

2007-02-01

A modified Tomlinson equation with fractal potential is studied. The effective potential is numerically generated and its mesoscopic structure is gradually adjusted to different scales by a number of Fourier modes. It is shown that with the change of scale the intensity of velocity-dependent damping in an effective Langevin equation can be gradually substituted by an equivalent constant "dry friction." For smooth macrosopic surfaces the effective equation completely reduces to the well known Coulomb law.

Tetramethylnorbornadiene, a versatile alkene for cyclopentenone synthesis through intermolecular Pauson-Khand reactions.

PubMed

Revés, Marc; Lledó, Agustí; Ji, Yining; Blasi, Emma; Riera, Antoni; Verdaguer, Xavier

2012-07-06

1,2,3,4-Tetramethyl-bicyclo[2.2.1]hepta-2,5-diene (TMNBD, for tetramethylnorbornadiene) has been prepared and used successfully as an acetylene equivalent in the synthesis of substituted cyclopentenones. TMNBD is easily accessible on a multigram scale and displays excellent reactivity toward the intermolecular Pauson-Khand reaction. Conjugate additions on the resulting tricyclic compounds proceed with exquisite diastereoselectivity. The retro-Diels-Alder reaction of these TMNBD derivatives occurs under much smoother conditions than those required for its norbornadiene homologues.

New Polyisoimides: An Approach to In Situ Rigid-Rod Polyimide Formation

DTIC Science & Technology

1987-10-01

substitution, hut because of the highly activated chloro leaving groups ( ortho to a nitro group) it was determined that only a stoichiometric equivalent was...dianhydride (0.5985 g, 2.740 mmol), 24 ml of freshly distilled m- cresol , and six drops of isoquinoline. After the diamine dissolved, 15 ml of toluene were...0 Um cyv W C4 0 LL z 0 20 AFIUAL-TR-87-4071 derivative. Tt was suggested, with good cause, that a pendent group located in the three position ( ortho

High Levels Of Capitation Payments Needed To Shift Primary Care Toward Proactive Team And Nonvisit Care.

PubMed

Basu, Sanjay; Phillips, Russell S; Song, Zirui; Bitton, Asaf; Landon, Bruce E

2017-09-01

Capitated payments in the form of fixed monthly payments to cover all of the costs associated with delivering primary care could encourage primary care practices to transform the way they deliver care. Using a microsimulation model incorporating data from 969 US practices, we sought to understand whether shifting to team- and non-visit-based care is financially sustainable for practices under traditional fee-for-service, capitated payment, or a mix of the two. Practice revenues and costs were computed for fee-for-service payments and a range of capitated payments, before and after the substitution of team- and non-visit-based services for low-complexity in-person physician visits. The substitution produced financial losses for simulated practices under fee-for-service payment of $42,398 per full-time-equivalent physician per year; however, substitution produced financial gains under capitated payment in 95 percent of cases, if more than 63 percent of annual payments were capitated. Shifting to capitated payment might create an incentive for practices to increase their delivery of team- and non-visit-based primary care, if capitated payment levels were sufficiently high. Project HOPE—The People-to-People Health Foundation, Inc.

Study on feasible technical potential of coal to electricity in china

NASA Astrophysics Data System (ADS)

Jia, Dexiang; Tan, Xiandong

2017-01-01

The control of bulk coal is one of the important work of air pollution control in China’s future. Existing research mainly focuses on the adaptability, economy, construction and renovation plan, and operation optimization of specific energy substitution utilization, and lacks the strategy research of long-term layout of energy substitution utilization in large area. This paper puts forward a technical potential prediction method of coal to electricity based on the thermal equivalent method, which is based on the characteristics of regional coal consumption, and combined with the trend of adaptability and economy of energy substitution utilization. Also, the paper calculates the comprehensive benefit of coal to electricity according to the varieties of energy consumption and pollutant emission level of unit energy consumption in China’s future. The research result shows that the development technical potential of coal to electricity in China is huge, about 1.8 trillion kWh, including distributed electric heating, heat pump and electric heating boiler, mainly located in North China, East China, and Northeast China. The implementation of coal to electricity has remarkable comprehensive benefits in energy conservation and emission reduction, and improvement of energy consumption safety level. Case study shows the rationality of the proposed method.

Cost comparison and economic implications of commonly used originator and generic chemotherapy drugs in India.

PubMed

Lopes, G de L

2013-09-01

Cancer treatments have improved outcomes but access to medications is an issue around the world and especially so in low- and middle-income countries, such as India. Generic substitution may lead to significant cost savings. The author aimed to compare the cost and estimate potential cost savings per cycle, per patient, and for the country as a whole with generic substitution of frequently used chemotherapy drugs in the treatment of common cancers in India. Generic paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine, oxaliplatin and irinotecan cost from 8.9% to 36% of their equivalent branded originator drug, resulting in cost savings of ~ Indian Rupees (INR) 11,000 to >INR 90,000 (USD 200-1600, Euro 160-1300) per cycle; and ~INR 50,000 to >INR 240,000 (USD 900-4300, Euro 700-3400) per patient. Overall, potential yearly savings for health systems in India were nearly INR 47 billion (~USD 843 million, Euro 670 million). In conclusion, generic substitution for frequently used chemotherapy drugs in the treatment of common cancers has an enormous potential to generate significant cost savings and increase access to cancer treatments in India and other low- and middle-income countries.

Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes.

PubMed

D'Ruiz, Carl D; Graff, Donald W; Robinson, Edward

2016-07-11

Electronic cigarettes (e-cigarettes) are popular alternatives to conventional cigarettes among adult smokers wishing to reduce their exposure to harmful smoke constituents. However, little information exists on the relative internal exposures resulting from the exclusive or dual use of e-cigarettes. Measurements of product use; adverse events; changes in smoking urge; and blood, urine and exhaled breath biomarkers of exposure (BoE) representing toxicants believed to contribute to smoking related diseases were made at baseline and after five days of product use in 105 clinically-confined smokers randomized into groups that partially or completely substituted their usual brand combustible cigarette with commercial e-cigarettes, or discontinued all nicotine and tobacco products. Subjects switching to e-cigarettes had significantly lower levels (29 %-95 %) of urinary BoEs after 5 days. Nicotine equivalents declined by 25 %-40 %. Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %-38 % reductions, but had increases (1 %-20 %) in nicotine equivalents. Blood nicotine biomarker levels were lower in the cessation (75 %-96 %) and e-cigarette use groups (11 %-83 %); dual users had no significant reductions. All groups experienced significant decreases in exhaled CO (27 %-89 %). Exhaled NO increases (46 %-63 %) were observed in the cessation and e-cigarette use groups; dual users had minimal changes. By Day 5, all groups had greater reductions in smoking urge compared to cessation. However, reductions were larger in the dual use group. No serious adverse events were observed. Exposures to harmful smoke toxicants were observed to be lower in smokers who completely or partially replaced their cigarettes with e-cigarettes over five days.

Reference drug programs: effectiveness and policy implications.

PubMed

Schneeweiss, Sebastian

2007-04-01

In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs (RDPs) or similar therapeutic substitution programs. This paper summarizes the mechanism and rationale of RDPs and presents evidence of their economic effectiveness and clinical safety. RDPs for pharmaceutical reimbursement are based on the assumption that drugs within specified medication groups are therapeutically equivalent and clinically interchangeable and that a common reimbursement level can thus be established. If the evidence documents that a higher price for a given drug does not buy greater effectiveness or reduced toxicity, then under RDP such extra costs are not covered. RDPs or therapeutic substitutions based on therapeutic equivalence are seen as logical extensions of generic substitution that is based on bioequivalence of drugs. If the goal is to achieve full drug coverage for as many patients as possible in the most efficient manner, then RDPs in combination with prior authorization programs are safer and more effective than simplistic fiscal drug policies, including fixed co-payments, co-insurances, or deductibles. RDPs will reduce spending in the less innovative but largest market, while fully covering all patients. Prior authorization will ensure that patients with a specified indication will benefit from the most innovative therapies with full coverage. In practice, however, not all patients and drugs will fit exactly into one of the two categories. Therefore, a process of medically indicated exemptions that will consider full coverage should accompany an RDP. In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs, and others are considering them. This paper summarizes the mechanism and rationale of RDPs, presents evidence of their economic effectiveness and clinical safety, and concludes with some practical implications of implementing RDP policies.

Reference drug programs: Effectiveness and policy implications☆

PubMed Central

Schneeweiss, Sebastian

2010-01-01

In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs (RDPs) or similar therapeutic substitution programs. This paper summarizes the mechanism and rationale of RDPs and presents evidence of their economic effectiveness and clinical safety. RDPs for pharmaceutical reimbursement are based on the assumption that drugs within specified medication groups are therapeutically equivalent and clinically interchangeable and that a common reimbursement level can thus be established. If the evidence documents that a higher price for a given drug does not buy greater effectiveness or reduced toxicity, then under RDP such extra costs are not covered. RDPs or therapeutic substitutions based on therapeutic equivalence are seen as logical extensions of generic substitution that is based on bioequivalence of drugs. If the goal is to achieve full drug coverage for as many patients as possible in the most efficient manner, then RDPs in combination with prior authorization programs are safer and more effective than simplistic fiscal drug policies, including fixed co-payments, co-insurances, or deductibles. RDPs will reduce spending in the less innovative but largest market, while fully covering all patients. Prior authorization will ensure that patients with a specified indication will benefit from the most innovative therapies with full coverage. In practice, however, not all patients and drugs will fit exactly into one of the two categories. Therefore, a process of medically indicated exemptions that will consider full coverage should accompany an RDP. In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs, and others are considering them. This paper summarizes the mechanism and rationale of RDPs, presents evidence of their economic effectiveness and clinical safety, and concludes with some practical implications of implementing RDP policies. PMID:16777256

Use of Consumer Acceptability as a Tool to Determine the Level of Sodium Reduction: A Case Study on Beef Soup Substituted With Potassium Chloride and Soy-Sauce Odor.

PubMed

Lee, Cho Long; Lee, Soh Min; Kim, Kwang-Ok

2015-11-01

In this study, consumer acceptability was considered as a tool of reducing sodium rather than just using it as a final examination of the successfulness of the substitution. This study consisted of 4 experimental steps. First, by gradually reducing the concentrations of NaCl, consumer rejection threshold (CRT) of NaCl in beef soup was examined. Then, the amount of KCl that can increase preference was examined in 2 low sodium beef soups, with sodium concentrations slightly above or below the CRT. Relative saltiness of various KCl and NaCl/KCl mixtures were also measured. Finally, consumers evaluated acceptability and intensities of sensory characteristics for 9 beef soup samples that differed with respect to NaCl content and/or KCl content with/without addition of salty-congruent odor (soy-sauce odor). The results showed that in the "above CRT" system, consumer acceptability as well as sensory profile of low sodium beef soup substituted using KCl had similar profile to the control although saltiness was not fully recovered, whereas in the "below CRT" system, consumer acceptability was not recovered using KCl solely as a substitute. Potential of using salty-congruent odor as a final touch to induce salty taste was observed; however, the results inferred the importance of having almost no artificialness in the odor and having harmony with the final product when using it as a strategy to substitute sodium. Overall, the results of the study implied the importance of considering consumer acceptability when approaching sodium reduction to better understand the potentials of the sodium substitutes and salty-congruent odor. Strategies attempting to reduce sodium contents in food have mainly substituted sodium to the level that provides equivalent salty taste and then examined consumer liking. However, these approaches may result in failure for consumer appeal. This study attempted to consider consumer acceptability as a tool of reducing sodium in beef soup substituted using potassium chloride and salty-congruent odor. The result showed that considering consumer acceptability during sodium reduction enabled to better understand the potentials of the sodium substitutes and salty-congruent odor. © 2015 Institute of Food Technologists®

Mechanistically Driven Development of Iridium Catalysts for Asymmetric Allylic Substitution

PubMed Central

Hartwig, John F.; Stanley, Levi M.

2010-01-01

Conspectus Enantioselective allylic substitution reactions comprise some of the most versatile methods for preparing enantiomerically enriched materials. These reactions form products that contain multiple functionalities by creating carbon–nitrogen, carbon–oxygen, carbon–carbon, and carbon–sulfur bonds. For many years, the development of catalysts for allylic substitution focused on palladium complexes. However, studies of complexes of other metals have revealed selectivities that often complement those of palladium systems. Most striking is the observation that reactions with unsymmetrical allylic electrophiles that typically occur with palladium catalysts at the less hindered site of an allylic electrophile occur at the more hindered site with catalysts based on other metals. In this Account, we describe an iridium precursor and a phosphoramidite ligand that catalyze reactions with a particularly broad scope of nucleophiles. The active form of this iridium catalyst is not generated by the simple binding of the phosphoramidite ligand to the metal precursor. Instead, the initial phosphoramidite and iridium precursor react in the presence of base to form a metallacyclic species that is the active catalyst. This species is generated either in situ or separately in isolated form by reactions with added base. The identification of the structure of the active catalyst led to the development of simplified catalysts as well as the most active form of the catalyst now available, which is stabilized by a loosely bound ethylene. Most recently, this structure was used to prepare intermediates containing allyl ligands, the structures of which provide a model for the enantioselectivities discussed here. Initial studies from our laboratory on the scope of iridium-catalyzed allylic substitution showed that reactions of primary and secondary amines, including alkylamines, benzylamines, and allylamines, and reactions of phenoxides and alkoxides occurred in high yields, with high branched-to-linear ratios and high enantioselectivities. Parallel mechanistic studies had revealed the metallacyclic structure of the active catalyst, and subsequent experiments with the purposefully formed metallacycle increased the reaction scope dramatically. Aromatic amines, azoles, ammonia, and amides and carbamates as ammonia equivalents all reacted with high selectivities and yields. Moreover, weakly basic enolates (such as silyl enol ethers) and enolate equivalents (such as enamines) also reacted, and other research groups have used this catalyst to conduct reactions of stabilized carbon nucleophiles in the absence of additional base. One hallmark of the reactions catalyzed by this iridium system is the invariably high enantioselectivity, which reflects a high stereoselectivity for formation of the allyl intermediate. Enantioselectivity typically exceeds 95%, regioselectivity for formation of branched over linear products is usually near 20:1, and yields generally exceed 75% and are often greater than 90%. Thus, the development of iridium catalysts for enantioselective allylic substitution shows how studies of reaction mechanism can lead to a particularly active and a remarkably general system for an enantioselective process. In this case, a readily accessible catalyst effects allylic substitution, with high enantioselectivity and regioselectivity complementary to that of the venerable palladium systems. PMID:20873839

Structure and mechanism of Cu- and Ni-substituted analogs of metallo-β-lactamase L1

PubMed Central

Hu, Zhenxin; Spadafora, Lauren J.; Hajdin, Christine E.; Bennett, Brian; Crowder, Michael W.

2009-01-01

In an effort to further probe metal binding to metallo-β-lactamase L1 (mβl L1), Cu- (Cu-L1) and Ni-substituted (Ni-L1) L1 were prepared and characterized by kinetic and spectroscopic studies. Cu-L1 bound 1.7 equivalents of Cu and small amounts of Zn(II) and Fe. The EPR spectrum of Cu-L1 exhibited two overlapping, axial signals, indicative of type 2 sites with distinct affinities for Cu(II). Both signals indicated multiple nitrogen ligands. Despite the expected proximity of the Cu(II) ions, however, only indirect evidence was found for spin-spin coupling. Cu-L1 exhibited higher kcat (96 s−1) and Km (224 μM) values, as compared to the values of dinuclear Zn(II)-containing L1, when nitrocefin was used as substrate. The Ni-L1 bound 1 equivalent of Ni and 0.3 equivalents of Zn(II). Ni-L1 was EPR-silent, suggesting that the oxidation state of nickel was +2; this suggestion was confirmed by 1H NMR spectra, which showed relatively sharp proton resonances. Stopped-flow kinetic studies showed that ZnNi-L1 stabilized significant amounts of the nitrocefin-derived intermediate and that the decay of intermediate is rate-limiting. 1H NMR spectra demonstrate that Ni(II) binds in the Zn2 site and that the ring-opened product coordinates Ni(II). Both Cu-L1 and ZnNi-L1 hydrolyze cephalosporins and carbapenems, but not penicillins, suggesting that the Zn2 site modulates substrate preference in mβ1 L1. These studies demonstrate that the Zn2 site in L1 is very flexible and can accommodate a number of different transition metal ions; this flexibility could possibly offer an organism that produces L1 an evolutionary advantage when challenged with β-lactam containing antibiotics. PMID:19228020

Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source.

PubMed

Pinto, A; Almeida, M F; Ramos, P C; Rocha, S; Guimas, A; Ribeiro, R; Martins, E; Bandeira, A; MacDonald, A; Rocha, J C

2017-10-01

Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP. Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews. The mean time taking AA was 13±5 months and GMP 13±7 months. Blood phenylalanine (PHE) and tyrosine (TYR) were analysed before and after GMP introduction. Both GMP and AA protein substitutes provided similar protein equivalent intake (0.85 vs 0.75 g/kg/day, P=0.182). In the GMP group, it contributed 57% (27-100%) of the protein substitute intake (with AA delivering the rest of protein substitute intake), providing an additional 34±12 mg/day PHE. Nutritional intake, anthropometry and body composition measurements were similar in both the groups. Median blood PHE did not change (P=0.594), although values within target range improved (36 vs 46%), but this was not statistically significant. Mean blood TYR increased (52.0±19.2 vs 63.2±25.6 μmol/l, P=0.033), and all biochemical markers remained stable, except for a lower A1C haemoglobin (P=0.011). Partial GMP contribution to total protein substitute intake did not affect nutritional status in patients with PKU. Blood PHE control was not adversely affected. The increased blood TYR after GMP introduction necessitates further study.

How Does Recycling of Livestock Manure in Agroecosystems Affect Crop Productivity, Reactive Nitrogen Losses, and Soil Carbon Balance?

PubMed

Xia, Longlong; Lam, Shu Kee; Yan, Xiaoyuan; Chen, Deli

2017-07-05

Recycling of livestock manure in agroecosystems to partially substitute synthetic fertilizer nitrogen (N) input is recommended to alleviate the environmental degradation associated with synthetic N fertilization, which may also affect food security and soil greenhouse gas (GHG) emissions. However, how substituting livestock manure for synthetic N fertilizer affects crop productivity (crop yield; crop N uptake; N use efficiency), reactive N (Nr) losses (ammonia (NH 3 ) emission, N leaching and runoff), GHG (methane, CH 4 ; and nitrous oxide, N 2 O; carbon dioxide) emissions and soil organic carbon (SOC) sequestration in agroecosystems is not well understood. We conducted a global meta-analysis of 141 studies and found that substituting livestock manure for synthetic N fertilizer (with equivalent N rate) significantly increased crop yield by 4.4% and significantly decreased Nr losses via NH 3 emission by 26.8%, N leaching by 28.9% and N runoff by 26.2%. Moreover, annual SOC sequestration was significantly increased by 699.6 and 401.4 kg C ha -1 yr -1 in upland and paddy fields, respectively; CH 4 emission from paddy field was significantly increased by 41.2%, but no significant change of that was observed from upland field; N 2 O emission was not significantly affected by manure substitution in upland or paddy fields. In terms of net soil carbon balance, substituting manure for fertilizer increased carbon sink in upland field, but increased carbon source in paddy field. These results suggest that recycling of livestock manure in agroecosystems improves crop productivity, reduces Nr pollution and increases SOC storage. To attenuate the enhanced carbon source in paddy field, appropriate livestock manure management practices should be adopted.

Structural, Magnetic and Microwave Absorption Properties of Hydrothermally Synthesized (Gd, Mn, Co) Substituted Ba-Hexaferrite Nanoparticles

NASA Astrophysics Data System (ADS)

Torabi, Z.; Arab, A.; Ghanbari, F.

2018-02-01

Gd, Mn and Co substituted barium hexagonal ferrite nanoparticles, according to the formula Ba1- x Gd x Fe12-2 y (MnCo) y O19 and the proportion of y = x/2 (and x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1), have been prepared by hydrothermal method. Structural, magnetic and absorption microwave properties of the compositions were evaluated by x-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), vibrating sample magnetometry, and vector network analysis. Studying the XRDs data showed the single-phase structure of all samples without any impurities at 900°C calcination temperature. FE-SEM micrographs demonstrated that the morphology of the nanoparticles has planar and nearly hexagonal morphology. The nanoparticles size calculated within the range of 62-85 nm. Study of the room temperature hysteresis loops of calcined samples indicated that maximum magnetizations and coercivities decreased compared to undoped composite with respect to x. The alterations of magnetizations and coercivities are related to the site occupation of substituted ions, change in grain growth inhibition and the effect of spin canting. Moreover, the results of microwave absorption measurements demonstrated that the maximum reflection loss of substituted Ba-hexaferrite equivalent to - 47 dB in sample x = 0.5 with thickness 5.6 mm at a frequency about 17.2 GHz and a bandwidth of 2 GHz greater than - 10 dB. The results showed that Gd has good potential for use as a rare-earth substitution in permanent magnet hexaferrites and these composites can be employed as absorbers in the gigahertz frequency range.

New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: synthesis, and in vitro antimalarial activity.

PubMed

Guillon, Jean; Moreau, Stéphane; Mouray, Elisabeth; Sinou, Véronique; Forfar, Isabelle; Fabre, Solene Belisle; Desplat, Vanessa; Millet, Pascal; Parzy, Daniel; Jarry, Christian; Grellier, Philippe

2008-10-15

Following our search for antimalarial compounds, novel series of ferrocenic pyrrolo[1,2-a]quinoxaline derivatives 1-2 were synthesized from various substituted nitroanilines and tested for in vitro activity upon the erythrocytic development of Plasmodiumfalciparum strains with different chloroquine-resistance status. The pyrrolo[1,2-a]quinoxalines 1 were prepared in 6-8 steps through a regioselective palladium-catalyzed monoamination by coupling 4-chloropyrrolo[1,2-a]quinoxalines with 1,3-bis(aminopropyl)piperazine or -methylamine using Xantphos as the ligand. The ferrocenic bispyrrolo[1,2-a]quinoxalines 2 were prepared by reductive amination of previously described bispyrrolo[1,2-a]quinoxalines 9 with ferrocene-carboxaldehyde, by treatment with NaHB(OAc)(3). The best results were observed with ferrocenic pyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus and no substitution on the terminal N-ferrocenylmethylamine function enhanced the pharmacological activity. Selected compounds 1b, 1f-h, 1l and 2a were tested for their ability to inhibit beta-haematin formation, the synthetic equivalent of hemozoin, by using the HPIA (heme polymerization inhibitory activity) assay. Of the tested compounds, only 2a showed a beta-haematin formation inhibition, but no inhibition of haem polymerization was observed with the other selected ferrocenic monopyrrolo[1,2-a]quinoxaline derivatives 1b, 1f-h and 1l, as the IC(50) values were superior to 10 equivalents.

Impact of altered phosphorylation on loss of function of juvenile Parkinsonism-associated genetic variants of the E3 ligase parkin.

PubMed

Aguirre, Jacob D; Dunkerley, Karen M; Lam, Rica; Rusal, Michele; Shaw, Gary S

2018-04-27

Autosomal recessive juvenile Parkinsonism (ARJP) is an inherited neurodegenerative disease in which 50% of affected individuals harbor mutations in the gene encoding the E3 ligase parkin. Parkin regulates the mitochondrial recycling pathway, which is induced by oxidative stress. In its native state, parkin is auto-inhibited by its N-terminal ubiquitin-like (Ubl) domain, which blocks the binding site for an incoming E2∼ubiquitin conjugate, needed for parkin's ubiquitination activity. Parkin is activated via phosphorylation of Ser-65 in its Ubl domain by PTEN-induced putative kinase 1 (PINK1) and a ubiquitin molecule phosphorylated at a position equivalent to Ser-65 in parkin. Here we have examined the underlying molecular mechanism of phosphorylation of parkin's Ubl domain carrying ARJP-associated substitutions and how altered phosphorylation modulates parkin activation and ubiquitination. We found that three substitutions in the Ubl domain (G12R, R33Q, and R42P) significantly decrease PINK1's ability to phosphorylate the Ubl domain. We noted that two basic loss-of-function substitutions (R33Q and R42P) are close to acidic patches in the proposed PINK1-parkin interface, indicating that ionic interactions at this site may be important for efficient parkin phosphorylation. Increased auto-ubiquitination with unique ubiquitin chain patterns was observed for two other Ubl domain substitutions (G12R and T55I), suggesting that these substitutions, along with phosphorylation, increase parkin degradation. Moreover, Ubl domain phosphorylation decreased its affinity for the potential effector protein ataxin-3, which edits ubiquitin chain building by parkin. Overall, our work provides a framework for the mechanisms of parkin's loss-of-function, indicating an interplay between ARJP-associated substitutions and phosphorylation of its Ubl domain. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Radiation Induced Degradation of the White Thermal Control Paints Z-93 and Z-93P

NASA Technical Reports Server (NTRS)

Edwards, D. L.; Zwiener, J. M.; Wertz, G. E.; Vaughn, J. A.; Kamenetzky, R. R.; Finckenor, M. M.; Meshishnek, M. J.

1996-01-01

This paper details a comparison analysis of the zinc oxide pigmented white thermal control paints Z-93 and Z-93P. Both paints were simultaneously exposed to combined space environmental effects and analyzed using an in-vacuo reflectance technique. The dose applied to the paints was approximately equivalent to 5 years in a geosynchronous orbit. This comparison analysis showed that Z-93P is an acceptable substitute for Z-93. Irradiated samples of Z-93 and Z-93P were subjected to additional exposures of ultraviolet (UV) radiation and analyzed using the in-vacuo reflectance technique to investigate UV activated reflectance recovery. Both samples showed minimal UV activated reflectance recovery after an additional 190 equivalent sun hour (ESH) exposure. Reflectance response utilizing nitrogen as a repressurizing gas instead of air was also investigated. This investigation found the rates of reflectance recovery when repressurized with nitrogen are slower than when repressurized with air.

Radiation Induced Degradation of White Thermal Control Paint

NASA Technical Reports Server (NTRS)

Edwards, D. L.; Zwiener, J. M.; Wertz, G. E.; Vaughn, Jason A.; Kamenetzky, Rachel R.; Finckenor, M. M.; Meshishnek, M. J.

1999-01-01

This paper details a comparison analysis of the zinc-oxide pigmented white thermal control paints Z-93 and Z-93P. Both paints were simultaneously exposed to combined space environmental effects and analyzed using an in-vacuo reflectance technique. The dose applied to the paints was approximately equivalent to 5 yr in a geosynchronous orbit. This comparison analysis showed that Z-93P is an acceptable substitute for Z-93. Irradiated samples of Z-93 and Z-93P were subjected to additional exposures of ultraviolet (UV) radiation and analyzed using the in-vacuo reflectance technique to investigate UV activated reflectance recovery. Both samples showed minimal UV activated reflectance recovery after an additional 190 equivalent Sun hour (ESH) exposure. Reflectance response utilizing nitrogen as a repressurizing gas instead of air was also investigated. This investigation found the rates of reflectance recovery when repressurized with nitrogen are slower than when repressurized with air.

Dependence of equivalent thermal conductivity coefficients of single-wall carbon nanotubes on their chirality

NASA Astrophysics Data System (ADS)

Zarubin, V. S.; Sergeeva, E. S.

2018-04-01

Composite materials (composites) composed of a matrix and reinforcing components are currently widely used as structural materials for various engineering devices designed to operate under extreme thermal and mechanical loads. By modifying a composite with structure-sensitive inclusions such as single-wall carbon nanotubes, one can significantly improve the thermomechanical properties of the resulting material. The paper presents relationships obtained for the equivalent thermal conductivity coefficients of single-wall carbon nanotubes versus their chirality using a simulation model developed to simulate the heat transfer process through thermal conductivity in a transversely isotropic environment. With these coefficients, one can conventionally substitute a single-wall carbon nanotube with a continuous anisotropic fiber, thus allowing one to estimate the thermal properties of composites reinforced with objects of this sort by using the well-known models developed for fibered composites. The results presented here can be used to estimate the thermal properties of carbon nanotube-reinforced composites.

Equivalent threshold sound pressure levels (ETSPL) for Sennheiser HDA 280 supra-aural audiometric earphones in the frequency range 125 Hz to 8000 Hz.

PubMed

Poulsen, Torben; Oakley, Sebastian

2009-05-01

Hearing threshold sound pressure levels were measured for the Sennheiser HDA 280 audiometric earphone. Hearing thresholds were measured for 25 normal-hearing test subjects at the 11 audiometric test frequencies from 125 Hz to 8000 Hz. Sennheiser HDA 280 is a supra-aural earphone that may be seen as a substitute for the classical Telephonics TDH 39. The results are given as the equivalent threshold sound pressure level (ETSPL) measured in an acoustic coupler specified in IEC 60318-3. The results are in good agreement with an independent investigation from PTB, Braunschweig, Germany. From acoustic laboratory measurements ETSPL values are calculated for the ear simulator specified in IEC 60318-1. Fitting of earphone and coupler is discussed. The data may be used for a future update of the RETSPL standard for supra-aural audiometric earphones, ISO 389-1.

Effects of substitution, pressure, and temperature on the phonon mode in layered-rocksalt-type Li{sub (1−x)/2}Ga{sub (1−x)/2}Zn{sub x}O (x = 0.036–0.515) alloys

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

Tan, Lijie; Hu, Qiwei; Lei, Li, E-mail: lei@scu.edu.cn

2015-11-14

ZnO-based semiconductor alloys, Li{sub (1−x)/2}Ga{sub (1−x)/2}Zn{sub x}O (x = 0.036–0.515) with a layered-rocksalt-type structure, have been prepared under high pressure. The composition, pressure, and temperature dependence of phonons have been studied by Raman spectroscopy. We observe two disorder-activated Raman (DAR) modes when the Zn composition x increases: a broad Raman peak at ca. 400 cm{sup −1} and a left-shoulder peak at ca. 530 cm{sup −1} on the low-frequency side of A{sub 1g} mode at ca. 580 cm{sup −1}, which can be explained by reference to the phonon density of states for rocksalt-type ZnO. With the increase of the pressure and temperature, the left-shoulder DAR modemore » induced by substitution does not change at the same pace with the A{sub 1g} mode at Brillouin-zone center. We find that ion substitution can be seen as a kind of chemical pressure, and the chemical pressure caused by internal substitution and the physical pressure caused by external compression have equivalent effects on the shortening of correlation length, the distortion of crystal lattice, and the change of atomic occupation.« less

Effectiveness, safety and cost of drug substitution in hypertension

PubMed Central

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-01-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended. PMID:20716230

Effectiveness, safety and cost of drug substitution in hypertension.

PubMed

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-09-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the 'inactive' components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.

Birth-date dependent population ethics: critical-level principles.

PubMed

Blackorby, C; Bossert, W; Donaldson, D

1997-12-01

"This paper investigates birth-date dependent principles for social evaluation in an intertemporal framework in which population size may vary. We weaken the strong Pareto principle in order to allow individuals' birth dates to matter in establishing a social ordering. Using the axiom independence of the utilities of the dead, we characterize population principles with a recursive structure. If the individual substitution principle and an individual intertemporal equivalence axiom are added, birth-date dependent generalizations of the critical-level generalized utilitarian principles result. Stationarity leads to the special case of geometric discounting." excerpt

Electron density of Rhizophora spp. wood using Compton scattering technique at 15.77, 17.48 and 22.16 keV XRF energies

NASA Astrophysics Data System (ADS)

Shakhreet, B. Z.; Bauk, S.; Shukri, A.

2015-02-01

Compton (incoherently) scattered photons which are directly proportional to the electron density of the scatterer, have been employed in characterizing Rhizophora spp. as breast tissue equivalent. X-ray fluorescent scattered incoherently from Rhizophora spp. sample was measured using Si-PIN detector and three XRF energy values 15.77, 17.48 and 22.16 keV. This study is aimed at providing electron density information in support of the introduction of new tissue substitute materials for mammography phantoms.

Critical Directed Energy Test and Evaluation Infrastructure Shortfalls: Results of the Directed Energy Test and Evaluation Capability Tri-Service Study Update

DTIC Science & Technology

2009-06-01

Sensor H11 HPM Chamber Test Capability—Explosive Equivalent Substitute H12 HEL Irradiance & Temperature H13 HEL Near/In-Beam Path Quality H14 HPM Sensor...such things as artillery shells or UAVs and may impact the earth. Possible targets include missiles in flight or a relatively close command, control...capability is a synergy of four high priority shortfalls identified by the T-SS Update. H13 —HEL near/in-beam path quality H13 is the need for a

Equivalent Indels – Ambiguous Functional Classes and Redundancy in Databases

PubMed Central

Assmus, Jens; Kleffe, Jürgen; Schmitt, Armin O.; Brockmann, Gudrun A.

2013-01-01

There is considerable interest in studying sequenced variations. However, while the positions of substitutions are uniquely identifiable by sequence alignment, the location of insertions and deletions still poses problems. Each insertion and deletion causes a change of sequence. Yet, due to low complexity or repetitive sequence structures, the same indel can sometimes be annotated in different ways. Two indels which differ in allele sequence and position can be one and the same, i.e. the alternative sequence of the whole chromosome is identical in both cases and, therefore, the two deletions are biologically equivalent. In such a case, it is impossible to identify the exact position of an indel merely based on sequence alignment. Thus, variation entries in a mutation database are not necessarily uniquely defined. We prove the existence of a contiguous region around an indel in which all deletions of the same length are biologically identical. Databases often show only one of several possible locations for a given variation. Furthermore, different data base entries can represent equivalent variation events. We identified 1,045,590 such problematic entries of insertions and deletions out of 5,860,408 indel entries in the current human database of Ensembl. Equivalent indels are found in sequence regions of different functions like exons, introns or 5' and 3' UTRs. One and the same variation can be assigned to several different functional classifications of which only one is correct. We implemented an algorithm that determines for each indel database entry its complete set of equivalent indels which is uniquely characterized by the indel itself and a given interval of the reference sequence. PMID:23658777

Structure cristalline du composé Hg3-xSbx(S+Se)2+xI2-x (x ≃ 0.1)

PubMed Central

Kars, Mohammed; Herrero, Adrian Gómez; Roisnel, Thierry; Rebbah, Allaoua; Otero-Diáz, L. Carlos

2016-01-01

Single crystals of the mercury chalcohalide Hg3-xSbx(S+Se)2+xI2-x (x ≃ 0.1) (mercury anti­mony sulfide selenide iodide), were grown by a chemical transport reaction. The structure contains three independent A (Hg/Sb) atoms; each atom is strongly covalently bonded with two X (Se/S) atoms to form approximately linear X–A–X units. The X–A–X units link to form A 4 X 4 rings, which are combined into infinite crankshaft-type bands running along the [100] direction. Four equatorial E (I/X = Se,S) atoms at relatively long distances complete the distorted octa­hedral coordination of A (Hg/Sb). The crystal under investigation was twinned by non-merohedry with a refined twin domain fraction of 0.814 (6):0.186 (6). The structure is isotypic with Hg3Se2I2 [Beck & Hedderich (2000 ▸). J. Solid State Chem. 151, 73–76], but the current determination reveals a coupled substitution, with partial replacement of Hg+2 by Sb+3, balanced by the equivalent substitution of I−1 by S−2 and Se−2. Bond-valence calculations are consistent with this relative substitution model. PMID:27006793

Tailoring the surface properties of LiNi 0.4Mn 0.4Co 0.2O₂ by titanium substitution for improved high voltage cycling performance

DOE PAGES

Wolff-Goodrich, Silas; Xin, Huolin L.; Lin, Feng; ...

2015-07-30

The present research aims to provide insights into the behavior of LiNi0.4Mn0.4Co0.2O2 (NMC442) and LiNi 0.4Mn 0.4Co 0.2O₂ (NMC442-Ti02) cathode materials under galvanostatic cycling to high potentials, in the context of previous work which predicted that Ti-substituted variants should deliver higher capacities and exhibit better cycling stability than the unsubstituted compounds. It is found that NMC cathodes containing Ti show equivalent capacity fading but greater specific capacity than those without Ti in the same potential range. When repeatedly charged to the same degree of delithiation, NMC cathodes containing Ti showed better capacity retention. Soft x-ray absorption spectroscopy (XAS) spectra formore » Mn and Co indicated increased reduction in these elements for NMC cathodes without Ti, indicating that the substitution of Ti for Co acts to suppress the formation of a high impedance rock salt phase at the surface of NMC cathode particles. The results of this study validate the adoption of a facile change to existing NMC chemistries to improve cathode capacity retention under high voltage cycling conditions.« less

Electron spin echo envelope modulation studies of the Cu(II)-substituted derivative of isopenicillin N synthase: A structural and spectroscopic model

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

Feng Jiang; Peisach, J.; Lijune Ming

Electron spin echo envelope modulation spectroscopy (ESEEM) was used to study the active site structure of isopenicillin N synthase (IPNS) from Cephalosporium acremonium with Cu(II) as a spectroscopic probe. Fourier transform of the simulated electron spin-echo envelope for the Cu(II)-substituted enzyme, Cu(II)IPNS, revealed two nearly magnetically equivalent, equatorially coordinated His imidazoles. The superhyperfine coupling constant, A{sub iso}, for the remote {sup 14}N of each imidazole was 1.65 MHz. The binding of substrate to the enzyme altered the magnetic coupling so that A{sub iso} is 1.30 MHz for one nitrogen and 2.16 MHz for the other. From a comparison of themore » ESSEM of Cu(II)IPNS in D{sub 2}O and H{sub 2}O, it is suggested that water is a ligand of Cu(II) and this is displaced upon the addition of substrate.« less

Substituent and ring effects on enthalpies of formation: 2-methyl- and 2-ethylbenzimidazoles versus benzene- and imidazole-derivatives

NASA Astrophysics Data System (ADS)

Jiménez, Pilar; Roux, María Victoria; Dávalos, Juan Z.; Temprado, Manuel; Ribeiro da Silva, Manuel A. V.; Ribeiro da Silva, Maria Das Dores M. C.; Amaral, Luísa M. P. F.; Cabildo, Pilar; Claramunt, Rosa M.; Mó, Otilia; Yáñez, Manuel; Elguero, José

The enthalpies of combustion, heat capacities, enthalpies of sublimation and enthalpies of formation of 2-methylbenzimidazole (2MeBIM) and 2-ethylbenzimidazole (2EtBIM) are reported and the results compared with those of benzimidazole itself (BIM). Theoretical estimates of the enthalpies of formation were obtained through the use of atom equivalent schemes. The necessary energies were obtained in single-point calculations at the B3LYP/6-311+G(d,p) on B3LYP/6-31G* optimized geometries. The comparison of experimental and calculated values of benzenes, imidazoles and benzimidazoles bearing H (unsubstituted), methyl and ethyl groups shows remarkable homogeneity. The energetic group contribution transferability is not followed, but either using it or adding an empirical interaction term, it is possible to generate an enormous collection of reasonably accurate data for different substituted heterocycles (pyrazole-derivatives, pyridine-derivatives, etc.) from the large amount of values available for substituted benzenes and those of the parent (pyrazole, pyridine) heterocycles.

Do single-use medical devices containing biopolymers reduce the environmental impacts of surgical procedures compared with their plastic equivalents?

PubMed

Unger, Scott R; Hottle, Troy A; Hobbs, Shakira R; Thiel, Cassandra L; Campion, Nicole; Bilec, Melissa M; Landis, Amy E

2017-01-01

Background While petroleum-based plastics are extensively used in health care, recent developments in biopolymer manufacturing have created new opportunities for increased integration of biopolymers into medical products, devices and services. This study compared the environmental impacts of single-use disposable devices with increased biopolymer content versus typically manufactured devices in hysterectomy. Methods A comparative life cycle assessment of single-use disposable medical products containing plastic(s) versus the same single-use medical devices with biopolymers substituted for plastic(s) at Magee-Women's Hospital (Magee) in Pittsburgh, PA and the products used in four types of hysterectomies that contained plastics potentially suitable for biopolymer substitution. Magee is a 360-bed teaching hospital, which performs approximately 1400 hysterectomies annually. Results There are life cycle environmental impact tradeoffs when substituting biopolymers for petroplastics in procedures such as hysterectomies. The substitution of biopolymers for petroleum-based plastics increased smog-related impacts by approximately 900% for laparoscopic and robotic hysterectomies, and increased ozone depletion-related impacts by approximately 125% for laparoscopic and robotic hysterectomies. Conversely, biopolymers reduced life cycle human health impacts, acidification and cumulative energy demand for the four hysterectomy procedures. The integration of biopolymers into medical products is correlated with reductions in carcinogenic impacts, non-carcinogenic impacts and respiratory effects. However, the significant agricultural inputs associated with manufacturing biopolymers exacerbate environmental impacts of products and devices made using biopolymers. Conclusions The integration of biopolymers into medical products is correlated with reductions in carcinogenic impacts, non-carcinogenic impacts and respiratory effects; however, the significant agricultural inputs associated with manufacturing biopolymers exacerbate environmental impacts.

Substitution urethroplasty using oral mucosa graft for male anterior urethral stricture disease: Current topics and reviews.

PubMed

Horiguchi, Akio

2017-07-01

Male anterior urethral stricture is scarring of the subepithelial tissue of the corpus spongiosum that constricts the urethral lumen, decreasing the urinary stream. Its surgical management is a challenging problem, and has changed dramatically in the past several decades. Open surgical repair using grafts or flaps, called substitution urethroplasty, has become the gold standard procedure for anterior urethral strictures that are not amenable to excision and primary anastomosis. Oral mucosa harvested from the inner cheek (buccal mucosa) is an ideal material, and is most commonly used for substitution urethroplasty, and lingual mucosa harvested from the underside of the tongue has recently emerged as an alternative material with equivalent outcome. Onlay augmentation of oral mucosa graft on the ventral side (ventral onlay) or dorsal side (dorsal onlay, Barbagli procedure) has been widely used for bulbar urethral stricture with comparable success rates. In bulbar urethral strictures containing obliterative or nearly obliterative segments, either a two-sided dorsal plus ventral onlay (Palminteri technique) or a combination of excision and primary anastomosis and onlay augmentation (augmented anastomotic urethroplasty) are the procedures of choice. Most penile urethral strictures can be repaired in a one-stage procedure either by dorsal inlay with ventral sagittal urethrotomy (Asopa technique) or dorsolateral onlay with one-sided urethral dissection (Kulkarni technique); however, staged urethroplasty remains the procedure of choice for complex strictures, including strictures associated with genital lichen sclerosus or failed hypospadias. This article presents an overview of substitution urethroplasty using oral mucosa graft, and reviews current topics. © 2017 The Japanese Urological Association.

Financial incentives increase fruit and vegetable intake among Supplemental Nutrition Assistance Program participants: a randomized controlled trial of the USDA Healthy Incentives Pilot.

PubMed

Olsho, Lauren Ew; Klerman, Jacob A; Wilde, Parke E; Bartlett, Susan

2016-08-01

US fruit and vegetable (FV) intake remains below recommendations, particularly for low-income populations. Evidence on effectiveness of rebates in addressing this shortfall is limited. This study evaluated the USDA Healthy Incentives Pilot (HIP), which offered rebates to Supplemental Nutrition Assistance Program (SNAP) participants for purchasing targeted FVs (TFVs). As part of a randomized controlled trial in Hampden County, Massachusetts, 7500 randomly selected SNAP households received a 30% rebate on TFVs purchased with SNAP benefits. The remaining 47,595 SNAP households in the county received usual benefits. Adults in 5076 HIP and non-HIP households were randomly sampled for telephone surveys, including 24-h dietary recall interviews. Surveys were conducted at baseline (1-3 mo before implementation) and in 2 follow-up rounds (4-6 mo and 9-11 mo after implementation). 2784 adults (1388 HIP, 1396 non-HIP) completed baseline interviews; data were analyzed for 2009 adults (72%) who also completed ≥1 follow-up interview. Regression-adjusted mean TFV intake at follow-up was 0.24 cup-equivalents/d (95% CI: 0.13, 0.34 cup-equivalents/d) higher among HIP participants. Across all fruit and vegetables (AFVs), regression-adjusted mean intake was 0.32 cup-equivalents/d (95% CI: 0.17, 0.48 cup-equivalents/d) higher among HIP participants. The AFV-TFV difference was explained by greater intake of 100% fruit juice (0.10 cup-equivalents/d; 95% CI: 0.02, 0.17 cup-equivalents/d); juice purchases did not earn the HIP rebate. Refined grain intake was 0.43 ounce-equivalents/d lower (95% CI: -0.69, -0.16 ounce-equivalents/d) among HIP participants, possibly indicating substitution effects. Increased AFV intake and decreased refined grain intake contributed to higher Healthy Eating Index-2010 scores among HIP participants (4.7 points; 95% CI: 2.4, 7.1 points). The HIP significantly increased FV intake among SNAP participants, closing ∼20% of the gap relative to recommendations and increasing dietary quality. More research on mechanisms of action is warranted. The HIP trial was registered at clinicaltrials.gov as NCT02651064. © 2016 American Society for Nutrition.

Handheld fetal Doppler device for assessing heart rate in neonatal resuscitation.

PubMed

Shimabukuro, Rinshu; Takase, Kozo; Ohde, Sachiko; Kusakawa, Isao

2017-10-01

The use of neonatal three-lead electrocardiograms (Neo-ECG) is suggested for the assessment of heart rate (HR) in neonatal resuscitation, but primary childbirth facilities (i.e. maternity clinics or maternity homes) are not sufficiently equipped for this. The aim of this study was to therefore to confirm the potential of a handheld fetal Doppler device (FDD), widely used to assess HR in labor room resuscitation, and to compare its equivalency to Neo-ECG. In low-risk full-term infants, HR was measured five times per minute in minutes 1-5 after delivery using the FDD and Neo-ECG, and their equivalence compared. The equivalence margin was set at a HR difference of <±5 beats/min and <±5%. Moreover, the times at which HR was displayed were measured for both methods. FDD and Neo-ECG HR correlated strongly (r = 0.977) in 155 measurements in 33 cases. The mean HR difference was -0.123 beats/min (95%CI: -0.594 to +0.345), and the logarithmic transformation of the HR ratio was -0.0003 (95%CI: -0.0020 to +0.0015). The mean HR difference and HR ratio were within the equivalence margin. For HR assessment using the FDD, 155 of 165 measurements (93.9%) could be obtained in <10 s. In HR assessment, FDD is a valid substitute for Neo-ECG in primary childbirth facilities that are not sufficiently equipped for Neo-ECG. © 2017 Japan Pediatric Society.

Development of a Thiolysis HPLC Method for the Analysis of Procyanidins in Cranberry Products.

PubMed

Gao, Chi; Cunningham, David G; Liu, Haiyan; Khoo, Christina; Gu, Liwei

2018-03-07

The objective of this study was to develop a thiolysis HPLC method to quantify total procyanidins, the ratio of A-type linkages, and A-type procyanidin equivalents in cranberry products. Cysteamine was utilized as a low-odor substitute of toluene-α-thiol for thiolysis depolymerization. A reaction temperature of 70 °C and reaction time of 20 min, in 0.3 M of HCl, were determined to be optimum depolymerization conditions. Thiolytic products of cranberry procyanidins were separated by RP-HPLC and identified using high-resolution mass spectrometry. Standards curves of good linearity were obtained on thiolyzed procyanidin dimer A2 and B2 external standards. The detection and quantification limits, recovery, and precision of this method were validated. The new method was applied to quantitate total procyanidins, average degree of polymerization, ratio of A-type linkages, and A-type procyanidin equivalents in cranberry products. Results showed that the method was suitable for quantitative and qualitative analysis of procyanidins in cranberry products.

Drivers of cultural success: The case of sensory metaphors.

PubMed

Akpinar, Ezgi; Berger, Jonah

2015-07-01

Why do some cultural items catch on and become more popular than others? Language is one of the basic foundations of culture. But what leads some phrases to become more culturally successful? There are multiple ways to convey the same thing and phrases with similar meanings often act as substitutes, competing for usage. A not so friendly person, for example, can be described as unfriendly or cold. We study how the senses shape cultural success, suggesting that compared with their semantic equivalents (e.g., unfriendly person), phrases which relate to senses in metaphoric ways (e.g., cold person) should be more culturally successful. Data from 5 million books over 200 years support this prediction: Sensory metaphors are used more frequently over time than are their semantic equivalents. Experimental evidence demonstrates that sensory metaphors are more memorable because they relate more to the senses and have more associative cues. These findings shed light on how senses shape language and the psychological foundations of culture more broadly. (c) 2015 APA, all rights reserved).

Use of Incineration Solid Waste Bottom Ash as Cement Mixture in Cement Production

NASA Astrophysics Data System (ADS)

Jun, N. H.; Abdullah, M. M. A. B.; Jin, T. S.; Kadir, A. A.; Tugui, C. A.; Sandu, A. V.

2017-06-01

Incineration solid waste bottom ash was use to examine the suitability as a substitution in cement production. This study enveloped an innovative technology option for designing new equivalent cement that contains incineration solid waste bottom ash. The compressive strength of the samples was determined at 7, 14, 28 and 90 days. The result was compared to control cement with cement mixture containing incineration waste bottom ash where the result proved that bottom ash cement mixture able achieve its equivalent performance compared to control cement which meeting the requirement of the standards according to EN 196-1. The pozzolanic activity index of bottom ash cement mixture reached 0.92 at 28 days and 0.95 at 90 and this values can be concluded as a pozzolanic material with positive pozzolanic activity. Calcium hydroxide in Portland cement decreasing with the increasing replacement of bottom ash where the reaction occur between Ca(OH)2 and active SiO2.

Measurement equivalence of the KINDL questionnaire across child self-reports and parent proxy-reports: a comparison between item response theory and ordinal logistic regression.

PubMed

Jafari, Peyman; Sharafi, Zahra; Bagheri, Zahra; Shalileh, Sara

2014-06-01

Measurement equivalence is a necessary assumption for meaningful comparison of pediatric quality of life rated by children and parents. In this study, differential item functioning (DIF) analysis is used to examine whether children and their parents respond consistently to the items in the KINDer Lebensqualitätsfragebogen (KINDL; in German, Children Quality of Life Questionnaire). Two DIF detection methods, graded response model (GRM) and ordinal logistic regression (OLR), were applied for comparability. The KINDL was completed by 1,086 school children and 1,061 of their parents. While the GRM revealed that 12 out of the 24 items were flagged with DIF, the OLR identified 14 out of the 24 items with DIF. Seven items with DIF and five items without DIF were common across the two methods, yielding a total agreement rate of 50 %. This study revealed that parent proxy-reports cannot be used as a substitute for a child's ratings in the KINDL.

Lipases as biocatalysts for the synthesis of structured lipids.

PubMed

Jala, Ram Chandra Reddy; Hu, Peng; Yang, Tiankui; Jiang, Yuanrong; Zheng, Yan; Xu, Xuebing

2012-01-01

Structured lipids (SL) are broadly referred to as modified or synthetic oils and fats or lipids with functional or pharmaceutical applications. Some structured lipids, such as triglycerides that contain both long-chain (mainly essential) fatty acids and medium- or short-chain fatty acids and also artificial products that mimic the structure of natural materials, namely human milk fat substitutes and cocoa butter equivalents, have been discussed. Further, other modified or synthetic lipids, such as structured phospholipids and synthetic phenolic lipids are also included in this chapter. For all the products described in this chapter, enzymatic production in industry has been already conducted in one way or another. Cocoa butter equivalents, healthy oil containing medium-chain fatty acids, phosphatidyl serine, and phenol lipids from enzyme technology have been reported for commercial operation. As the demand for better quality functional lipids is increasing, the production of structured lipids becomes an interesting area. Thus, in this chapter we have discussed latest developments as well as present industrial situation of all commercially important structured lipids.

Preparation and Identification of Benzoic Acids and Benzamides: An Organic "Unknown" Lab

NASA Astrophysics Data System (ADS)

Taber, Douglass F.; Nelson, Jade D.; Northrop, John P.

1999-06-01

The reaction of an unknown substituted benzene derivative (illustrated by toluene) with oxalyl chloride and aluminum chloride gives the acid chloride. Hydrolysis of the acid chloride gives the acid, and reaction of the acid with concentrated aqueous ammonia gives the benzamide.

Laboratory spectra of C-13 ethane

NASA Technical Reports Server (NTRS)

Kurtz, Joe; Reuter, Dennis C.; Jennings, Donald E.; Hillman, John J.

1991-01-01

The laboratory infrared spectrum of C-13 monosubstituted ethane has been obtained at high resolution (0.0025/cm) using the McMath Fourier transform spectrometer at Kitt Peak National Observatory in May 1990. A preliminary analysis of the nu12 rQ0 branch (substituted species) suggests that its intensity is 1.15 + or - 0.05 times stronger than the equivalent nu9 branch in the normal (C-12)2H6 species. This result leads to a correction of a previously published estimate for the C-12/C-13 ratio in the atmosphere of Jupiter from about 94 to about 106.

PEROXIDASE-MEDIATED MAMMALIAN CELL CYTOTOXICITY

PubMed Central

Edelson, Paul J.; Cohn, Zanvil A.

1973-01-01

Lactoperoxidase, in the presence of hydrogen peroxide and iodide is cytotoxic for human and mouse lymphoid cells, and human erythrocytes. Myeloperoxidase, in amounts equivalent to 1.5 x 106 neutrophils, readily replaces lactoperoxidase, and allows the substitution of the iodide ion by chloride. The myeloperoxidase-mediated reaction is rapid, and highly efficient, leading to 85–90% cell death in 90 min, as measured by 51chromium release and dye exclusion. The mixture of granulocytes. monocytes, and lymphocytes present in an inflammatory exudate, and the intimate cell-to-cell association characteristic of cytotoxic phenomena may provide the in vivo requirements for such a system. PMID:4717124

Editorial Commentary: Polyurethane Meniscal Scaffold: A Perfect Fit or Flop?

PubMed

Barber, F Alan

2018-05-01

The goal of using a synthetic scaffold to establish a biomechanically functioning meniscus or provide an equivalent meniscus substitute is not achieved by the polycaprolactone-polyurethane Actifit scaffold. Recent research, that did not include a control group, shows that the revision rate is significant, and any improvements in patient outcomes could reflect the associated reconstructive surgery. Based on these data and similar published reports, it is premature to conclude that this implant is clinically indicated. The technique is currently more flop than fit. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Non-equilibrium GaNAs Alloys with Band Gap Ranging from 0.8-3.4 eV

DTIC Science & Technology

2010-01-01

isova- lent atoms substitute more electronegative host atoms as occurs in the dilute N-rich GaN1-xAsx alloys. In this case due to the substantial...6]. In this study low temperature MBE (LT-MBE) has been employed to overcome the mis- cibility gap in the GaN1-xAsx, allowing the synthesis of GaN1...600 °C. The same active N flux with the total N beam equivalent pressure ( BEP ) ~1.5 10-5 Torr and the same deposition time (2hr) were used for the

Redox non-innocent bis(2,6-diimine-pyridine) ligand-iron complexes as anolytes for flow battery applications.

PubMed

Duarte, Gabriel M; Braun, Jason D; Giesbrecht, Patrick K; Herbert, David E

2017-12-21

Diiminepyridines are a well-known class of "non-innocent" ligands that confer additional redox activity to coordination complexes beyond metal-centred oxidation/reduction. Here, we demonstrate that metal coordination complexes (MCCs) of diiminepyridine (DIP) ligands with iron are suitable anolytes for redox-flow battery applications, with enhanced capacitance and stability compared with bipyridine analogs, and access to storage of up to 1.6 electron equivalents. Substitution of the ligand is shown to be a key factor in the cycling stability and performance of MCCs based on DIP ligands, opening the door to further optimization.

United States Air Force Research Initiation Program. 1984 Research Reports. Volume 1.

DTIC Science & Technology

1986-05-01

storage , several 8" floppy disk drives were substituteu; to gain the equivalent speed, an 8088 microprocessor faster than the Intel version and a 2-wegabyte... RAil .. cnory and ram-drive software were substituted. 2. Not included above is one item which was listed in the RISE proposal budget (the Z-204...FUSOIONCAL/JM. 280 REM C4IHEAT CAPACITYiCAL/GM-K. 2,90 C=0.46 00’ REM E1=ACTIVATION ENERGYiCAL /MOL. 3 2’ REM R-GAS CONSTANTiCAL/MOL-K. F!’ = 1. 9 B37 .* 3

Angle-resolved and core-level photoemission study of interfacing the topological insulator Bi1.5Sb0.5Te1.7Se1.3 with Ag, Nb, and Fe

NASA Astrophysics Data System (ADS)

de Jong, N.; Frantzeskakis, E.; Zwartsenberg, B.; Huang, Y. K.; Wu, D.; Hlawenka, P.; Sańchez-Barriga, J.; Varykhalov, A.; van Heumen, E.; Golden, M. S.

2015-08-01

Interfaces between a bulk-insulating topological insulator (TI) and metallic adatoms have been studied using high-resolution, angle-resolved, and core-level photoemission. Fe, Nb, and Ag were evaporated onto Bi1 .5Sb0 .5Te1 .7Se1 .3 (BSTS) surfaces both at room temperature and 38 K. The coverage and temperature dependence of the adsorption and interfacial formation process have been investigated, highlighting the effects of the overlayer growth on the occupied electronic structure of the TI. For all coverages at room temperature and for those equivalent to less than 0.2 monolayer at low temperature all three metals lead to a downward shift of the TI bands with respect to the Fermi level. At room temperature Ag appears to intercalate efficiently into the van der Waals gap of BSTS, accompanied by low-level substitution for the Te/Se atoms of the termination layer of the crystal. This Te/Se substitution with silver increases significantly for low temperature adsorption, and can even dominate the electrostatic environment of the Bi/Sb atoms in the BSTS near-surface region. On the other hand, Fe and Nb evaporants remain close to the termination layer of the crystal. On room temperature deposition, they initially substitute isoelectronically for Bi as a function of coverage, before substituting for Te/Se atoms. For low temperature deposition, Fe and Nb are too immobile for substitution processes and show a behavior consistent with clustering on the surface. For both Ag and Fe/Nb, these differing adsorption pathways still lead to the qualitatively similar and remarkable behavior for low temperature deposition that the chemical potential first moves downward (p -type dopant behavior) and then upward (n -type behavior) on increasing coverage.

SU-E-J-210: Characterizing Tissue Equivalent Materials for the Development of a Dual MRI-CT Heterogeneous Anthropomorphic Phantom Designed Specifically for MRI Guided Radiotherapy Systems

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

Steinmann, A; Stafford, R; Yung, J

Purpose: MRI guided radiotherapy (MRIgRT) is an emerging technology which will eventually require a proficient quality auditing system. Due to different principles in which MR and CT acquire images, there is a need for a multi-imaging-modality, end-to-end QA phantom for MRIgRT. The purpose of this study is to identify lung, soft tissue, and tumor equivalent substitutes that share similar human-like CT and MR properties (i.e. Hounsfield units and relaxation times). Methods: Materials of interested such as common CT QA phantom materials, and other proprietary gels/silicones from Polytek, SmoothOn, and CompositeOne were first scanned on a GE 1.5T Signa HDxT MR.more » Materials that could be seen on both T1-weighted and T2-weighted images were then scanned on a GE Lightspeed RT16 CT simulator and a GE Discovery 750HD CT scanner and their HU values were then measured. The materials with matching HU values of lung (−500 to −700HU), muscle (+40HU) and soft tissue (+100 to +300HU) were further scanned on GE 1.5T Signa HDx to measure their T1 and T2 relaxation times from varying parameters of TI and TE. Results: Materials that could be visualized on T1-weighted and T2-weighted images from a 1.5T MR unit and had an appropriate average CT number, −650, −685, 46,169, and 168 HUs were: compressed cork saturated with water, Polytek Platsil™ Gel-00 combined with mini styrofoam balls, radiotherapy bolus material, SmoothOn Dragon-Skin™ and SmoothOn Ecoflex™, respectively. Conclusion: Post processing analysis is currently being performed to accurately map T1 and T2 values for each material tested. From previous MR visualization and CT examinations it is expected that Dragon-Skin™, Ecoflex™ and bolus will have values consistent with tissue and tumor substitutes. We also expect compressed cork statured with water, and Polytek™-styrofoam combination to have approximate T1 and T2 values suitable for lung-equivalent materials.« less

COMPARISON STUDY OF VARIOUS PLASTICS AS THE WALL MATERIAL OF THGEM-BASED MICRODOSEMETERS FOR FAST NEUTRON MEASUREMENTS.

PubMed

Moslehi, A; Raisali, G; Lamehi, M

2017-04-15

To find appropriate substitutions for the expensive plastics of A-150 and rexolite used in the construction of thick gas electron multiplier (THGEM)-based tissue-equivalent proportional counters, in the present work, the responses of a THGEM-based microdosimetric detector made of A-150 and rexolite and three others composed of plexiglas (PMMA), polyethylene and polystyrene plastics as the wall materials have been compared. Lineal energy distribution, frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent for 0.1, 1 and 10 MeV neutrons and also for 241Am-Be neutrons are calculated using Geant4 simulation toolkit. Frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent values for all plastics are found similar. In addition, the response of an indigenously constructed microdosemeter with PMMA walls is also measured for 241Am-Be neutrons. The experimental results are in good agreement with the simulation predictions. Conclusively, it was found that the three considered plastics can be used as good candidates instead of A-150 and rexolite plastics in fast neutron microdosimetry. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase.

PubMed Central

Fox, T.; Coll, J. T.; Xie, X.; Ford, P. J.; Germann, U. A.; Porter, M. D.; Pazhanisamy, S.; Fleming, M. A.; Galullo, V.; Su, M. S.; Wilson, K. P.

1998-01-01

Mitogen-activated protein (MAP) kinases are serine/threonine kinases that mediate intracellular signal transduction pathways. Pyridinyl imidazole compounds block pro-inflammatory cytokine production and are specific p38 kinase inhibitors. ERK2 is related to p38 in sequence and structure, but is not inhibited by pyridinyl imidazole inhibitors. Crystal structures of two pyridinyl imidazoles complexed with p38 revealed these compounds bind in the ATP site. Mutagenesis data suggested a single residue difference at threonine 106 between p38 and other MAP kinases is sufficient to confer selectivity of pyridinyl imidazoles. We have changed the equivalent residue in human ERK2, Q105, into threonine and alanine, and substituted four additional ATP binding site residues. The single residue change Q105A in ERK2 enhances the binding of SB202190 at least 25,000-fold compared to wild-type ERK2. We report enzymatic analyses of wild-type ERK2 and the mutant proteins, and the crystal structure of a pyridinyl imidazole, SB203580, bound to an ERK2 pentamutant, I103L, Q105T, D106H, E109G. T110A. These ATP binding site substitutions induce low nanomolar sensitivity to pyridinyl imidazoles. Furthermore, we identified 5-iodotubercidin as a potent ERK2 inhibitor, which may help reveal the role of ERK2 in cell proliferation. PMID:9827991

Effective atomic numbers of some tissue substitutes by different methods: A comparative study.

PubMed

Singh, Vishwanath P; Badiger, N M

2014-01-01

Effective atomic numbers of some human organ tissue substitutes such as polyethylene terephthalate, red articulation wax, paraffin 1, paraffin 2, bolus, pitch, polyphenylene sulfide, polysulfone, polyvinylchloride, and modeling clay have been calculated by four different methods like Auto-Zeff, direct, interpolation, and power law. It was found that the effective atomic numbers computed by Auto-Zeff, direct and interpolation methods were in good agreement for intermediate energy region (0.1 MeV < E < 5 MeV) where the Compton interaction dominates. A large difference in effective atomic numbers by direct method and Auto-Zeff was observed in photo-electric and pair-production regions. Effective atomic numbers computed by power law were found to be close to direct method in photo-electric absorption region. The Auto-Zeff, direct and interpolation methods were found to be in good agreement for computation of effective atomic numbers in intermediate energy region (100 keV < E < 10 MeV). The direct method was found to be appropriate method for computation of effective atomic numbers in photo-electric region (10 keV < E < 100 keV). The tissue equivalence of the tissue substitutes is possible to represent by any method for computation of effective atomic number mentioned in the present study. An accurate estimation of Rayleigh scattering is required to eliminate effect of molecular, chemical, or crystalline environment of the atom for estimation of gamma interaction parameters.

Effective atomic numbers of some tissue substitutes by different methods: A comparative study

PubMed Central

Singh, Vishwanath P.; Badiger, N. M.

2014-01-01

Effective atomic numbers of some human organ tissue substitutes such as polyethylene terephthalate, red articulation wax, paraffin 1, paraffin 2, bolus, pitch, polyphenylene sulfide, polysulfone, polyvinylchloride, and modeling clay have been calculated by four different methods like Auto-Zeff, direct, interpolation, and power law. It was found that the effective atomic numbers computed by Auto-Zeff, direct and interpolation methods were in good agreement for intermediate energy region (0.1 MeV < E < 5 MeV) where the Compton interaction dominates. A large difference in effective atomic numbers by direct method and Auto-Zeff was observed in photo-electric and pair-production regions. Effective atomic numbers computed by power law were found to be close to direct method in photo-electric absorption region. The Auto-Zeff, direct and interpolation methods were found to be in good agreement for computation of effective atomic numbers in intermediate energy region (100 keV < E < 10 MeV). The direct method was found to be appropriate method for computation of effective atomic numbers in photo-electric region (10 keV < E < 100 keV). The tissue equivalence of the tissue substitutes is possible to represent by any method for computation of effective atomic number mentioned in the present study. An accurate estimation of Rayleigh scattering is required to eliminate effect of molecular, chemical, or crystalline environment of the atom for estimation of gamma interaction parameters. PMID:24600169

Biochar as a Substitute for Peat in Greenhouse Growing Media: Soil Water Characteristics and Carbon Leaching Dynamics

NASA Astrophysics Data System (ADS)

Johnson, M. S.; Hilbert, I.; Jollymore, A. J.

2012-12-01

Biochar (charcoal derived from waste biomass via pyrolysis) has the potential to be used as part of regional scale carbon sequestration strategies. By providing a stable form of carbon that is resistant to decay in soils, biochar can be utilized in a wide range of applications to improve the sustainability of land use management practices. Due to its high water holding capacity, surface area and charge density, it could provide a substitute for peat that is widely used in horticultural activities. Globally, peat production in 2010 amounted to 23.4 Mt, with more than a third of this used for horticulture. In Canada, essentially all peat produced is used for horticulture, with each ton of peat extracted also contributing about 0.7 t CO2e in combined greenhouse gas emissions related to production, transportation and use of peat. We evaluated biochar produced on farm from red alder as a peat substitute in terms of soil water characteristics and carbon leaching in greenhouse growing media (e.g. potting mix). Biochar mixing ratios of 10% (v/v) and greater provided water holding capacity equivalent to peat-based potting mixes. We also present results from a laboratory wetting experiment in which we characterized leachate for dissolved organic carbon (DOC) concentration and DOC characteristics using spectral methods (uV-Vis and fluorescence spectroscopy).

Optimisation of resistant starch II and III levels in durum wheat pasta to reduce in vitro digestibility while maintaining processing and sensory characteristics.

PubMed

Aravind, Nisha; Sissons, Mike; Fellows, Christopher M; Blazek, Jaroslav; Gilbert, Elliot P

2013-01-15

Foods with elevated levels of resistant starch (RS) may have beneficial effects on human health. Pasta was enriched with commercial resistant starches (RSII, Hi Maize™ 1043; RSIII, Novelose 330™) at 10%, 20% and 50% substitution of semolina for RSII and 10% and 20% for RSIII and compared with pasta made from 100% durum wheat semolina to investigate technological, sensory, in vitro starch digestibility and structural properties. The resultant RS content of pasta increased from 1.9% to ∼21% and was not reduced on cooking. Significantly, the results indicate that 10% and 20% RSII and RSIII substitution of semolina had no significant effects on pasta cooking loss, texture and sensory properties, with only a minimal reduction in pasta yellowness. Both RS types lowered the extent of in vitro starch hydrolysis compared to that of control pasta. X-ray diffraction and small-angle scattering verified the incorporation of RS and, compared to the control sample, identified enhanced crystallinity and a changed molecular arrangement following digestion. These results can be contrasted with the negative impact on pasta resulting from substitution with equivalent amounts of more traditional dietary fibre such as bran. The study suggests that these RS-containing formulations may be ideal sources for the preparation of pasta with reduced starch digestibility. Copyright © 2012 Elsevier Ltd. All rights reserved.

In Vivo Evaluation and Imaging of a Bilayered Self-Assembled Skin Substitute Using a Decellularized Dermal Matrix Grafted on Mice.

PubMed

Beaudoin Cloutier, Chanel; Goyer, Benjamin; Perron, Cindy; Guignard, Rina; Larouche, Danielle; Moulin, Véronique J; Germain, Lucie; Gauvin, Robert; Auger, François A

2017-04-01

As time to final coverage is the essence for better survival outcome in severely burned patients, we have continuously strived to reduce the duration for the preparation of our bilayered self-assembled skin substitutes (SASS). These SASS produced in vitro by the self-assembly approach have a structure and functionality very similar to native skin. Recently, we have shown that a decellularized dermal matrix preproduced by the self-assembly approach could be used as a template to further obtain self-assembled skin substitute using a decellularized dermal template (SASS-DM) in vitro. Thus, the production period with patient cells was then reduced to about 1 month. Herein, preclinical animal experiments have been performed to confirm the integration and evolution of such a graft and compare the maturation of SASS and SASS-DM in vivo. Both tissues, reconstructed from adult or newborn cells, were grafted on athymic mice. Green fluorescent protein-transfected keratinocytes were also used to follow grafted tissues weekly for 6 weeks using an in vivo imaging system (IVIS). Cell architecture and differentiation were studied with histological and immunofluorescence analyses at each time point. Graft integration, macroscopic evolution, histological analyses, and expression of skin differentiation markers were similar between both skin substitutes reconstructed from either newborn or adult cells, and IVIS observations confirmed the efficient engraftment of SASS-DM. In conclusion, our in vivo graft experiments on a mouse model demonstrated that the SASS-DM had equivalent macroscopic, histological, and differentiation evolution over a 6-week period, when compared with the SASS. The tissue-engineered SASS-DM could improve clinical availability and advantageously shorten the time necessary for the definitive wound coverage of severely burned patients.

Effective non-viral delivery of siRNA to acute myeloid leukemia cells with lipid-substituted polyethylenimines.

PubMed

Landry, Breanne; Aliabadi, Hamidreza Montazeri; Samuel, Anuja; Gül-Uludağ, Hilal; Jiang, Xiaoyan; Kutsch, Olaf; Uludağ, Hasan

2012-01-01

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ≈ 0.5 and led to siRNA/polymer complexes of ≈ 100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia.

Effective Non-Viral Delivery of siRNA to Acute Myeloid Leukemia Cells with Lipid-Substituted Polyethylenimines

PubMed Central

Landry, Breanne; Aliabadi, Hamidreza Montazeri; Samuel, Anuja; Gül-Uludağ, Hilal; Jiang, Xiaoyan; Kutsch, Olaf; Uludağ, Hasan

2012-01-01

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ∼0.5 and led to siRNA/polymer complexes of ∼100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia. PMID:22952927

Neutron diffraction studies of some rare earth-transition metal deuterides

NASA Astrophysics Data System (ADS)

James, W. J.

1984-04-01

Neutron diffraction studies of the ternary alloy system Y6(Fel-xMnx)23 reveal that the unusual magnetic behavior upon substitution of Mn or Fe into the end members, is a consequence of atomic ordering wherein there is strong site preference of Mn for the f sub 2 sites and of Fe for the f sub 1 sites. In the Mn-rich compositions, Fe is found to have no spontaneous moments. Therefore, the long range magnetic ordering arises solely from Mn-Mn interactions. Upon substitution of Mn into the Fe-rich ternaries, the Fe moments are considerably reduced. Neutron diffraction studies of Y6Mn23D23 show that a transition occurs below 180K from a fcc structure to a primitive tetragonal structure, space group P4/mmm with the onset of antiferromagnetic ordering. The Mn moments are directed along the c-axis. The transition probably results from atomic ordering of the D atoms at low temperature which induces c axis magnetic ordering. The question of the appropriate space group of LaNi4.5Al0.5D4.5, P6/mmm or P3/m has been resolved by a careful refinement and analysis of neutron diffraction data. The preferred space group is P6/mmm. Neutron powder diffraction and thermal magnetization measurements on small single crystals of ErNi3, ErCo3, and ErFe3 (space group R3m) show that the magnetocrystalline properties are a consequence of competing local site anisotropies between the two non-equivalent crystallographic sites of Er and two of the three non-equivalent sites of the 3d-transition metal.

Shelf-life evaluation of bilayered human skin equivalent, MyDerm™.

PubMed

Seet, Wan Tai; Manira, Maarof; Maarof, Manira; Khairul Anuar, Khairoji; Chua, Kien-Hui; Ahmad Irfan, Abdul Wahab; Ng, Min Hwei; Aminuddin, Bin Saim; Ruszymah, Bt Hj Idrus

2012-01-01

Skin plays an important role in defense against infection and other harmful biological agents. Due to its fragile structure, skin can be easily damaged by heat, chemicals, traumatic injuries and diseases. An autologous bilayered human skin equivalent, MyDerm™, was engineered to provide a living skin substitute to treat critical skin loss. However, one of the disadvantages of living skin substitute is its short shelf-life, hence limiting its distribution worldwide. The aim of this study was to evaluate the shelf-life of MyDerm™ through assessment of cell morphology, cell viability, population doubling time and functional gene expression levels before transplantation. Skin samples were digested with 0.6% Collagenase Type I followed by epithelial cells dissociation with TrypLE Select. Dermal fibroblasts and keratinocytes were culture-expanded to obtain sufficient cells for MyDerm™ construction. MyDerm™ was constructed with plasma-fibrin as temporary biomaterial and evaluated at 0, 24, 48 and 72 hours after storage at 4°C for its shelf-life determination. The morphology of skin cells derived from MyDerm™ remained unchanged across storage times. Cells harvested from MyDerm™ after storage appeared in good viability (90.5%±2.7% to 94.9%±1.6%) and had short population doubling time (58.4±8.7 to 76.9±19 hours). The modest drop in cell viability and increased in population doubling time at longer storage duration did not demonstrate a significant difference. Gene expression for CK10, CK14 and COL III were also comparable between different storage times. In conclusion, MyDerm™ can be stored in basal medium at 4°C for at least 72 hours before transplantation without compromising its functionality.

Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol.

PubMed

Eaton, Megan M; Germann, Allison L; Arora, Ruby; Cao, Lily Q; Gao, Xiaoyi; Shin, Daniel J; Wu, Albert; Chiara, David C; Cohen, Jonathan B; Steinbach, Joe Henry; Evers, Alex S; Akk, Gustav

2016-01-01

Propofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the γ-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the &quot;+&quot; of the β subunit, in the β-α interface, meta-azipropofol labels the M286 residue in the third transmembrane domain. Substitution of this residue with tryptophan results in loss of potentiation by propofol. At the &quot;-&quot; side of the β subunit, in the α-β interface (or β-β interface, in the case of homomeric β receptors), ortho-propofol diazirine labels the H267 residue in the second transmembrane domain. Structural modeling indicates that the β(H267) residue lines a cavity that docks propofol with favorable interaction energy. We used two-electrode voltage clamp to determine the functional effects of mutations to the "+" and "-" sides of the β subunit on activation of the α1β3 GABAA receptor by propofol. We found that while the individual mutations had a small effect, the combination of the M286W mutation with tryptophan mutations of selected residues at the α-β interface leads to strong reduction in gating efficacy for propofol. We conclude that α1β3 GABAA receptors can be activated by propofol interactions with the β-β, α-β, and β-α interfaces, where distinct, non-equivalent regions control channel gating. Any interface can mediate activation, hence substitutions at all interfaces are required for loss of activation by propofol.

Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol

PubMed Central

Eaton, Megan M.; Germann, Allison L.; Arora, Ruby; Cao, Lily Q.; Gao, Xiaoyi; Shin, Daniel J.; Wu, Albert; Chiara, David C.; Cohen, Jonathan B.; Steinbach, Joe Henry; Evers, Alex S.; Akk, Gustav

2016-01-01

Abstract: Background Propofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the γ-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the “+” of the β subunit, in the β-α interface, meta-azipropofol labels the M286 residue in the third transmembrane domain. Substitution of this residue with tryptophan results in loss of potentiation by propofol. At the “-” side of the β subunit, in the α-β interface (or β-β interface, in the case of homomeric β receptors), ortho-propofol diazirine labels the H267 residue in the second transmembrane domain. Structural modeling indicates that the β(H267) residue lines a cavity that docks propofol with favorable interaction energy. Method We used two-electrode voltage clamp to determine the functional effects of mutations to the 
“+” and “-” sides of the β subunit on activation of the α1β3 GABAA receptor by propofol. Results We found that while the individual mutations had a small effect, the combination of the M286W mutation with tryptophan mutations of selected residues at the α-β interface leads to strong reduction in gating efficacy for propofol. Conclusion We conclude that α1β3 GABAA receptors can be activated by propofol interactions with the β-β, α-β, and β-α interfaces, where distinct, non-equivalent regions control channel gating. Any interface can mediate activation, hence substitutions at all interfaces are required for loss of activation by propofol. PMID:26830963

De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms.

PubMed

Weiss, Karin; Terhal, Paulien A; Cohen, Lior; Bruccoleri, Michael; Irving, Melita; Martinez, Ariel F; Rosenfeld, Jill A; Machol, Keren; Yang, Yaping; Liu, Pengfei; Walkiewicz, Magdalena; Beuten, Joke; Gomez-Ospina, Natalia; Haude, Katrina; Fong, Chin-To; Enns, Gregory M; Bernstein, Jonathan A; Fan, Judith; Gotway, Garrett; Ghorbani, Mohammad; van Gassen, Koen; Monroe, Glen R; van Haaften, Gijs; Basel-Vanagaite, Lina; Yang, Xiang-Jiao; Campeau, Philippe M; Muenke, Maximilian

2016-10-06

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the role of CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification. Published by Elsevier Inc.

Evidence-based alternatives for autogenous grafts around teeth: outcomes, attachment, and stability.

PubMed

McGuire, Michael K

2014-06-01

Although the use of autogenous harvested tissues has proven to be the gold standard for soft tissue augmentation procedures involving root coverage or generation of keratinized tissue, harvest site morbidity and limited supply have prompted clinicians to seek graft alternatives. Using a hierarchy of evidence, the author reviews both clinical and patient-reported results for harvest graft substitutes and, considering his own research experience, reviews autogenous graft substitute outcomes, attachment, and stability over time. Overall, when the goal is keratinized-tissue generation, living cellular constructs and xenogeneic collagen matrices have provided acceptable clinical results, but with better esthetics and patient preference than autogenous free gingival grafts. For root coverage therapy, enamel matrix derivatives, platelet-derived growth factors, and xenogeneic collagen matrices have provided acceptable results with equivalent esthetics to autogenous connective tissue grafts, while also being preferred by patients. Longterm results for enamel matrix derivatives, platelet-derived growth factors, and xenogeneic collagen matrices indicate root coverage can be maintained over time. In the author's hands, xenogeneic collagen matrices have been the only harvest graft alternatives that can be used either covered or uncovered by soft tissue.

Charge transfer and optical properties of trifluoromethyl substituted benzodithiophene (TFMBDT): A theoretical study

NASA Astrophysics Data System (ADS)

Sahoo, Smruti Ranjan; Sahu, Sridhar; Sharma, Sagar

2018-05-01

We present density functional study of the charge transport and optical properties of trifluoromethyl substituted benzodithiophene (TFMBDT) molecule. We found the hole reorganization energy, reduced by 0.354 eV compared to the electron reorganization energy, thus favoring the hole transport across the molecular barrier. We found the maximum tH and tL at the tilting angle 85°, to be 0.473 eV and 0.472 eV, respectively. Although, both tH and tL are found to equivalent, however, low λh can contribute to the larger hole mobility. In the TD-DFT calculation, the low energy electronic transition (H→L) was found to be accordance with the electronic HOMO-LUMO energy gap of the conjugated organic molecule. The calculated gas phase maximum absorption (λmax) of TFMBDT molecule was observed at 337.31 nm (3.67 eV) for B3LYP/6-311+G(d, p) level and 328.04 nm (3.77 eV) for PBE1PBE/6-311+G(d, p) level, which is mostly associated with HOMO→LUMO transition.

Formal properties of the probability of fixation: identities, inequalities and approximations.

PubMed

McCandlish, David M; Epstein, Charles L; Plotkin, Joshua B

2015-02-01

The formula for the probability of fixation of a new mutation is widely used in theoretical population genetics and molecular evolution. Here we derive a series of identities, inequalities and approximations for the exact probability of fixation of a new mutation under the Moran process (equivalent results hold for the approximate probability of fixation under the Wright-Fisher process, after an appropriate change of variables). We show that the logarithm of the fixation probability has particularly simple behavior when the selection coefficient is measured as a difference of Malthusian fitnesses, and we exploit this simplicity to derive inequalities and approximations. We also present a comprehensive comparison of both existing and new approximations for the fixation probability, highlighting those approximations that induce a reversible Markov chain when used to describe the dynamics of evolution under weak mutation. To demonstrate the power of these results, we consider the classical problem of determining the total substitution rate across an ensemble of biallelic loci and prove that, at equilibrium, a strict majority of substitutions are due to drift rather than selection. Copyright © 2014 Elsevier Inc. All rights reserved.

LSB-Based Steganography Using Reflected Gray Code

NASA Astrophysics Data System (ADS)

Chen, Chang-Chu; Chang, Chin-Chen

Steganography aims to hide secret data into an innocuous cover-medium for transmission and to make the attacker cannot recognize the presence of secret data easily. Even the stego-medium is captured by the eavesdropper, the slight distortion is hard to be detected. The LSB-based data hiding is one of the steganographic methods, used to embed the secret data into the least significant bits of the pixel values in a cover image. In this paper, we propose an LSB-based scheme using reflected-Gray code, which can be applied to determine the embedded bit from secret information. Following the transforming rule, the LSBs of stego-image are not always equal to the secret bits and the experiment shows that the differences are up to almost 50%. According to the mathematical deduction and experimental results, the proposed scheme has the same image quality and payload as the simple LSB substitution scheme. In fact, our proposed data hiding scheme in the case of G1 (one bit Gray code) system is equivalent to the simple LSB substitution scheme.

Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity.

PubMed

Cameron, Alan J; Edwards, Patrick J B; Harjes, Elena; Sarojini, Vijayalekshmi

2017-12-14

The d-Phe-Pro β-turn of the cyclic β-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the β-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable β-hairpin libraries. Unlike traditional β-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized.

Enzymatically catalyzed synthesis of low-calorie structured lipid in a solvent-free system: optimization by response surface methodology.

PubMed

Han, Lu; Xu, Zijian; Huang, Jianhua; Meng, Zong; Liu, Yuanfa; Wang, Xingguo

2011-12-14

A kind of low-calorie structured lipid (LCSL) was obtained by interesterification of tributyrin (TB) and methyl stearate (St-ME), catalyzed by a commercially immobilized 1,3-specific lipase, Lipozyme RM IM from Rhizomucor miehei . The condition optimization of the process was conducted by using response surface methodology (RSM). The optimal conditions for highest conversion of St-ME and lowest content LLL-TAG (SSS and SSP; S, stearic acid; P, palmitic acid) were determined to be a reaction time 6.52 h, a substrate molar ratio (St-ME:TB) of 1.77:1, and an enzyme amount of 10.34% at a reaction temperature of 65 °C; under these conditions, the actually measured conversion of St-ME and content of LLL-TAG were 78.47 and 4.89% respectively, in good agreement with predicted values. The target product under optimal conditions after short-range molecular distillation showed solid fat content (SFC) values similar to those of cocoa butter substitutes (CBS), cocoa butter equivalent (CBE), and cocoa butters (CB), indicating its application for inclusion with other fats as cocoa butter substitutes.

Environmental and economic evaluation of bioenergy in Ontario, Canada

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

Yimin Zhang; Shiva Habibi; Heather L. MacLean

2007-08-15

We examined life cycle environmental and economic implications of two near-term scenarios for converting cellulosic biomass to energy, generating electricity from cofiring biomass in existing coal power plants, and producing ethanol from biomass in stand-alone facilities in Ontario, Canada. The study inventories near-term biomass supply in the province, quantifies environmental metrics associated with the use of agricultural residues for producing electricity and ethanol, determines the incremental costs of switching from fossil fuels to biomass, and compares the cost-effectiveness of greenhouse gas (GHG) and air pollutant emissions abatement achieved through the use of the bioenergy. Implementing a biomass cofiring rate of 10% in existing coal-fired power plants would reduce annual GHG emissions by 2.3 million metric tons (t) of CO{sub 2} equivalent (7% of the province's coal power plant emissions). The substitution of gasoline with ethanol/gasoline blends would reduce annual provincial light-duty vehicle fleet emissions between 1.3 and 2.5 million t of CO{sub 2} equivalent (3.5-7% of fleet emissions). If biomass sources other than agricultural residues were used, additional emissions reductions could be realized. At current crude oil prices (more » $70/barrel) and levels of technology development of the bioenergy alternatives, the biomass electricity cofiring scenario analyzed is more cost-effective for mitigating GHG emissions ($$22/t of CO{sub 2} equivalent for a 10% cofiring rate) than the stand-alone ethanol production scenario ($$92/t of CO{sub 2} equivalent). 67 refs., 5 figs., 7 tabs.« less

Evaluation and Control of Mechanical Degradation of Austenitic Stainless 310S Steel Substrate During Coated Superconductor Processing

NASA Astrophysics Data System (ADS)

Kim, Seung-Gyu; Kim, Najung; Shim, Hyung-Seok; Kwon, Oh Min; Kwon, Dongil

2018-05-01

The superconductor industry considers cold-rolled austenitic stainless 310S steel a less expensive substitute for Hastelloy X as a substrate for coated superconductor. However, the mechanical properties of cold-rolled 310S substrate degrade significantly in the superconductor deposition process. To overcome this, we applied hot rolling at 900 °C (or 1000 °C) to the 310S substrate. To check the property changes, a simulated annealing condition equivalent to that used in manufacturing was determined and applied. The effects of the hot rolling on the substrate were evaluated by analyzing its physical properties and texture.

Conducted-Susceptibility Testing as an Alternative Approach to Unit-Level Radiated-Susceptibility Verifications

NASA Astrophysics Data System (ADS)

Badini, L.; Grassi, F.; Pignari, S. A.; Spadacini, G.; Bisognin, P.; Pelissou, P.; Marra, S.

2016-05-01

This work presents a theoretical rationale for the substitution of radiated-susceptibility (RS) verifications defined in current aerospace standards with an equivalent conducted-susceptibility (CS) test procedure based on bulk current injection (BCI) up to 500 MHz. Statistics is used to overcome the lack of knowledge about uncontrolled or uncertain setup parameters, with particular reference to the common-mode impedance of equipment. The BCI test level is properly investigated so to ensure correlation of currents injected in the equipment under test via CS and RS. In particular, an over-testing probability quantifies the severity of the BCI test with respect to the RS test.

Thomas-Reiche-Khun populations in X-CH 3 and X-C 2H 5 series of molecules

NASA Astrophysics Data System (ADS)

Zitto, M. E.; Caputo, M. C.; Ferraro, M. B.; Lazzeretti, P.

2000-09-01

Calculations of nuclear electric shieldings, equivalent to dipole moment geometric derivatives, and related to atomic polar tensors, are presented for X-CH 3 and X-C 2H 5 molecules with X=NH 2, OH and F. The electric shielding tensors satisfy a constraint for the electrostatic equilibrium, i.e., the mixed length-acceleration Thomas-Reiche-Khun sum rule, which gives important indications on the reliability of theoretical predictions of IR intensities and leads to the definition of atomic populations. Numerical evidence was found for the additivity and transferability of atomic populations, within the X-substituted alkane series.

Calibration of a rotating accelerometer gravity gradiometer using centrifugal gradients

NASA Astrophysics Data System (ADS)

Yu, Mingbiao; Cai, Tijing

2018-05-01

The purpose of this study is to calibrate scale factors and equivalent zero biases of a rotating accelerometer gravity gradiometer (RAGG). We calibrate scale factors by determining the relationship between the centrifugal gradient excitation and RAGG response. Compared with calibration by changing the gravitational gradient excitation, this method does not need test masses and is easier to implement. The equivalent zero biases are superpositions of self-gradients and the intrinsic zero biases of the RAGG. A self-gradient is the gravitational gradient produced by surrounding masses, and it correlates well with the RAGG attitude angle. We propose a self-gradient model that includes self-gradients and the intrinsic zero biases of the RAGG. The self-gradient model is a function of the RAGG attitude, and it includes parameters related to surrounding masses. The calibration of equivalent zero biases determines the parameters of the self-gradient model. We provide detailed procedures and mathematical formulations for calibrating scale factors and parameters in the self-gradient model. A RAGG physical simulation system substitutes for the actual RAGG in the calibration and validation experiments. Four point masses simulate four types of surrounding masses producing self-gradients. Validation experiments show that the self-gradients predicted by the self-gradient model are consistent with those from the outputs of the RAGG physical simulation system, suggesting that the presented calibration method is valid.

Effect of Zr Doping on Structural and Ferroelectric Properties of Lead-Free Bi0.5(Na0.80K0.20)0.5TiO3 Films

NASA Astrophysics Data System (ADS)

Quan, Ngo Duc; Hung, Vu Ngoc; Dung, Dang Duc

2017-10-01

Environmentally friendly lead-free Bi0.5(Na0.80K0.20)0.5(Ti1- x Zr x )O3 (BNKT- xZr) ferroelectric films with Zr4+ doping concentration x in the range from 0 to 0.05 have been grown on Pt/Ti/SiO2/Si substrates via chemical solution deposition. The effects of Zr4+ substitution on the crystal structure and ferroelectric properties of the films were investigated. X-ray diffraction data revealed that the BNKT- xZr films possessed rhombohedral and tetragonal symmetries at a morphotropic phase boundary when a small amount of Zr4+ doping was added. P- E hysteresis loops typical of ferroelectric materials were observed for all compositions. Zr4+ substituted for Ti4+ in the BNKT- xZr films and remarkably enhanced the ferroelectric properties. The remanent ( P r) and maximum polarization ( P m) reached their highest values of 14.0 μC/cm2 and 35.7 μC/cm2, respectively, at x = 0.02. These values, which are equivalent to the highest P r and P m values in previous reports on lead-free films with different compositions, compare well with those of Pb(Zr,Ti)O3 (PZT) films. Therefore, BNKT- xZr films with optimal Zr4+ concentration could substitute for PZT films in lead-free piezo-microelectromechanical systems (MEMS) devices.

Low-dose caffeine physical dependence in humans.

PubMed

Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

1990-12-01

This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review.

PubMed

Gothe, H; Schall, I; Saverno, K; Mitrovic, M; Luzak, A; Brixner, D; Siebert, U

2015-08-01

Generic drugs are considered therapeutically equivalent to their original counterparts and lower in acquisition costs. However, the overall impact of generic substitution (GS) on global clinical and economic outcomes has not been conclusively evaluated. To test whether (1) generics and original products yield the same health outcomes, and (2) generic therapies save economic resources versus original therapies. We performed a systematic literature review in Medline, Embase, and the Cochrane Database of Systematic Reviews to identify original studies that examine clinical or economic outcomes of GS. After standardized data extraction, reported outcomes were categorized as supporting or rejecting the hypotheses. Each reported outcome was assessed and accounted for supporting and opposing GS. One publication could provide multiple outcome comparisons. We included 40 studies across ten therapeutic areas. Fourteen studies examined patients on de novo therapy; 24 studies investigated maintenance drug therapy, and two studies considered both settings. Overall, 119 outcome comparisons were examined. Of 97 clinical outcome comparisons, 67% reported no significant difference between generic drugs and their off-patent counterparts. Of 22 economic comparisons, 64% suggested that GS increased costs. Consequently, hypothesis (1) was supported but hypothesis (2) was not. We found no major differences among studies that investigated clinical outcomes with de novo or maintenance therapy. The review suggests that clinical effects are similar after GS. However, economic savings are not guaranteed. More systematic research comparing clinical and economic outcomes with or without GS is needed to inform policy on the use of generic substitution.

Determination of 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and -furans at the part per trillion level in United States beef fat using high-resolution gas chromatography/high-resolution mass spectrometry

NASA Technical Reports Server (NTRS)

Ferrario, J.; Byrne, C.; McDaniel, D.; Dupuy, A. Jr; Harless, R.

1996-01-01

As part of the U.S. EPA Dioxin Reassessment Program, the 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and furans were measured at part per trillion (ppt) levels in beef fat collected from slaughter facilities in the United States. This is the first statistically designed national survey of these compounds in the U.S. beef supply. Analyte concentrations were determined by high-resolution gas chromatography/high-resolution mass spectrometry, using isotope dilution methodology. Method limits of detection on a whole weight basis were 0.05 ppt for TCDD and 0.10 ppt for TCDF, 0.50 ppt for the pentas (PeCDDs/PeCDFs)/hexas (HxCDDs/HxCDFs)/heptas (HpCDDs/HpCDFs), and 3.00 ppt for the octas (OCDD/OCDF). Method detection and quantitation limits were established on the basis of demonstrated performance criteria utilizing fortified samples rather than by conventional signal-to-noise or variability of response methods. The background subtraction procedures developed for this study minimized the likelihood of false positives and increased the confidence associated with reported values near the detection limits. Mean and median values for each of the 2,3,7,8-Cl-substituted dioxins and furans are reported, along with the supporting information required for their interpretation. The mean toxic equivalence values for the samples are 0.35 ppt (nondetects = 0) and 0.89 ppt (nondetects = 1/2 LOD).

Comparison of the organic waste management systems in the Danish-German border region using life cycle assessment (LCA).

PubMed

Jensen, Morten Bang; Møller, Jacob; Scheutz, Charlotte

2016-03-01

This study assessed the management of the organic household waste in the Danish-German border region and points out major differences between the systems and their potential effects on the environment using life cycle assessment (LCA). The treatment of organic waste from households in the Danish-German border region is very different on each side of the border; the Danish region only uses incineration for the treatment of organic household waste while the German region includes combined biogas production and composting, mechanical and biological treatment (MBT) and incineration. Data on all parts of the organic waste treatment was collected including waste composition data and data from treatment facilities and their respective energy systems. Based on that the organic waste management systems in the border region were modelled using the EASETECH waste management LCA-model. The main output is a life cycle assessment showing large differences in the environmental performance of the two different regions with the Danish region performing better in 10 out of 14 impact categories. Furthermore, the importance of the substituted district heating systems was investigated showing an impact up to 34% of the entire system for one impact category and showing large difference between each heating system substituted, e.g. in "Global Warming" the impact was from -16 to -1.1 milli person equivalent/tonne treated waste from substitution of centralised hard coal and decentralised natural gas, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural characterisation of xyloglucan secreted by suspension-cultured cells of Nicotiana plumbaginifolia.

PubMed

Sims, I M; Munro, S L; Currie, G; Craik, D; Bacic, A

1996-10-31

Linkage analysis of a xyloglucan from the extracellular medium of suspension cultures of Nicotiana plumbaginifolia showed mostly 4-Glcp and 4,6-Glcp, terminal Xylp and 2-Xylp, and terminal Araf, along with approximately 10% (w/w) O-acetyl groups, equivalent to approximately 0.28 mol acetyl per mol of glycosyl residue. Methylation with methyl trifluoromethanesulfonate under neutral conditions, followed by re-methylation with CD3I under basic conditions, and conversion into partially methylated alditol acetates showed that O-acetyl groups were primarily attached to C-6 of approximately 44% of the 4-Glcp backbone not substituted with Xylp residues and to C-5 of approximately 15% of the terminal Araf residues. These positions of the O-acetyl groups were confirmed by 1H-NMR. Oligosaccharides generated by digestion of native xyloglucan with endo-(1-->4)-beta-glucanase were separated by a combination of gel-filtration chromatography and anion-exchange HPLC, and analysed by glycosyl linkage analysis and by electrospray ionisation-mass spectrometry (ESI-MS). The major oligosaccharide subunits were Glc4Xyl2 and Glc5Xyl2, of which 50-60% are substituted with one terminal Araf residue attached to O-2 of a Xylp residue, and a further 20-25% are substituted with two terminal Araf residues attached to O-2 of the Xylp residues. ESI-MS showed that many of the oligosaccharide subunits carried one, two, and, occasionally three O-acetyl groups.

Cross-sectional Associations between Exposure to Persistent Organic Pollutants and Leukocyte Telomere Length among U.S. Adults in NHANES, 2001–2002

PubMed Central

Mitro, Susanna D.; Birnbaum, Linda S.; Needham, Belinda L.; Zota, Ami R.

2015-01-01

Background: Exposure to persistent organic pollutants (POPs) such as dioxins, furans, and polychlorinated biphenyls (PCBs) may influence leukocyte telomere length (LTL), a biomarker associated with chronic disease. In vitro research suggests dioxins may bind to the aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL. However, few epidemiologic studies have investigated associations between POPs and LTL. Objectives: We examined the association between 18 PCBs, 7 dioxins, and 9 furans and LTL among 1,330 U.S. adults from NHANES 2001–2002. Methods: We created three summed POP metrics based on toxic equivalency factor (TEF), a potency measure including affinity for the AhR: a) non–dioxin-like PCBs (composed of 10 non–dioxin-like PCBs; no AhR affinity and no TEF); b) non-ortho PCBs (composed of 2 non–ortho-substituted PCBs with high TEFs); and c) toxic equivalency (TEQ) (composed of 7 dioxins, 9 furans, 2 non–ortho-substituted PCBs, and 6 mono–ortho-substituted PCBs; weighted by TEF). We tested the association between each metric and LTL using linear regression, adjusting for demographics, blood cell count and distribution, and another metric with a different TEF (i.e., non-ortho PCBs and TEQ adjusted for non–dioxin-like PCBs; non–dioxin-like PCBs adjusted for non-ortho PCBs). Results: In adjusted models, each doubling of serum concentrations of non-ortho PCBs and TEQ was associated with 3.74% (95% CI: 2.10, 5.40) and 5.29% (95% CI: 1.66, 9.05) longer LTLs, respectively. Compared with the lowest quartile, the highest quartile of exposure was associated with 9.16% (95% CI: 2.96, 15.73) and 7.84% (95% CI: –0.53, 16.92) longer LTLs, respectively. Non–dioxin-like PCBs were not associated with LTL. Conclusions: POPs with high TEFs and AhR affinity were associated with longer LTL. Because many dioxin-associated cancers are also associated with longer LTL, these results may provide insight into the mechanisms underlying PCB- and dioxin-related carcinogenesis. Citation: Mitro SD, Birnbaum LS, Needham BL, Zota AR. 2016. Cross-sectional associations between exposure to persistent organic pollutants and leukocyte telomere length among U.S. adults in NHANES, 2001–2002. Environ Health Perspect 124:651–658; http://dx.doi.org/10.1289/ehp.1510187 PMID:26452299

A systematic review of high-oleic vegetable oil substitutions for other fats and oils on cardiovascular disease risk factors: implications for novel high-oleic soybean oils.

PubMed

Huth, Peter J; Fulgoni, Victor L; Larson, Brian T

2015-11-01

High-oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable oils, H-OSBO is predicted to replace large amounts of soybean oil in the US diet. However, there is little evidence concerning the effects of H-OSBO on coronary heart disease (CHD)(6) risk factors and CHD risk. We examined and quantified the effects of substituting high-oleic acid (HO) oils for fats and oils rich in saturated FAs (SFAs), TFAs, or n-6 (ω-6) polyunsaturated FAs (PUFAs) on blood lipids in controlled clinical trials. Searches of online databases through June 2014 were used to select studies that defined subject characteristics; described control and intervention diets; substituted HO oils compositionally similar to H-OSBO (i.e., ≥70% oleic acid) for equivalent amounts of oils high in SFAs, TFAs, or n-6 PUFAs for ≥3 wk; and reported changes in blood lipids. Studies that replaced saturated fats or oils with HO oils showed significant reductions in total cholesterol (TC), LDL cholesterol, and apolipoprotein B (apoB) (P < 0.05; mean percentage of change: -8.0%, -10.9%, -7.9%, respectively), whereas most showed no changes in HDL cholesterol, triglycerides (TGs), the ratio of TC to HDL cholesterol (TC:HDL cholesterol), and apolipoprotein A-1 (apoA-1). Replacing TFA-containing oil sources with HO oils showed significant reductions in TC, LDL cholesterol, apoB, TGs, TC:HDL cholesterol and increased HDL cholesterol and apoA-1 (mean percentage of change: -5.7%, -9.2%, -7.3%, -11.7%, -12.1%, 5.6%, 3.7%, respectively; P < 0.05). In most studies that replaced oils high in n-6 PUFAs with equivalent amounts of HO oils, TC, LDL cholesterol, TGs, HDL cholesterol, apoA-1, and TC:HDL cholesterol did not change. These findings suggest that replacing fats and oils high in SFAs or TFAs with either H-OSBO or oils high in n-6 PUFAs would have favorable and comparable effects on plasma lipid risk factors and overall CHD risk. © 2015 American Society for Nutrition.

A Systematic Review of High-Oleic Vegetable Oil Substitutions for Other Fats and Oils on Cardiovascular Disease Risk Factors: Implications for Novel High-Oleic Soybean Oils12

PubMed Central

Huth, Peter J; Fulgoni, Victor L; Larson, Brian T

2015-01-01

High–oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable oils, H-OSBO is predicted to replace large amounts of soybean oil in the US diet. However, there is little evidence concerning the effects of H-OSBO on coronary heart disease (CHD)6 risk factors and CHD risk. We examined and quantified the effects of substituting high-oleic acid (HO) oils for fats and oils rich in saturated FAs (SFAs), TFAs, or n–6 (ω-6) polyunsaturated FAs (PUFAs) on blood lipids in controlled clinical trials. Searches of online databases through June 2014 were used to select studies that defined subject characteristics; described control and intervention diets; substituted HO oils compositionally similar to H-OSBO (i.e., ≥70% oleic acid) for equivalent amounts of oils high in SFAs, TFAs, or n–6 PUFAs for ≥3 wk; and reported changes in blood lipids. Studies that replaced saturated fats or oils with HO oils showed significant reductions in total cholesterol (TC), LDL cholesterol, and apolipoprotein B (apoB) (P < 0.05; mean percentage of change: −8.0%, −10.9%, −7.9%, respectively), whereas most showed no changes in HDL cholesterol, triglycerides (TGs), the ratio of TC to HDL cholesterol (TC:HDL cholesterol), and apolipoprotein A-1 (apoA-1). Replacing TFA-containing oil sources with HO oils showed significant reductions in TC, LDL cholesterol, apoB, TGs, TC:HDL cholesterol and increased HDL cholesterol and apoA-1 (mean percentage of change: −5.7%, −9.2%, −7.3%, −11.7%, −12.1%, 5.6%, 3.7%, respectively; P < 0.05). In most studies that replaced oils high in n–6 PUFAs with equivalent amounts of HO oils, TC, LDL cholesterol, TGs, HDL cholesterol, apoA-1, and TC:HDL cholesterol did not change. These findings suggest that replacing fats and oils high in SFAs or TFAs with either H-OSBO or oils high in n–6 PUFAs would have favorable and comparable effects on plasma lipid risk factors and overall CHD risk. PMID:26567193

Dioxins, Furans and PCBs in Recycled Water for Indirect Potable Reuse

PubMed Central

Rodriguez, Clemencia; Cook, Angus; Devine, Brian; Van Buynder, Paul; Lugg, Richard; Linge, Kathryn; Weinstein, Philip

2008-01-01

An assessment of potential health impacts of dioxin and dioxin-like compounds in recycled water for indirect potable reuse was conducted. Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (PCBs) congeners have been developed by the World Health Organization to simplify the risk assessment of complex mixtures. Samples of secondary treated wastewater in Perth, Australia were examined pre-and post-tertiary treatment in one full-scale and one pilot water reclamation plant. Risk quotients (RQs) were estimated by expressing the middle-bound toxic equivalent (TEQ) and the upper-bound TEQ concentration in each sampling point as a function of the estimated health target value. The results indicate that reverse osmosis (RO) is able to reduce the concentration of PCDD, PCDF and dioxin-like PCBs and produce water of high quality (RQ after RO=0.15). No increased human health risk from dioxin and dioxin-like compounds is anticipated if highly treated recycled water is used to augment drinking water supplies in Perth. Recommendations for a verification monitoring program are offered. PMID:19151430

Developmentally distinct MYB genes encode functionally equivalent proteins in Arabidopsis.

PubMed

Lee, M M; Schiefelbein, J

2001-05-01

The duplication and divergence of developmental control genes is thought to have driven morphological diversification during the evolution of multicellular organisms. To examine the molecular basis of this process, we analyzed the functional relationship between two paralogous MYB transcription factor genes, WEREWOLF (WER) and GLABROUS1 (GL1), in Arabidopsis. The WER and GL1 genes specify distinct cell types and exhibit non-overlapping expression patterns during Arabidopsis development. Nevertheless, reciprocal complementation experiments with a series of gene fusions showed that WER and GL1 encode functionally equivalent proteins, and their unique roles in plant development are entirely due to differences in their cis-regulatory sequences. Similar experiments with a distantly related MYB gene (MYB2) showed that its product cannot functionally substitute for WER or GL1. Furthermore, an analysis of the WER and GL1 proteins shows that conserved sequences correspond to specific functional domains. These results provide new insights into the evolution of the MYB gene family in Arabidopsis, and, more generally, they demonstrate that novel developmental gene function may arise solely by the modification of cis-regulatory sequences.

Aromatic C=C bonds as dipolarophiles: facile reactions of uncomplexed electron-deficient benzene derivatives and other aromatic rings with a non-stabilized azomethine ylide.

PubMed

Lee, Sunyoung; Diab, Sonia; Queval, Pierre; Sebban, Muriel; Chataigner, Isabelle; Piettre, Serge R

2013-05-27

Non-stabilized azomethine ylide 4a reacts smoothly at room temperature with a variety of uncomplexed aromatic heterocycles and carbocycles on the condition that the ring contains at least one or two electron-withdrawing substituents, respectively. Aromatic substrates, including pyridine and benzene derivatives, participate as 2π components in [3+2] cycloaddition reactions and interact with one, two, or three equivalent(s) of the ylide, depending on their structure and substitution pattern. Thus, this process affords highly functionalized polycyclic structures that contain between one and three pyrrolidinyl ring(s) in useful yields. These results indicate that the site selectivity of the cycloaddition reactions strongly depends on both the nature and the positions of the substituents. In most cases, the second 1,3-dipolar reaction occurs on the opposite face to the one that contains the first pyrrolidinyl ring. DFT calculations on model compounds indicate that a concerted mechanism features a low activation barrier. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonlocal torque operators in ab initio theory of the Gilbert damping in random ferromagnetic alloys

NASA Astrophysics Data System (ADS)

Turek, I.; Kudrnovský, J.; Drchal, V.

2015-12-01

We present an ab initio theory of the Gilbert damping in substitutionally disordered ferromagnetic alloys. The theory rests on introduced nonlocal torques which replace traditional local torque operators in the well-known torque-correlation formula and which can be formulated within the atomic-sphere approximation. The formalism is sketched in a simple tight-binding model and worked out in detail in the relativistic tight-binding linear muffin-tin orbital method and the coherent potential approximation (CPA). The resulting nonlocal torques are represented by nonrandom, non-site-diagonal, and spin-independent matrices, which simplifies the configuration averaging. The CPA-vertex corrections play a crucial role for the internal consistency of the theory and for its exact equivalence to other first-principles approaches based on the random local torques. This equivalence is also illustrated by the calculated Gilbert damping parameters for binary NiFe and FeCo random alloys, for pure iron with a model atomic-level disorder, and for stoichiometric FePt alloys with a varying degree of L 10 atomic long-range order.

Assessing the end-of-life impacts of buildings.

PubMed

Vieira, Pedro Santos; Horvath, Arpad

2008-07-01

This paper builds on previous research on end of life of products by synthesizing some of the theories proposed in the literature and presenting a method for environmental decision-making related to buildings. This is achieved through different solutions, but most significantly through the use of hybrid life-cycle assessment and the definition of allocation boundaries in a way that decreases the uncertainty associated with technologicalforecasting. Results show that there is no significant difference between the results of two major end-of-life assessment approaches (attributional and consequential), and that the choice between the use of one or the other for buildings may not be a critical decision. Assessing the impacts of recycling polices requires accounting for product substitutions, market analysis, and the full supply chain impacts of the recycling chains. Increasing the recycling of concrete from deconstructed buildings from the current 27% rate to 50% could yield a 2-3% (2.7-5.6 million metric tons of CO2 equivalents) reduction in buildings' greenhouse gas emissions, or the equivalent of removing 408,000-847,000 typical cars from U.S. roads.

Monitoring sodium removal and delivered dialysis by conductivity.

PubMed

Locatelli, F; Di Filippo, S; Manzoni, C; Corti, M; Andrulli, S; Pontoriero, G

1995-11-01

As cardiovascular stability and the delivery of the prescribed dialysis "dose" seem to be the main factors in determining the morbidity and mortality of hemodialyzer patients today, it is of paramount importance to match hydro-sodium removal with interdialytic load and to verify the delivered dialysis at each session. A specially designed Biofeedback Module (BM--COT Hospal) allows the automatic determination of plasma water conductivity and effective ionic dialysance with no need for blood samples. Using BM, we evaluated the validity of "conductivity kinetic modelling" (CKM) and the possibility that this may substitute "sodium kinetic modelling". Moreover, we evaluated the "in vivo" relationship between ionic dialysance and effective urea clearance. Our results demonstrate that: 1) CKM makes it possible to obtain programmed end-dialysis plasma water conductivity with an error of less than +/- 0.14 mS/cm, roughly equivalent to a sodium concentration of +/- 1.4 mEq/L. 2). Ionic dialysance and effective urea clearance are not equivalent but, as the interrelationship between these is known, the BM allows the routine monitoring of delivered dialysis.

Ignition in an Atomistic Model of Hydrogen Oxidation.

PubMed

Alaghemandi, Mohammad; Newcomb, Lucas B; Green, Jason R

2017-03-02

Hydrogen is a potential substitute for fossil fuels that would reduce the combustive emission of carbon dioxide. However, the low ignition energy needed to initiate oxidation imposes constraints on the efficiency and safety of hydrogen-based technologies. Microscopic details of the combustion processes, ephemeral transient species, and complex reaction networks are necessary to control and optimize the use of hydrogen as a commercial fuel. Here, we report estimates of the ignition time of hydrogen-oxygen mixtures over a wide range of equivalence ratios from extensive reactive molecular dynamics simulations. These data show that the shortest ignition time corresponds to a fuel-lean mixture with an equivalence ratio of 0.5, where the number of hydrogen and oxygen molecules in the initial mixture are identical, in good agreement with a recent chemical kinetic model. We find two signatures in the simulation data precede ignition at pressures above 200 MPa. First, there is a peak in hydrogen peroxide that signals ignition is imminent in about 100 ps. Second, we find a strong anticorrelation between the ignition time and the rate of energy dissipation, suggesting the role of thermal feedback in stimulating ignition.

Recycling of wood for particle board production: accounting of greenhouse gases and global warming contributions.

PubMed

Merrild, Hanna; Christensen, Thomas H

2009-11-01

The greenhouse gas (GHG) emissions related to the recycling of wood waste have been assessed with the purpose to provide useful data that can be used in accounting of greenhouse gas emissions. Here we present data related to the activities in a material recovery facility (MRF) where wood waste is shredded and foreign objects are removed in order to produce wood chips for use in the production of particleboard. The data are presented in accordance with the UOD (upstream, operational, downstream) framework presented in Gentil et al. (Waste Management & Research, 27, 2009). The GHG accounting shows that the emissions related to upstream activities (5 to 41 kg CO(2)-equivalents tonne( -1) wood waste) and to activities at the MRF (approximately 5 kg CO(2)-equivalents tonne(-1) wood waste) are negligible compared to the downstream processing (-560 to -120 kg CO(2)equivalents tonne(-1) wood waste). The magnitude of the savings in GHG emissions downstream are mainly related to savings in energy consumption for drying of fresh wood for particleboard production. However, the GHG account highly depends on the choices made in the modelling of the downstream system. The inclusion of saved electricity from avoided chipping of virgin wood does not change the results radically (-665 to -125 kg CO(2)-equivalents tonne(- 1) wood waste). However, if in addition it is assumed that the GHG emissions from combustion of wood has no global warming potential (GWP) and that the energy produced from excess wood due to recycling substitutes energy from fossil fuels, here assumed to be coal, potentially large downstream GHG emissions savings can be achieved by recycling of waste wood (-1.9 to -1.3 tonnes CO(2)-equivalents tonne(- 1) wood waste). As the data ranges are broad, it is necessary to carefully evaluate the feasibility of the data in the specific system which the GHG accounting is to be applied to.

Cantu syndrome-associated SUR2 (ABCC9) mutations in distinct structural domains result in KATP channel gain-of-function by differential mechanisms.

PubMed

McClenaghan, Conor; Hanson, Alex; Sala-Rabanal, Monica; Roessler, Helen I; Josifova, Dragana; Grange, Dorothy K; van Haaften, Gijs; Nichols, Colin G

2018-02-09

The complex disorder Cantu syndrome (CS) arises from gain-of-function mutations in either KCNJ8 or ABCC9 , the genes encoding the Kir6.1 and SUR2 subunits of ATP-sensitive potassium (K ATP ) channels, respectively. Recent reports indicate that such mutations can increase channel activity by multiple molecular mechanisms. In this study, we determined the mechanism by which K ATP function is altered by several substitutions in distinct structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E, M1060I, and R1154Q/R1154W in TMD2. We engineered substitutions at their equivalent positions in rat SUR2A (D207E, Y981S, G985E, M1056I, and R1150Q/R1150W) and investigated functional consequences using macroscopic rubidium ( 86 Rb + ) efflux assays and patch-clamp electrophysiology. Our results indicate that D207E increases K ATP channel activity by increasing intrinsic stability of the open state, whereas the cluster of Y981S/G985E/M1056I substitutions, as well as R1150Q/R1150W, augmented Mg-nucleotide activation. We also tested the responses of these channel variants to inhibition by the sulfonylurea drug glibenclamide, a potential pharmacotherapy for CS. None of the D207E, Y981S, G985E, or M1056I substitutions had a significant effect on glibenclamide sensitivity. However, Gln and Trp substitution at Arg-1150 significantly decreased glibenclamide potency. In summary, these results provide additional confirmation that mutations in CS-associated SUR2 mutations result in K ATP gain-of-function. They help link CS genotypes to phenotypes and shed light on the underlying molecular mechanisms, including consequences for inhibitory drug sensitivity, insights that may inform the development of therapeutic approaches to manage CS. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

The responses of the four main substitution mechanisms of H in olivine to H2O activity at 1050 °C and 3 GPa

NASA Astrophysics Data System (ADS)

Tollan, Peter M. E.; Smith, Rachel; O'Neill, Hugh St. C.; Hermann, Jörg

2017-12-01

The water solubility in olivine ({C}_{{H}_2O}) has been investigated at 1050 °C and 3 GPa as a function of water activity ({a}_{{H}_2O}) at subsolidus conditions in the piston-cylinder apparatus, with {a}_{{H}_2O} varied using H2O-NaCl fluids. Four sets of experiments were conducted to constrain the effect of {a}_{{H}_2O} on the four main substitution mechanisms. The experiments were designed to grow olivine in situ and thus achieve global equilibrium (G-type), as opposed to hydroxylating olivine with a pre-existing point-defect structure and impurity content (M-type). Olivine grains from the experiments were analysed with polarised and unpolarised FTIR spectroscopy, and where necessary, the spectra have been deconvoluted to quantify the contribution of each substitution mechanism. Olivine buffered with magnesiowüstite produced absorbance bands at high wavenumbers ranging from 3566 to 3612 cm-1. About 50% of the total absorbance was found parallel to the a-axis, 30% parallel to the b-axis and 20% parallel to the c-axis. The total absorbance and hence water concentration in olivine follows the relationship of {C}_{{H}_2O}∝ {a_{{H}_2O}}^2 , indicating that the investigated defect must involve four H atoms substituting for one Si atom (labelled as [Si]). Forsterite buffered with enstatite produced an absorbance band exclusively aligned parallel the c-axis at 3160 cm-1. The band position, polarisation and observed {C}_{{H}_2O}∝ {a}_{{H}_2O} are consistent with two H substituting for one Mg (labelled as [Mg]). Ti-doped, enstatite-buffered olivine displays absorption bands, and polarisation typical of Ti-clinohumite point defects where two H on the Si-site are charge-balanced by one Ti on a Mg-site (labelled as [Ti]). This is further supported by {C}_{{H}_2O}∝ {a}_{{H}_2O} and a 1:1 relationship of molar H2O and TiO2 in these experiments. Sc-doped, enstatite-buffered experiments display a main absorption band at 3355 cm-1 with {C}_{{H}_2O}∝ {a_{{H}_2O}}^{0.5} and a positive correlation of Sc and H, indicating the coupled substitution of a trivalent cation plus a H for two Mg (labelled as [triv]). Our data demonstrate that extreme care has to be taken when inferences from experiments conducted at {a}_{{H}_2O}=1 are applied to the mantle, where in most cases, a low {a}_{{H}_2O} persists. In particular, the higher exponent of the [Si] substitution mechanism means that the contribution of this hydrous defect to total water content will decrease more rapidly with decreasing {a}_{{H}_2O} than the contributions of the other substitution mechanisms. The experiments confirm previous results that the [Mg] mechanism holds an almost negligible amount of water under nearly all T-P-fO2-fH2O conditions that may be anticipated in nature. However, the small amounts of H2O we find in substituting by this mechanism are similar in the experiments on forsterite doped with either Sc or Ti to those in the undoped forsterite at equivalent {a}_{{H}_2O} (all buffered by enstatite), confirming the assumption that, thermodynamically, {C}_{{H}_2O} substituting by each mechanism does not depend on the water concentration that substitutes by other mechanisms.

Green-house gas mitigation capacity of a small scale rural biogas plant calculations for Bangladesh through a general life cycle assessment.

PubMed

Rahman, Khondokar M; Melville, Lynsey; Fulford, David; Huq, Sm Imamul

2017-10-01

Calculations towards determining the greenhouse gas mitigation capacity of a small-scale biogas plant (3.2 m 3 plant) using cow dung in Bangladesh are presented. A general life cycle assessment was used, evaluating key parameters (biogas, methane, construction materials and feedstock demands) to determine the net environmental impact. The global warming potential saving through the use of biogas as a cooking fuel is reduced from 0.40 kg CO 2 equivalent to 0.064 kg CO 2 equivalent per kilogram of dung. Biomethane used for cooking can contribute towards mitigation of global warming. Prior to utilisation of the global warming potential of methane (from 3.2 m 3 biogas plant), the global warming potential is 13 t of carbon dioxide equivalent. This reduced to 2 t as a result of complete combustion of methane. The global warming potential saving of a bioenergy plant across a 20-year life cycle is 217 t of carbon dioxide equivalent, which is 11 t per year. The global warming potential of the resultant digestate is zero and from construction materials is less than 1% of total global warming potential. When the biogas is used as a fuel for cooking, the global warming potential will reduce by 83% compare with the traditional wood biomass cooking system. The total 80 MJ of energy that can be produced from a 3.2 m 3 anaerobic digestion plant would replace 1.9 t of fuel wood or 632 kg of kerosene currently used annually in Bangladesh. The digestate can also be used as a nutrient rich fertiliser substituting more costly inorganic fertilisers, with no global warming potential impact.

Epigone migraine vertigo (EMV): a late migraine equivalent.

PubMed

Pagnini, P; Vannucchi, P; Giannoni, B; Pecci, R

2014-02-01

Migrainous headache is determined by pathogenetic mechanisms that are also able to affect the peripheral and/or central vestibular system, so that vestibular symptoms may substitute and/or present with headache. We are convinced that there can be many different manifestations of vestibular disorders in migrainous patients, representing true different clinical entities due to their different characteristics and temporal relashionship with headache. Based on such considerations, we proposed a classification of vertigo and other vestibular disorders related to migraine, and believe that a particular variant of migraine-related vertigo should be introduced, namely "epigone migraine vertigo" (EMV): this could be a kind of late migraine equivalent, i.e. a kind of vertigo, migrainous in origin, starting late in the lifetime that substitutes, as an equivalent, pre-existing migraine headache. To clarify this particular clinical picture, we report three illustrative clinical cases among 28 patients collected during an observation period of 13 years (November 1991 - November 2004). For all patients, we collected complete personal clinical history. All patients underwent standard neurotological examination, looking for spontaneous-positional, gaze-evoked and caloric induced nystagmus, using an infrared video camera. We also performed a head shaking test (HST) and an head thrust test (HTT). Ocular motility was tested looking at saccades and smooth pursuit. To exclude other significant neurological pathologies, a brain magnetic resonance imaging (MRI) with gadolinium was performed. During the three months after the first visit, patients were invited to keep a diary noting frequency, intensity and duration of vertigo attacks. After that period, we suggested that they use prophylactic treatment with flunarizine (5 mg per day) and/or acetylsalicylic acid (100 mg per day), or propranolol (40 mg twice a day). All patients were again recommended to note in their diary the frequency and intensity of both headache and vertigo while taking prophylactic therapy. Control visits were programmed after 4, 12 and 24 months of therapy. All patients considerably improved symptoms with therapy: 19 subjects (68%) reported complete disappearance of vestibular symptoms, while 9 (32%) considered symptoms very improved. The subjective judgement was corroborated by data from patients diaries. We conclude that EMV is a clinical variant of typical migraine-related vertigo: a migraineassociated vertigo, headache spell independent, following a headache period, during the lifetime of a patient.

The microwave properties of composites including lightweight core-shell ellipsoids

NASA Astrophysics Data System (ADS)

Yuan, Liming; Xu, Yonggang; Dai, Fei; Liao, Yi; Zhang, Deyuan

2016-12-01

In order to study the microwave properties of suspensions including lightweight core-shell ellipsoids, the calculation formula was obtained by substituting an equivalent ellipsoid for the original core-shell ellipsoid. Simulations for Fe-coated diatomite/paraffin suspensions were performed. Results reveal that the calculated results fitted the measured results very well when the inclusion concentration was no more than 15 vol%, but there was an obvious deviation when the inclusion concentration reached 24 vol%. By comparisons, the formula for less diluted suspensions was more suitable for calculating the electromagnetic parameter of suspensions especially when the ratio was smaller between the electromagnetic parameter of the inclusion and that of the host medium.

C20H4(C4F8)3: a fluorine-containing annulated corannulene that is a better electron acceptor than C60.

PubMed

Kuvychko, Igor V; Dubceac, Cristina; Deng, Shihu H M; Wang, Xue-Bin; Granovsky, Alexander A; Popov, Alexey A; Petrukhina, Marina A; Strauss, Steven H; Boltalina, Olga V

2013-07-15

At sixes and sevens: The reaction of corannulene with 35 equivalents of 1,4-C4F8I2 is an efficient and a relatively selective process that yields two main products in which six H atoms are substituted with three C4F8 moieties that form six- and seven-membered rings. Low-temperature photoelectron spectroscopy showed the electron affinity of the major isomer (shown) exceeds that of C60 (2.74±0.02 and 2.689±0.008 eV, respectively). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental Research into Noise Emission of A Gear Micropump with Plastic Rotor

NASA Astrophysics Data System (ADS)

Rodionov, L. V.; Rekadze, P. D.

2018-01-01

The previous researches show that it’s possible to replace several parts of gear pump to plastic ones. This substitution leads to cost and noise reduction of the pump. Therefore, the series of acoustic experiments on a test bench were carry-out. Sound pressure levels were recorded with microphone, located in a pipe made of a vacuum rubber. Conducted experiment shows that acoustic characteristics of the micropump depend on the different material of driven rotor. Experimental result indicates that the proposed measures for replacing metal rotor to plastic one reduce micropump noise on the studied modes. The maximum achieved acoustic efficiency on equivalent level is 11 dB.

Comparative Study of Light Sources for Household

NASA Astrophysics Data System (ADS)

Pawlak, Andrzej; Zalesińska, Małgorzata

2017-03-01

The article describes test results that provided the ground to define and evaluate basic photometric, colorimetric and electric parameters of selected, widely available light sources, which are equivalent to a traditional incandescent 60-Watt light bulb. Overall, one halogen light bulb, three compact fluorescent lamps and eleven LED light sources were tested. In general, it was concluded that in most cases (branded products, in particular) the measured and calculated parameters differ from the values declared by manufacturers only to a small degree. LED sources prove to be the most beneficial substitute for traditional light bulbs, considering both their operational parameters and their price, which is comparable with the price of compact fluorescent lamps or, in some instances, even lower.

Design, synthesis, and herbicidal activity of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives.

PubMed

Xie, Yong; Chi, Hui-Wei; Guan, Ai-Ying; Liu, Chang-Ling; Ma, Hong-Juan; Cui, Dong-Liang

2014-12-31

A series of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives were designed and synthesized using 2-phenylpridines as the lead compound by intermediate derivatization methods in an attempt to obtain novel compound candidates for weed control. The herbicidal activity assay in glasshouse tests showed several compounds (II6, II7, II8, II9, II10, II11, III2, III3, III4, and III5) could efficiently control velvet leaf, youth-and-old age, barnyard grass, and foxtail at the 37.5 g/ha active substance. Especially, the activities of II6, II7, III2, and III4 were proved roughly equivalent to the saflufenacil and better than 95% sulcotrione at the same concentration. The result of the herbicidal activity assay in field tests demonstrated that II7 at 60 g/ha active substance could give the same effect as bentazon at 1440 g/ha active substance to control dayflower and nightshade, meanwhile II7 showed better activity than oxyfluorfen to control arrowhead and security to rice. The present work indicates that II7 may be a novel compound candidate for potential herbicide.

Calcium ascorbate as a potential partial substitute for NaCl in dry fermented sausages: effect on colour, texture and hygienic quality at different concentrations.

PubMed

Gimeno, O; Astiasarán, I; Bello, J

2001-01-01

A control product (2.6% NaCl) and different treatments with reduced levels of salt (1, 2.3% NaCl; 2, 2.0% NaCl; 3, 1.7% NaCl; 4, 1.4% NaCl) and increased amounts of calcium ascorbate with an equivalent ionic strength to that of the control were assayed. The percentages of reduction of sodium content in relation to the control were 15, 24, 37 and 45% and the supply of calcium was 26, 33, 42 and 50% of the Recommended Dietary Allowance (RDAs established by NRC, US) for treatments 1, 2, 3 and 4, respectively. Partial substitution of NaCl by calcium ascorbate caused higher acidification related with the higher lactic acid bacteria development and probably with the presence of calcium. The instrumental measurement of colour gave rise to some significant differences especially with the highest amount of calcium ascorbate (treatment 4), giving rise to significant higher a* and b* values and lower L* values in relation to the control. Treatments 2, 3 and 4 lead to products with lower hardness and gumminess values than the control. No problems related to the hygienic quality were observed.

Improvement of operational stability of Ogataea minuta carbonyl reductase for chiral alcohol production.

PubMed

Honda, Kohsuke; Inoue, Mizuha; Ono, Tomohiro; Okano, Kenji; Dekishima, Yasumasa; Kawabata, Hiroshi

2017-06-01

Directed evolution of enantio-selective carbonyl reductase from Ogataea minuta was conducted to improve the operational stability of the enzyme. A mutant library was constructed by an error-prone PCR and screened using a newly developed colorimetric assay. The stability of a mutant with two amino acid substitutions was significantly higher than that of the wild type at 50°C in the presence of dimethyl sulfoxide. Site-directed mutagenesis analysis showed that the improved stability of the enzyme can be attributed to the amino acid substitution of V166A. The half-lives of the V166A mutant were 11- and 6.1-times longer than those of the wild type at 50°C in the presence and absence, respectively, of 20% (v/v) dimethyl sulfoxide. No significant differences in the substrate specificity and enantio-selectivity of the enzyme were observed. The mutant enzyme converted 60 mM 2,2,2-trifluoroacetophenone to (R)-(-)-α-(trifluoromethyl)benzyl alcohol in a molar yield of 71% whereas the conversion yield with an equivalent concentration of the wild-type enzyme was 27%. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Using Polymeric Materials to Control Stem Cell Behavior for Tissue Regeneration

PubMed Central

Zhang, Nianli; Kohn, David H.

2017-01-01

Patients with organ failure often suffer from increased morbidity and decreased quality of life. Current strategies of treating organ failure have limitations, including shortage of donor organs, low efficiency of grafts, and immunological problems. Tissue engineering emerged about two decades ago as a strategy to restore organ function with a living, functional engineered substitute. However, the ability to engineer a functional organ substitute is limited by a limited understanding of the interactions between materials and cells that are required to yield functional tissue equivalents. Polymeric materials are one of the most promising classes of materials for use in tissue engineering due to their biodegradability, flexibility in processing and property design, and the potential to use polymer properties to control cell function. Stem cells offer potential in tissue engineering because of their unique capacity to self renew and differentiate into neurogenic, osteogenic, chondrogenic, myogenic lineages under appropriate stimuli from extracellular components. This review examines recent advances in stem cell-polymer interactions for tissue regeneration, specifically highlighting control of polymer properties to direct adhesion, proliferation, and differentiation of stem cells, and how biomaterials can be designed to provide some of the stimuli to cells that the natural extracellular matrix does. PMID:22457178

Structure of the cyclic peptide [W8S]contryphan Vn: effect of the tryptophan/serine substitution on trans-cis proline isomerization.

PubMed

Nepravishta, Ridvan; Mandaliti, Walter; Melino, Sonia; Eliseo, Tommaso; Paci, Maurizio

2014-12-01

The structural characterization of [W8S]contryphan Vn, an analogue of Contryphan Vn with tryptophan 8 substituted with a serine residue (W8S), was performed by NMR spectroscopy, molecular dynamics simulations and fluorescence spectroscopy. Contryphan Vn, a bioactive cyclic peptide from the venom of the cone snail Conus ventricosus, contains an S-S bridge between two cysteines and a D-tryptophan. Like other Contryphans, [W8S]contryphan Vn has proline 7 isomerized trans, while the proline 4 has nearly equivalent populations of cis and trans configurations. The thermodynamic and kinetic parameters of the trans-cis isomerization of proline 4 were measured. The isomers of [W8S]contryphan Vn with proline 4 in cis and trans show structural differences. The absence of the salt bridge between the same Asp2 and Lys6, present in Contryphan Vn, may be attributed to the lack of the hydrophobic side chain of Trp8 where it likely protects the electrostatic interactions. These results may contribute to identifying, in these cyclic peptides, the structural determinants of the mechanism of proline trans-cis isomerization, this being also an important step in protein folding.

Skin bioprinting: a novel approach for creating artificial skin from synthetic and natural building blocks.

PubMed

Augustine, Robin

2018-05-12

Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue. Bioprinting facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Bioprinted skin substitutes or equivalents containing dermal and epidermal components offer a promising approach in skin bioengineering. Various materials including synthetic and natural biopolymers and cells with or without signalling molecules like growth factors are being utilized to produce functional skin constructs. This technology emerging as a novel strategy to overcome the current bottle-necks in skin tissue engineering such as poor vascularization, absence of hair follicles and sweat glands in the construct.

Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms.

PubMed

Park, Hae Jeong; Lee, Soojung; Ju, Eunji; Jones, Jayre A; Choi, Inyeong

2017-03-01

Genome-wide association studies have identified the single nucleotide polymorphism (SNP) rs3278 in the human SLC4A7 gene as one of the marker loci for addiction vulnerability. This marker is located in an intron of the gene, and its genomic role has been unknown. In this study, we examined rs3278 and three adjacent SNPs prevalent in alcoholics for their effects on an alternative promoter that would lead to the production of the NH 2 -terminally truncated protein NBCn1ΔN450, missing the first 450 amino acids. Analysis of the transcription start site database and a promoter prediction algorithm identified a cluster of three promoters in intron 7 and two short CpG-rich sites in intron 6. The promoter closest to rs3278 showed strong transcription activity in luciferase reporter gene assays. Major-to-minor allele substitution at rs3278 resulted in increased transcription activity. Equivalent substitutions at adjacent rs3772723 (intron 7) and rs13077400 (exon 8) had negligible effect; however, the substitution at nonsynonymous rs3755652 (exon 8) increased the activity by more than twofold. The concomitant substitution at rs3278/rs3755652 produced an additive effect. The rs3755652 had more profound effects on the promoter than the upstream regulatory CpG sites. The amino acid change E326K caused by rs3755652 had negligible effect on transporter function. In HEK 293 cells, NBCn1ΔN450 was expressed in plasma membranes, but at significantly lower levels than the nontruncated NBCn1-E. The pH change mediated by NBCn1ΔN450 was also low. We conclude that rs3278 and rs3755652 stimulate an alternative transcription of the SLC4A7 gene, increasing the production of a defective transporter. Copyright © 2017 the American Physiological Society.

Recent trends in global emissions of hydrochlorofluorocarbons and hydrofluorocarbons: reflecting on the 2007 adjustments to the Montreal Protocol.

PubMed

Montzka, S A; McFarland, M; Andersen, S O; Miller, B R; Fahey, D W; Hall, B D; Hu, L; Siso, C; Elkins, J W

2015-05-14

Global-scale atmospheric measurements are used to investigate the effectiveness of recent adjustments to production and consumption controls on hydrochlorofluorocarbons (HCFCs) under the Montreal Protocol on Substances that Deplete the Ozone Layer (Montreal Protocol) and to assess recent projections of large increases in hydrofluorocarbon (HFC) production and emission. The results show that aggregate global HCFC emissions did not increase appreciably during 2007-2012 and suggest that the 2007 Adjustments to the Montreal Protocol played a role in limiting HCFC emissions well in advance of the 2013 cap on global production. HCFC emissions varied between 27 and 29 kt CFC-11-equivalent (eq)/y or 0.76 and 0.79 GtCO2-eq/y during this period. Despite slower than projected increases in aggregate HCFC emissions since 2007, total emissions of HFCs used as substitutes for HCFCs and chlorofluorocarbons (CFCs) have not increased more rapidly than rates projected [Velders, G. J. M.; Fahey, D. W.; Daniel, J. S.; McFarland, M.; Andersen, S. O. The Large Contribution of Projected HFC Emissions to Future Climate Forcing. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 10949-10954] for 2007-2012. HFC global emission magnitudes related to this substitution totaled 0.51 (-0.03, +0.04) GtCO2-eq/y in 2012, a magnitude about two times larger than emissions reported to the United Nations Framework Convention on Climate Change (UNFCCC) for these HFCs. Assuming accurate reporting to the UNFCCC, the results imply that developing countries (non-Annex I Parties) not reporting to the UNFCCC now account for nearly 50% of global HFC emissions used as substitutes for ozone-depleting substances (ODSs). Global HFC emissions (as CO2-eq) from ODS substitution can be attributed approximately equally to mobile air conditioning, commercial refrigeration, and the sum of all other applications.

Potential savings in prescription drug costs for hypertension, hyperlipidemia, and diabetes mellitus by equivalent drug substitution in Austria: a nationwide cohort study.

PubMed

Heinze, Georg; Hronsky, Milan; Reichardt, Berthold; Baumgärtel, Christoph; Müllner, Marcus; Bucsics, Anna; Winkelmayer, Wolfgang C

2015-04-01

Healthcare systems spend considerable proportions of their budgets on pharmaceutical treatment of hypertension, hyperlipidemia, and diabetes mellitus. From data on almost all residents of Austria, a country with mandatory health insurance and universal health coverage, we estimated potential cost savings by substituting prescribed medicines with the cheapest medicines that were of the same chemical substance and strength, and available during the same time. Data from 8.3 million persons (98.5 % of the total Austrian insured population) from 2009-2012 were analyzed. Real prescription costs for antihypertensive, lipid-lowering, and hypoglycemic medicines achievable by same-substance, same-strength drug substitution were computed for each active ingredient, and per gender and 1-year age category of patients. In 2012, health insurance providers spent 231.3 million, 77.8 million, and 91.9 million for antihypertensive, lipid-lowering, and diabetes medications, of which 52.2 million (22.6 %), 15.9 million (20.5 %), and 4.1 million (4.5 %), respectively, could have been saved by same-substance drug substitution. Highest potential savings were calculated for amlodipine (8.0 million, 65.4 %), simvastatin (12.2 million, 59.3 %), and metformin (2.4 million, 54.6 %), respectively. Higher savings for men than for women resulted from differing prescribed cumulative dosages and proportions of patients with co-payment waiver. Potential cost savings in antihypertensive and lipid-lowering drugs increased from 2009-2012. Our study highlights the cost-savings potential from arguably the most acceptable of interventions, simply switching to the cheapest available same-substance, same-strength product. In 2012, this strategy could have reduced costs for antihypertensive, lipid-lowering, and hypoglycemic treatment by up to 18.0 %.

Solar Radiation during Rewarming from Torpor in Elephant Shrews: Supplementation or Substitution of Endogenous Heat Production?

PubMed Central

Thompson, Michelle L.; Mzilikazi, Nomakwezi; Bennett, Nigel C.; McKechnie, Andrew E.

2015-01-01

Many small mammals bask in the sun during rewarming from heterothermy, but the implications of this behaviour for their energy balance remain little understood. Specifically, it remains unclear whether solar radiation supplements endogenous metabolic thermogenesis (i.e., rewarming occurs through the additive effects of internally-produced and external heat), or whether solar radiation reduces the energy required to rewarm by substituting (i.e, replacing) metabolic heat production. To address this question, we examined patterns of torpor and rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in outdoor cages with access to either natural levels of solar radiation or levels that were experimentally reduced by means of shade cloth. We also tested whether acclimation to solar radiation availability was manifested via phenotypic flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST) capacity and/or summit metabolism (Msum). Rewarming rates varied significantly among treatments, with elephant shrews experiencing natural solar radiation levels rewarming faster than conspecifics experiencing solar radiation levels equivalent to approximately 20% or 40% of natural levels. BMR differed significantly between individuals experiencing natural levels of solar radiation and conspecifics experiencing approximately 20% of natural levels, but no between-treatment difference was evident for NST capacity or Msum. The positive relationship between solar radiation availability and rewarming rate, together with the absence of acclimation in maximum non-shivering and total heat production capacities, suggests that under the conditions of this study solar radiation supplemented rather than substituted metabolic thermogenesis as a source of heat during rewarming from heterothermy. PMID:25853244

Alprazolam use and related harm among opioid substitution treatment clients - 12 months follow up after regulatory rescheduling.

PubMed

Deacon, Rachel M; Nielsen, Suzanne; Leung, Stefanie; Rivas, Gonzalo; Cubitt, Tim; Monds, Lauren A; Ezard, Nadine; Larance, Briony; Lintzeris, Nicholas

2016-10-01

Alprazolam, has been associated with disproportionate harms compared to other benzodiazepines, especially among people in opioid substitution treatment (OST). We examine the effect of the rescheduling of alprazolam in Australia, from Schedule 4 to Schedule 8 in February 2014 amongst a high-risk population of clients in OST. OST participants who reported recent (last month) alprazolam use were recruited from three Sydney clinics. Participants (n=57) were interviewed immediately prior to rescheduling and again three months and 12 months after rescheduling. We examined self-reported patterns of drug use, drug availability, mental and physical health. A linear mixed models approach was used to analyse changes in alprazolam and other benzodiazepine use. Mean days of alprazolam use in the past 28 days decreased from 13.7 to 7.1 days, and mean weekly alprazolam dose decreased from 15.1mg to 6.1mg at 12 months follow-up (p=0.001). Total weekly benzodiazepine use also reduced from a mean of 222mg diazepam equivalent to 157mg (p=0.044). Other substance use did not change significantly. Reported mode of cost price of street alprazolam doubled from $5 to $10 over the 12-month period. Alprazolam rescheduling resulted in an overall reduction in alprazolam and total benzodiazepine use, without substitution with other drugs, in the short term. Unintended harms were not observed. Rescheduling appears to have been effective in reducing alprazolam use in this high-risk population. Copyright © 2016 Elsevier B.V. All rights reserved.

Solar radiation during rewarming from torpor in elephant shrews: supplementation or substitution of endogenous heat production?

PubMed

Thompson, Michelle L; Mzilikazi, Nomakwezi; Bennett, Nigel C; McKechnie, Andrew E

2015-01-01

Many small mammals bask in the sun during rewarming from heterothermy, but the implications of this behaviour for their energy balance remain little understood. Specifically, it remains unclear whether solar radiation supplements endogenous metabolic thermogenesis (i.e., rewarming occurs through the additive effects of internally-produced and external heat), or whether solar radiation reduces the energy required to rewarm by substituting (i.e, replacing) metabolic heat production. To address this question, we examined patterns of torpor and rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in outdoor cages with access to either natural levels of solar radiation or levels that were experimentally reduced by means of shade cloth. We also tested whether acclimation to solar radiation availability was manifested via phenotypic flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST) capacity and/or summit metabolism (Msum). Rewarming rates varied significantly among treatments, with elephant shrews experiencing natural solar radiation levels rewarming faster than conspecifics experiencing solar radiation levels equivalent to approximately 20% or 40% of natural levels. BMR differed significantly between individuals experiencing natural levels of solar radiation and conspecifics experiencing approximately 20% of natural levels, but no between-treatment difference was evident for NST capacity or Msum. The positive relationship between solar radiation availability and rewarming rate, together with the absence of acclimation in maximum non-shivering and total heat production capacities, suggests that under the conditions of this study solar radiation supplemented rather than substituted metabolic thermogenesis as a source of heat during rewarming from heterothermy.

Synthesis and biological evaluation of 5-substituted derivatives of the potent antiherpes agent (north)-methanocarbathymine.

PubMed

Russ, Pamela; Schelling, Pierre; Scapozza, Leonardo; Folkers, Gerd; Clercq, Erik De; Marquez, Victor E

2003-11-06

The conformationally locked nucleoside, (north)-methanocarbathymine (1a), is a potent and selective anti-herpes agent effective against herpes simplex type 1 (HSV1) and type 2 (HSV2) viruses. Hereby, we report on the synthesis and biological evaluation of a small set of 5-substituted pyrimidine nucleosides belonging to the same class of bicyclo[3.1.0]hexane nucleosides. Both the 5-bromovinyl (4) and the 5-bromo analogue (3) appeared to be exclusive substrates of HSV1 thymidine kinase (TK), contrasting with the 5-iodo analogue (2), which was significantly phosphorylated by the human cytosolic TK. The binding affinity constant and catalytic turnover for HSV1 TK were measured to assess the influence of the substitution on these parameters. In the plaque reduction and cytotoxicity assays, the 5-bromo analogue (3) showed good activity against HSV1 and HSV2 with less general toxicity than 1a. Against varicella-zoster virus (VZV), the north-locked 5-bromovinyl analogue (4) proved to be as potent as its conformationally unlocked 2'-deoxyriboside equivalent BVDU. The three compounds were also tested in vitro as prodrugs used in a gene therapy context on three osteosarcoma cell lines, either deficient in TK (TK(-)), nontransduced, or stably transduced with HSV1 TK. The 5-iodo compound (2, CC(50) 25 +/- 7 microM) was more efficient than ganciclovir (GCV, CC(50) 75 +/- 35 microM) in inhibiting growth of HSV1-TK transfected cells and less inhibitory than GCV toward TK(-) cells, whereas compound 3 inhibited transfected and nontransfected cell lines in a relatively similar dose-dependent manner.

Anaerobic digestion and digestate use: accounting of greenhouse gases and global warming contribution.

PubMed

Møller, Jacob; Boldrin, Alessio; Christensen, Thomas H

2009-11-01

Anaerobic digestion (AD) of source-separated municipal solid waste (MSW) and use of the digestate is presented from a global warming (GW) point of view by providing ranges of greenhouse gas (GHG) emissions that are useful for calculation of global warming factors (GWFs), i.e. the contribution to GW measured in CO(2)-equivalents per tonne of wet waste. The GHG accounting was done by distinguishing between direct contributions at the AD facility and indirect upstream or downstream contributions. GHG accounting for a generic AD facility with either biogas utilization at the facility or upgrading of the gas for vehicle fuel resulted in a GWF from -375 (a saving) to 111 (a load) kg CO(2)-eq. tonne(-1) wet waste. In both cases the digestate was used for fertilizer substitution. This large range was a result of the variation found for a number of key parameters: energy substitution by biogas, N(2)O-emission from digestate in soil, fugitive emission of CH( 4), unburned CH(4), carbon bound in soil and fertilizer substitution. GWF for a specific type of AD facility was in the range -95 to -4 kg CO(2)-eq. tonne(-1) wet waste. The ranges of uncertainty, especially of fugitive losses of CH(4) and carbon sequestration highly influenced the result. In comparison with the few published GWFs for AD, the range of our data was much larger demonstrating the need to use a consistent and robust approach to GHG accounting and simultaneously accept that some key parameters are highly uncertain.

Structural and functional role of bases 32 and 33 in the anticodon loop of yeast mitochondrial tRNAIle

PubMed Central

Montanari, Arianna; De Luca, Cristina; Di Micco, Patrizio; Morea, Veronica; Frontali, Laura; Francisci, Silvia

2011-01-01

Previous work has demonstrated the usefulness of the yeast model to investigate the molecular mechanisms underlying defects due to base substitutions in mitochondrial tRNA genes, and to identify suppressing molecules endowed with potential clinical relevance. The present paper extends these investigations to two human equivalent yeast mutations located at positions 32 and 33 in the anticodon loop of tRNAIle. Notwithstanding the proximity of the two T>C base substitutions, the effects of these mutations have been found to be quite different in yeast, as they are in human. The T32C substitution has a very severe effect in yeast, consisting in a complete inhibition of growth on nonfermentable substrates. Conversely, respiratory defects caused by the T33C mutation could only be observed in a defined genetic context. Analyses of available sequences and selected tRNA three-dimensional structures were performed to provide explanations for the different behavior of these adjacent mutations. Examination of the effects of previously identified suppressors demonstrated that overexpression of the TUF1 gene did not rescue the defective phenotypes determined by either mutation, possibly as a consequence of the lack of interactions between EF-Tu and the tRNA anticodon arm in known structures. On the contrary, both the cognate IleRS and the noncognate LeuRS and ValRS are endowed with suppressing activities toward both mutations. This allows us to extend to the tRNAIle mutants the cross-suppression activity of aminoacyl-tRNA synthetases previously demonstrated for tRNALeu and tRNAVal mutants. PMID:21914842

Investigation of real tissue water equivalent path lengths using an efficient dose extinction method

NASA Astrophysics Data System (ADS)

Zhang, Rongxiao; Baer, Esther; Jee, Kyung-Wook; Sharp, Gregory C.; Flanz, Jay; Lu, Hsiao-Ming

2017-07-01

For proton therapy, an accurate conversion of CT HU to relative stopping power (RSP) is essential. Validation of the conversion based on real tissue samples is more direct than the current practice solely based on tissue substitutes and can potentially address variations over the population. Based on a novel dose extinction method, we measured water equivalent path lengths (WEPL) on animal tissue samples to evaluate the accuracy of CT HU to RSP conversion and potential variations over a population. A broad proton beam delivered a spread out Bragg peak to the samples sandwiched between a water tank and a 2D ion-chamber detector. WEPLs of the samples were determined from the transmission dose profiles measured as a function of the water level in the tank. Tissue substitute inserts and Lucite blocks with known WEPLs were used to validate the accuracy. A large number of real tissue samples were measured. Variations of WEPL over different batches of tissue samples were also investigated. The measured WEPLs were compared with those computed from CT scans with the Stoichiometric calibration method. WEPLs were determined within  ±0.5% percentage deviation (% std/mean) and  ±0.5% error for most of the tissue surrogate inserts and the calibration blocks. For biological tissue samples, percentage deviations were within  ±0.3%. No considerable difference (<1%) in WEPL was observed for the same type of tissue from different sources. The differences between measured WEPLs and those calculated from CT were within 1%, except for some bony tissues. Depending on the sample size, each dose extinction measurement took around 5 min to produce ~1000 WEPL values to be compared with calculations. This dose extinction system measures WEPL efficiently and accurately, which allows the validation of CT HU to RSP conversions based on the WEPL measured for a large number of samples and real tissues.

Evaluation of discharge medication orders following automatic therapeutic substitution of commonly exchanged drug classes.

PubMed

Glaholt, Sarah; Hayes, Genevieve L; Wisniewski, Christopher S

2014-04-01

Automatic therapeutic substitution (ATS) is a mechanism that, upon patient hospitalization, prompts the pharmacist to exchange an equivalent formulary drug for a nonformulary medication, typically without prescriber contact. In facilities utilizing ATS, there is the possibility that physicians and patients may be unaware of the substitution, potentially leading to drug-drug interactions, therapeutic duplication, and/or increased patient expense following discharge should the original regimen not be resumed. The purpose of this study was to determine the frequency with which hospitalized patients subjected to an ATS protocol were not returned to outpatient drug therapy. A retrospective chart review of adult patients admitted to an academic medical center between January 1 and June 30, 2011, was conducted. Patients were included if they were admitted on angiotensin-converting enzyme (ACE) inhibitors, antidepressants, nonsedating antihistamines, histamine (H2) receptor antagonists, or proton pump inhibitors (PPIs), and were then prescribed a different agent via ATS. Admission and discharge medication reconciliation documents, dictated discharge summaries, and patient education documentation reports were reviewed for drug therapies and doses, as well as medication counseling evidence. The primary endpoint was the percentage of patients not returned to original outpatient therapy following ATS. Secondary endpoints included prescribing events in patients not returned to original therapy, the rate and source of drug therapy counseling at discharge, and the number of patients discharged on a potentially cost-prohibitive drug, defined as any drug available only as a branded product during the study period. A total of 317 interventions were identified through review of pharmacy records. Of these, 47 patients (15%) were not returned to original outpatient therapy. Within this subsection, 15 patients (32%) were discharged on the substituted drug, eight patients (17%) resumed initial therapy but received a dosage adjustment from previous outpatient therapy, and three patients (6%) were discharged on a drug that was neither the substituted product nor the previous outpatient therapy. The remaining 21 patients had therapy discontinued (n = 12/47, 26%) or lacked documentation of discharge therapy (9/47, 19%). Nursing staff provided medication counseling to 288 of the 317 patients (91%). Overall, 51 patients (16%) were identified as receiving a cost-prohibitive drug. Patients subject to ATS of commonly substituted drug classes were returned to their original outpatient drug therapy more than 85% of the time following inpatient hospitalizations, with similar rates of medication counseling at discharge. The prescribing of cost-prohibitive drugs has been identified as a potential area for pharmacist intervention at discharge.

Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity

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

Munoz-Munoz, Jose Luis; Berna, Jose; Garcia-Molina, Maria del Mar

2012-07-27

Highlights: Black-Right-Pointing-Pointer The action the copper complexes and tyrosinase on phenols is equivalent. Black-Right-Pointing-Pointer Isotope effect showed that nucleophilic attack to copper atom may be the slower step. Black-Right-Pointing-Pointer The value of {rho} (Hammett constant) supports an electrophilic aromatic substitution. Black-Right-Pointing-Pointer Data obtained in steady state pH 7 conditions support the mechanism of Scheme 1SM. -- Abstract: A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: k{sub cat}{sup m} and the Michaelis constant, K{sub M}{sup m}. Analysis of these data taking into account chemicalmore » shifts of the carbon atom supporting the hydroxyl group ({delta}) and {sigma}{sub p}{sup +}, enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form E{sub ox} (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant {rho} of -1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of k{sub cat}{sup f{sub n}}/k{sub cat}{sup f{sub 0}} against n (atom fractions of deuterium), where k{sub cat}{sup f{sub n}} is the catalytic constant for a molar fraction of deuterium (n) and k{sub cat}{sup f{sub 0}} is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that only one of the proton transfer processes from the hydroxyl groups involved the catalytic cycle is responsible for the isotope effects. We suggest that this step is the proton transfer from the hydroxyl group of C-1 to the peroxide of the oxytyrosinase form (E{sub ox}). After the nucleophilic attack, the incorporation of the oxygen in the benzene ring occurs by means of an electrophilic aromatic substitution mechanism in which there is no isotopic effect.« less

A review of the differences and similarities between generic drugs and their originator counterparts, including economic benefits associated with usage of generic medicines, using Ireland as a case study.

PubMed

Dunne, Suzanne; Shannon, Bill; Dunne, Colum; Cullen, Walter

2013-01-05

Generic medicines are those where patent protection has expired, and which may be produced by manufacturers other than the innovator company. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Generic medicines are typically 20 to 90% cheaper than originator equivalents. Our objective is to provide a high-level description of what generic medicines are and how they differ, at a regulatory and legislative level, from originator medicines. We describe the current and historical regulation of medicines in the world's two main pharmaceutical markets, in addition to the similarities, as well as the differences, between generics and their originator equivalents including the reasons for the cost differences seen between originator and generic medicines. Ireland is currently poised to introduce generic substitution and reference pricing. This article refers to this situation as an exemplar of a national system on the cusp of significant health policy change, and specifically details Ireland's history with usage of generic medicines and how the proposed changes could affect healthcare provision.

Clinical results of computerized tomography-based simulation with laser patient marking.

PubMed

Ragan, D P; Forman, J D; He, T; Mesina, C F

1996-02-01

Accuracy of a patient treatment portal marking device and computerized tomography (CT) simulation have been clinically tested. A CT-based simulator has been assembled based on a commercial CT scanner. This includes visualization software and a computer-controlled laser drawing device. This laser drawing device is used to transfer the setup, central axis, and/or radiation portals from the CT simulator to the patient for appropriate patient skin marking. A protocol for clinical testing is reported. Twenty-five prospectively, sequentially accessioned patients have been analyzed. The simulation process can be completed in an average time of 62 min. Under many cases, the treatment portals can be designed and the patient marked in one session. Mechanical accuracy of the system was found to be within +/- 1mm. The portal projection accuracy in clinical cases is observed to be better than +/- 1.2 mm. Operating costs are equivalent to the conventional simulation process it replaces. Computed tomography simulation is a clinical accurate substitute for conventional simulation when used with an appropriate patient marking system and digitally reconstructed radiographs. Personnel time spent in CT simulation is equivalent to time in conventional simulation.

A review of the differences and similarities between generic drugs and their originator counterparts, including economic benefits associated with usage of generic medicines, using Ireland as a case study

PubMed Central

2013-01-01

Generic medicines are those where patent protection has expired, and which may be produced by manufacturers other than the innovator company. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Generic medicines are typically 20 to 90% cheaper than originator equivalents. Our objective is to provide a high-level description of what generic medicines are and how they differ, at a regulatory and legislative level, from originator medicines. We describe the current and historical regulation of medicines in the world’s two main pharmaceutical markets, in addition to the similarities, as well as the differences, between generics and their originator equivalents including the reasons for the cost differences seen between originator and generic medicines. Ireland is currently poised to introduce generic substitution and reference pricing. This article refers to this situation as an exemplar of a national system on the cusp of significant health policy change, and specifically details Ireland’s history with usage of generic medicines and how the proposed changes could affect healthcare provision. PMID:23289757

On the conservation laws and solutions of a (2+1) dimensional KdV-mKdV equation of mathematical physics

NASA Astrophysics Data System (ADS)

Motsepa, Tanki; Masood Khalique, Chaudry

2018-05-01

In this paper, we study a (2+1) dimensional KdV-mKdV equation, which models many physical phenomena of mathematical physics. This equation has two integral terms in it. By an appropriate substitution, we convert this equation into two partial differential equations, which do not have integral terms and are equivalent to the original equation. We then work with the system of two equations and obtain its exact travelling wave solutions in form of Jacobi elliptic functions. Furthermore, we employ the multiplier method to construct conservation laws for the system. Finally, we revert the results obtained into the original variables of the (2+1) dimensional KdV-mKdV equation.

Transverse Laplacians for Substitution Tilings

NASA Astrophysics Data System (ADS)

Julien, Antoine; Savinien, Jean

2011-01-01

Pearson and Bellissard recently built a spectral triple - the data of Riemannian noncommutative geometry - for ultrametric Cantor sets. They derived a family of Laplace-Beltrami like operators on those sets. Motivated by the applications to specific examples, we revisit their work for the transversals of tiling spaces, which are particular self-similar Cantor sets. We use Bratteli diagrams to encode the self-similarity, and Cuntz-Krieger algebras to implement it. We show that the abscissa of convergence of the ζ-function of the spectral triple gives indications on the exponent of complexity of the tiling. We determine completely the spectrum of the Laplace-Beltrami operators, give an explicit method of calculation for their eigenvalues, compute their Weyl asymptotics, and a Seeley equivalent for their heat kernels.

Evolution of olfactory receptor in oriental fruit fly Dacus dorsalis

PubMed Central

Metcalf, Robert L.; Metcalf, Esther R.; Mitchell, W. C.; Lee, Lena W. Y.

1979-01-01

Male oriental fruit flies (Dacus dorsalis) from colonies in Taiwan and Hawaii were evaluated for limit of response to various analogues of methyl eugenol. The results are interpreted in terms of the geometry and allosteric requirements of the antennal receptor that triggers the characteristic methyl eugenol reflex. This receptor has evolved for complementarity to all portions of the methyl eugenol molecule and responds only to ortho-substituted benzenes with adjacent oxygen atoms or isoelectronic equivalents. Substantial differences in responses of Taiwan and Hawaiian D. dorsalis suggest that perceptible evolution of the receptor protein has occurred during the past 50 years. A plausible scheme for the coevolution of dacini flies with plants containing phenylpropionoid essential oils is outlined. Images PMID:16592640

Viability and proliferation of L929, tumour and hybridoma cells in the culture media containing sericin protein as a supplement or serum substitute.

PubMed

Cao, Ting-Ting; Zhang, Yu-Qing

2015-09-01

Cell cultures often require the addition of animal serum and other supplements. In this study, silk sericin, a bioactive protein, recovered from the waste of silk floss production was hydrolysed into three pepsin-degraded sericin peptides with different ranges of molecular mass. Normal animal cells, tumour cells and hybridoma cells were cultured systematically in FBS culture media containing sericin as a supplement or serum substitute. The culture test and microscopic observation of L929 cells showed that the smaller molecular weight of the degraded sericin is most suitable for cell culture. The cell culture results showed that with the degradation of sericin, for normal mouse fibroblast L929 cells, addition of 0.75 % sericin into FBS culture medium yields cell viability that is superior to FBS culture medium alone. When all serum was replaced by sericin, cell viability in the sericin medium could reach about one half of that in FBS medium. When in a medium containing a mixture of FBS: sericin (6:4, v/v), the cell culture effect is about 80 %. For the cultures of four tumour and one hybridoma cells, regardless of the molecular weight range, these degraded sericin peptides could substitute all serum in FBS media. The cell viability and proliferation of these tumour and hybridoma cells are equivalent or superior to that in FBS medium. In other words, cell viability and proliferation of these tumour and hybridoma cells in sericin media are more preferable to serum media. The mechanism of the sericin protein to promote cell growth and proliferation will be further investigated later.

Structure-function analysis of amino acid 74 of human RAMP1 and RAMP3 and its role in peptide interactions with adrenomedullin and calcitonin gene-related peptide receptors.

PubMed

Qi, Tao; Ly, Kien; Poyner, David R; Christopoulos, George; Sexton, Patrick M; Hay, Debbie L

2011-05-01

The receptors for calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are complexes of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMP). The CGRP receptor is a CLR/RAMP1 pairing whereas CLR/RAMP2 and CLR/RAMP3 constitute two subtypes of AM receptor: AM(1) and AM(2), respectively. Previous studies identified Glu74 in RAMP3 to be important for AM binding and potency. To further understand the importance of this residue and its equivalent in RAMP1 (Trp74) we substituted the native amino acids with several others. In RAMP3, these were Trp, Phe, Tyr, Ala, Ser, Thr, Arg and Asn; in RAMP1, Glu, Phe, Tyr, Ala and Asn substitutions were made. The mutant RAMPs were co-expressed with CLR in Cos7 cells; receptor function in response to AM, AM(2)/intermedin and CGRP was measured in a cAMP assay and cell surface expression was determined by ELISA. Phe reduced AM potency in RAMP3 but had no effect in RAMP1. In contrast, Tyr had no effect in RAMP3 but enhanced AM potency in RAMP1. Most other substitutions had a small effect on AM potency in both receptors whereas there was little impact on CGRP or AM(2) potency. Overall, these data suggest that the geometry and charge of the residue at position 74 contribute to how AM interacts with the AM(2) and CGRP receptors and confirms the role of this position in dictating differential AM pharmacology at the AM(2) and CGRP receptors. Copyright © 2011. Published by Elsevier Inc.

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

PubMed

Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

2016-08-01

Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

Handling or being the concept: An fMRI study on metonymy representations in coverbal gestures.

PubMed

Joue, Gina; Boven, Linda; Willmes, Klaus; Evola, Vito; Demenescu, Liliana R; Hassemer, Julius; Mittelberg, Irene; Mathiak, Klaus; Schneider, Frank; Habel, Ute

2018-01-31

In "Two heads are better than one," "head" stands for people and focuses the message on the intelligence of people. This is an example of figurative language through metonymy, where substituting a whole entity by one of its parts focuses attention on a specific aspect of the entity. Whereas metaphors, another figurative language device, are substitutions based on similarity, metonymy involves substitutions based on associations. Both are figures of speech but are also expressed in coverbal gestures during multimodal communication. The closest neuropsychological studies of metonymy in gestures have been nonlinguistic tool-use, illustrated by the classic apraxic problem of body-part-as-object (BPO, equivalent to an internal metonymy representation of the tool) vs. pantomimed action (external metonymy representation of the absent object/tool). Combining these research domains with concepts in cognitive linguistic research on gestures, we conducted an fMRI study to investigate metonymy resolution in coverbal gestures. Given the greater difficulty in developmental and apraxia studies, perhaps explained by the more complex semantic inferencing involved for external metonymy than for internal metonymy representations, we hypothesized that external metonymy resolution requires greater processing demands and that the neural resources supporting metonymy resolution would modulate regions involved in semantic processing. We found that there are indeed greater activations for external than for internal metonymy resolution in the temporoparietal junction (TPJ). This area is posterior to the lateral temporal regions recruited by metaphor processing. Effective connectivity analysis confirmed our hypothesis that metonymy resolution modulates areas implicated in semantic processing. We interpret our results in an interdisciplinary view of what metonymy in action can reveal about abstract cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

PubMed

Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

2016-07-20

The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

Porous calcium polyphosphate bone substitutes: additive manufacturing versus conventional gravity sinter processing-effect on structure and mechanical properties.

PubMed

Hu, Youxin; Shanjani, Yaser; Toyserkani, Ehsan; Grynpas, Marc; Wang, Rizhi; Pilliar, Robert

2014-02-01

Porous calcium polyphosphate (CPP) structures proposed as bone-substitute implants and made by sintering CPP powders to form bending test samples of approximately 35 vol % porosity were machined from preformed blocks made either by additive manufacturing (AM) or conventional gravity sintering (CS) methods and the structure and mechanical characteristics of samples so made were compared. AM-made samples displayed higher bending strengths (≈1.2-1.4 times greater than CS-made samples), whereas elastic constant (i.e., effective elastic modulus of the porous structures) that is determined by material elastic modulus and structural geometry of the samples was ≈1.9-2.3 times greater for AM-made samples. X-ray diffraction analysis showed that samples made by either method displayed the same crystal structure forming β-CPP after sinter annealing. The material elastic modulus, E, determined using nanoindentation tests also showed the same value for both sample types (i.e., E ≈ 64 GPa). Examination of the porous structures indicated that significantly larger sinter necks resulted in the AM-made samples which presumably resulted in the higher mechanical properties. The development of mechanical properties was attributed to the different sinter anneal procedures required to make 35 vol % porous samples by the two methods. A primary objective of the present study, in addition to reporting on bending strength and sample stiffness (elastic constant) characteristics, was to determine why the two processes resulted in the observed mechanical property differences for samples of equivalent volume percentage of porosity. An understanding of the fundamental reason(s) for the observed effect is considered important for developing improved processes for preparation of porous CPP implants as bone substitutes for use in high load-bearing skeletal sites. Copyright © 2013 Wiley Periodicals, Inc.

Kinetic study of bone ingrowth and ceramic resorption associated with the implantation of different injectable calcium-phosphate bone substitutes.

PubMed

Gauthier, O; Bouler, J M; Weiss, P; Bosco, J; Daculsi, G; Aguado, E

1999-10-01

This study investigated the in vivo performance of two composite injectable bone substitutes (IBS), each with different calcium-phosphate particles granulometries [40-80 (IBS 40-80) and 200-500 microm (IBS 200-500)]. These biomaterials were obtained by associating a biphasic calcium-phosphate (BCP) ceramic mineral phase with a 3% aqueous solution of a cellulosic polymer (hydroxy-propyl-methyl-cellulose). Both materials were injected for periods of 2, 3, 8, or 12 weeks into bone defects at the distal end of rabbit femurs. Quantitative results on new bone formation, BCP resorption, and staining for tartrate-resistant acid phosphatase (TRAP) activity were studied for statistical purposes. Measurements with scanning electron microscopy and image analysis showed that the final rates of newly formed bone were similar for both tested IBS after 12 weeks of implantation. Bone colonization occurred more extensively during early implantation times for IBS 40-80 than for IBS 200-500. For the latter, BCP degradation occurred regularly throughout the implantation period, whereas it was very intensive during the first 2 weeks for IBS 40-80. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than for IBS 200-500 regardless of implantation time. With the granulometry of either mineral phase, both tested IBS supported extensive bone colonization, which was greater than that previously reported for an equivalent block of macroporous BCP. The resorption-bone substitution process seemed to occur earlier and faster for IBS 40-80 than for IBS 200-500. Both tested IBS expressed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Copyright 1999 John Wiley & Sons, Inc.

Reframing the concept of alternative livelihoods

PubMed Central

Wright, Juliet H.; Hill, Nicholas A. O.; Roe, Dilys; Rowcliffe, J. Marcus; Kümpel, Noëlle F.; Day, Mike; Booker, Francesca; Milner‐Gulland, E. J.

2015-01-01

Abstract Alternative livelihood project (ALP) is a widely used term for interventions that aim to reduce the prevalence of activities deemed to be environmentally damaging by substituting them with lower impact livelihood activities that provide at least equivalent benefits. ALPs are widely implemented in conservation, but in 2012, an International Union for Conservation of Nature resolution called for a critical review of such projects based on concern that their effectiveness was unproven. We focused on the conceptual design of ALPs by considering their underlying assumptions. We placed ALPs within a broad category of livelihood‐focused interventions to better understand their role in conservation and their intended impacts. We dissected 3 flawed assumptions about ALPs based on the notions of substitution, the homogenous community, and impact scalability. Interventions based on flawed assumptions about people's needs, aspirations, and the factors that influence livelihood choice are unlikely to achieve conservation objectives. We therefore recommend use of a sustainable livelihoods approach to understand the role and function of environmentally damaging behaviors within livelihood strategies; differentiate between households in a community that have the greatest environmental impact and those most vulnerable to resource access restrictions to improve intervention targeting; and learn more about the social–ecological system within which household livelihood strategies are embedded. Rather than using livelihood‐focused interventions as a direct behavior‐change tool, it may be more appropriate to focus on either enhancing the existing livelihood strategies of those most vulnerable to conservation‐imposed resource access restrictions or on use of livelihood‐focused interventions that establish a clear link to conservation as a means of building good community relations. However, we recommend that the term ALP be replaced by the broader term livelihood‐focused intervention. This avoids the implicit assumption that alternatives can fully substitute for natural resource‐based livelihood activities. PMID:26310510

Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents.

PubMed

Jameel, Ehtesham; Meena, Poonam; Maqbool, Mudasir; Kumar, Jitendra; Ahmed, Waqar; Mumtazuddin, Syed; Tiwari, Manisha; Hoda, Nasimul; Jayaram, B

2017-08-18

In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC 50 values 0.065 and 0.092 μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ∼28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Michael Addition Reactions between Chiral Equivalents of a Nucleophilic Glycine and (S)- or (R)-3-[(E)-Enoyl]-4-phenyl-1,3-oxazolidin-2-ones as a General Method for Efficient Preparation of β-Substituted Pyroglutamic Acids. Case of Topographically Controlled Stereoselectivity

PubMed Central

Soloshonok*, Vadim A.; Cai, Chaozhong; Yamada, Takeshi; Ueki, Hisanori; Ohfune, Yasufumi; Hruby, Victor J.

2006-01-01

This paper describes a systematic study of addition reactions between the chiral Ni(II) complex of the Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone and (S)- or (R)-3-[(E)-enoyl]-4-phenyl-1,3-oxazolidin-2-ones as a general and synthetically efficient approach to β-substituted pyroglutamic acids and relevant compounds. These reactions were shown to occur at room temperature in the presence of nonchelating organic bases and, most notably, with very high (>98% diastereomeric excess (de)) stereoselectivity at both newly formed stereogenic centers. The stereochemical outcome of the reactions was found to be overwhelmingly controlled by the stereochemical preferences of the Michael acceptors, and the chirality of the glycine complex influenced only the reaction rate. Thus, in the reactions of both the (S)-configured Ni(II) complex and the Michael acceptors, the reaction rates were exceptionally high, allowing preparation of the corresponding products with virtually quantitative (>98%) chemical and stereochemical yields. In contrast, reactions of the (S)-configured Ni(II) complex and (R)-configured Michael acceptors proceeded at noticeably lower rates, but the addition products were obtained in high diastereo-and enantiomeric purity. To rationalize the remarkably high and robust stereoselectivity observed in these reactions, we consider an enzyme–substrate-like mode of interaction involing a topographical match or mismatch of two geometric figures. Excellent chemical and stereochemical yields, combined with the simplicity and operational convenience of the experimental procedures, render the present method of immediate use for preparing various β-substituted pyroglutamic acids and related compounds. PMID:16248672

Michael addition reactions between chiral equivalents of a nucleophilic glycine and (S)- or (R)-3-[(E)-enoyl]-4-phenyl-1,3-oxazolidin-2-ones as a general method for efficient preparation of beta-substituted pyroglutamic acids. Case of topographically controlled stereoselectivity.

PubMed

Soloshonok, Vadim A; Cai, Chaozhong; Yamada, Takeshi; Ueki, Hisanori; Ohfune, Yasufumi; Hruby, Victor J

2005-11-02

This paper describes a systematic study of addition reactions between the chiral Ni(II) complex of the Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone and (S)- or (R)-3-[(E)-enoyl]-4-phenyl-1,3-oxazolidin-2-ones as a general and synthetically efficient approach to beta-substituted pyroglutamic acids and relevant compounds. These reactions were shown to occur at room temperature in the presence of nonchelating organic bases and, most notably, with very high (>98% diastereomeric excess (de)) stereoselectivity at both newly formed stereogenic centers. The stereochemical outcome of the reactions was found to be overwhelmingly controlled by the stereochemical preferences of the Michael acceptors, and the chirality of the glycine complex influenced only the reaction rate. Thus, in the reactions of both the (S)-configured Ni(II) complex and the Michael acceptors, the reaction rates were exceptionally high, allowing preparation of the corresponding products with virtually quantitative (>98%) chemical and stereochemical yields. In contrast, reactions of the (S)-configured Ni(II) complex and (R)-configured Michael acceptors proceeded at noticeably lower rates, but the addition products were obtained in high diastereo- and enantiomeric purity. To rationalize the remarkably high and robust stereoselectivity observed in these reactions, we consider an enzyme-substrate-like mode of interaction involving a topographical match or mismatch of two geometric figures. Excellent chemical and stereochemical yields, combined with the simplicity and operational convenience of the experimental procedures, render the present method of immediate use for preparing various beta-substituted pyroglutamic acids and related compounds.

Engineering of a functional human NADH-dependent cytochrome P450 system

PubMed Central

Döhr, Olaf; Paine, Mark J. I.; Friedberg, Thomas; Roberts, Gordon C. K.; Wolf, C. Roland

2001-01-01

A functional human NADH-dependent cytochrome P450 system has been developed by altering the cofactor preference of human NADPH cytochrome P450 reductase (CPR), the redox partner for P450s. This has been achieved by a single amino acid change of the conserved aromatic amino acid Trp-676, which covers the re-side of the FAD isoalloxazine ring in the nicotinamide-binding site. Of the mutations made, the substitution of Trp-676 with alanine (W676A) resulted in a functional NADH-dependent enzyme, which catalyzed the reduction of cytochrome c and ferricyanide as well as facilitated the metabolism of 7-ethoxyresorufin by CYP1A2. Kinetic analysis measuring cytochrome c activity revealed that the NADH-dependent kcat of W676A is equivalent (90%) to the NADPH-dependent kcat of the wild-type enzyme, with W676A having an approximately 1,000-fold higher specificity for NADH. The apparent KMNADPH and KMNADH values of W676A are 80- and 150-fold decreased, respectively. In accordance with structural data, which show a bipartite binding mode of NADPH, substitution of Trp-676 does not affect 2′-AMP binding as seen by the inhibition of both wild-type CPR and the W676A mutant. Furthermore, NADPH was a potent inhibitor of the W676A NADH-dependent cytochrome c reduction and CYP1A2 activity. Overall, the results show that Trp-676 of human CPR plays a major role in cofactor discrimination, and substitution of this conserved aromatic residue with alanine results in an efficient NADH-dependent cytochrome P450 system. PMID:11136248

Importance of α–helix N–capping motif in stabilization of ββα fold

PubMed Central

Koscielska-Kasprzak, Katarzyna; Cierpicki, Tomasz; Otlewski, Jacek

2003-01-01

FSD-1 (full sequence design 1) is a protein folded in a ββα motif, designed on the basis of the second zinc finger domain of Zif268 by a substitution of its metal coordination site with a hydrophobic core. In this work, we analyzed the possibility of introducing the DNA recognition motif of the template zinc finger (S13RSDH17) into FSD-1 sequence in order to obtain a small DNA-binding module devoid of cross-link(s) or metal cofactors. The hybrid protein was unfolded, as judged by CD and NMR criteria. To reveal the role of each of the five amino acids, which form the N-capping motif of the α-helix, we analyzed conformational and stability properties of eight FSD-1 mutants. We used a shielded methyl group of Leu 18 and a CD signal at 215 nm as a convenient measure of the folded state. Glu 17→His substitution at the N3 in S13NEKE17 variant decreased the folded structure content from 90% to 25% (equivalent to 1.8 kcal • mole−1 destabilization) by disruption of N-capping interactions, and had the most significant effect among single mutants studied here. The Ncap Asn 14 substitution with Arg considerably decreased stability, reducing structure content from 90% to 40% (1.4 kcal • mole−1 destabilization) by disruption of a helix-capping hydrogen bond and destabilization of a helix macrodipole. The N1 Glu 15→Ser mutation also produced a considerable effect (1.0 kcal • mole−1 destabilization), again emphasizing the significance of electrostatic interactions in α-helix stabilization. PMID:12761399

Active Sites of Reduced Epidermal Fluorescence1 (REF1) Isoforms Contain Amino Acid Substitutions That Are Different between Monocots and Dicots

PubMed Central

Missihoun, Tagnon D.; Kotchoni, Simeon O.; Bartels, Dorothea

2016-01-01

Plant aldehyde dehydrogenases (ALDHs) play important roles in cell wall biosynthesis, growth, development, and tolerance to biotic and abiotic stresses. The Reduced Epidermal Fluorescence1 is encoded by the subfamily 2C of ALDHs and was shown to oxidise coniferaldehyde and sinapaldehyde to ferulic acid and sinapic acid in the phenylpropanoid pathway, respectively. This knowledge has been gained from works in the dicotyledon model species Arabidopsis thaliana then used to functionally annotate ALDH2C isoforms in other species, based on the orthology principle. However, the extent to which the ALDH isoforms differ between monocotyledons and dicotyledons has rarely been accessed side-by-side. In this study, we used a phylogenetic approach to address this question. We have analysed the ALDH genes in Brachypodium distachyon, alongside those of other sequenced monocotyledon and dicotyledon species to examine traits supporting either a convergent or divergent evolution of the ALDH2C/REF1-type proteins. We found that B. distachyon, like other grasses, contains more ALDH2C/REF1 isoforms than A. thaliana and other dicotyledon species. Some amino acid residues in ALDH2C/REF1 isoforms were found as being conserved in dicotyledons but substituted by non-equivalent residues in monocotyledons. One example of those substitutions concerns a conserved phenylalanine and a conserved tyrosine in monocotyledons and dicotyledons, respectively. Protein structure modelling suggests that the presence of tyrosine would widen the substrate-binding pocket in the dicotyledons, and thereby influence substrate specificity. We discussed the importance of these findings as new hints to investigate why ferulic acid contents and cell wall digestibility differ between the dicotyledon and monocotyledon species. PMID:27798665

Active Sites of Reduced Epidermal Fluorescence1 (REF1) Isoforms Contain Amino Acid Substitutions That Are Different between Monocots and Dicots.

PubMed

Missihoun, Tagnon D; Kotchoni, Simeon O; Bartels, Dorothea

2016-01-01

Plant aldehyde dehydrogenases (ALDHs) play important roles in cell wall biosynthesis, growth, development, and tolerance to biotic and abiotic stresses. The Reduced Epidermal Fluorescence1 is encoded by the subfamily 2C of ALDHs and was shown to oxidise coniferaldehyde and sinapaldehyde to ferulic acid and sinapic acid in the phenylpropanoid pathway, respectively. This knowledge has been gained from works in the dicotyledon model species Arabidopsis thaliana then used to functionally annotate ALDH2C isoforms in other species, based on the orthology principle. However, the extent to which the ALDH isoforms differ between monocotyledons and dicotyledons has rarely been accessed side-by-side. In this study, we used a phylogenetic approach to address this question. We have analysed the ALDH genes in Brachypodium distachyon, alongside those of other sequenced monocotyledon and dicotyledon species to examine traits supporting either a convergent or divergent evolution of the ALDH2C/REF1-type proteins. We found that B. distachyon, like other grasses, contains more ALDH2C/REF1 isoforms than A. thaliana and other dicotyledon species. Some amino acid residues in ALDH2C/REF1 isoforms were found as being conserved in dicotyledons but substituted by non-equivalent residues in monocotyledons. One example of those substitutions concerns a conserved phenylalanine and a conserved tyrosine in monocotyledons and dicotyledons, respectively. Protein structure modelling suggests that the presence of tyrosine would widen the substrate-binding pocket in the dicotyledons, and thereby influence substrate specificity. We discussed the importance of these findings as new hints to investigate why ferulic acid contents and cell wall digestibility differ between the dicotyledon and monocotyledon species.

Structure and function in rhodopsin: Rhodopsin mutants with a neutral amino acid at E134 have a partially activated conformation in the dark state*

PubMed Central

Kim, Jong-Myoung; Altenbach, Christian; Thurmond, Robin L.; Khorana, H. Gobind; Hubbell, Wayne L.

1997-01-01

The Glu-134–Arg-135 residues in rhodopsin, located near the cytoplasmic end of the C helix, are involved in G protein binding, or activation, or both. Furthermore, the charge-neutralizing mutation Glu-134 to Gln-134 produces hyperactivity in the activated state and produces constitutive activity in opsin. The Glu/Asp-Arg charge pair is highly conserved in equivalent positions in other G protein-coupled receptors. To investigate the structural consequences of charge-neutralizing mutations at Glu-134 and Arg-135 in rhodopsin, single spin-labeled side chains were introduced at sites in the cytoplasmic domains of helices C (140), E (227), F (250), or G (316) to serve as “molecular sensors” of the local helix bundle conformation. In each of the spin-labeled rhodopsins, a Gln substitution was introduced at either Glu-134 or Arg-135, and the electron paramagnetic resonance spectrum of the spin label was used to monitor the structural response of the helix bundle. The results indicate that a Gln substitution at Glu-134 induces a photoactivated conformation around helices C and G even in the dark state, an observation of potential relevance to the hyperactivity and constitutive activity of the mutant. In contrast, little change is induced in helix F, which has been shown to undergo a dominant motion upon photoactivation. This result implies that the multiple helix motions accompanying photoactivation are not strongly coupled and can be induced to take place independently. Gln substitution at Arg-135 produces only minor structural changes in the dark- or light-activated conformation, suggesting that this residue is not a determinant of structure in the regions investigated, although it may be functionally important. PMID:9405602

Changes in Dissolved Organic Matter Composition and Disinfection Byproduct Precursors in Advanced Drinking Water Treatment Processes.

PubMed

Phungsai, Phanwatt; Kurisu, Futoshi; Kasuga, Ikuro; Furumai, Hiroaki

2018-03-20

Molecular changes in dissolved organic matter (DOM) from treatment processes at two drinking water treatment plants in Japan were investigated using unknown screening analysis by Orbitrap mass spectrometry. DOM formulas with carbon, hydrogen and oxygen (CHO-DOM) were the most abundant class in water samples, and over half of them were commonly found at both plants. Among the treatment processes, ozonation induced the most drastic changes to DOM. Mass peak intensities of less saturated CHO-DOM (positive (oxygen subtracted double bond equivalent per carbon (DBE-O)/C)) decreased by ozonation, while more saturated oxidation byproducts (negative (DBE-O)/C) increased and new oxidation byproducts (OBPs) were detected. By Kendrick mass analysis, ozone reactions preferred less saturated CHO-DOM in the same alkylation families and produced more saturated alkylation families of OBPs. Following ozonation, biological activated carbon filtration effectively removed <300 Da CHO-DOM, including OBPs. Following chlorination, over 50 chlorinated formulas of disinfection byproducts (DBPs) were found in chlorinated water samples where at least half were unknown. Putative precursors of these DBPs were determined based on electrophilic substitutions and addition reactions. Ozonation demonstrated better decomposition of addition reaction-type precursors than electrophilic substitution-type precursors; over half of both precursor types decreased during biological activated carbon filtration.

Economic aspects of intraoperative coagulation management targeting higher fibrinogen concentrations during major craniosynostosis surgery.

PubMed

Haas, Thorsten; Spielmann, Nelly; Restin, Tanja; Schmidt, Alexander R; Schmugge, Markus; Cushing, Melissa M

2016-01-01

Results of a previously published study demonstrated a significant decrease in transfusion requirements and calculated blood loss for pediatric major craniosynostosis surgery, if a ROTEM(®) FIBTEM trigger of <13 mm (early substitution group) was applied as compared to a trigger of <8 mm (conventional group). The aim of this study was a posthoc analysis of the costs for this coagulation management. The total volume as well as the number of units or bags for all transfused blood products and coagulation factors were recorded for each case. The number of laboratory and point-of-care coagulation tests was also analyzed. Total blood product costs were calculated according to the local prices per unit. The total cost for all transfused/administered blood products/coagulation factors per patient was a median of 1023EUR (IQR 850EUR-1058EUR) in the early substitution group as compared to a median of 910EUR (IQR 719EUR-1351EUR) in the conventional group (P = 0.81). No difference in the number of coagulation tests performed was observed. In this study, the use of a higher fibrinogen trigger was not linked to a significant increase in total costs for transfused blood products and coagulation factors, and may offer an economically equivalent approach to coagulation management. © 2015 John Wiley & Sons Ltd.

A comparison of scaffold-free and scaffold-based reconstructed human skin models as alternatives to animal use.

PubMed

Kinikoglu, Beste

2017-12-01

Tissue engineered full-thickness human skin substitutes have various applications in the clinic and in the laboratory, such as in the treatment of burns or deep skin defects, and as reconstructed human skin models in the safety testing of drugs and cosmetics and in the fundamental study of skin biology and pathology. So far, different approaches have been proposed for the generation of reconstructed skin, each with its own advantages and disadvantages. Here, the classic tissue engineering approach, based on cell-seeded polymeric scaffolds, is compared with the less-studied cell self-assembly approach, where the cells are coaxed to synthesise their own extracellular matrix (ECM). The resulting full-thickness human skin substitutes were analysed by means of histological and immunohistochemical analyses. It was found that both the scaffold-free and the scaffold-based skin equivalents successfully mimicked the functionality and morphology of native skin, with complete epidermal differentiation (as determined by the expression of filaggrin), the presence of a continuous basement membrane expressing collagen VII, and new ECM deposition by dermal fibroblasts. On the other hand, the scaffold-free model had a thicker epidermis and a significantly higher number of Ki67-positive proliferative cells, indicating a higher capacity for self-renewal, as compared to the scaffold-based model. 2017 FRAME.

Human urinary bladder regeneration through tissue engineering - an analysis of 131 clinical cases.

PubMed

Pokrywczynska, Marta; Adamowicz, Jan; Sharma, Arun K; Drewa, Tomasz

2014-03-01

Replacement of urinary bladder tissue with functional equivalents remains one of the most challenging problems of reconstructive urology over the last several decades. The gold standard treatment for urinary diversion after radical cystectomy is the ileal conduit or neobladder; however, this technique is associated with numerous complications including electrolyte imbalances, mucus production, and the potential for malignant transformation. Tissue engineering techniques provide the impetus to construct functional bladder substitutes de novo. Within this review, we have thoroughly perused the literature utilizing PubMed in order to identify clinical studies involving bladder reconstruction utilizing tissue engineering methodologies. The idea of urinary bladder regeneration through tissue engineering dates back to the 1950s. Many natural and synthetic biomaterials such as plastic mold, gelatin sponge, Japanese paper, preserved dog bladder, lyophilized human dura, bovine pericardium, small intestinal submucosa, bladder acellular matrix, or composite of collagen and polyglycolic acid were used for urinary bladder regeneration with a wide range of outcomes. Recent progress in the tissue engineering field suggest that in vitro engineered bladder wall substitutes may have expanded clinical applicability in near future but preclinical investigations on large animal models with defective bladders are necessary to optimize the methods of bladder reconstruction by tissue engineering in humans.

Structure-Energy Relationships of Halogen Bonds in Proteins.

PubMed

Scholfield, Matthew R; Ford, Melissa Coates; Carlsson, Anna-Carin C; Butta, Hawera; Mehl, Ryan A; Ho, P Shing

2017-06-06

The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

Regulatory and cost barriers are likely to limit biosimilar development and expected savings in the near future.

PubMed

Grabowski, Henry G; Guha, Rahul; Salgado, Maria

2014-06-01

In March 2010 Congress established an abbreviated Food and Drug Administration approval pathway for biosimilars-drugs that are very similar but not identical to a reference biological product and cost less. Because bringing biosimilars to the market currently requires large investments of money, fewer biosimilars are expected to enter the biologics market than has been the case with generic drugs entering the small-molecule drug market. Additionally, given the high regulatory hurdles to obtaining interchangeability-which would allow pharmacists to substitute a biosimilar for its reference product, subject to evolving state substitution laws-most biosimilars will likely compete as therapeutic alternatives instead of as therapeutic equivalents. In other words, biosimilars will need to compete with their reference product on the basis of quality; price; and manufacturer's reputation with physicians, insurers, and patient groups. Biosimilars also will face dynamic competition from new biologics in the same therapeutic class-including "biobetters," which offer incremental improvements on reference products, such as extended duration of action. The prospects for significant cost savings from the use of biosimilars appear to be limited for the next several years, but their use should increase over time because of both demand- and supply-side factors. Project HOPE—The People-to-People Health Foundation, Inc.

Constant phycobilisome size in chromatically adapted cells of the cyanobacterium Tolypothrix tenuis, and variation in Nostoc sp

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

Ohki, K.; Gantt, E.; Lipschultz, C.A.

1985-12-01

Phycobilisomes of Tolypothrix tenuis, a cyanobacterium capable of complete chromatic adaptation, were studied from cells grown in red and green light, and in darkness. The phycobilisome size remained constant irrespective of the light quality. The hemidiscoidal phycobilisomes had an average diameter of about 52 nanometers and height of about 33 nanometers, by negative staining. The thickness was equivalent to a physocyanin molecule (about 10 nanometers). The molar ratio of allophycocyanin, relative to other phycobiliproteins always remained at about 1:3. Phycobilisomes from red light grown cells and cells grown heterotrophically in darkness were indistinguishable in their pigment composition, polypeptide pattern, andmore » size. Eight polypeptides were resolved in the phycobilin region (17.5 to 23.5 kilodaltons) by isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Half of these were invariable, while others were variable in green and red light. It is inferred that phycoerythrin synthesis in green light resulted in a one for one substitution of phycocyanin, thus retaining a constant phycobilisome size. Tolypothrix appears to be one of the best examples of phycobiliprotein regulation with wavelength. By contrast, in Nostoc sp., the decrease in phycoerythrin in red light cells was accompanied by a decrease in phycobilisome size but not a regulated substitution.« less

Equivalence between the Energy Stable Flux Reconstruction and Filtered Discontinuous Galerkin Schemes

NASA Astrophysics Data System (ADS)

Zwanenburg, Philip; Nadarajah, Siva

2016-02-01

The aim of this paper is to demonstrate the equivalence between filtered Discontinuous Galerkin (DG) schemes and the Energy Stable Flux Reconstruction (ESFR) schemes, expanding on previous demonstrations in 1D [1] and for straight-sided elements in 3D [2]. We first derive the DG and ESFR schemes in strong form and compare the respective flux penalization terms while highlighting the implications of the fundamental assumptions for stability in the ESFR formulations, notably that all ESFR scheme correction fields can be interpreted as modally filtered DG correction fields. We present the result in the general context of all higher dimensional curvilinear element formulations. Through a demonstration that there exists a weak form of the ESFR schemes which is both discretely and analytically equivalent to the strong form, we then extend the results obtained for the strong formulations to demonstrate that ESFR schemes can be interpreted as a DG scheme in weak form where discontinuous edge flux is substituted for numerical edge flux correction. Theoretical derivations are then verified with numerical results obtained from a 2D Euler testcase with curved boundaries. Given the current choice of high-order DG-type schemes and the question as to which might be best to use for a specific application, the main significance of this work is the bridge that it provides between them. Clearly outlining the similarities between the schemes results in the important conclusion that it is always less efficient to use ESFR schemes, as opposed to the weak DG scheme, when solving problems implicitly.

Environmental and economic evaluation of bioenergy in Ontario, Canada.

PubMed

Zhang, Yimin; Habibi, Shiva; MacLean, Heather L

2007-08-01

We examined life cycle environmental and economic implications of two near-term scenarios for converting cellulosic biomass to energy, generating electricity from cofiring biomass in existing coal power plants, and producing ethanol from biomass in stand-alone facilities in Ontario, Canada. The study inventories near-term biomass supply in the province, quantifies environmental metrics associated with the use of agricultural residues for producing electricity and ethanol, determines the incremental costs of switching from fossil fuels to biomass, and compares the cost-effectiveness of greenhouse gas (GHG) and air pollutant emissions abatement achieved through the use of the bioenergy. Implementing a biomass cofiring rate of 10% in existing coal-fired power plants would reduce annual GHG emissions by 2.3 million metric tons (t) of CO2 equivalent (7% of the province's coal power plant emissions). The substitution of gasoline with ethanol/gasoline blends would reduce annual provincial lightduty vehicle fleet emissions between 1.3 and 2.5 million t of CO2 equivalent (3.5-7% of fleet emissions). If biomass sources other than agricultural residues were used, additional emissions reductions could be realized. At current crude oil prices ($70/barrel) and levels of technology development of the bioenergy alternatives, the biomass electricity cofiring scenario analyzed is more cost-effective for mitigating GHG emissions ($22/t of CO2 equivalent for a 10% cofiring rate) than the stand-alone ethanol production scenario ($92/t of CO2 equivalent). The economics of biomass cofiring benefits from existing capital, whereas the cellulosic ethanol scenario does not. Notwithstanding this result, there are several factors that increase the attractiveness of ethanol. These include uncertainty in crude oil prices, potential for marked improvements in cellulosic ethanol technology and economics, the province's commitment to 5% ethanol content in gasoline, the possibility of ethanol production benefiting from existing capital, and there being few alternatives for moderate-to-large-scale GHG emissions reductions in the transportation sector.

Carbon Nanotube Bolometer for Absolute FTIR Spectroscopy

NASA Astrophysics Data System (ADS)

Woods, Solomon; Neira, Jorge; Tomlin, Nathan; Lehman, John

We have developed and calibrated planar electrical-substitution bolometers which employ absorbers made from vertically-aligned carbon nanotube arrays. The nearly complete absorption of light by the carbon nanotubes from the visible range to the far-infrared can be exploited to enable a device with read-out in native units equivalent to optical power. Operated at cryogenic temperatures near 4 K, these infrared detectors are designed to have time constant near 10 ms and a noise floor of about 10 pW. Built upon a micro-machined silicon platform, each device has an integrated heater and thermometer, either a carbon nanotube thermistor or superconducting transition edge sensor, for temperature control. We are optimizing temperature-controlled measurement techniques to enable high resolution spectral calibrations using these devices with a Fourier-transform spectrometer.

Promoting and regulating generic medicines: Brazil in comparative perspective.

PubMed

da Fonseca, Elize Massard; Shadlen, Kenneth C

2017-04-20

Promoting the use of generic drugs can constitute a core instrument for countries' national pharmaceutical policies, one that reduces drug expenditure while expanding health care access. Despite the potential importance of such policy measures and the differences among national practices, scholars embarking on comparative analysis lack a roadmap for determining which dimensions of generic drug policy to assess and compare. This report fills that gap by considering national rules and regulations across four dimensions deemed crucial to any evaluation: demonstrated therapeutic equivalence; pharmaceutical packaging and labeling; drug prescription; and drug substitution. Furthermore, this report examines how the diverse interests of public and private sector stakeholders might shape generic drug policy and its implementation. To illustrate the challenges and conflicts behind policy development and implementation, this report focuses on the case of Brazil.

A comparison of upper mantle subcontinental electrical conductivity for North America, Europe, and Asia.

USGS Publications Warehouse

Campbell, W.H.; Schiffmacher, E.R.

1986-01-01

Spherical harmonic analysis coefficients of the external and internal parts of the quiet-day geomagnetic field variations (Sq), separated for the N American, European, Central Asian and E Asian regions, were used to determine conductivity profiles to depths of about 600km by the Schmucker equivalent-substitute conductor method. All 3 regions showed a roughly exponential increase of conductivity with depth. Distinct discontinuities seemed to be evident near 255-300km and near 450-600km. Regional differences in the conductivity profiles were shown by the functional fittings to the data. For depths less than about 275km, the N American conductivities seemed to be significantly higher than the other regions. For depths greater than about 300km, the E Asian conductivities were largest. -Authors

Ionic liquids containing symmetric quaternary phosphonium cations and phosphorus-containing anions, and their use as lubricant additives

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

Qu, Jun; Luo, Huimin

An ionic liquid composition having the following generic structural formula: ##STR00001## wherein R 1, R 2, R 3, and R 4 are equivalent and selected from hydrocarbon groups containing at least three carbon atoms, and X - is a phosphorus-containing anion, particularly an organophosphate, organophosphonate, or organophosphinate anion, or a thio-substituted analog thereof containing hydrocarbon groups with at least three carbon atoms. Also described are lubricant compositions comprising the above ionic liquid and a base oil, wherein the ionic liquid is dissolved in the base oil. Further described are methods for applying the ionic liquid or lubricant composition onto amore » mechanical device for which lubrication is beneficial, with resulting improvement in friction reduction, wear rate, and/or corrosion inhibition.« less

Measurement of active constitutive beta-D-glucosidase (esculinase) in the presence of sodium desoxycholate.

PubMed Central

Edberg, S C; Trepeta, R W; Kontnick, C M; Torres, A R

1985-01-01

The hydrolysis of esculin in the presence of bile has been utilized for many years for the identification of bacteria. It is especially useful in differentiating species of the genus Streptococcus. The procedure is a two-step one. First, the bacterium must grow in a particular concentration of bile, and second, it must hydrolyze esculin. The hydrolysis of esculin has traditionally been determined by the brown-black color that results when one of the hydrolysate products, esculetin, reacts with iron in the medium. The procedure requires incubation for 24 h or more. A method was developed based on the measurement of constitutive beta-glucosidase (esculinase) with the repression of this enzyme by bile equivalent (sodium desoxycholate) that required only 30 min. p-Nitrophenyl-beta-D-glucopyranoside was the esculinase substrate, and sodium desoxycholate was substituted for bile salts. After inoculation, a yellow color was equivalent to the brown-black seen in the 40% bile-esculin reaction. The reagent was dispensed in test tubes and was stable for 6 months. The 30-min procedure correlated well with the conventional 24-h bile-esculin agar tube. Streptococcus pneumoniae could also be identified because of the rapid lysis it exhibited in the substrate solution. PMID:3920240

Fiber inhalability and head deposition in rats and humans. ...

EPA Pesticide Factsheets

Due to their dimensions and long durability, inhaled asbestos fibers clear slowly from lung airways. Retained fibers may injure the epithelium, interact with macrophages, or translocate to the interstitium to result in various respiratory diseases. Therefore, calculations of fiber inhalability, deposition, and retention in respiratory tract regions of both rats and humans are crucial, both to assess the health risk of fiber exposures and to facilitate inferences from rat inhalation studies. Rat inhalation experiments are underway at the EPA and NIEHS. A model of fiber inhalability and initial deposition in the human and rat nasal cavity was developed. Existing models for particles were extended to fibers by replacing particle diameter with an equivalent fiber diameter. Since fiber inhalability into the respiratory tract and deposition in the extra thoracic airways depended mainly on its inertia, equivalent impaction diameters were derived and substituted in expressions for spherical particle diameter to determine fiber inhalability and nasal losses. Fiber impaction diameter depended strongly on its orientation in the air. Highest inhalability was obtained when fibers were aligned perpendicular to the flow streamlines in the inhaled air. However, detailed calculations of fiber transport in slow moving air such as that in the atmosphere and in lung airways showed that fibers stayed primarily aligned (parallel) to the flow. Therefore, for inhalability calculations,

Youth access to tobacco: the effects of age, gender, vending machine locks, and "it's the law" programs.

PubMed Central

DiFranza, J R; Savageau, J A; Aisquith, B F

1996-01-01

OBJECTIVES. This study evaluated the influence of age, gender, vending machine lockout devices, and tobacco industry-sponsored voluntary compliance programs ("It's the Law" programs) on underage youths' ability to purchase tobacco. METHODS. Twelve youths made 480 attempts to purchase tobacco in Massachusetts from over-the-counter retailers and vending machines with and without remote control lockout devices. Half the vendors were participating in It's the Law programs. RESULTS. In communities with no requirements for lockout devices, illegal sales were far more likely from vending machines than from over-the-counter sources (odds ratio [OR] = 5.9, 95% confidence interval [CI] = 3.3, 10.3). Locks on vending machines made them equivalent to over-the-counter sources in terms of illegal sales to youths. Vendors participating in It's the Law programs were as likely to make illegal sales as nonparticipants (OR = 0.87, 95% CI = 0.57, 1.35). Girls and youths 16 years of age and older were more successful at purchasing tobacco. CONCLUSIONS. The It's the Law programs are ineffective in preventing illegal sales. While locks made vending machines equivalent to over-the-counter sources in their compliance with the law, they are not a substitute for law enforcement. PMID:8633739

Reduction of greenhouse gas emissions from feed supply chains by utilizing regionally produced protein sources: the case of Austrian dairy production.

PubMed

Hörtenhuber, Stefan Josef; Lindenthal, Thomas; Zollitsch, Werner

2011-04-01

The aim of this study was to analyse the potential greenhouse gas emissions (GHGE) for regionally alternative produced protein-rich feedstuffs (APRFs) which are utilized for dairy cattle in Austria in comparison to solvent-extracted soybean meal (SBME). In addition to GHGE from agriculture and related upstream supply chains, the effects of land use change were calculated and were included in the results for GHGE. Furthermore, mixtures of APRFs were evaluated which provided energy and utilizable protein equivalent to SBME. Highest GHGE were estimated for SBME, mainly due to land use change-related emissions. Medium GHGE were found for distillers' dried grains with solubles, for seed cake and solvent-extracted meal from rapeseed and for lucerne cobs. Cake and solvent-extracted meal from sunflower seed as well as faba beans were loaded with lowest GHGE. Substituting SBME by nutritionally equivalent mixtures of APRFs, on average, resulted in a reduction of GHGE of 42% (22-62%). Utilization of locally produced APRFs shows clear advantages in terms of GHGE. Balanced mixtures of APRFs may offer specific benefits, as they allow for a combination of desirable nutritional value and reduced GHGE. Copyright © 2011 Society of Chemical Industry.

A random forest learning assisted "divide and conquer" approach for peptide conformation search.

PubMed

Chen, Xin; Yang, Bing; Lin, Zijing

2018-06-11

Computational determination of peptide conformations is challenging as it is a problem of finding minima in a high-dimensional space. The "divide and conquer" approach is promising for reliably reducing the search space size. A random forest learning model is proposed here to expand the scope of applicability of the "divide and conquer" approach. A random forest classification algorithm is used to characterize the distributions of the backbone φ-ψ units ("words"). A random forest supervised learning model is developed to analyze the combinations of the φ-ψ units ("grammar"). It is found that amino acid residues may be grouped as equivalent "words", while the φ-ψ combinations in low-energy peptide conformations follow a distinct "grammar". The finding of equivalent words empowers the "divide and conquer" method with the flexibility of fragment substitution. The learnt grammar is used to improve the efficiency of the "divide and conquer" method by removing unfavorable φ-ψ combinations without the need of dedicated human effort. The machine learning assisted search method is illustrated by efficiently searching the conformations of GGG/AAA/GGGG/AAAA/GGGGG through assembling the structures of GFG/GFGG. Moreover, the computational cost of the new method is shown to increase rather slowly with the peptide length.

Gain-of-Function Alleles in Caenorhabditis elegans Nuclear Hormone Receptor nhr-49 Are Functionally Distinct

PubMed Central

Lee, Kayoung; Goh, Grace Ying Shyen; Wong, Marcus Andrew; Klassen, Tara Leah

2016-01-01

Nuclear hormone receptors (NHRs) are transcription factors that regulate numerous physiological and developmental processes and represent important drug targets. NHR-49, an ortholog of Hepatocyte Nuclear Factor 4 (HNF4), has emerged as a key regulator of lipid metabolism and life span in the nematode worm Caenorhabditis elegans. However, many aspects of NHR-49 function remain poorly understood, including whether and how it regulates individual sets of target genes and whether its activity is modulated by a ligand. A recent study identified three gain-of-function (gof) missense mutations in nhr-49 (nhr-49(et7), nhr-49(et8), and nhr-49(et13), respectively). These substitutions all affect the ligand-binding domain (LBD), which is critical for ligand binding and protein interactions. Thus, these alleles provide an opportunity to test how three specific residues contribute to NHR-49 dependent gene regulation. We used computational and molecular methods to delineate how these mutations alter NHR-49 activity. We find that despite originating from a screen favoring the activation of specific NHR-49 targets, all three gof alleles cause broad upregulation of NHR-49 regulated genes. Interestingly, nhr-49(et7) and nhr-49(et8) exclusively affect nhr-49 dependent activation, whereas the nhr-49(et13) surprisingly affects both nhr-49 mediated activation and repression, implicating the affected residue as dually important. We also observed phenotypic non-equivalence of these alleles, as they unexpectedly caused a long, short, and normal life span, respectively. Mechanistically, the gof substitutions altered neither protein interactions with the repressive partner NHR-66 and the coactivator MDT-15 nor the subcellular localization or expression of NHR-49. However, in silico structural modeling revealed that NHR-49 likely interacts with small molecule ligands and that the missense mutations might alter ligand binding, providing a possible explanation for increased NHR-49 activity. In sum, our findings indicate that the three nhr-49 gof alleles are non-equivalent, and highlight the conserved V411 residue affected by et13 as critical for gene activation and repression alike. PMID:27618178

Marketing messages accompanying online selling of low/er and regular strength wine and beer products in the UK: a content analysis.

PubMed

Vasiljevic, Milica; Coulter, Lucia; Petticrew, Mark; Marteau, Theresa M

2018-02-08

Increased availability of low/er strength alcohol products has the potential to reduce alcohol consumption if they are marketed as substitutes for higher strength products rather than as additional products. The current study compares the main marketing messages conveyed by retailers and producers for low/er and regular strength wine and beer products. A content analysis of the marketing messages stated (in text) or depicted (in image) for low/er and regular strength wines and beers sold online on the websites of the four main UK retailers (Tesco, ASDA, Sainsbury's, and Morrisons), and the producers of these products between February-March 2016. Four themes were identified: (a) suggested occasions for consumption, (b) health-related associations, (c) alcohol content, and (d) taste. Compared with regular strength products, low/er strength equivalents were more often marketed in association with occasions deemed to be suitable for their consumption including lunchtimes [wine: X 2 (1, n = 172) = 11.75, p = .001], outdoor events/barbeques [beer: X 2 (1, n = 96) = 11.16, p = .001] and on sport/fitness occasions [beer: X 2 (1, n = 96) = 7.55, p = .006]. Compared with regular strength wines and beers, low/er strength equivalents were more frequently marketed with images or text associated with health. These included images of fruit [wine: X 2 (1, n = 172) = 7.78, p = .005; beer: X 2 (1, n = 96) = 22.00, p < .001] and the provision of their energy (calorie) content [wine: X 2 (1, n = 172) = 47.97, p < .001; beer: X 2 (1, n = 96) = 15.10, p < .001]. Low/er strength products were also more often marketed with information about their alcohol content. There were few differences in the marketing messages regarding taste. Low/er strength wines and beers appear to be marketed not as substitutes for higher strength products but as ones that can be consumed on additional occasions with an added implication of healthiness.

Rupture model based on non-associated plasticity

NASA Astrophysics Data System (ADS)

Pradeau, Adrien; Yoon, Jeong Whan; Thuillier, Sandrine; Lou, Yanshan; Zhang, Shunying

2018-05-01

This research work is about modeling the mechanical behavior of metallic sheets of AA6016 up to rupture using non-associated flow rule. Experiments were performed at room temperature in uniaxial tension and simple shear in different directions according to the rolling direction and an additional hydraulic bulge test. The anisotropy of the material is described by a Yld2000-2d yield surface [1], calibrated by stress ratios, and a plastic potential represented by Hill1948 [2], calibrated using Lankford coefficients. That way, the former is able to reproduce the yield stresses in different directions and the latter is able to reproduce the deformations in different directions as well [3], [4]. Indeed, the non-associated flow rule allows for the direction of the plastic flow not to be necessarily normal to the yield surface. Concerning the rupture, the macroscopic ductile fracture criterion DF2014 was used [5]. It indirectly uses the three invariants of the stress tensor by using the three following parameters: the stress triaxiality η, the Lode parameter L and the equivalent plastic strain to fracture ∈f-p . In order to be consistent with the plastic model and to add more flexibility to the p criterion, the equivalent stress σ ¯ and the equivalent strain to fracture ∈f-p have been substituted respectively as Yld2000-2d and Hill1948 in the DF2014 fracture criterion. The parameters for the fracture criterion were obtained by optimization and the fracture locus can be plotted in the (η ,L ,∈-p) space. The damage indicator D is then numerically predicted with respect of average strain values. A good correlation with the experimental results is obtained.

Polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in tree swallows from the upper Hudson River, New York State, USA

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

Secord, A.L.; McCarty, J.P.; Echols, K.R.

1999-11-01

The upper Hudson River of New York State, USA, is contaminated with polychlorinated biphenyls (PCBs) as a result of industrial discharges throughout the latter half of this century. In 1994 and 1995, the authors monitored the transfer of PCBs from aquatic sediments to a terrestrial wildlife community using the tree swallow (Tachycineta bicolor) as a model organism. Tree swallow eggs and nestlings were collected at four colonies established along a 40-km stretch of the upper Hudson River watershed. Samples were analyzed for total PCBs and PCB congeners, including non-ortho- and mono-ortho-substituted PCBs. Mean concentrations of PCBs in tree swallow eggsmore » and nestlings ranged from 721 to 62,200 ng/g and were as much as 15 times greater than PCB concentrations in tree swallow eggs and nestlings collected from PCB-contaminated areas within the Great Lakes ecosystem. The corresponding 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) calculated using avian toxic equivalency factors ranged from 410 to 25,400 pg/g. Concentrations of PCB congener 77 (3.3{prime}, 4,4{prime}-tetrachlorobiphenyl) were extremely elevated and were major contributors to the calculated TEQs. Homologue pattern comparisons between Hudson River and Saginaw River (Michigan, USA) ecosystems supported the hypothesis that a consistent Hudson River PCB source was the major contributor to PCBs in Hudson River tree swallows. The high concentrations of PCBs in Hudson River sediments and resultant concentrations observed in tree swallows were indicative of a potential elevated risk to these and other wildlife linked to the aquatic food web of the Hudson River ecosystem.« less

On Statistical Approaches for Demonstrating Analytical Similarity in the Presence of Correlation.

PubMed

Yang, Harry; Novick, Steven; Burdick, Richard K

Analytical similarity is the foundation for demonstration of biosimilarity between a proposed product and a reference product. For this assessment, currently the U.S. Food and Drug Administration (FDA) recommends a tiered system in which quality attributes are categorized into three tiers commensurate with their risk and approaches of varying statistical rigor are subsequently used for the three-tier quality attributes. Key to the analyses of Tiers 1 and 2 quality attributes is the establishment of equivalence acceptance criterion and quality range. For particular licensure applications, the FDA has provided advice on statistical methods for demonstration of analytical similarity. For example, for Tier 1 assessment, an equivalence test can be used based on an equivalence margin of 1.5 σ R , where σ R is the reference product variability estimated by the sample standard deviation S R from a sample of reference lots. The quality range for demonstrating Tier 2 analytical similarity is of the form X̄ R ± K × σ R where the constant K is appropriately justified. To demonstrate Tier 2 analytical similarity, a large percentage (e.g., 90%) of test product must fall in the quality range. In this paper, through both theoretical derivations and simulations, we show that when the reference drug product lots are correlated, the sample standard deviation S R underestimates the true reference product variability σ R As a result, substituting S R for σ R in the Tier 1 equivalence acceptance criterion and the Tier 2 quality range inappropriately reduces the statistical power and the ability to declare analytical similarity. Also explored is the impact of correlation among drug product lots on Type I error rate and power. Three methods based on generalized pivotal quantities are introduced, and their performance is compared against a two-one-sided tests (TOST) approach. Finally, strategies to mitigate risk of correlation among the reference products lots are discussed. A biosimilar is a generic version of the original biological drug product. A key component of a biosimilar development is the demonstration of analytical similarity between the biosimilar and the reference product. Such demonstration relies on application of statistical methods to establish a similarity margin and appropriate test for equivalence between the two products. This paper discusses statistical issues with demonstration of analytical similarity and provides alternate approaches to potentially mitigate these problems. © PDA, Inc. 2016.

Protein Oxidation and Sensory Quality of Brine-Injected Pork Loins Added Ascorbate or Extracts of Green Tea or Maté during Chill-Storage in High-Oxygen Modified Atmosphere.

PubMed

Jongberg, Sisse; Tørngren, Mari Ann; Skibsted, Leif H

2018-01-15

Background: Ascorbate is often applied to enhance stability and robustness of brine-injected pork chops sold for retail, but may affect protein oxidation, while plant extracts are potential substitutes. Methods: Brine-injected pork chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea extract (25 ppm gallic acid equivalents (GAE)), or maté extract (25 ppm GAE) stored (5 °C, seven days) in high-oxygen atmosphere packaging (MAP: 80% O₂ and 20% CO₂) were analyzed for color changes, sensory quality, and protein oxidation compared to a control without antioxidant. Results: No significant differences were observed for green tea and maté extracts as compared to ascorbate when evaluated based on lipid oxidation derived off-flavors, except for stale flavor, which maté significantly reduced. All treatments increased the level of the protein oxidation product, α-aminoadipic semialdehyde as compared to the control, and ascorbate was further found to increase thiol loss and protein cross-linking, with a concomitant decrease in the sensory perceived tenderness. Conclusions: Green tea and maté were found to equally protect against lipid oxidation derived off-flavors, and maté showed less prooxidative activity towards proteins as compared to ascorbate, resulting in more tender meat. Maté is a valuable substitute for ascorbate in brine-injected pork chops.

Insights into RNA polymerase catalysis and adaptive evolution gained from mutational analysis of a locus conferring rifampicin resistance

PubMed Central

Yurieva, Olga; Nikiforov, Vadim; O’Donnell, Michael

2017-01-01

Abstract S531 of Escherichia coli RNA polymerase (RNAP) β subunit is a part of RNA binding domain in transcription complex. While highly conserved, S531 is not involved in interactions within the transcription complex as suggested by X-ray analysis. To understand the basis for S531 conservation we performed systematic mutagenesis of this residue. We find that the most of the mutations significantly decreased initiation-to-elongation transition by RNAP. Surprisingly, some changes enhanced the production of full-size transcripts by suppressing abortive loss of short RNAs. S531-R increased transcript retention by establishing a salt bridge with RNA, thereby explaining the R substitution at the equivalent position in extremophilic organisms, in which short RNAs retention is likely to be an issue. Generally, the substitutions had the same effect on bacterial doubling time when measured at 20°. Raising growth temperature to 37° ablated the positive influence of some mutations on the growth rate in contrast to their in vitro action, reflecting secondary effects of cellular environment on transcription and complex involvement of 531 locus in the cell biology. The properties of generated RNAP variants revealed an RNA/protein interaction network that is crucial for transcription, thereby explaining the details of initiation-to-elongation transition on atomic level. PMID:29036608

Optimal self-cleavage activity of the hepatitis delta virus RNA is dependent on a homopurine base pair in the ribozyme core.

PubMed Central

Been, M D; Perrotta, A T

1995-01-01

A non-Watson-Crick G.G interaction within the core region of the hepatitis delta virus (HDV) antigenomic ribozyme is required for optimal rates of self-cleavage activity. Base substitutions for either one or both G's revealed that full activity was obtained only when both G's were replaced with A's. At those positions, substitutions that generate potential Watson-Crick, G.U, heteropurine, or homopyrimidine combinations resulted in dramatically lower cleavage activity. A homopurine symmetric base pair, of the same type identified in the high-affinity binding site of the HIV RRE, is most consistent with this data. Additional features shared between the antigenomic ribozyme and the Rev binding site in the vicinity of the homopurine pairs suggest some structural similarity for this region of the two RNAs and a possible motif associated with this homopurine interaction. Evidence for a homopurine pair at the equivalent position in a modified form of the HDV genomic ribozyme was also found. With the postulated symmetric pairing scheme, large distortions in the nucleotide conformation, the sugar-phosphate backbone, or both would be necessary to accommodate this interaction at the end of a helix; we hypothesize that this distortion is critical to the structure of the active site of the ribozyme and it is stabilized by the homopurine base pair. PMID:8595561

The effects of couplings to symmetric and antisymmetric modes and minor asymmetry on the spectral properties of mixed-valence and related charge-transfer systems

NASA Astrophysics Data System (ADS)

Reimers, J. R.; Hush, N. S.

1996-08-01

The most common methods used to describe the energy levels of charge-transfer systems (including mixed-valence systems) are the linear response approach of Rice and co-workers and the essentially equivalent PKS model described initially by Piepho, Krausz, and Schatz. While these methods were quite successful, in their original form they omitted the effects of overall symmetric vibrations. As a consequence, in particular they were not capable of adequately describing the electronic band width in the strong-coupling limit: Hush and later Ondrechen et al. demonstrated that symmetric modes are essential in this case, and modern versions of these models now include them. Here, we explore the relationship between symmetric and antisymmetric modes, concentrating on how this is modified by the presence of weak (e.g., environmentally or substitutionally induced) asymmetry. For the symmetric case, we show that when the electronic Hamiltonian operators are transformed from their usual localized diabatic representation into a delocalized diabatic representation, the effects of the symmetric and antisymmetric modes are interchanged. The primary effect of weak asymmetry is to mix the properties of the various modes, and possible consequences of this for the spectroscopy of bacterial photosynthetic reaction centre and substituted Creutz—Taube cations are discussed. We also consider the problem from an adiabatic Bom—Oppenheimer perspective and examine the regions in which this approach is appropriate.

Evaluation of the phototoxicity of unsubstituted and alkylated polycyclic aromatic hydrocarbons to mysid shrimp (Americamysis bahia): Validation of predictive models.

PubMed

Finch, Bryson E; Marzooghi, Solmaz; Di Toro, Dominic M; Stubblefield, William A

2017-08-01

Crude oils are composed of an assortment of hydrocarbons, some of which are polycyclic aromatic hydrocarbons (PAHs). Polycyclic aromatic hydrocarbons are of particular interest due to their narcotic and potential phototoxic effects. Several studies have examined the phototoxicity of individual PAHs and fresh and weathered crude oils, and several models have been developed to predict PAH toxicity. Fingerprint analyses of oils have shown that PAHs in crude oils are predominantly alkylated. However, current models for estimating PAH phototoxicity assume toxic equivalence between unsubstituted (i.e., parent) and alkyl-substituted compounds. This approach may be incorrect if substantial differences in toxic potency exist between unsubstituted and substituted PAHs. The objective of the present study was to examine the narcotic and photo-enhanced toxicity of commercially available unsubstituted and alkylated PAHs to mysid shrimp (Americamysis bahia). Data were used to validate predictive models of phototoxicity based on the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap approach and to develop relative effect potencies. Results demonstrated that photo-enhanced toxicity increased with increasing methylation and that phototoxic PAH potencies vary significantly among unsubstituted compounds. Overall, predictive models based on the HOMO-LUMO gap were relatively accurate in predicting phototoxicity for unsubstituted PAHs but are limited to qualitative assessments. Environ Toxicol Chem 2017;36:2043-2049. © 2017 SETAC. © 2017 SETAC.

Recombination–deletion between homologous cassettes in retrovirus is suppressed via a strategy of degenerate codon substitution

PubMed Central

Im, Eung Jun; Bais, Anthony J; Yang, Wen; Ma, Qiangzhong; Guo, Xiuyang; Sepe, Steven M; Junghans, Richard P

2014-01-01

Transduction and expression procedures in gene therapy protocols may optimally transfer more than a single gene to correct a defect and/or transmit new functions to recipient cells or organisms. This may be accomplished by transduction with two (or more) vectors, or, more efficiently, in a single vector. Occasionally, it may be useful to coexpress homologous genes or chimeric proteins with regions of shared homology. Retroviridae include the dominant vector systems for gene transfer (e.g., gamma-retro and lentiviruses) and are capable of such multigene expression. However, these same viruses are known for efficient recombination–deletion when domains are duplicated within the viral genome. This problem can be averted by resorting to two-vector strategies (two-chain two-vector), but at a penalty to cost, convenience, and efficiency. Employing a chimeric antigen receptor system as an example, we confirm that coexpression of two genes with homologous domains in a single gamma-retroviral vector (two-chain single-vector) leads to recombination–deletion between repeated sequences, excising the equivalent of one of the chimeric antigen receptors. Here, we show that a degenerate codon substitution strategy in the two-chain single-vector format efficiently suppressed intravector deletional loss with rescue of balanced gene coexpression by minimizing sequence homology between repeated domains and preserving the final protein sequence. PMID:25419532

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.

CyDNA: Synthesis and Replication of Highly Cy-Dye Substituted DNA by an Evolved Polymerase

PubMed Central

2010-01-01

DNA not only transmits genetic information but can also serve as a versatile supramolecular scaffold. Here we describe a strategy for the synthesis and replication of DNA displaying hundreds of substituents using directed evolution of polymerase function by short-patch compartmentalized self-replication (spCSR) and the widely used fluorescent dye labeled deoxinucleotide triphosphates Cy3-dCTP and Cy5-dCTP as substrates. In just two rounds of spCSR selection, we have isolated a polymerase that allows the PCR amplification of double stranded DNA fragments up to 1kb, in which all dC bases are substituted by its fluorescent dye-labeled equivalent Cy3- or Cy5-dC. The resulting “CyDNA” displays hundreds of aromatic heterocycles on the outside of the DNA helix and is brightly colored and highly fluorescent. CyDNA also exhibits significantly altered physicochemical properties compared to standard B-form DNA, including loss of silica and intercalating dye binding, resistance to cleavage by some endonucleases, an up to 40% increased apparent diameter as judged by atomic force microscopy and organic phase partitioning during phenol extraction. CyDNA also displays very bright fluorescence enabling significant signal gains in microarray and microfluidic applications. CyDNA represents a step toward a long-term goal of the encoded synthesis of DNA-based polymers of programmable and evolvable sequence and properties. PMID:20235594

The trimethylammonium headgroup of choline is a major determinant for substrate binding and specificity in choline oxidase.

PubMed

Gadda, Giovanni; Powell, Nichole L N; Menon, Prashanthi

2004-10-15

Choline oxidase catalyzes the oxidation of choline to glycine betaine via two sequential flavin-linked transfers of hydride equivalents to molecular oxygen and formation of a betaine aldehyde intermediate. In the present study, choline and glycine betaine analogs were used as substrates and inhibitors for the enzyme to investigate the structural determinants that are relevant for substrate recognition and specificity. Competitive inhibition patterns with respect to choline were determined for a number of substituted amines at pH 6.5 and 25 degrees C. The Kis values for the carboxylate-containing ligands glycine betaine, N,N-dimethylglycine, and N-methylglycine increased monotonically with decreasing number of methyl groups, consistent with the trimethylammonium portion of the ligand being important for binding. In contrast, the acetate portion of glycine betaine did not contribute to binding, as suggested by lack of changes in the Kis values upon substituting glycine betaine with inhibitors containing methyl, ethyl, allyl, and 2-amino-ethyl side chains. In agreement with the inhibition data, the specificity of the enzyme for the organic substrate (kcat/Km value) decreased when N,N-dimethylethanolamine, N-methylethanolamine, and the isosteric substrate 3,3-dimethyl-1-butanol were used as substrate instead of choline; a contribution of approximately 7 kcal mol(-1) toward substrate discrimination was estimated for the interaction of the trimethylammonium portion of the substrate with the active site of choline oxidase.

CyDNA: synthesis and replication of highly Cy-dye substituted DNA by an evolved polymerase.

PubMed

Ramsay, Nicola; Jemth, Ann-Sofie; Brown, Anthony; Crampton, Neal; Dear, Paul; Holliger, Philipp

2010-04-14

DNA not only transmits genetic information but can also serve as a versatile supramolecular scaffold. Here we describe a strategy for the synthesis and replication of DNA displaying hundreds of substituents using directed evolution of polymerase function by short-patch compartmentalized self-replication (spCSR) and the widely used fluorescent dye labeled deoxinucleotide triphosphates Cy3-dCTP and Cy5-dCTP as substrates. In just two rounds of spCSR selection, we have isolated a polymerase that allows the PCR amplification of double stranded DNA fragments up to 1kb, in which all dC bases are substituted by its fluorescent dye-labeled equivalent Cy3- or Cy5-dC. The resulting "CyDNA" displays hundreds of aromatic heterocycles on the outside of the DNA helix and is brightly colored and highly fluorescent. CyDNA also exhibits significantly altered physicochemical properties compared to standard B-form DNA, including loss of silica and intercalating dye binding, resistance to cleavage by some endonucleases, an up to 40% increased apparent diameter as judged by atomic force microscopy and organic phase partitioning during phenol extraction. CyDNA also displays very bright fluorescence enabling significant signal gains in microarray and microfluidic applications. CyDNA represents a step toward a long-term goal of the encoded synthesis of DNA-based polymers of programmable and evolvable sequence and properties.

Computational Design of a Krueger Flap Targeting Conventional Slat Aerodynamics

NASA Technical Reports Server (NTRS)

Akaydin, H. Dogus; Housman, Jeffrey A.; Kiris, Cetin C.; Bahr, Christopher J.; Hutcheson, Florence V.

2016-01-01

In this study, we demonstrate the design of a Krueger flap as a substitute for a conventional slat in a high-lift system. This notional design, with the objective of matching equivalent-mission performance on aircraft approach, was required for a comparative aeroacoustic study with computational and experimental components. We generated a family of high-lift systems with Krueger flaps based on a set of design parameters. Then, we evaluated the high-lift systems using steady 2D RANS simulations to find a good match for the conventional slat, based on total lift coefficients in free-air. Finally, we evaluated the mean aerodynamics of the high-lift systems with Krueger flap and conventional slat as they were installed in an open-jet wind tunnel flow. The surface pressures predicted with the simulations agreed well with experimental results.

The development of the advanced cryogenic radiometer facility at NRC

NASA Astrophysics Data System (ADS)

Gamouras, A.; Todd, A. D. W.; Côté, É.; Rowell, N. L.

2018-02-01

The National Research Council (NRC) of Canada has established a next generation facility for the primary realization of optical radiant power. The main feature of this facility is a new cryogenic electrical substitution radiometer with a closed-cycle helium cryocooler. A monochromator-based approach allows for detector calibrations at any desired wavelength. A custom-designed motion apparatus includes two transfer standard radiometer mounting ports which has increased our measurement capability by allowing the calibration of two photodetectors in one measurement cycle. Measurement uncertainties have been improved through several upgrades, including newly designed and constructed transimpedance amplifiers for the transfer standard radiometers, and a higher power broadband light source. The most significant improvements in uncertainty arise from the enhanced characteristics of the new cryogenic radiometer including its higher cavity absorptance and reduced non-equivalence effects.

Development of new materials and structures based on managed physical-chemical factors of local interaction

NASA Astrophysics Data System (ADS)

Urakov, A. L.

2016-04-01

The paper states that assigning certain physical and chemical characteristics to pills and medical drugs solutions can substitute for the development of new drugs (which is essentially equivalent to the creation of new medicines). It is established that the purposeful change of physical and chemical characteristics of the standard ("old") materials (in other words, the known substances) is fundamental for the production of solid and liquid medicines, which allows us to get "new" structures and materials. The paper shows that assigning new physical and chemical properties to "old" materials and their further usage for the production of tablets and solutions from the "old" and well-known medicines can turn even very "old" medicine into very "novel" (moreover, even very fashionable) one with unprecedented (fantastic) pharmacological activity and new mechanisms of action.

Application of low-temperature CP-Sil 88 column for the isomeric analysis of toxic 2,378-substituted PCDD/Fs in incinerator flyash and sewage sludge using a triple quadrupole GC-MS/MS.

PubMed

Onwudili, Jude A; Hajizadeh, Yaghoub; Zainal, Safari; Upton, John; Williams, Paul T

2011-12-15

The seventeen 2378-substituted polychlorinated dibenzo-p-dioxins and dibenzo-p-furans (PCDD/Fs) congeners have been separated and analyzed in sewage sludge and incinerator flyash samples using a CP-Sil 88 column (50 m × 0.25 mm I.D., 0.25 μm film thickness) operating at a maximum oven temperature of 240°C. The column was used on a Varian 450-GC with a Varian 320-MS Triple Quadrupole. Calibration standards were used to determine the transition chemistries of the 2378-substituted PCDD/F congeners in the gas chromatography/mass spectrometry (GC-MS/MS) system. The five-point calibration curve for each of the congeners showed very good linearity with R(2) values greater than 0.999. The recovery of labelled compounds ranged from 50% to 120%. Analytical results from a reference flyash (BCR-490) and a reference sewage sludge (BCR-677) compared very well with the certified values, giving percentage deviations in I-TEQ (international toxic equivalents) of 4.93% and 0.53%, respectively. Results from 'real' flyash samples underscored the level of progress made in the abatement of dioxin emissions from incinerators; the old incinerator flyash contained much higher PCDD/F concentrations than the modern one. In addition, the concentrations profiles of PCDD/Fs in the 'real' sewage sludge from two UK wastewater treatment plants (WWTPs) showed that one contained a total PCDD/Fs content of 314 ng I-TEQ kg(-1), while the other gave a total of 53 ng I-TEQ kg(-1). Over an 18-month period of operation, no significant loss of analytical performance was observed from the low-temperature column. Copyright © 2011 Elsevier B.V. All rights reserved.

Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine.

PubMed

Blair, J B; Marona-Lewicka, D; Kanthasamy, A; Lucaites, V L; Nelson, D L; Nichols, D E

1999-03-25

The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b substituted for LSD or DOI up to doses of 50 micromol/kg. By comparison, 1a fully substituted in LSD-trained rats. However, 3a and 3b fully substituted for the 5-HT1A agonist LY293284 ((-)-(4R)-6-acetyl-4-(di-n-propylamino)-1,3,4, 5-tetrahydrobenz[c,d]indole). Both 3a and 3b induced a brief "serotonin syndrome" and salivation, an indication of 5-HT1A receptor activation. At the cloned human 5-HT2A receptor 3b had about twice the affinity of 3a. At the cloned human 5-HT2B and 5-HT2C receptors, however, 3a had about twice the affinity of 3b. Therefore, thiophene lacks equivalence as a replacement for the phenyl ring in the indole nucleus of tryptamines that bind to 5-HT2 receptor subtypes and possess LSD-like behavioral effects. Whereas both of the thienopyrroles had lower affinity than the corresponding 1a at 5-HT2 receptors, 3a and 3b had significantly greater affinity than 1a at the 5-HT1A receptor. Thus, thienopyrrole does appear to serve as a potent bioisostere for the indole nucleus in compounds that bind to the serotonin 5-HT1A receptor. These differences in biological activity suggest that serotonin receptor isoforms are very sensitive to subtle changes in the electronic character of the aromatic systems of indole compounds.

Reframing the concept of alternative livelihoods.

PubMed

Wright, Juliet H; Hill, Nicholas A O; Roe, Dilys; Rowcliffe, J Marcus; Kümpel, Noëlle F; Day, Mike; Booker, Francesca; Milner-Gulland, E J

2016-02-01

Alternative livelihood project (ALP) is a widely used term for interventions that aim to reduce the prevalence of activities deemed to be environmentally damaging by substituting them with lower impact livelihood activities that provide at least equivalent benefits. ALPs are widely implemented in conservation, but in 2012, an International Union for Conservation of Nature resolution called for a critical review of such projects based on concern that their effectiveness was unproven. We focused on the conceptual design of ALPs by considering their underlying assumptions. We placed ALPs within a broad category of livelihood-focused interventions to better understand their role in conservation and their intended impacts. We dissected 3 flawed assumptions about ALPs based on the notions of substitution, the homogenous community, and impact scalability. Interventions based on flawed assumptions about people's needs, aspirations, and the factors that influence livelihood choice are unlikely to achieve conservation objectives. We therefore recommend use of a sustainable livelihoods approach to understand the role and function of environmentally damaging behaviors within livelihood strategies; differentiate between households in a community that have the greatest environmental impact and those most vulnerable to resource access restrictions to improve intervention targeting; and learn more about the social-ecological system within which household livelihood strategies are embedded. Rather than using livelihood-focused interventions as a direct behavior-change tool, it may be more appropriate to focus on either enhancing the existing livelihood strategies of those most vulnerable to conservation-imposed resource access restrictions or on use of livelihood-focused interventions that establish a clear link to conservation as a means of building good community relations. However, we recommend that the term ALP be replaced by the broader term livelihood-focused intervention. This avoids the implicit assumption that alternatives can fully substitute for natural resource-based livelihood activities. © 2015 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Exploring community pharmacists' views on generic medicines: a nationwide study from Malaysia.

PubMed

Chong, Chee Ping; Hassali, Mohamed Azmi; Bahari, Mohd Baidi; Shafie, Asrul Akmal

2011-02-01

To evaluate the Malaysian community pharmacists' views on generic medicines. A sample of 1419 Malaysian community pharmacies with resident pharmacists. A cross-sectional nationwide survey using a self-completed mailing questionnaire. Pharmacists' views on generic medicines including issues surrounding efficacy, safety, quality and bioequivalence. Responses were received from 219 pharmacies (response rate 15.4%). Only 50.2% of the surveyed pharmacists agreed that all products that are approved as generic equivalents can be considered therapeutically equivalent with the innovator medicines. Around 76% of respondents indicated that generic substitution of narrow therapeutic index medicines is inappropriate. The majority of the pharmacists understood that a generic medicine must contain the same amount of active ingredient (84.5%) and must be in the same dosage form as the innovator brand (71.7%). About 21% of respondents though that generic medicines are of inferior quality compared to innovator medicines. Most of the pharmacists (61.6%) disagreed that generic medicines produce more side-effects than innovator brand. Pharmacists graduated from Malaysian universities, twinning program and overseas universities were not differed significantly in their views on generic medicines. Additionally, the respondents appeared to have difficulty in ascertaining the bioequivalent status of the marketed generic products in Malaysia. The Malaysian pharmacists' have lack of information and/or trust in the generic manufacturing and/or approval system in Malaysia. This issue should be addressed by pharmacy educators and relevant government agencies.

Integration of different data gap filling techniques to facilitate ...

EPA Pesticide Factsheets

Data gap filling techniques are commonly used to predict hazard in the absence of empirical data. The most established techniques are read-across, trend analysis and quantitative structure-activity relationships (QSARs). Toxic equivalency factors (TEFs) are less frequently used data gap filling techniques which are applied to estimate relative potencies for mixtures of chemicals that contribute to an adverse outcome through a common biological target. For example, The TEF approach has been used for dioxin-like effects comparing individual chemical activity to that of the most toxic dioxin: 2,3,7,8-tetrachlorodibenzo-p-dioxin. The aim of this case study was to determine whether integration of two data gap filling techniques: QSARs and TEFs improved the predictive outcome for the assessment of a set of polychlorinated biphenyl (PCB) congeners and their mixtures. PCBs are associated with many different adverse effects, including their potential for neurotoxicity, which is the endpoint of interest in this study. The dataset comprised 209 PCB congeners, out of which 87 altered in vitro Ca(2+) homeostasis from which neurotoxic equivalency values (NEQs) were derived. The preliminary objective of this case study was to develop a QSAR model to predict NEQ values for the 122 untested PCB congeners. A decision tree model was developed using the number of position specific chlorine substitutions on the biphenyl scaffold as a fingerprint descriptor. Three different positiona

The Construction of Impossibility: A Logic-Based Analysis of Conjuring Tricks

PubMed Central

Smith, Wally; Dignum, Frank; Sonenberg, Liz

2016-01-01

Psychologists and cognitive scientists have long drawn insights and evidence from stage magic about human perceptual and attentional errors. We present a complementary analysis of conjuring tricks that seeks to understand the experience of impossibility that they produce. Our account is first motivated by insights about the constructional aspects of conjuring drawn from magicians' instructional texts. A view is then presented of the logical nature of impossibility as an unresolvable contradiction between a perception-supported belief about a situation and a memory-supported expectation. We argue that this condition of impossibility is constructed not simply through misperceptions and misattentions, but rather it is an outcome of a trick's whole structure of events. This structure is conceptualized as two parallel event sequences: an effect sequence that the spectator is intended to believe; and a method sequence that the magician understands as happening. We illustrate the value of this approach through an analysis of a simple close-up trick, Martin Gardner's Turnabout. A formalism called propositional dynamic logic is used to describe some of its logical aspects. This elucidates the nature and importance of the relationship between a trick's effect sequence and its method sequence, characterized by the careful arrangement of four evidence relationships: similarity, perceptual equivalence, structural equivalence, and congruence. The analysis further identifies two characteristics of magical apparatus that enable the construction of apparent impossibility: substitutable elements and stable occlusion. PMID:27378959

Refractive indices measurement of (GaInP)m/(AlInP)n quasi-quanternaries and GaInP/AllnP multiple quantum wells

NASA Astrophysics Data System (ADS)

Kaneko, Yawara; Kishino, Katsumi

1994-08-01

Measurements of the refractive indices of (GaInP)m/(AlInP)n quasi-quaternaries (QQs), GaInP/AlInP multiple quantum wells (MQWs), and (Al(x)Ga(1 - x))(0.5) In(0.5)P quanternaries were made systematically, using the reflectance method, in photon energy ranges nearly as high as up to the band gap. Data was fitted using the modified single effective oscillator (MSEO) method. A single oscillator energy E(sub zero) of 4.17 + 0.49 x(sub eg) and dispersion energy (E(sub d) of 35.79 - 1.16 x(sub eg) was obtained for (GaInP)m/(AlInP)2 QQs, where the equivalent Al composition x(sub eg) is defined by the stacking film thickness ratio x(sub eg) = d(AlInP)/(d(GaInP) + d(AlInP). Agreement of refractive indices obtained for QQs and quaternary compounds with equivalent x(sub eg) has been confirmed. Still, for the GaInP/AlInP MQWs, MSEO fitting was also agreeable, using the same oscillator energy E(sub zero) and dispersion energy E(sub d) of the (GaInP)m/(AlInP)2 QQs with the same thickness ratio, and substituting band gap energy E(sub Gamma) values shifted due to quantum effects.

Hydrofluorocarbon (HFC) Emissions in China: An Inventory for 2005-2013 and Projections to 2050.

PubMed

Fang, Xuekun; Velders, Guus J M; Ravishankara, A R; Molina, Mario J; Hu, Jianxin; Prinn, Ronald G

2016-02-16

Many hydrofluorocarbons (HFCs) that are widely used as substitutes for ozone-depleting substances (now regulated under the Montreal Protocol) are very potent greenhouse gases (GHGs). China's past and future HFC emissions are of great interest because China has emerged as a major producer and consumer of HFCs. Here, we present for the first time a comprehensive inventory estimate of China's HFC emissions during 2005-2013. Results show a rapid increase in HFC production, consumption, and emissions in China during the period and that the emissions of HFC with a relatively high global warming potential (GWP) grew faster than those with a relatively low GWP. The proportions of China's historical HFC CO2-equivalent emissions to China's CO2 emissions or global HFC CO2-equivalent emissions increased rapidly during 2005-2013. Using the "business-as-usual" (BAU) scenario, in which HFCs are used to replace a significant fraction of hydrochlorofluorocarbons (HCFCs) in China (to date, there are no regulations on HFC uses in China), emissions of HFCs are projected to be significant components of China's and global future GHG emissions. However, potentials do exist for minimizing China's HFC emissions (for example, if regulations on HFC uses are established in China). Our findings on China's historical and projected HFC emission trajectories could also apply to other developing countries, with important implications for mitigating global GHG emissions.

Reconnaissance for radioactive materials in northeastern United States during 1952

USGS Publications Warehouse

McKeown, Francis A.; Klemic, Harry

1953-01-01

Reconnaissance for radioactive materials was made in parts of Maine, New York, New Jersey, and Pennsylvania. The primary objective was to examine the iron ore deposits and associated rocks in the Adirondack Mountains of New York and the Highlands of New Jersey. In addition, several deposits known or reported to contain radioactive minerals were examined to delimit their extent. Most of the deposits examined are not significant as possible sources of radioactive elements and the data pertaining to them are summarized in table form. Deposits that do warrant more description than can be given in table form are: Benson Mines, St. Lawrence County, N. Y.; Rutgers mine, Clinton County, N. Y.; Mineville Mines, Essex County, N. Y.l Canfield phosphate mine, Morris County, N. J.; Mullgan quarry, Hunterdon County, N. J.; and the Chestnut Hill-Marble Mountain area, Pennsylvania and New Jersey. The Old Bed in the Mineville district is the only deposit that may be economically significant. Apatite from Old Bed ore contains as much as 4.9 percent total rare earth. 0.04 percent thorium, and 0.018 percent uranium. Magnetite ore at the Rutgers mine contains radioactive zircon and apatite. Radioactivity measurements of outcrops and dump material show that the ore contains from 0.005 to 0.010 percent equivalent uranium. One sample of lean magnetite ore contains 0.006 percent equivalent uranium. Garnet-rich zones in the Benson Mines magnetite deposit contain as much as 0.017 equivalent uranium. Most of the rock and ore, however, contains about 0.005 percent equivalent uranium. Available data indicate that the garnet-rich zones are enriched in radioactive allanite. A shear zone in the Kittatinny limestone of Cambrian age at the Mulligan quarry contains uraniferous material. Radioactivity anomalies elsewhere in the quarry and in adjacent fields indicate that there may be other uraniferous shear zones. Assays of samples and measurements of outcrop radioactivity indicate that the uranium content of these zones is low; samples contain from 0.008 to 0.068 percent equivalent uranium. The anomalies, however, may indicate greater concentrations of uranium below surficial leached zones. The Chestnut Hill-Marble Mountain area contains radioactivity anomalies for about 2 miles along the strike of the contact of pre-Cambrian Pickering gneiss and Franklin limestone formations. In places this contact is injected with pegmatite, which probably was the source of the radioelements. The most favorable area for further study is at Marble Mountain, where a nearly continuous anomaly extends for about 1500 feet. Samples from part of this area contain as much as 0.044 percent equivalent uranium and 0.005 percent uranium. Radioactive hematite and florencite, in which thorium may have substituted for cerium, are the only radioactive minerals observed in the Marble Mountain area.

Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds.

PubMed

Kishore, Kranti G; Ghashghaei, Ouldouz; Estarellas, Carolina; Mestre, M Mar; Monturiol, Cristina; Kielland, Nicola; Kelly, John M; Francisco, Amanda Fortes; Jayawardhana, Shiromani; Muñoz-Torrero, Diego; Pérez, Belén; Luque, F Javier; Gámez-Montaño, Rocío; Lavilla, Rodolfo

2016-07-25

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N-Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N-Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The yellow fever 17D virus as a platform for new live attenuated vaccines.

PubMed

Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

2014-01-01

The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

Sound absorption of a finite micro-perforated panel backed by a shunted loudspeaker.

PubMed

Tao, Jiancheng; Jing, Ruixiang; Qiu, Xiaojun

2014-01-01

Deep back cavities are usually required for micro-perforated panel (MPP) constructions to achieve good low frequency absorption. To overcome the problem, a close-box loudspeaker with a shunted circuit is proposed to substitute the back wall of the cavity of the MPP constructions to constitute a composite absorber. Based on the equivalent circuit model, the acoustic impedance of the shunted loudspeaker is formulated first, then a prediction model of the sound absorption of the MPP backed by shunted loudspeaker is developed by employing the mode solution of a finite size MPP coupled by an air cavity with an impendence back wall. The MPP absorbs mid to high frequency sound, and with properly adjusted electrical parameters of its shunted circuit, the shunted loudspeaker absorbs low frequency sound, so the composite absorber provides a compact solution to broadband sound control. Numerical simulations and experiments are carried out to validate the model.

Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management.

PubMed

Carrá, Adriana; Macías Islas, Miguel Angel; Tarulla, Adriana; Bichuetti, Denis Bernardi; Finkelsztejn, Alessandro; Fragoso, Yara Dadalti; Árcega-Revilla, Raul; Cárcamo Rodríguez, Claudia; Durán, Juan Carlos; Bonitto, Juan García; León, Rosalba; Oehninger Gatti, Carlos; Orozco, Geraldine; Vizcarra Escobar, Darwin

2015-06-01

Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

Re-examining the phosphorus-protein dilemma: Does phosphorus restriction compromise protein status?

PubMed Central

St-Jules, David E; Woolf, Kathleen; Pompeii, Mary-Lou; Kalantar-Zadeh, Kamyar; Sevick, Mary Ann

2015-01-01

Dietary phosphorus restriction is recommended to help control hyperphosphatemia in hemodialysis (HD) patients, but many high-phosphorus foods are important sources of protein. In this review, we examine whether restricting dietary phosphorus compromises protein status in HD patients. Although dietary phosphorus and protein are highly correlated, phosphorus intakes can range up to 600 mg/day for a given energy and protein intake level. Further, the collinearity of phosphorus and protein may be biased because the phosphorus burden of food depends on: (1) the presence of phosphate additives; (2) food preparation method; and (3) bioavailability of phosphorus; which are often unaccounted for in nutrition assessments. Ultimately, we argue that clinically relevant reductions in phosphorus intake can be made without limiting protein intake by avoiding phosphate additives in processed foods, using wet cooking methods such as boiling, and if needed, substituting high-phosphorus foods for nutritionally-equivalent foods that are lower in bioavailable phosphorus. PMID:26873260

Arbitrary Inequality in Reputation Systems

NASA Astrophysics Data System (ADS)

Frey, Vincenz; van de Rijt, Arnout

2016-12-01

Trust is an essential condition for exchange. Large societies must substitute the trust traditionally provided through kinship and sanctions in small groups to make exchange possible. The rise of internet-supported reputation systems has been celebrated for providing trust at a global scale, enabling the massive volumes of transactions between distant strangers that are characteristic of modern human societies. Here we problematize an overlooked side-effect of reputation systems: Equally trustworthy individuals may realize highly unequal exchange volumes. We report the results of a laboratory experiment that shows emergent differentiation between ex ante equivalent individuals when information on performance in past exchanges is shared. This arbitrary inequality results from cumulative advantage in the reputation-building process: Random initial distinctions grow as parties of good repute are chosen over those lacking a reputation. We conjecture that reputation systems produce artificial concentration in a wide range of markets and leave superior but untried exchange alternatives unexploited.

An evaluation method of power quality about electrified railways connected to power grid based on PSCAD/EMTDC

NASA Astrophysics Data System (ADS)

Liang, Weibin; Ouyang, Sen; Huang, Xiang; Su, Weijian

2017-05-01

The existing modeling process of power quality about electrified railways connected to power grid is complicated and the simulation scene is incomplete, so this paper puts forward a novel evaluation method of power quality based on PSCAD/ETMDC. Firstly, a model of power quality about electrified railways connected to power grid is established, which is based on testing report or measured data. The equivalent model of electrified locomotive contains power characteristic and harmonic characteristic, which are substituted by load and harmonic source. Secondly, in order to make evaluation more complete, an analysis scheme has been put forward. The scheme uses a combination of three-dimensions of electrified locomotive, which contains types, working conditions and quantity. At last, Shenmao Railway is taken as example to evaluate the power quality at different scenes, and the result shows electrified railways connected to power grid have significant effect on power quality.

[Concentrations, distribution characteristics and electron beam radiolysis degradation of PCDD/Fs in waste water from a paper mill].

PubMed

Qing, Xian; Huang, Jin-Qiong; Yu, Xiao-Wei; Zhang, Su-Kun; Yang, Yan-Yan; Ren, Ming-Zhong; Wen, Yu-Long

2014-07-01

Concentrations and distribution characteristics of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (2,3,7,8-PCDD/Fs) were analyzed in waste water from a paper mill. And concentrations of 2,3,7,8-PCDD/Fs in waste water before and after electron beam irradiation with different doses were compared. The feasibility, mechanism and rates of 2,3,7,8-PCDD/Fs degradation were discussed. The PCDD/Fs concentrations and corresponding I-TEQ (toxic equivalent quantity) values were 239 pg x L(-1) and 41.0 pg x L(-1), respectively, in the waste water. The concentrations of total 2,3,7,8-PCDD/Fs decreased after electron beam radiolysis at a dose of 30 kGy and 60 kGy with degradation rates of 5.27% and 23.6%, respectively.

XANES and EXAFS study of Au-substituted YBa2Cu3O(7-delta)

NASA Technical Reports Server (NTRS)

Ruckman, Mark W.; Hepp, Aloysius F.

1990-01-01

The near-edge structure (XANES) of the Au L3 and Cu K edges of YBa2Au(0.3)Cu(2.7)O(7-delta) was studied. X ray diffraction suggests that Au goes on the Cu(1) site and XANES shows that this has little effect on the oxidation state of the remaining copper. The gold L3 edge develops a white line feature whose position lies between that of trivalent gold oxide (Au2O3) and monovalent potassium gold cyanide (KAu(CN)2) and whose intensity relative to the edge step is smaller than in the two reference compounds. The L3 EXAFS for Au in the superconductor resembles that of Au2O3. However, differences in the envelope of the Fourier filtered component for the first shell suggest that the local structure of the Au in the superconductor is not equivalent to Au2O3.

The yellow fever 17D virus as a platform for new live attenuated vaccines

PubMed Central

Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

2014-01-01

The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms. PMID:24553128

Arbitrary Inequality in Reputation Systems

PubMed Central

Frey, Vincenz; van de Rijt, Arnout

2016-01-01

Trust is an essential condition for exchange. Large societies must substitute the trust traditionally provided through kinship and sanctions in small groups to make exchange possible. The rise of internet-supported reputation systems has been celebrated for providing trust at a global scale, enabling the massive volumes of transactions between distant strangers that are characteristic of modern human societies. Here we problematize an overlooked side-effect of reputation systems: Equally trustworthy individuals may realize highly unequal exchange volumes. We report the results of a laboratory experiment that shows emergent differentiation between ex ante equivalent individuals when information on performance in past exchanges is shared. This arbitrary inequality results from cumulative advantage in the reputation-building process: Random initial distinctions grow as parties of good repute are chosen over those lacking a reputation. We conjecture that reputation systems produce artificial concentration in a wide range of markets and leave superior but untried exchange alternatives unexploited. PMID:27995957

Upper mantle electrical conductivity for seven subcontinental regions of the Earth

USGS Publications Warehouse

Campbell, W.H.; Schiffmacher, E.R.

1988-01-01

Spherical harmonic analysis coefficients of the external and internal parts of the quiet-day geomagnetic field variations (Sq) separated for the 7 continental regions of the observatories have been used to determine conductivity profiles to depths of about 600 km by the Schmucker equivalent substitute conductor method. The profiles give evidence of increases in conductivity between about 150 and 350 km depth, then a general increase in conductivity thereafter. For South America we found a high conductivity at shallow depths. The European profile showed a highly conducting layer near 125 km. At the greater depths, Europe, Australia and South America had the lowest values of conductivity. North America and east Asia had intermediate values whereas the African and central Asian profiles both showed the conductivities rising rapidly beyond 450 km depth. The regional differences indicate that there may be considerable lateral heterogeneity of electrical conductivity in the Earth's upper mantle. -Authors

Pivotal Advance: Interconversion between pure chemotactic ligands and chemoattractant/secretagogue ligands of neutrophil C5a receptor by a single amino acid substitution.

PubMed

Jia, Nan; Semba, Umeko; Nishiura, Hiroshi; Kuniyasu, Akihiko; Nsiama, Tienabe K; Nishino, Norikazu; Yamamoto, Tetsuro

2010-06-01

Skp derived from Escherichia coli attracts leukocytes as a pure chemotactic ligand of the C5a receptor. We identified the submolecular region of Skp that binds and activates the C5a receptor to be -Gln103-Asp104-Arg105- using synthetic peptide fragments and site-directed mutants of Skp. As the C5a amino acid residue equivalent to Gln103 of Skp is Leu72, we prepared a Gln103Leu-Skp mutant as a recombinant protein. With this mutation, Skp gained secretagogue functions including induction of the respiratory burst and granule release reactions and leukotriene generation, in addition to the chemoattraction displayed by C5a. However, when we substituted Leu72 with Gln in C5a, the L72Q-C5a mutant largely lost its secretagogue function. These functional conversions were reproduced using synthetic peptides mimicking the receptor-binding/-activating regions of the recombinant proteins. Receptor-binding assays using the mimicking peptides demonstrated only a small difference between the Leu72-C5a and Gln72-C5a peptides. Consistently, L72Q-C5a apparently antagonized C5a secretagogue function. These results indicate that the difference between a chemotactic response and a combined chemotactic/secretory response can be attributed not to the nature of the receptor but to guidance by the ligand, at least in the case of C5a receptor-mediated leukocyte responses.

Influence of Al3+ substitution on the electrical resistivity and dielectric behavior of Ni0.25Cu0.20Zn0.55AlxFe2-xO4 ferrites synthesized by solid state reaction technique

NASA Astrophysics Data System (ADS)

Rahman, K. R.; Chowdhury, F.-U.-Z.; Khan, M. N. I.

2017-12-01

In this paper, the effect of Al3+ substitution on the electrical and dielectric properties of Ni0.25Cu0.20Zn0.55AlxFe2-xO4 ferrites with x = 0.0, 0.05. 0.10, 0.15 and 0.20, synthesized by solid state reaction has been reported. Using two probe method, the DC resistivity has been investigated in the temperature range from 30 °C to 300 °C. Activation energy was calculated from the Arrhenius plot. The electrical conduction is explained on the basis of the hopping mechanism. The frequency dependent dielectric properties of these spinel ferrites have been studied at room temperature by measuring AC resistivity, conductivity (σac), dielectric constant and dielectric loss tangent (tan δ) in the frequency range between 1 kHz and 120 MHz. The study of dielectric properties showed that the dielectric constant and dielectric loss increased with increasing non-magnetic Al ions. The dependence of dielectric constant with frequency has been explained by Maxwell-Wagner interfacial polarization. Cole-Cole plots show semicircular arc(s) for the samples, and equivalent RC circuits have been proposed to clarify the phenomena involved therein. The analysis of complex impedance spectroscopy has been used to distinguish between the grain and grain boundary contribution to the total resistance.

Missing portion sizes in FFQ--alternatives to use of standard portions.

PubMed

Køster-Rasmussen, Rasmus; Siersma, Volkert; Halldorsson, Thorhallur I; de Fine Olivarius, Niels; Henriksen, Jan E; Heitmann, Berit L

2015-08-01

Standard portions or substitution of missing portion sizes with medians may generate bias when quantifying the dietary intake from FFQ. The present study compared four different methods to include portion sizes in FFQ. We evaluated three stochastic methods for imputation of portion sizes based on information about anthropometry, sex, physical activity and age. Energy intakes computed with standard portion sizes, defined as sex-specific medians (median), or with portion sizes estimated with multinomial logistic regression (MLR), 'comparable categories' (Coca) or k-nearest neighbours (KNN) were compared with a reference based on self-reported portion sizes (quantified by a photographic food atlas embedded in the FFQ). The Danish Health Examination Survey 2007-2008. The study included 3728 adults with complete portion size data. Compared with the reference, the root-mean-square errors of the mean daily total energy intake (in kJ) computed with portion sizes estimated by the four methods were (men; women): median (1118; 1061), MLR (1060; 1051), Coca (1230; 1146), KNN (1281; 1181). The equivalent biases (mean error) were (in kJ): median (579; 469), MLR (248; 178), Coca (234; 188), KNN (-340; 218). The methods MLR and Coca provided the best agreement with the reference. The stochastic methods allowed for estimation of meaningful portion sizes by conditioning on information about physiology and they were suitable for multiple imputation. We propose to use MLR or Coca to substitute missing portion size values or when portion sizes needs to be included in FFQ without portion size data.

Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis.

PubMed

Müllers, Erik; Uhlig, Tobias; Stirnnagel, Kristin; Fiebig, Uwe; Zentgraf, Hanswalter; Lindemann, Dirk

2011-02-01

Prototype foamy virus (PFV) Gag lacks the characteristic orthoretroviral Cys-His motifs that are essential for various steps of the orthoretroviral replication cycle, such as RNA packaging, reverse transcription, infectivity, integration, and viral assembly. Instead, it contains three glycine-arginine-rich boxes (GR boxes) in its C terminus that putatively represent a functional equivalent. We used a four-plasmid replication-deficient PFV vector system, with uncoupled RNA genome packaging and structural protein translation, to analyze the effects of deletion and various substitution mutations within each GR box on particle release, particle-associated protein composition, RNA packaging, DNA content, infectivity, particle morphology, and intracellular localization. The degree of viral particle release by all mutants was similar to that of the wild type. Only minimal effects on Pol encapsidation, exogenous reverse transcriptase (RT) activity, and genomic viral RNA packaging were observed. In contrast, particle-associated DNA content and infectivity were drastically reduced for all deletion mutants and were undetectable for all alanine substitution mutants. Furthermore, GR box I mutants had significant changes in particle morphology, and GR box II mutants lacked the typical nuclear localization pattern of PFV Gag. Finally, it could be shown that GR boxes I and III, but not GR box II, can functionally complement each other. It therefore appears that, similar to the orthoretroviral Cys-His motifs, the PFV Gag GR boxes are important for RNA encapsidation, genome reverse transcription, and virion infectivity as well as for particle morphogenesis.

Drosophila vitelline membrane assembly: A critical role for an evolutionarily conserved cysteine in the “VM domain” of sV23

PubMed Central

Wu, T; Manogaran, A.L; Beauchamp, J.M.; Waring, G.L.

2010-01-01

The vitelline membrane (VM), the oocyte proximal layer of the Drosophila eggshell, contains four major proteins (VMPs) that possess a highly conserved “VM domain” which includes three precisely spaced, evolutionarily conserved, cysteines (CX7CX8C). Focusing on sV23, this study showed that the three cysteines are not functionally equivalent. While substitution mutations at the first (C123S) or third (C140S) cysteines were tolerated, females with a substitution at the second position (C131S) were sterile. Fractionation studies showed sV23 incorporates into a large disulfide linked network well after its secretion ceases, suggesting post-depositional mechanisms are in place to restrict disulfide bond formation until late oogenesis, when the oocyte no longer experiences large volume increases. Affinity chromatography utilizing histidine tagged sV23 alleles revealed small sV23 disulfide linked complexes during the early stages of eggshell formation that included other VMPs, namely sV17 and Vml. The early presence but late loss of these associations in an sV23 double cysteine mutant suggests reorganization of disulfide bonds may underlie the regulated growth of disulfide-linked networks in the vitelline membrane. Found within the context of a putative thioredoxin active site (CXXS) C131, the critical cysteine in sV23, may play an important enzymatic role in isomerizing intermolecular disulfide bonds during eggshell assembly. PMID:20832396

Reform of prescription drug reimbursement and pricing in the German social health insurance market: a comparison of three scenarios.

PubMed

Gress, Stefan; Niebuhr, Dea; May, Uwe; Wasem, Jürgen

2007-01-01

We review regulation of two important parameters for third-party payers and manufacturers of prescription drugs: regulation of reimbursement and pricing. We find that centralised regulation of reimbursement and pricing prevails in the 15 original EU member countries (EU-15) and in European Free Trade Association (EFTA) countries. Compared with countries such as Switzerland, The Netherlands, France and England, regulation in the German social health insurance system is rather unique. First, market approval is nearly always equivalent to reimbursement. Second, manufacturers are free to determine prices but internal reference prices restrict them from actually doing so for generics and therapeutic substitutes. In order to contain rising expenditures for prescription drugs in Germany, and to set incentives for physicians to consider the costs as well as the benefits of prescriptions, three reform scenarios are feasible. The first scenario maintains centralised reimbursement and centralised pricing; the second maintains centralised reimbursement but switches to decentralised pricing (similar to social health insurance in Israel and Medicare in the US). Third-party payers would be able to negotiate with manufacturers about discounts and market shares for genetic and therapeutic substitutes. In the third scenario, pricing and reimbursement would be decentralised (similar to private health insurance in the US). We suggest that the second scenario is a viable compromise between consumer protection and a more competitive and cost-effective market for prescription drugs in German social health insurance and other similar markets for prescription drugs.

Tissue Kallikrein Inhibitors Based on the Sunflower Trypsin Inhibitor Scaffold – A Potential Therapeutic Intervention for Skin Diseases

PubMed Central

Chen, Wenjie; Kinsler, Veronica A.

2016-01-01

Tissue kallikreins (KLKs), in particular KLK5, 7 and 14 are the major serine proteases in the skin responsible for skin shedding and activation of inflammatory cell signaling. In the normal skin, their activities are controlled by an endogenous protein protease inhibitor encoded by the SPINK5 gene. Loss-of-function mutations in SPINK5 leads to enhanced skin kallikrein activities and cause the skin disease Netherton Syndrome (NS). We have been developing inhibitors based on the Sunflower Trypsin Inhibitor 1 (SFTI-1) scaffold, a 14 amino acids head-to-tail bicyclic peptide with a disulfide bond. To optimize a previously reported SFTI-1 analogue (I10H), we made five analogues with additional substitutions, two of which showed improved inhibition. We then combined those substitutions and discovered a variant (Analogue 6) that displayed dual inhibition of KLK5 (tryptic) and KLK7 (chymotryptic). Analogue 6 attained a tenfold increase in KLK5 inhibition potency with an Isothermal Titration Calorimetry (ITC) Kd of 20nM. Furthermore, it selectively inhibits KLK5 and KLK14 over seven other serine proteases. Its biological function was ascertained by full suppression of KLK5-induced Protease-Activated Receptor 2 (PAR-2) dependent intracellular calcium mobilization and postponement of Interleukin-8 (IL-8) secretion in cell model. Moreover, Analogue 6 permeates through the cornified layer of in vitro organotypic skin equivalent culture and inhibits protease activities therein, providing a potential drug lead for the treatment of NS. PMID:27824929

Protein Oxidation and Sensory Quality of Brine-Injected Pork Loins Added Ascorbate or Extracts of Green Tea or Maté during Chill-Storage in High-Oxygen Modified Atmosphere

PubMed Central

Tørngren, Mari Ann

2018-01-01

Background: Ascorbate is often applied to enhance stability and robustness of brine-injected pork chops sold for retail, but may affect protein oxidation, while plant extracts are potential substitutes. Methods: Brine-injected pork chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea extract (25 ppm gallic acid equivalents (GAE)), or maté extract (25 ppm GAE) stored (5 °C, seven days) in high-oxygen atmosphere packaging (MAP: 80% O2 and 20% CO2) were analyzed for color changes, sensory quality, and protein oxidation compared to a control without antioxidant. Results: No significant differences were observed for green tea and maté extracts as compared to ascorbate when evaluated based on lipid oxidation derived off-flavors, except for stale flavor, which maté significantly reduced. All treatments increased the level of the protein oxidation product, α-aminoadipic semialdehyde as compared to the control, and ascorbate was further found to increase thiol loss and protein cross-linking, with a concomitant decrease in the sensory perceived tenderness. Conclusions: Green tea and maté were found to equally protect against lipid oxidation derived off-flavors, and maté showed less prooxidative activity towards proteins as compared to ascorbate, resulting in more tender meat. Maté is a valuable substitute for ascorbate in brine-injected pork chops. PMID:29342928

Ecological analysis of a typical farm-scale biogas plant in China

NASA Astrophysics Data System (ADS)

Duan, Na; Lin, Cong; Wang, Pingzhi; Meng, Jing; Chen, Hui; Li, Xue

2014-09-01

The aim of this work was to present the common anaerobic digestion technologies in a typical farm-scale biogas plant in China. The comprehensive benefits of most biogas plants in China have not been fully assessed in past decades due to the limited information of the anaerobic digestion processes in biogas plants. This paper analyzed four key aspects (i.e., operational performance, nonrenewable energy (NE) savings, CO2 emission reduction (CER) and economic benefits (EBs)) of a typical farm-scale biogas plant, where beef cattle manure was used as feedstock. Owing to the monitoring system, stable operation was achieved with a hydraulic retention time of 18-22 days and a production of 876,000 m3 of biogas and 37,960 t of digestate fertilizer annually. This could substantially substitute for the nonrenewable energy and chemical fertilizer. The total amount of NE savings and CER derived from biogas and digestate fertilizer was 2.10×107 MJ (equivalent to 749.7 tce) and 9.71×105 kg, respectively. The EBs of the biogas plant was 6.84×105 CNY·yr-1 with an outputs-to-inputs ratio of 2.37. As a result, the monitoring system was proved to contribute significantly to the sound management and quantitative assessment of the biogas plant. Biogas plants could produce biogas which could be used to substitute fossil fuels and reduce the emissions of greenhouse gases, and digestate fertilizer is also an important bio-product.

Mechanism of quinolone resistance in anaerobic bacteria.

PubMed

Oh, H; Edlund, C

2003-06-01

Several recently developed quinolones have excellent activity against a broad range of aerobic and anaerobic bacteria and are thus potential drugs for the treatment of serious anaerobic and mixed infections. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. Two main mechanisms, alteration of target enzymes (gyrase and topoisomerase IV) caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. These mechanisms have also been found in anaerobic species. High-level resistance to the newer broad-spectrum quinolones often requires stepwise mutations in target genes. The increasing emergence of resistance among anaerobes may be a consequence of previous widespread use of quinolones, which may have enriched first-step mutants in the intestinal tract. Quinolone resistance in the Bacteroides fragilis group strains is strongly correlated with amino acid substitutions at positions 82 and 86 in GyrA (equivalent to positions 83 and 87 of Escherichia coli). Several studies have indicated that B. fragilis group strains possess efflux pump systems that actively expel quinolones, leading to resistance. DNA gyrase seems also to be the primary target for quinolones in Clostridium difficile, since amino acid substitutions in GyrA and GyrB have been detected in resistant strains. To what extent other mechanisms, such as mutational events in other target genes or alterations in outer-membrane proteins, contribute to resistance among anaerobes needs to be further investigated.

Calibration of a mosfet detection system for 6-MV in vivo dosimetry.

PubMed

Scalchi, P; Francescon, P

1998-03-01

Metal oxide semiconductor field-effect transistor (MOSFET) detectors were calibrated to perform in vivo dosimetry during 6-MV treatments, both in normal setup and total body irradiation (TBI) conditions. MOSFET water-equivalent depth, dependence of the calibration factors (CFs) on the field sizes, MOSFET orientation, bias supply, accumulated dose, incidence angle, temperature, and spoiler-skin distance in TBI setup were investigated. MOSFET reproducibility was verified. The correlation between the water-equivalent midplane depth and the ratio of the exit MOSFET readout divided by the entrance MOSFET readout was studied. MOSFET midplane dosimetry in TBI setup was compared with thermoluminescent dosimetry in an anthropomorphic phantom. By using ionization chamber measurements, the TBI midplane dosimetry was also verified in the presence of cork as a lung substitute. The water-equivalent depth of the MOSFET is about 0.8 mm or 1.8 mm, depending on which sensor side faces the beam. The field size also affects this quantity; Monte Carlo simulations allow driving this behavior by changes in the contaminating electron mean energy. The CFs vary linearly as a function of the square field side, for fields ranging from 5 x 5 to 30 x 30 cm2. In TBI setup, varying the spoiler-skin distance between 5 mm and 10 cm affects the CFs within 5%. The MOSFET reproducibility is about 3% (2 SD) for the doses normally delivered to the patients. The effect of the accumulated dose on the sensor response is negligible. For beam incidence ranging from 0 degrees to 90 degrees, the MOSFET response varies within 7%. No monotonic correlation between the sensor response and the temperature is apparent. Good correlation between the water-equivalent midplane depth and the ratio of the exit MOSFET readout divided by the entrance MOSFET readout was found (the correlation coefficient is about 1). The MOSFET midplane dosimetry relevant to the anthropomorphic phantom irradiation is in agreement with TLD dosimetry within 5%. Ionization chamber and MOSFET midplane dosimetry in inhomogeneous phantoms are in agreement within 2%. MOSFET characteristics are suitable for the in vivo dosimetry relevant to 6-MV treatments, both in normal and TBI setup. The TBI midplane dosimetry using MOSFETs is valid also in the presence of the lung, which is the most critical organ, and allows verifying that calculation of the lung attenuator thicknesses based only on the density is not correct. Our MOSFET dosimetry system can be used also to determine the surface dose by using the water-equivalent depth and extrapolation methods. This procedure depends on the field size used.

Evaluation of dermal-epidermal skin equivalents ('composite-skin') of human keratinocytes in a collagen-glycosaminoglycan matrix(Integra artificial skin).

PubMed

Kremer, M; Lang, E; Berger, A C

2000-09-01

Integra artificial skin (Integra LifeSciences Corp., Plainsboro, NJ, USA) is a dermal template consisting of bovine collagen, chondroitin-6-sulphate and a silastic membrane manufactured as Integra. This product has gained widespread use in the clinical treatment of third degree burn wounds and full thickness skin defects of different aetiologies. The product was designed to significantly reduce the time needed to achieve final wound closure in the treatment of major burn wounds, to optimise the sparse autologous donor skin resources and to improve the durable mechanical quality of the skin substitute. The clinical procedure requires two stages. The first step creates a self neodermis, the second creates a self epidermis on the neodermis. However, it is desirable to cover major burn wounds early in a single step by a skin substitute consisting of a dermal equivalent seeded in vitro with autologous keratinocytes ('composite-skin') out of which a full thickness skin develops in vivo.The goal of this experimental study was to develop a method to integrate human keratinocytes in homogeneous distribution and depth into Integra Artificial Skin. The seeded cell-matrix composites were grafted onto athymic mice in order to evaluate their potential to reconstitute a human epidermis in vivo. We were able to demonstrate that the inoculated human keratinocytes reproducibly displayed a homogeneous pattern of distribution, adherence, proliferation and confluence. The cell-matrix composites grafted in this model exhibited good wound adherence, complete healing, minor wound contraction and had the potential to reconstitute an elastic, functional and durable human skin. Histologically we were able to show that the inoculated human keratinocytes in vivo colonised the matrix in a histomorphologically characteristic epidermal pattern (keratomorula, keratinocyte bubbling) and developed a persisting, stratified, keratinising epidermis which immunohistologically proved to be of human origin. These experimental results demonstrate the establishment of an effective cell cultivation process which may be suitable for scale-up production of the epidermal component as large-scale composite-skin grafts. When seeded into Integratrade mark and grafted onto the nude mouse a replacement skin with normal functioning dermal-epidermal components was developed. These results encourage the design of a clinical trial to assess the function of this composite graft in man.

PubMed Central

PAGNINI, P.; VANNUCCHI, P.; GIANNONI, B.; PECCI, R.

2014-01-01

SUMMARY Migrainous headache is determined by pathogenetic mechanisms that are also able to affect the peripheral and/or central vestibular system, so that vestibular symptoms may substitute and/or present with headache. We are convinced that there can be many different manifestations of vestibular disorders in migrainous patients, representing true different clinical entities due to their different characteristics and temporal relashionship with headache. Based on such considerations, we proposed a classification of vertigo and other vestibular disorders related to migraine, and believe that a particular variant of migraine-related vertigo should be introduced, namely "epigone migraine vertigo" (EMV): this could be a kind of late migraine equivalent, i.e. a kind of vertigo, migrainous in origin, starting late in the lifetime that substitutes, as an equivalent, pre-existing migraine headache. To clarify this particular clinical picture, we report three illustrative clinical cases among 28 patients collected during an observation period of 13 years (November 1991 - November 2004). For all patients, we collected complete personal clinical history. All patients underwent standard neurotological examination, looking for spontaneous-positional, gaze-evoked and caloric induced nystagmus, using an infrared video camera. We also performed a head shaking test (HST) and an head thrust test (HTT). Ocular motility was tested looking at saccades and smooth pursuit. To exclude other significant neurological pathologies, a brain magnetic resonance imaging (MRI) with gadolinium was performed. During the three months after the first visit, patients were invited to keep a diary noting frequency, intensity and duration of vertigo attacks. After that period, we suggested that they use prophylactic treatment with flunarizine (5 mg per day) and/or acetylsalicylic acid (100 mg per day), or propranolol (40 mg twice a day). All patients were again recommended to note in their diary the frequency and intensity of both headache and vertigo while taking prophylactic therapy. Control visits were programmed after 4, 12 and 24 months of therapy. All patients considerably improved symptoms with therapy: 19 subjects (68%) reported complete disappearance of vestibular symptoms, while 9 (32%) considered symptoms very improved. The subjective judgement was corroborated by data from patients diaries. We conclude that EMV is a clinical variant of typical migraine-related vertigo: a migraineassociated vertigo, headache spell independent, following a headache period, during the lifetime of a patient. PMID:24711685

40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

Code of Federal Regulations, 2010 CFR

2010-07-01

... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo...

40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

Code of Federal Regulations, 2011 CFR

2011-07-01

... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2014 CFR

2014-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2013 CFR

2013-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2012 CFR

2012-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2011 CFR

2011-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

Folate-conjugated chitosan-polylactide nanoparticles for enhanced intracellular uptake of anticancer drug

NASA Astrophysics Data System (ADS)

Huang, Shengtang; Wan, Ying; Wang, Zheng; Wu, Jiliang

2013-12-01

Chitosan was conjugated with folic acid (FA) and the resulting chitosan derivatives with a FA-substitution degree of around 6 % was used to synthesize FA-conjugated chitosan-polylactide (FA-CH-PLA) copolymers to build a drug carrier with active targeting characteristics for the anticancer drug of paclitaxel (PTX). Selected FA-CH-PLAs with various polylactide percentages of about 40 wt% or lower were employed to fabricate nanoparticles using sodium tripolyphosphate as a crosslinker, and different types of nanoparticles were endued with similar average particle-sizes located in a range between 100 and 200 nm. Certain types of PTX-loaded FA-CH-PLA nanoparticles having encapsulation efficiency of around 90 % and initial load of about 12 % were able to release PTX in a controlled manner with significant regulation by polylactide content in FA-CH-PLAs. Targeting characteristic of achieved nanoparticles was confirmed using FA-receptor-expressed MCF-7 breast cancer cells. The uptake of PTX revealed that optimized FA-CH-PLA nanoparticles with an equivalent PTX-dose of around 1 μg/mL could have more than sixfold increasing abilities to facilitate intracellular paclitaxel accumulation in MCF-7 cells after 24 h treatment as compared to free PTX. At a relatively safe equivalent PTX-dose for normal MCF-10A mammary epithelial cells, the obtained results from Hoechst 33342 staining indicated that optimized PTX-loaded FA-CH-PLA nanoparticles had more than threefold increasing abilities to induce MCF-7 cell apoptosis in comparison to free PTX.

The common C-terminal sequences of substance P and neurokinin A contact the same region of the NK-1 receptor.

PubMed

Bremer, A A; Leeman, S E; Boyd, N D

2000-12-01

Although neurokinin A (NKA), a tachykinin peptide with sequence homology to substance P (SP), is a weak competitor of radiolabeled SP binding to the NK-1 receptor (NK-1R), more recent direct binding studies using radiolabeled NKA have demonstrated an unexpected high-affinity interaction with this receptor. To document the site of interaction between NKA and the NK-1R, we have used a photoreactive analogue of NKA containing p-benzoyl-L-phenylalanine (Bpa) substituted in position 7 of the peptide. Peptide mapping studies of the receptor photolabeled by (125)I-iodohistidyl(1)-Bpa(7)NKA have established that the site of photoinsertion is located within a segment of the receptor extending from residues 178 to 190 (VVCMIEWPEHPNR). We have previously shown that (125)I-BH-Bpa(8)SP, a photoreactive analogue of SP, covalently attaches to M(181) within this same receptor sequence. Importantly, both of these peptides ((125)I-iodohistidyl(1)-Bpa(7)NKA and (125)I-BH-Bpa(8)SP) have the photoreactive amino acid in an equivalent position within the conserved tachykinin carboxyl-terminal tail. In this report, we also show that site-directed mutagenesis of M(181) to A(181) in the NK-1R results in a complete loss of photolabeling of both peptides to this receptor site, indicating that the equivalent position of SP and NKA, when bound to the NK-1R, contact the same residue.

Chromatographic and mass spectral methods of identification for the side-chain and ring regioisomers of methylenedioxymethamphetamine.

PubMed

Aalberg, L; DeRuiter, J; Noggle, F T; Sippola, E; Clark, C R

2000-08-01

The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) is one of a total of 10 regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines of MW 193 that yields regioisomeric fragment ions with equivalent mass (m/z 58 and 135/136) in the electron-impact (EI) mass spectrum. Thus, these 10 methylenedioxyphenethylamines are uniquely isomeric; they have the same molecular weight and equivalent major fragments in their mass spectra. The specific identification of one of these compounds (i.e., Ecstasy or 3,4-MDMA) in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This study reports the synthesis, chemical properties, spectral characterization, and chromatographic analysis of these 10 unique regioisomers. The ten 2,3- and 3,4-regioisomers of MDMA are synthesized from commercially available precursor chemicals. In the EI mass spectra, the side-chain regioisomers show some variation in the relative intensity of the major ions, with the exception of only one or two minor ions that might be considered side-chain specific fragments. The position of substitution for the methylenedioxy ring is not easily determined by mass spectral techniques, and the ultimate identification of any one of these amines with the elimination of the other nine must depend heavily upon chromatographic methods. The chromatographic separation of these 10 uniquely regioisomeric amines are studied using reversed-phase liquid chromatographic methods with gradient elution and gas chromatographic techniques with temperature program optimization.

Clinical and economic outcomes in patients switched to simvastatin in a community-based family medicine practice.

PubMed

Willey, V J; Reinhold, J A; Willey, K H; Kelly, B L; Cziraky, M J

2010-08-01

The introduction of a generic formulation of simvastatin has created the potential to provide significant low-density lipoprotein cholesterol (LDL-C) reduction in a highly cost-effective manner. This retrospective cohort analysis utilised electronic medical record data from a United States, community-based, independent physician family medicine practice. Patients switched from other statins or statin combinations to simvastatin by the family medicine physicians during routine patient care from January 2002 to October 2008 were identified. Equivalent statin dosing, lipid panel changes and National Cholesterol Education Program--Adult Treatment Panel III (NCEP) LDL-C goal attainment rates were compared preswitch and postswitch. The potential economic impact of simvastatin switching was also evaluated. A total of 78 patients were identified, and in 76.9% of the switches, an equipotent dose of simvastatin was prescribed. All lipid fractions showed small, non-significant increases, with LDL-C having a 2.2 mg/dl (0.06 mmol/l) increase after switching (p = 0.476). NCEP LDL-C goal attainment rates were 79.5% and 78.2% before and after switching, respectively (p = 1.00). Modelled annual cost savings associated with switching were estimated at $671.99 per patient. These results demonstrate that an independent family medicine physician practice can successfully perform statin therapeutic substitution during routine patient care. Equivalent clinical outcomes with regards to changes in lipid fractions and NCEP LDL-C goal attainment were observed in conjunction with the potential for reduced costs for patients.

2,3,7,8-Tetrachlorodibenzo-p-dioxin equivalents in tissues of birds at Green Bay, Wisconsin, USA

USGS Publications Warehouse

Jones, Paul D.; Giesy, John P.; Newsted, John L.; Verbrugge, David A.; Beaver, Donald L.; Ankley, Gerald T.; Tillitt, Donald E.; Lodge, Keith B.; Niemi, Gerald J.

1993-01-01

The environment has become contaminated with complex mixtures of planar, chlorinated hydrocarbons (PCHs) such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and structurally similar compounds. Because the potencies of individual congeners to cause the same adverse effects vary greatly and the relative as well as absolute concentrations of individual PCH vary among samples from different locations, it is difficult to assess the toxic effects of these mixtures on wildlife. These compounds can cause a number of adverse effects, however, because the toxic effects which occur at ecologically-relevant concentrations such as embryo-lethality and birth defects appear to be mediated through the same mechanism, the potency of individual congeners can be reported relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) which is the most toxic congener in the PCH class. The concentations of 2,3,7,8-TCDD Equivalents (TCDD-EQ) were determined in the tissues of aquatic and terrestrial birds of Green Bay, Wisconsin by the H4IIE bioassay system and compared toxic equivalency factors (TEFs) with the concentration predicted by the use of toxic equivalency factors applied to concentrations of PCH, which were determined by instrumental analyses. Concentrations of TCDD-EQ ranged from 0.52 to 440 ng/kg, wet weight. The greatest concentrations occurred in the fish-eating birds. Concentrations of TCDD-EQ, which were determined by the two methods were significantly correlated, but the additive model which used the TEFs with concentrations of measured PCB, PCDD and PCDF congeners underestimated the concentrations of TCDD-EQ measured by the H4IIE bioassay by an average of 57%. This is thought to be due to contributions from un-quantified PCH, which are known to occur in the environment. Of the quantified PCH congeners, PCDD and PCDF contributed a small portion of the TCDD-EQ in the aquatic birds, while most of the TCDD-EQ were due to non-ortho-substituted PCBs. In the terrestrial birds, the proportion of the TCDD-EQ contributed by the PCDD and PCDF was greater.This paper has been reviewed in accord with U.S. Environmental Protection Agency policy. Mention of specific products or trade names does not imply endorsement by the U.S. Government.

Analysis by mutagenesis of the ATP binding site of the gamma subunit of skeletal muscle phosphorylase kinase expressed using a baculovirus system.

PubMed

Lee, J H; Maeda, S; Angelos, K L; Kamita, S G; Ramachandran, C; Walsh, D A

1992-11-03

Active gamma subunit of skeletal muscle phosphorylase kinase has been obtained by expression of the rat soleus cDNA in a baculovirus system. The protein exhibited the expected pH 6.8/8.2 activity ratio of 0.6, and its activity was insensitive to Ca2+ addition, indicating that it was free gamma subunit and not a gamma subunit-calmodulin complex. It was stimulated approximately 2-fold by Ca(2+)-calmodulin addition, demonstrating that it had retained high-affinity calmodulin binding. By site-directed mutagenesis, we have examined the role of six of the amino acids that constitute the consensus ATP binding site of the protein kinase, which in the gamma subunit is represented by the sequence 26Gly.Arg.Gly.Val.Ser.Ser.Val.Val33. Changes were evaluated by the kinetic determination of the dissociation constants of gamma-ATP, gamma-ADP, gamma-AMP.PCP, and gamma-phosphorylase and the maximum catalytic activity. The mutants Ser26-gamma, Ser29-gamma, Phe30-gamma, and Gly31-gamma each exhibited an essentially identical dissociation constant for gamma subunit phosphorylase, indicating that these mutations had not caused a global alteration in the protein structure but were limited to changes in the nucleotide binding site domain. Substitution of either Val33 (by Gly) or Gly28 (by Ser), two of the most conserved residues in all protein kinases, resulted in enzyme with marginally detectable activity. In noted contrast, the Ser26 mutant, which substituted the first glycine of the consensus glycine trio motif, and which is also very highly conserved, retained at least 25% of the enzymatic activity. The Gly31 substitution, which restored a glycine to a position characteristic for most protein kinases, had little overall effect upon the maximum rate of catalysis. Restoration of Ser30 to the more typical phenylalanine, which is present in most protein kinases, had minimal effect on catalysis. These data provide the first direct evaluation of the roles that different residues play within this consensus glycine trio/valine motif of the protein kinases, which up to now have only been surmised to be of importance because of their conservation. Two unexpected findings are that for one residue that is very conserved (Gly26) there is some flexibility of substitution not apparent from the evolutionary conservation and that a second quite conserved residue in protein kinases (equivalent to Gly at position 31) does not produce a protein optimized for nucleotide binding.

Dioxin-like pcb emissions from cement kilns during the use of alternative fuels.

PubMed

Richards, Glen; Agranovski, Igor E

2017-02-05

The substitution of combustion fuels in cement plants is increasing throughout many countries, and its individual performance is constantly assessed against strict regulatory standards. For cement plants within Australia, normal operations remain to use petroleum coal as the dominate energy source at the precalciner, avoiding the opportunity to reduce carbon-based resources and pollutant emissions (such as carbon dioxide, oxides of nitrogen, persistent organic pollutants) whilst providing the necessary energy needs through resource recovery. This paper presents stack emission monitoring of health-critical dl-PCB (dioxin-like polychlorinated biphenyl) congeners during the substitution of alternative fuels at ten Australian cement plants, and to distinguish statistical similarities between other key pollutants (such as polychlorinated dibenzo-p-dioxins and furans (PCDD-F) and hydrogen halogens) and amongst the fuels used. Sampling of plant emissions was performed during normal operations (as baseline trials) and with the varied substitution rates of waste oil, solvents, chipped wood, refuge waste, carbon dust, shredded tyres and black sand (as experimental trials). The extraction of field and analytical data during these trials allowed for determining the total and individual unit mass of dl-PCB and PCDD-F isomers, standardised to 10% O 2 and to World Health Organization (2005) toxicity equivalence (TEQ) values. The findings showed waste co-incineration during cement operations does reduce health-critical congeners of dioxins and dl-PCBs whilst providing the necessary energy and calcination needs. Experimental trials showed all dl-PCBs and PCB TEQ are below the internationally regulated Stockholm Convention article of 10pg TEQ/Nm 3 . In several cases, an increased rate of substituted fuel also identified a consistent reduction to baseline dl-PCBs. The distribution of toxic isomers (TCDD-F and PeCDD-F) were shown to be predominate during waste oil, wood chips, and solvent trials. Whereas the use of TDFs consistently showed a lower toxicity contribution. The distribution of dl-PCBs toxic congeners showed PCB-126 (3,3',4,4',5-Pentachlorobiphenyl) to be greatly present during the co-incineration of waste oil, wood chips, solvents and TDF trials. Principle component analysis identified a statistical predominance from the 1,2,3,7,8-PeCDF (Pentachlorodibenzofuran) and 1,2,3,4,7,8-HxCDF (Hexachlorodibenzofuran) congeners, while dl-PCBs TEQs had similar correlation amongst combustion fuels with major contributions being from the PCB-126 and PCB-169 (3,3',4,4',5,5'-Hexachlorobiphenyl) congeners. Copyright © 2016 Elsevier B.V. All rights reserved.

40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted phenyl...

The consequences of unemployment on diet composition and purchase behaviour: a longitudinal study from Denmark.

PubMed

Smed, Sinne; Tetens, Inge; Bøker Lund, Thomas; Holm, Lotte; Ljungdalh Nielsen, Annemette

2018-02-01

To explore and describe quantitatively the effect over time of unemployment on food purchase behaviour and diet composition. Longitudinal data from 2008-2012, with monthly food purchase data aligned with register data on unemployment measured as a dichotomous indicator as well as a trend accounting for the duration. A household panel which registers daily food purchases combined with detailed nutritional information and registration of the duration of unemployment at individual level. The structure of the data set facilitates the detection of effects or associations between duration of unemployment and diet composition, purchase behaviour in terms of food expenditure, and share of food purchased on offer and in discounters while controlling for important confounding factors. Danish households of working age (n 3440) adjusted to household equivalents. We use fixed-effects econometric methods to control for unobserved heterogeneity. In the short run, unemployment led to substitution in favour of discount stores and increases in food expenditure and in consumption of saturated fat, total fat and protein due to increased consumption of animal-based foods. In the medium run food expenditure declined together with consumption of fresh animal-based foods and saturated fat, total fat and protein. In the even longer run these nutrients were substituted by carbohydrates and added sugar. Unemployment has a substantial influence on diet composition, but effects vary with duration of the unemployment period, which may have potential health implications. This ought to be taken into consideration in evaluations of existing reforms and in future reforms of welfare systems.

Influence of partial replacement of soya bean meal by faba beans or peas in heavy pigs diet on meat quality, residual anti-nutritional factors and phytoestrogen content.

PubMed

Gatta, Domenico; Russo, Claudia; Giuliotti, Lorella; Mannari, Claudio; Picciarelli, Piero; Lombardi, Lara; Giovannini, Luca; Ceccarelli, Nello; Mariotti, Lorenzo

2013-06-01

The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as additional protein sources in diets destined for typical Italian heavy pig production. It compared animal performances, meat quality, the presence of residual anti-nutritional factors (ANF) and phytoestrogens in plasma and meat and the possible effects on pig health, by evaluating oxidative, inflammatory and pro-atherogenic markers. The results showed that the productive performances, expressed as body weight and feed conversion ratio, of pigs fed with faba bean and pea diets were similar to those of pigs fed only the soybean meal. Meat quality of pigs fed with the three diets was similar in colour, water-holding capacity, tenderness and chemical composition. Despite the higher levels of phytoestrogen in the plasma of pigs fed only the soybean meal, phytoestrogen concentration in the muscle was equivalent to that of animals fed diets with faba beans, whereas pigs fed a diet with peas showed a lower concentration. Inflammation and pro-atherogenic parameters did not show significant differences among the three diets. Overall, the partial substitution of soybean meal by faba beans appears more interesting than with peas, particularly in relation to the higher amount of polyphenols in the diet and the highest concentration of phytoestrogens found in the plasma and muscle of animals, while the pyrimidine anti-nutritional compounds present in the diet did not appear to accumulate and had no effect on the growth performance of animals.

Generics and substitution modalities: proposed methods for the evaluation of equivalence, traceability and pharmacovigilance reporting.

PubMed

Lamarque, Véronique; Merle, Louis; Demarez, Jean Paul

2008-01-01

The use of generics results in savings for the budget of the health insurance, and no player of health could question seriously the principle. The generic drug of a reference medicinal product defines itself as a drug having the same qualitative and quantitative composition in active ingredients, the same dosage form and the bioequivalence with this reference medicinal product was demonstrated by appropriate studies of bioavailability. It is the right to switch granted to the pharmacists in 1999 that is at the origin of the real development of these specialties on the French pharmaceutical market. Nevertheless, about 10 years later, it seems that the system in place does not offer all the necessary securities with regard to pharmacovigilance, notably for the products with narrow therapeutic margin. By strengthening and/or by completing the role played by the health care professionals and the public institutions concerned, it is highly possible to improve the robustness of the system. Also, the recent arrival in Europe of the biosimilars, similar molecules but not bioequivalent to biological products, cause an even more tricky specific situation than that of the generics because of their nature, of the difficulty to manufacture them, and of the risk of immunogenicity. If the substitution is not permitted in several European countries including France, the other issues can appear especially in case of interchangeability requiring also, the reinforcement of certain measures.The various aspects are described in this article with concrete proposals on how the current system can be made safer, both for the generics and the biosimilars.

Engineering a Cysteine-Free Form of Human Fibroblast Growth Factor-1 for “Second Generation” Therapeutic Application

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

Xia, Xue; Kumru, Ozan S.; Blaber, Sachiko I.

Human fibroblast growth factor-1 (FGF-1) has broad therapeutic potential in regenerative medicine but has undesirable biophysical properties of low thermostability and 3 buried cysteine (Cys) residues (at positions 16, 83, and 117) that interact to promote irreversible protein unfolding under oxidizing conditions. Mutational substitution of such Cys residues eliminates reactive buried thiols but cannot be accomplished simultaneously at all 3 positions without also introducing further substantial instability. The mutational introduction of a novel Cys residue (Ala66Cys) that forms a stabilizing disulfide bond (i.e., cystine) with one of the extant Cys residues (Cys83) effectively eliminates one Cys while increasing overall stability.more » This increase in stability offsets the associated instability of remaining Cys substitution mutations and permits production of a Cys-free form of FGF-1 (Cys16Ser/Ala66Cys/Cys117Ala) with only minor overall instability. The addition of a further stabilizing mutation (Pro134Ala) creates a Cys-free FGF-1 mutant with essentially wild-type biophysical properties. The elimination of buried free thiols in FGF-1 can substantially increase the protein half-life in cell culture. Here, we show that the effective cell survival/mitogenic functional activity of a fully Cys-free form is also substantially increased and is equivalent to wild-type FGF-1 formulated in the presence of heparin sulfate as a stabilizing agent. The results identify this Cys-free FGF-1 mutant as an advantageous “second generation” form of FGF-1 for therapeutic application.« less

Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume

PubMed Central

Niu, Xiaowei

2011-01-01

Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger. PMID:21576375

Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease.

PubMed

Lin, Ying-Chuan; Torbett, Bruce E; Elder, John H

2010-07-01

Feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) proteases (PRs) share only 23% amino acid identity and exhibit distinct specificities yet have very similar 3-dimensional structures. Chimeric PRs in which HIV residues were substituted in structurally equivalent positions in FIV PR were prepared in order to study the molecular basis of PR specificity. Previous in vitro analyses showed that such substitutions dramatically altered the inhibitor specificity of mutant PRs but changed the rate and specificity of Gag cleavage so that chimeric FIVs were not infectious. Chimeric PRs encoding combinations of the I37V, N55M, M56I, V59I, L97T, I98P, Q99V, and P100N mutations were cloned into FIV Gag-Pol, and those constructs that best approximated the temporal cleavage pattern generated by wild-type FIV PR, while maintaining HIV-like inhibitor specificity, were selected. Two mutations, M56I and L97T, were intolerant to change and caused inefficient cleavage at NC-p2. However, a mutant PR with six substitutions (I37V, N55M, V59I, I98P, Q99V, and P100N) was selected and placed in the context of full-length FIV-34TF10. This virus, termed YCL6, had low-level infectivity ex vivo, and after passage, progeny that exhibited a higher growth rate emerged. The residue at the position of one of the six mutations, I98P, further mutated on passage to either P98H or P98S. Both PRs were sensitive to the HIV-1 PR inhibitors lopinavir (LPV) and darunavir (DRV), as well as to the broad-based inhibitor TL-3, with 50% inhibitory concentrations (IC(50)) of 30 to 40 nM, consistent with ex vivo results obtained using mutant FIVs. The chimeras offer an infectivity system with which to screen compounds for potential as broad-based PR inhibitors, define structural parameters that dictate specificity, and investigate pathways for drug resistance development.

Generation of Infectious Feline Immunodeficiency Virus (FIV) Encoding FIV/Human Immunodeficiency Virus Chimeric Protease▿

PubMed Central

Lin, Ying-Chuan; Torbett, Bruce E.; Elder, John H.

2010-01-01

Feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) proteases (PRs) share only 23% amino acid identity and exhibit distinct specificities yet have very similar 3-dimensional structures. Chimeric PRs in which HIV residues were substituted in structurally equivalent positions in FIV PR were prepared in order to study the molecular basis of PR specificity. Previous in vitro analyses showed that such substitutions dramatically altered the inhibitor specificity of mutant PRs but changed the rate and specificity of Gag cleavage so that chimeric FIVs were not infectious. Chimeric PRs encoding combinations of the I37V, N55M, M56I, V59I, L97T, I98P, Q99V, and P100N mutations were cloned into FIV Gag-Pol, and those constructs that best approximated the temporal cleavage pattern generated by wild-type FIV PR, while maintaining HIV-like inhibitor specificity, were selected. Two mutations, M56I and L97T, were intolerant to change and caused inefficient cleavage at NC-p2. However, a mutant PR with six substitutions (I37V, N55M, V59I, I98P, Q99V, and P100N) was selected and placed in the context of full-length FIV-34TF10. This virus, termed YCL6, had low-level infectivity ex vivo, and after passage, progeny that exhibited a higher growth rate emerged. The residue at the position of one of the six mutations, I98P, further mutated on passage to either P98H or P98S. Both PRs were sensitive to the HIV-1 PR inhibitors lopinavir (LPV) and darunavir (DRV), as well as to the broad-based inhibitor TL-3, with 50% inhibitory concentrations (IC50) of 30 to 40 nM, consistent with ex vivo results obtained using mutant FIVs. The chimeras offer an infectivity system with which to screen compounds for potential as broad-based PR inhibitors, define structural parameters that dictate specificity, and investigate pathways for drug resistance development. PMID:20410281

Hospital disaster response using business impact analysis.

PubMed

Suginaka, Hiroshima; Okamoto, Ken; Hirano, Yohei; Fukumot, Yuichi; Morikawa, Miki; Oode, Yasumasa; Sumi, Yuka; Inoue, Yoshiaki; Matsuda, Shigeru; Tanaka, Hiroshi

2014-12-01

The catastrophic Great East Japan Earthquake in 2011 created a crisis in a university-affiliated hospital by disrupting the water supply for 10 days. In response, this study was conducted to analyze water use and prioritize water consumption in each department of the hospital by applying a business impact analysis (BIA). Identifying the minimum amount of water necessary for continuing operations during a disaster was an additional goal. Water is essential for many hospital operations and disaster-ready policies must be in place for the safety and continued care of patients. A team of doctors, nurses, and office workers in the hospital devised a BIA questionnaire to examine all operations using water. The questionnaire included department name, operation name, suggested substitutes for water, and the estimated daily amount of water consumption. Operations were placed in one of three ranks (S, A, or B) depending on the impact on patients and the need for operational continuity. Recovery time objective (RTO), which is equivalent to the maximum tolerable period of disruption, was determined. Furthermore, the actual use of water and the efficiency of substitute methods, practiced during the water-disrupted periods, were verified in each operation. There were 24 activities using water in eight departments, and the estimated water consumption in the hospital was 326 (SD = 17) m³ per day: 64 (SD = 3) m³ for S (20%), 167 (SD = 8) m³ for A (51%), and 95 (SD = 5) m³ for B operations (29%). During the disruption, the hospital had about 520 m³ of available water. When the RTO was set to four days, the amount of water available would have been 130 m³ per day. During the crisis, 81% of the substitute methods were used for the S and A operations. This is the first study to identify and prioritize hospital operations necessary for the efficient continuation of medical treatment during suspension of the water supply by applying a BIA. Understanding the priority of operations and the minimum daily water requirement for each operation is important for a hospital in the event of an unexpected adverse situation, such as a major disaster.

Simple, heart-smart substitutions

MedlinePlus

Coronary artery disease - heart smart substitutions; Atherosclerosis - heart smart substitutions; Cholesterol - heart smart substitutions; Coronary heart disease - heart smart substitutions; Healthy diet - heart ...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted...

A multi-material coating containing chemically-modified apatites for combined enhanced bioactivity and reduced infection via a drop-on-demand micro-dispensing technique.

PubMed

Lim, Poon Nian; Wang, Zuyong; Chang, Lei; Konishi, Toshiisa; Choong, Cleo; Ho, Bow; Thian, Eng San

2017-01-01

Prevention of infection and enhanced osseointegration are closely related, and required for a successful orthopaedic implant, which necessitate implant designs to consider both criteria in tandem. A multi-material coating containing 1:1 ratio of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite as the top functional layer, and hydroxyapatite as the base layer, was produced via the drop-on-demand micro-dispensing technique, as a strategic approach in the fight against infection along with the promotion of bone tissue regeneration. The homogeneous distribution of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets at alternate position in silicon-substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite coating delayed the exponential growth of Staphylococcus aureus for up to 24 h, and gave rise to up-regulated expression of alkaline phosphatase activity, type I collagen and osteocalcin as compared to hydroxyapatite and silver-substituted hydroxyapatite coatings. Despite containing reduced amounts of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets over the coated area than silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite coatings, silicon-substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite coating exhibited effective antibacterial property with enhanced bioactivity. By exhibiting good controllability of distributing silicon-substituted hydroxyapatite, silver-substituted hydroxyapatite and hydroxyapatite micro-droplets, it was demonstrated that drop-on-demand micro-dispensing technique was capable in harnessing the advantages of silver-substituted hydroxyapatite, silicon-substituted hydroxyapatite and hydroxyapatite to produce a multi-material coating along with enhanced bioactivity and reduced infection.

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.981 Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new...

Emissive polymeric materials for optoelectronic devices

DOEpatents

Shiang, Joseph John [Niskayuna, NY; Chichak, Kelly Scott [Clifton Park, NY; Cella, James Anthony [Clifton Park, NY; Lewis, Larry Neil [Scotia, NY; Janora, Kevin Henry [Schenectady, NY

2011-07-05

Polymers including at least one structural unit derived from a compound of formula I or including at least one pendant group of formula II may be used in optoelectronic devices ##STR00001## wherein R.sup.1, R.sup.3, R.sup.4 and R.sup.6 are independently hydrogen, alkyl, alkoxy, oxaalkyl, alkylaryl, aryl, arylalkyl, heteroaryl, substituted alkyl; substituted alkoxy, substituted oxaalkyl, substituted alkylaryl, substituted aryl, substituted arylalkyl, or substituted heteroaryl; R.sup.1a is hydrogen or alkyl; R.sup.2 is alkylene, substituted alkylene, oxaalkylene, CO, or CO.sub.2; R.sup.2a is alkylene; R.sup.5 is independently at each occurrence hydrogen, alkyl, alkylaryl, aryl, arylalkyl, alkoxy, carboxy, substituted alkyl; substituted alkylaryl, substituted aryl, substituted arylalkyl, or substituted alkoxy, X is halo, triflate, --B(OR.sup.1a).sub.2, or ##STR00002## located at the 2, 5- or 2, 7-positions; and L is derived from phenylpyridine, tolylpyridine, benzothienylpyridine, phenylisoquinoline, dibenzoquinozaline, fluorenylpyridine, ketopyrrole, 2-(1-naphthyl)benzoxazole)), 2-phenylbenzoxazole, 2-phenylbenzothiazole, coumarin, thienylpyridine, phenylpyridine, benzothienylpyridine, 3-methoxy-2-phenylpyridine, thienylpyridine, phenylimine, vinylpyridine, pyridylnaphthalene, pyridylpyrrole, pyridylimidazole, phenylindole, derivatives thereof or combinations thereof.

Impedance Spectroscopy Study of the Electrical Properties of Cation-Substituted Barium Hexaaluminate Ceramics

NASA Astrophysics Data System (ADS)

Belyaev, B. A.; Drokin, N. A.; Poluboyarov, V. A.

2018-02-01

We report on the behavior of frequency and temperature dependences of the impedance of a measuring cell in the form of a parallel-plate capacitor filled with barium hexaaluminate ceramics with four aluminum cations replaced by iron (BaO · 2Fe2O3 · 4Al2O3). The measurements have been performed in the frequency range of 0.5-108 Hz at temperatures of 20-375°C. A technique for determining the electrical properties of the investigated ceramics is proposed, which is based on an equivalent electric circuit allowing the recorded impedance spectra to be approximated with sufficiently high accuracy. The established spectral features are indicative of the presence of two electric relaxation times different from each other by three orders of magnitude. This fact is explained by the difference between the charge transport processes in the bulk of crystallites and thin intercrystallite spacers, for which the charge activation energies have been determined.

Numerical methods for analyzing electromagnetic scattering

NASA Technical Reports Server (NTRS)

Lee, S. W.; Lo, Y. T.; Chuang, S. L.; Lee, C. S.

1985-01-01

Attenuation properties of the normal modes in an overmoded waveguide coated with a lossy material were analyzed. It is found that the low-order modes, can be significantly attenuated even with a thin layer of coating if the coating material is not too lossy. A thinner layer of coating is required for large attenuation of the low-order modes if the coating material is magnetic rather than dielectric. The Radar Cross Section (RCS) from an uncoated circular guide terminated by a perfect electric conductor was calculated and compared with available experimental data. It is confirmed that the interior irradiation contributes to the RCS. The equivalent-current method based on the geometrical theory of diffraction (GTD) was chosen for the calculation of the contribution from the rim diffraction. The RCS reduction from a coated circular guide terminated by a PEC are planned schemes for the experiments are included. The waveguide coated with a lossy magnetic material is suggested as a substitute for the corrugated waveguide.

[Animal experiment studies on the changes in lipid and protein metabolism in L-carnitine-supplemented total parenteral nutrition].

PubMed

Böhles, H; Segerer, H; Fekl, W; Stehr, K

1983-02-01

The influence of i.v. L-carnitine on parameters of lipid- and nitrogen metabolism was studied during total parenteral nutrition of mini pigs (x: 4077; n = 9). The infusion protocol was divided into isocaloric and isonitrogenous 48-hour-periods. Amino acids (3 g/kg/day) were administered throughout all three periods. 140 Cal/kg/day were given as non-protein calories, consisting only of glucose during period 1. During periods 2 and 3 an amount of glucose calorically equivalent to 4 g fat/kg/day was substituted with a lipid emulsion. In period 3, L-carnitine (1,5 mg/kg/day) was added. During the entire regime key parameters of fat and nitrogen metabolism were determined. During all three periods indirect calorimetry was performed and the respiratory quotient calculated. The results demonstrate a more effective lipolysis and oxydation of fatty acids during L-carnitine supplementation. This results in an increased energy gain from exogenously administered fat and a distinct improvement of nitrogen balance.

Iron-catalyzed urea synthesis: dehydrogenative coupling of methanol and amines† †Electronic supplementary information (ESI) available: Experimental details, characterization data, and select NMR spectra. See DOI: 10.1039/c8sc00775f

PubMed Central

Lane, Elizabeth M.; Hazari, Nilay

2018-01-01

Substituted ureas have numerous applications but their synthesis typically requires the use of highly toxic starting materials. Herein we describe the first base-metal catalyst for the selective synthesis of symmetric ureas via the dehydrogenative coupling of methanol with primary amines. Using a pincer supported iron catalyst, a range of ureas was generated with isolated yields of up to 80% (corresponding to a catalytic turnover of up to 160) and with H2 as the sole byproduct. Mechanistic studies indicate a stepwise pathway beginning with methanol dehydrogenation to give formaldehyde, which is trapped by amine to afford a formamide. The formamide is then dehydrogenated to produce a transient isocyanate, which reacts with another equivalent of amine to form a urea. These mechanistic insights enabled the development of an iron-catalyzed method for the synthesis of unsymmetric ureas from amides and amines. PMID:29780531

Thermodynamic and kinetic modeling of grain boundary equilibrium segregation of P in α-Fe

DOE PAGES

Yang, Y.; Chen, S. -L.

2017-04-18

Phosphorus is a primary contributor to interface fracture and embrittlement in steels because of its strong segregation tendency at grain boundaries (GBs). The lack of consistency in literature data imposes great difficulties in performing segregation modeling that is compatible with both the Langmuir-Mclean segregation theory and the thermodynamic description of the Bcc(Fe,P) phase. Our work carefully evaluated experimental data for phosphorus segregation at GBs in -Fe and provided a new formula for converting the auger electron spectroscopy (AES) peak height ratio to GBs. Furthermore, based on newly assessed literature data, this work proposes that the major driving force for phosphorusmore » segregation is the formation of Fe 3P-type clusters at GBs, which is supported not only by the almost equivalent Gibbs energy of _Fe using the Bcc(Fe,P) substitutional model and the Bcc(Fe,Fe 3P, P) associate model, but also by the good agreement between thermodynamic/kinetic modeling results and experimental data.« less

Lead-free hunting rifle ammunition: product availability, price, effectiveness, and role in global wildlife conservation.

PubMed

Thomas, Vernon George

2013-10-01

Proposals to end the use of lead hunting ammunition because of the established risks of lead exposure to wildlife and humans are impeded by concerns about the availability, price, and effectiveness of substitutes. The product availability and retail prices of different calibers of lead-free bullets and center-fire rifle ammunition were assessed for ammunition sold in the USA and Europe. Lead-free bullets are made in 35 calibers and 51 rifle cartridge designations. Thirty-seven companies distribute internationally ammunition made with lead-free bullets. There is no major difference in the retail price of equivalent lead-free and lead-core ammunition for most popular calibers. Lead-free ammunition has set bench-mark standards for accuracy, lethality, and safety. Given the demonstrated wide product availability, comparable prices, and the effectiveness of high-quality lead-free ammunition, it is possible to phase out the use of lead hunting ammunition world-wide, based on progressive policy and enforceable legislation.

RE12 derivatives displaying Vaccinia H1-related phosphatase (VHR) inhibition in the presence of detergent and their anti-proliferative activity against HeLa cells.

PubMed

Thuaud, Frédéric; Kojima, Shuntaro; Hirai, Go; Oonuma, Kana; Tsuchiya, Ayako; Uchida, Takako; Tsuchimoto, Teruhisa; Sodeoka, Mikiko

2014-05-01

New derivatives of Vaccinia H1-related phosphatase (VHR) inhibitor RE12 (5) were designed by replacing the long straight alkyl chain with other hydrophobic functionalities containing two aromatic rings, with the aim of obtaining potent, cell-active inhibitors. We established a direct coupling reaction between tetronic acid derivative and thioimidate to prepare the RE derivatives 6a-6i efficiently. These compounds all showed VHR-inhibitory activity in the presence of 0.001% NP-40, whereas RE12 (5) was inactive under this condition, even at 100 μM. Further structure-activity studies focused on terminal substitution afforded trifluoromethyl derivative 6k (RE176) and nitro derivative 6l (RE177). The IC50 value of 6l in the presence of NP-40 was almost equivalent to that of RE12 (5) in its absence. Compound 6k (RE176) potently inhibited proliferation of HeLa cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

Economic principles for resource allocation decisions at national level to mitigate the effects of disease in farm animal populations.

PubMed

Howe, K S; Häsler, B; Stärk, K D C

2013-01-01

This paper originated in a project to develop a practical, generic tool for the economic evaluation of surveillance for farm animal diseases at national level by a state veterinary service. Fundamental to that process is integration of epidemiological and economic perspectives. Using a generalized example of epidemic disease, we show that an epidemic curve maps into its economic equivalent, a disease mitigation function, that traces the relationship between value losses avoided and mitigation resources expended. Crucially, elementary economic principles show that mitigation, defined as loss reduction achieved by surveillance and intervention, must be explicitly conceptualized as a three-variable process, and the relative contributions of surveillance and intervention resources investigated with regard to the substitution possibilities between them. Modelling the resultant mitigation surfaces for different diseases should become a standard approach to animal health policy analysis for economic efficiency, a contribution to the evolving agenda for animal health economics research.

Te(II)/Te(IV) Mediated C-N Bond Formation on 2,5-Diphenyltellurophene and a Reassignment of the Product from the Reaction of PhI(OAc)2 with 2 TMS-OTf.

PubMed

Aprile, Antonino; Iversen, Kalon J; Wilson, David J D; Dutton, Jason L

2015-05-18

We report a novel C-H to C-N bond metathesis at the 3-position of 1,2-diphenyltellurophene via oxidation of the Te(II) center to Te(IV) using the I(III) oxidant [PhI(4-DMAP)2](2+). Spontaneous reduction of a transient Te(IV) coordination compound to Te(II) generates an electrophilic equivalent of 4-DMAP that substitutes at a C-H bond at the 3-position of the tellurophene. Theoretical and synthetic reaction pathway studies confirm that a Te(IV) coordination complex with 4-DMAP is an intermediate. In the course of these pathway studies, it was also found that the identity of the I(III) oxidant generated from PhI(OAc)2 and 2 TMS-OTf is PhI(OAc)(OTf) and not PhI(OTf)2, as had been previously thought.

Numerical solution to generalized Burgers'-Fisher equation using Exp-function method hybridized with heuristic computation.

PubMed

Malik, Suheel Abdullah; Qureshi, Ijaz Mansoor; Amir, Muhammad; Malik, Aqdas Naveed; Haq, Ihsanul

2015-01-01

In this paper, a new heuristic scheme for the approximate solution of the generalized Burgers'-Fisher equation is proposed. The scheme is based on the hybridization of Exp-function method with nature inspired algorithm. The given nonlinear partial differential equation (NPDE) through substitution is converted into a nonlinear ordinary differential equation (NODE). The travelling wave solution is approximated by the Exp-function method with unknown parameters. The unknown parameters are estimated by transforming the NODE into an equivalent global error minimization problem by using a fitness function. The popular genetic algorithm (GA) is used to solve the minimization problem, and to achieve the unknown parameters. The proposed scheme is successfully implemented to solve the generalized Burgers'-Fisher equation. The comparison of numerical results with the exact solutions, and the solutions obtained using some traditional methods, including adomian decomposition method (ADM), homotopy perturbation method (HPM), and optimal homotopy asymptotic method (OHAM), show that the suggested scheme is fairly accurate and viable for solving such problems.

Numerical Solution to Generalized Burgers'-Fisher Equation Using Exp-Function Method Hybridized with Heuristic Computation

PubMed Central

Malik, Suheel Abdullah; Qureshi, Ijaz Mansoor; Amir, Muhammad; Malik, Aqdas Naveed; Haq, Ihsanul

2015-01-01

In this paper, a new heuristic scheme for the approximate solution of the generalized Burgers'-Fisher equation is proposed. The scheme is based on the hybridization of Exp-function method with nature inspired algorithm. The given nonlinear partial differential equation (NPDE) through substitution is converted into a nonlinear ordinary differential equation (NODE). The travelling wave solution is approximated by the Exp-function method with unknown parameters. The unknown parameters are estimated by transforming the NODE into an equivalent global error minimization problem by using a fitness function. The popular genetic algorithm (GA) is used to solve the minimization problem, and to achieve the unknown parameters. The proposed scheme is successfully implemented to solve the generalized Burgers'-Fisher equation. The comparison of numerical results with the exact solutions, and the solutions obtained using some traditional methods, including adomian decomposition method (ADM), homotopy perturbation method (HPM), and optimal homotopy asymptotic method (OHAM), show that the suggested scheme is fairly accurate and viable for solving such problems. PMID:25811858

A computer program for borehole compensation of dual-detector density well logs

USGS Publications Warehouse

Scott, James Henry

1978-01-01

The computer program described in this report was developed for applying a borehole-rugosity and mudcake compensation algorithm to dual-density logs using the following information: the water level in the drill hole, hole diameter (from a caliper log if available, or the nominal drill diameter if not), and the two gamma-ray count rate logs from the near and far detectors of the density probe. The equations that represent the compensation algorithm and the calibration of the two detectors (for converting countrate or density) were derived specifically for a probe manufactured by Comprobe Inc. (5.4 cm O.D. dual-density-caliper); they are not applicable to other probes. However, equivalent calibration and compensation equations can be empirically determined for any other similar two-detector density probes and substituted in the computer program listed in this report. * Use of brand names in this report does not necessarily constitute endorsement by the U.S. Geological Survey.

Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas

PubMed Central

Palles, Claire; Cazier, Jean-Baptiste; Howarth, Kimberley M; Domingo, Enric; Jones, Angela M.; Broderick, Peter; Kemp, Zoe; Spain, Sarah L; Almeida, Estrella Guarino; Salguero, Israel; Sherborne, Amy; Chubb, Daniel; Carvajal-Carmona, Luis G; Ma, Yusanne; Kaur, Kulvinder; Dobbins, Sara; Barclay, Ella; Gorman, Maggie; Martin, Lynn; Kovac, Michal B; Humphray, Sean; Lucassen, Anneke; Holmes, Christopher; Bentley, David; Donnelly, Peter; Taylor, Jenny; Petridis, Christos; Roylance, Rebecca; Sawyer, Elinor J; Kerr, David J.; Clark, Susan; Grimes, Jonathan; Kearsey, Stephen E; Thomas, Huw JW; McVean, Gilean; Houlston, Richard S; Tomlinson, Ian

2013-01-01

Many individuals with multiple or large colorectal adenomas, or early-onset colorectal cancer (CRC), have no detectable germline mutations in the known cancer predisposition genes. Using whole-genome sequencing, supplemented by linkage and association analysis, we identified specific heterozygous POLE or POLD1 germline variants in several multiple adenoma and/or CRC cases, but in no controls. The susceptibility variants appear to have high penetrance. POLD1 is also associated with endometrial cancer predisposition. The mutations map to equivalent sites in the proof-reading (exonuclease) domain of DNA polymerases ε and δ, and are predicted to impair correction of mispaired bases inserted during DNA replication. In agreement with this prediction, mutation carriers’ tumours were microsatellite-stable, but tended to acquire base substitution mutations, as confirmed by yeast functional assays. Further analysis of published data showed that the recently-described group of hypermutant, microsatellite-stable CRCs is likely to be caused by somatic POLE exonuclease domain mutations. PMID:23263490

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

Muresan, Ioana Cristina; Balc, Roxana

Beam-to-column end-plate bolted connections are usually used as moment-resistant connections in steel framed structures. For this joint type, the deformability is governed by the deformation capacity of the column flange and end-plate under tension and elongation of the bolts. All these elements around the beam tension flange form the tension region of the joint, which can be modeled by means of equivalent T-stubs. In this paper a beam-to-column end-plate bolted connection is substituted with a T-stub of appropriate effective length and it is analyzed using the commercially available finite element software ABAQUS. The performance of the model is validated bymore » comparing the behavior of the T-stub from the numerical simulation with the behavior of the connection as a whole. The moment-rotation curve of the T-stub obtained from the numerical simulation is compared with the behavior of the whole extended end-plate connection, obtained by numerical simulation, experimental tests and analytical approach.« less

Dibenzo-p-dioxins in the environment from ceramics and pottery produced from ball clay mined in the United States

NASA Technical Reports Server (NTRS)

Ferrario, Joseph; Byrne, Christian

2002-01-01

Processed ball clay samples used in the production of ceramics and samples of the ceramic products were collected and analyzed for the presence and concentration of the 2,3,7,8-Cl substituted polychlorinated dibenzo-p-dioxins and -furans (PCDDs/PCDFs). The processed ball clay had average PCDD concentrations of 3.2 ng/g toxic equivalents, a congener profile, and isomer distribution consistent with those found previously in raw ball clay. The PCDF concentrations were below the average limit of detection (LOD) of 0.5 pg/g. The final fired ceramic products were found to be free of PCDDs/PCDFs at the LODs. A consideration of the conditions involved in the firing process suggests that the PCDDs, if not destroyed, may be released to the atmosphere and could represent an as yet unidentified source of dioxins to the environment. In addition, the PCDDs in clay dust generated during manufacturing operations may represent a potential occupational exposure.

Flexible planar microfluidic chip employing a light emitting diode and a PIN-photodiode for portable flow cytometers.

PubMed

Kettlitz, Siegfried W; Valouch, Sebastian; Sittel, Wiebke; Lemmer, Uli

2012-01-07

Detection of fluorescence particles is a key method of flow cytometry. We evaluate the performance of a design for a microfluidic fluorescence particle detection device. Due to the planar design with low layer thicknesses, we avoid optical components such as lenses or dichroic mirrors and substitute them with a shadow mask and colored film filters. A commercially available LED is used as the light source and a PIN-photodiode as detector. This design approach reduces component cost and power consumption and enables supplying the device with power from a standard USB port. From evaluation of this design, we obtain a maximum particle detection frequency of up to 600 particles per second at a sensitivity of better than 4.7 × 10(5) MESF (molecules of equivalent soluble fluorochrome) measured with particles for FITC sensitivity calibration. Lowering the flow rate increases the instrument sensitivity by an order of magnitude enabling the detection of particles with 4.5 × 10(4) MESF.

In-Plane Multimagnetron Approach

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

Johnson, Grant E.; Laskin, Julia

2017-04-01

Nanoparticles (NPs) and sub-nanometer clusters containing controlled amounts of different atoms are of interest for a variety of potential applications including catalysis,1, 2 optics,3, 4 magnetics,5-7 sensors,8, 9 and biotheraputics.10, 11 Alloy NPs may possess enhanced physical and chemical properties compared to single metal species due to the additional interplay between their different elemental components. By reducing the quantity of expensive precious metals in alloy NPs by substituting cheaper base metals, it may also be possible to achieve equivalent or even superior performance to pure noble metal NPs for applications such as heterogeneous catalysis at substantially reduced material costs.12 Inmore » addition, alloying of elements that are immiscible in bulk form is possible in NPs because the enthalpy of mixing decreases and becomes negative at small particle sizes.13, 14 As a result, a substantially broader array of alloy species may be generated in the form of NPs and sub-nanometer clusters.« less

Dual Functionalization of White Phosphorus: Formation, Characterization, and Reactivity of Rare-Earth-Metal Cyclo-P3 Complexes.

PubMed

Du, Shanshan; Yin, Jianhao; Chi, Yue; Xu, Ling; Zhang, Wen-Xiong

2017-12-11

The [3+1] fragmentation reaction of rare-earth metallacyclopentadienes 1 a-c with 0.5 equivalents of P 4 affords a series of rare-earth metal cyclo-P 3 complexes 2 a-c and a phospholyl anion 3. 2 a-c demonstrate an unusual η 3 coordination mode with one P-P bond featuring partial π-bonding character. 2 a-c are the first cyclo-P 3 complexes of rare-earth metals, and also the first organo-substituted polyphosphides in the category of Group 3 and f-block elements. Rare-earth metallacyclopentadienes play a dual role in the combination of aromatization and Diels-Alder reaction. Compounds 2 a-c can coordinate to one or two [W(CO) 5 ] units, yielding 4 a-c or 5 c, respectively. Furthermore, oxidation of 2 a with p-benzoquinone produces its corresponding phospholyllithium and regenerated P 4 . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Comparison of Carbon Footprint and Production Cost of Different Pasta Products Based on Whole Egg and Pea Flour

PubMed Central

Nette, Antonia; Wolf, Patricia; Schlüter, Oliver; Meyer-Aurich, Andreas

2016-01-01

Feed and food production are inter alia reasons for high greenhouse gas emissions. Greenhouse gas emissions could be reduced by the replacement of animal components with plant components in processed food products, such as pasta. The main components currently used for pasta are semolina, and water, as well as additional egg. The hypothesis of this paper is that the substitution of whole egg with plant-based ingredients, for example from peas, in such a product might lead to reduced greenhouse gas emissions (GHG) and thus a reduced carbon footprint at economically reasonable costs. The costs and carbon footprints of two pasta types, produced with egg or pea protein, are calculated. Plant protein–based pasta products proved to cause 0.57 kg CO2 equivalents (CO2eq) (31%) per kg pasta less greenhouse gas emissions than animal-based pasta, while the cost of production increases by 10% to 3.00 €/kg pasta. PMID:28231112

Hybrid bioinorganic approach to solar-to-chemical conversion.

PubMed

Nichols, Eva M; Gallagher, Joseph J; Liu, Chong; Su, Yude; Resasco, Joaquin; Yu, Yi; Sun, Yujie; Yang, Peidong; Chang, Michelle C Y; Chang, Christopher J

2015-09-15

Natural photosynthesis harnesses solar energy to convert CO2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by living cells as a source of reducing equivalents for conversion of CO2 to the value-added chemical product methane. Using platinum or an earth-abundant substitute, α-NiS, as biocompatible hydrogen evolution reaction (HER) electrocatalysts and Methanosarcina barkeri as a biocatalyst for CO2 fixation, we demonstrate robust and efficient electrochemical CO2 to CH4 conversion at up to 86% overall Faradaic efficiency for ≥ 7 d. Introduction of indium phosphide photocathodes and titanium dioxide photoanodes affords a fully solar-driven system for methane generation from water and CO2, establishing that compatible inorganic and biological components can synergistically couple light-harvesting and catalytic functions for solar-to-chemical conversion.

Dibenzo-p-dioxins in the environment from ceramics and pottery produced from ball clay mined in the United States.

PubMed

Ferrario, Joseph; Byrne, Christian

2002-03-01

Processed ball clay samples used in the production of ceramics and samples of the ceramic products were collected and analyzed for the presence and concentration of the 2,3,7,8-Cl substituted polychlorinated dibenzo-p-dioxins and -furans (PCDDs/PCDFs). The processed ball clay had average PCDD concentrations of 3.2 ng/g toxic equivalents, a congener profile, and isomer distribution consistent with those found previously in raw ball clay. The PCDF concentrations were below the average limit of detection (LOD) of 0.5 pg/g. The final fired ceramic products were found to be free of PCDDs/PCDFs at the LODs. A consideration of the conditions involved in the firing process suggests that the PCDDs, if not destroyed, may be released to the atmosphere and could represent an as yet unidentified source of dioxins to the environment. In addition, the PCDDs in clay dust generated during manufacturing operations may represent a potential occupational exposure.

Positive effects of vegetation: urban heat island and green roofs.

PubMed

Susca, T; Gaffin, S R; Dell'osso, G R

2011-01-01

This paper attempts to evaluate the positive effects of vegetation with a multi-scale approach: an urban and a building scale. Monitoring the urban heat island in four areas of New York City, we have found an average of 2 °C difference of temperatures between the most and the least vegetated areas, ascribable to the substitution of vegetation with man-made building materials. At micro-scale, we have assessed the effect of surface albedo on climate through the use of a climatological model. Then, using the CO(2) equivalents as indicators of the impact on climate, we have compared the surface albedo, and the construction, replacement and use phase of a black, a white and a green roof. By our analyses, we found that both the white and the green roofs are less impactive than the black one; with the thermal resistance, the biological activity of plants and the surface albedo playing a crucial role. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hexaphyrin as a Potential Theranostic Dye for Photothermal Therapy and 19 F Magnetic Resonance Imaging.

PubMed

Higashino, Tomohiro; Nakatsuji, Hirotaka; Fukuda, Ryosuke; Okamoto, Haruki; Imai, Hirohiko; Matsuda, Tetsuya; Tochio, Hidehito; Shirakawa, Masahiro; Tkachenko, Nikolai V; Hashida, Mitsuru; Murakami, Tatsuya; Imahori, Hiroshi

2017-05-18

Two features of meso-Aryl-substituted expanded porphyrins suggest suitability as theranostic agents. They have excellent absorption in near infrared (NIR) region, and they offer the possibility of introduction of multiple fluorine atoms at structurally equivalent positions. Here, hexaphyrin (hexa) was synthesized from 2,6-bis(trifluoromethyl)-4-formyl benzoate and pyrrole and evaluated as a novel expanded porphyrin with the above features. Under NIR illumination hexa showed intense photothermal and weak photodynamic effects, which were most likely due to its low excited states, close to singlet oxygen. The sustained photothermal effect caused ablation of cancer cells more effectively than the photodynamic effect of indocyanine green (a clinical dye). In addition, hexa showed potential for use in the visualization of tumors by 19 F magnetic resonance imaging (MRI), because of the multiple fluorine atoms. Our results strongly support the utility of expanded porphyrins as theranostic agents in both photothermal therapy and 19 F MRI. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reexamining the Phosphorus-Protein Dilemma: Does Phosphorus Restriction Compromise Protein Status?

PubMed

St-Jules, David E; Woolf, Kathleen; Pompeii, Mary Lou; Kalantar-Zadeh, Kamyar; Sevick, Mary Ann

2016-05-01

Dietary phosphorus restriction is recommended to help control hyperphosphatemia in hemodialysis patients, but many high-phosphorus foods are important sources of protein. In this review, we examine whether restricting dietary phosphorus compromises protein status in hemodialysis patients. Although dietary phosphorus and protein are highly correlated, phosphorus intakes can range up to 600 mg/day for a given energy and protein intake level. Furthermore, the collinearity of phosphorus and protein may be biased because the phosphorus burden of food depends on: (1) the presence of phosphate additives, (2) food preparation method, and (3) bioavailability of phosphorus, which are often unaccounted for in nutrition assessments. Ultimately, we argue that clinically relevant reductions in phosphorus intake can be made without limiting protein intake by avoiding phosphate additives in processed foods, using wet cooking methods such as boiling, and if needed, substituting high-phosphorus foods for nutritionally equivalent foods that are lower in bioavailable phosphorus. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Outcome of a ceftriaxone/cefotaxime interchange programme in a major teaching hospital.

PubMed

Gutensohn, A; Bunz, D; Frighetto, L; Jewesson, P

1991-01-01

A two-stage intervention programme was performed to enable the effective substitution of ceftriaxone for cefotaxime in a teaching hospital with large numbers of transient prescribers. One hundred and sixteen patients with a variety of bacterial infections were randomized to an open, historical control comparative study to determine if ceftriaxone was an acceptable replacement for cefotaxime. For 6 months prior to the intervention, both cephalosporins were available on formulary. Following an initial informational stage, a therapeutic interchange programme was implemented to convert prescriptions for cefotaxime to ceftriaxone. Ceftriaxone and cefotaxime were equivalent in terms of microbiological and clinical efficacy and patient tolerance in 77 evaluable patients. No changes in prescriber service occurred after the changeover. Post-intervention treatment courses required a ceftriaxone/cefotaxime interchange in 28% of the cases. Ceftriaxone appeared to be a suitable and cost-effective alternative to cefotaxime in this hospital. The intervention programme successfully invoked the formulary change with minimal expense and prescriber opposition.

GC-MS and GC-IR Analyses of the Methoxy-1-n-pentyl-3-(1-naphthoyl)-indoles: Regioisomeric Designer Cannabinoids.

PubMed

Thaxton-Weissenfluh, Amber; Belal, Tarek S; DeRuiter, Jack; Smith, Forrest; Abiedalla, Younis; Neel, Logan; Abdel-Hay, Karim M; Clark, C Randall

2018-06-16

The indole ring regioisomeric methoxy-1-n-pentyl-3-(1-naphthoyl)-indoles represent indole ring-substituted analogs of the synthetic cannabinoid JWH-018. The electron ionization mass spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. The characteristic (M-17)+ fragment ion at m/z 354 resulting from the loss of OH group is significant in the mass spectra of all four compounds. Fragmentation of the naphthoyl and/or pentyl groups yields the cations at m/z 314, 300, 244 and 216. The vapor-phase infrared spectra provide a number of characteristic absorption bands to identify the individual isomers. Gas chromatographic separations on a capillary column containing a film of trifluoropropylmethyl polysiloxane (Rtx-200) provided excellent resolution of these compounds, their precursor indoles and intermediate pentylindoles. The elution order appears related to the degree of crowding of indole ring substituents.

Final report, PT IP-535-C: Test of smaller VSR`s in DR reactor

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

Vaughn, A.D.

1963-04-17

Because of rod-sticking problems at DR Reactor, a knuckle rod of B Reactor design was installed in vertical safety channel number 28. The substitute VSR, which has a smaller diameter than the original DR rod, has been tested for its operational feasibility including both drop time and reactivity effect. The reactivity effect of the rod was estimated by comparison of the reactivity transient caused by insertion of the specific B-type rod after scramming into the pile, with similar transients caused by normal vertical safety rod in an adjacent channel. This document lists the indicated relative control strength of the rodmore » as an empirical basis for future safety calculations. Results indicate that the B-type knuckel rod in DR reactor is about 80% as strong as a normal DR vertical safety rod if used in equivalent flux distribution and location; this makes it reasonable to assume that the local control strength of the B-type knuckel rod is 98 {mu}b.« less

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

Fente, Antón; Correa-Orellana, Alexandre; Böhmer, Anna E.

We show that biaxial strain induces alternating tetragonal superconducting and orthorhombic nematic domains in Co substituted CaFe 2As 2. We use Atomic Force, Magnetic Force and Scanning Tunneling Microscopy (AFM, MFM and STM) to identify the domains and characterize their properties, nding in particular that tetragonal superconducting domains are very elongated, more than several tens of μm long and about 30 nm wide, have the same Tc than unstrained samples and hold vortices in a magnetic eld. Thus, biaxial strain produces a phase separated state, where each phase is equivalent to what is found at either side of the rstmore » order phase transition between antiferromagnetic orthorhombic and superconducting tetragonal phases found in unstrained samples when changing Co concentration. Having such alternating superconducting domains separated by normal conducting domains with sizes of order of the coherence length opens opportunities to build Josephson junction networks or vortex pinning arrays and suggests that first order quantum phase transitions lead to nanometric size phase separation under the influence of strain.« less

EOL-1, the Homolog of the Mammalian Dom3Z, Regulates Olfactory Learning in C. elegans

PubMed Central

Shen, Yu; Zhang, Jiangwen; Calarco, John A.

2014-01-01

Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity. PMID:25274815

A Comparison of Carbon Footprint and Production Cost of Different Pasta Products Based on Whole Egg and Pea Flour.

PubMed

Nette, Antonia; Wolf, Patricia; Schlüter, Oliver; Meyer-Aurich, Andreas

2016-03-04

Feed and food production are inter alia reasons for high greenhouse gas emissions. Greenhouse gas emissions could be reduced by the replacement of animal components with plant components in processed food products, such as pasta. The main components currently used for pasta are semolina, and water, as well as additional egg. The hypothesis of this paper is that the substitution of whole egg with plant-based ingredients, for example from peas, in such a product might lead to reduced greenhouse gas emissions (GHG) and thus a reduced carbon footprint at economically reasonable costs. The costs and carbon footprints of two pasta types, produced with egg or pea protein, are calculated. Plant protein-based pasta products proved to cause 0.57 kg CO₂ equivalents (CO₂eq) (31%) per kg pasta less greenhouse gas emissions than animal-based pasta, while the cost of production increases by 10% to 3.00 €/kg pasta.

Hybrid bioinorganic approach to solar-to-chemical conversion

PubMed Central

Nichols, Eva M.; Gallagher, Joseph J.; Liu, Chong; Su, Yude; Resasco, Joaquin; Yu, Yi; Sun, Yujie; Yang, Peidong; Chang, Michelle C. Y.; Chang, Christopher J.

2015-01-01

Natural photosynthesis harnesses solar energy to convert CO2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by living cells as a source of reducing equivalents for conversion of CO2 to the value-added chemical product methane. Using platinum or an earth-abundant substitute, α-NiS, as biocompatible hydrogen evolution reaction (HER) electrocatalysts and Methanosarcina barkeri as a biocatalyst for CO2 fixation, we demonstrate robust and efficient electrochemical CO2 to CH4 conversion at up to 86% overall Faradaic efficiency for ≥7 d. Introduction of indium phosphide photocathodes and titanium dioxide photoanodes affords a fully solar-driven system for methane generation from water and CO2, establishing that compatible inorganic and biological components can synergistically couple light-harvesting and catalytic functions for solar-to-chemical conversion. PMID:26305947

Numerical Study on Section Constitutive Relations of Members Reinforced by Steel-BFRP Composite Bars

NASA Astrophysics Data System (ADS)

Xiao, Tongliang; Qiu, Hongxing

2017-06-01

Steel-Basalt FRP Composite Bar (S-BFCB) is a new kind of substitute material for longitudinal reinforcement, with high elastic modulus, stable post-yield stiffness and excellent corrosive resistance. Based on mechanical properties of S-BFCB and the plane cross-section assumption, the moment-curvature curves of beam and column members are simulated. Some parameters such as equivalent rebar ratio, postyeild stiffness, concrete strength and axial compression ratio of column were discussed. Results show that the constitutive relation of the cross section is similar with RC member in elastic and cracking stages, while different in post-yield stage. With the increase of postyeild stiffness ratio of composite bar, the ultimate bearing capacity of component improved observably, member may turn out over-reinforced phenomenon, concrete crushing may appear before the fibersarefractured. The effect of concrete strength increase in lower postyeild stiffness ratio is not obvious than in higher. The increase of axial compression ratio has actively influence on bearing capacity of column, but decreases on the ductility.

Selenomethionine as a Safer Substitute for Barium Selenate in Long-Acting Injectable Se Supplements for Food-Producing Animals.

PubMed

Knowles, Scott O; Grace, Neville D

2017-09-20

Nutritional supplementation with selenium (Se) can prevent Se deficiency in food-producing animals. Injection with slow-release formulations is a preferred method for free-range grazing sheep and cattle, and barium selenate (BaSeO 4 ) provides optimal efficacy. This chemical can become a health risk to humans if the concentrated depot of an injection site is consumed, and consequently such use is recently banned in the EU. A possible replacement is selenomethionine (SeMet), a naturally occurring form of Se supplementation hitherto only administered orally. In four animal studies we found that injection with SeMet maintained nutritionally adequate concentrations of Se in blood and tissues of lambs for at least 191 days and in blood and milk of dairy cows for at least 95 days. Stereoisomer forms L- and DL-SeMet were functionally equivalent. This is the first demonstration that injectable SeMet can deliver efficacy similar to BaSeO 4 but with less risk of undesirable residues in edible tissues.

Maleate/vinyl ether UV-cured coatings: Effects of composition on curing and properties

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

Noren, G.K.

1996-10-01

The effect of the composition of the maleate polyester and the vinyl ether terminated compound on their UV-curing and properties has been investigated. Linear unsaturated polyester resins based on maleic anhydride and 1,5-pentane diol were synthesized. The molecular weight of the unsaturated polyesters was varied by changing the ratio of maleic anhydride to 1,5-pentane diol and the double bond equivalent weight was varied by replacing maleic anhydride with succinic anhydride. Coating formulations containing these unsaturated polyesters, triethylene glycol divinyl ether and a free radical photoinitiator were crosslinked in the presence of UV light. The coatings were very brittle, exhibiting tensilemore » strengths in the range of 1.5-4.0 MPa and elongations of only 3-7%. Diethyl maleate and isobutyl vinyl ether were effective diluents for reducing viscosity but reduced the cure speed. A vinyl ether urethane oligomer was synthesized and enhanced the flexibility and toughness of the coatings when substituted for triethylene glycol divinyl ether.« less

Evaluation of a human bio-engineered skin equivalent for drug permeation studies.

PubMed

Asbill, C; Kim, N; El-Kattan, A; Creek, K; Wertz, P; Michniak, B

2000-09-01

To test the barrier function of a bio-engineered human skin (BHS) using three model drugs (caffeine, hydrocortisone, and tamoxifen) in vitro. To investigate the lipid composition and microscopic structure of the BHS. The human skin substitute was composed of both epidermal and dermal layers, the latter having a bovine collagen matrix. The permeability of the BHS to three model drugs was compared to that obtained in other percutaneous testing models (human cadaver skin, hairless mouse skin, and EpiDerm). Lipid analysis of the BHS was performed by high performance thin layered chromatography. Histological evaluation of the BHS was performed using routine H&E staining. The BHS mimicked human skin in terms of lipid composition, gross ultrastructure, and the formation of a stratum corneum. However, the permeability of the BHS to caffeine, hydrocortisone, and tamoxifen was 3-4 fold higher than that of human cadaver skin. In summary, the results indicate that the BHS may be an acceptable in vitro model for drug permeability testing.

Chords and harmonies in mixed optical and acoustical stimuli

NASA Astrophysics Data System (ADS)

Hahlweg, Cornelius; Dannenberg, Florian; Dörfler, Joachim; Weber, Bernhard; Weyer, Cornelia; Gercke-Hahn, Harald; Freimuth, Steffen; Heucke, Sören; Gutzmann, Holger Ludwig

2014-09-01

The paper is a follow up of the work presented in last year's Optics and Music session on the perception of coherence between low frequency power modulated light and periodical acoustic stimuli. The composition of chords and harmonies from power modulated light sources and their effect as stand-alone stimulus and in conjunction with the equivalent acoustic signal is discussed. Of special interest here is the modulation near perceptible flicker frequency. The substitution of acoustical chord components by their optical counterpart and vice versa is investigated. Further, concepts of a training application for trombone players and other instrumentalists are presented: since the mean slide of the trombone does not have fixed positions, the note must be found and two players might influence each other. The possibility of helping them to synchronize by optical stimuli derived from their playing is investigated. Beside possible applications in emotional reinforcing multimedia oriented entertainment and training support for musicians, again implications for occupational medicine are discussed.

Recent Research Trends on the Enzymatic Synthesis of Structured Lipids.

PubMed

Kim, Byung Hee; Akoh, Casimir C

2015-08-01

Structured lipids (SLs) are lipids that have been chemically or enzymatically modified from their natural biosynthetic form. Because SLs are made to possess desired nutritional, physicochemical, or textural properties for various applications in the food industry, many research activities have been aimed at their commercialization. The production of SLs by enzymatic procedures has a great potential in the future market because of the specificity of lipases and phospholipases used as the biocatalysts. The aim of this review is to provide concise information on the recent research trends on the enzymatic synthesis of SLs of commercial interest, such as medium- and long-chain triacylglycerols, human milk fat substitutes, cocoa butter equivalents, trans-free or low-trans plastic fats (such as margarines and shortenings), low-calorie fats/oils, health-beneficial fatty acid-rich fats/oils, mono- or diacylglycerols, and structurally modified phospholipids. This limited review covers 108 research articles published between 2010 and 2014 which were searched in Web of Science. © 2015 Institute of Food Technologists®

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

Resource and activity substitutes for recreational salmon fishing in New Zealand

Treesearch

Bo Shelby

1985-01-01

Substitutes become an issue when people are constrained from participating in desired activities. This study investigates and compares activity and resource substitutes for recreational salmon fishing in New Zealand. Results suggest that resource substitution and inventories need more attention, user perceptions of substitutes are important, substitutes can be...

40 CFR 721.10078 - Butanamide, 2-[(2-methoxy-4-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted...-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted...]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted]phenyl...

Influence of mandatory generic substitution on pharmaceutical sales patterns: a national study over five years.

PubMed

Andersson, Karolina A; Petzold, Max G; Allebeck, Peter; Carlsten, Anders

2008-02-29

Mandatory generic substitution was introduced in Sweden in October 2002 in order to try to curb escalating pharmaceutical expenditure. The aim of this study was to investigate how sales patterns for substitutable and non-substitutable pharmaceuticals have developed since the introduction of mandatory generic substitution; furthermore, to compare sales patterns in different groups of the population, based on patients' age and gender. Five therapeutic groups comprising both substitutable and non-substitutable pharmaceuticals were included. The study period was from January 2000 to June 2005. National sales data were used, covering volumes of dispensed prescription medicines (expressed in defined daily doses per 1000 inhabitants and day) of each pharmacological substance in the therapeutic groups for each age and gender group. Sales patterns for substitutable and non-substitutable pharmaceuticals were compared using a descriptive approach. In most therapeutic groups there has been an increase in the volumes of substitutable pharmaceuticals sold since the introduction of the reform, ranging from one third to three times the initial volume; whereas the volumes of non-substitutable pharmaceuticals have levelled out or declined. There were few gender differences in sales patterns of substitutable and non-substitutable drugs. In three therapeutic groups, sales patterns differed across different age groups, and there was a tendency for volumes of recently introduced non-substitutable pharmaceuticals to be proportionally higher in the youngest age groups. Since the introduction of the reform, there has been a proportionally larger increase in sales of substitutable pharmaceuticals compared with sales of non-substitutable pharmaceuticals. This indicates that the reform might have contributed to larger sales of less expensive pharmaceuticals.

Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

PubMed

Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

2004-01-01

A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels.

PubMed

Shang, Lijun; Tucker, Stephen J

2008-02-01

Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K(+) channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the "helix-bundle crossing". However, in the inwardly rectifying (Kir) potassium channel family, the role of this "hinge" residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper "hinge" residues are in close contact with the base of the pore alpha-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the "lower" gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue.

Intramolecular chalcogen-tin interactions in [(o-MeE-C6H4)CH2]2SnPh2-nCln; E = S, O, CH2, n = 0, 1, 2 and intermolecular chlorine-tin interactions in the meta and para-methoxy isomers

PubMed Central

Vargas-Pineda, Diana Gabriela; Guardado, Tanya; Cervantes-Lee, Francisco; Metta-Magana, Alejandro J.

2010-01-01

Organotin(IV) compounds of the type [(o-MeE-C6H4)CH2]2SnPh2-nCln were synthesized, E = O, n = 0 (1), n = 1 (2), n = 2 (3), E = S, n = 0 (4), n = 1 (5), n = 2 (6) and E = CH2, n = 0 (7), n = 1 (8), n = 2 (9). The dichloro compounds 3 and 6 have been investigated by single crystal X-ray diffraction and exhibit bi-capped tetrahedral geometry at the tin atom as a consequence of significant intramolecular Sn⋯O (3) and Sn⋯S (6) secondary bonding, in monomolecular units. Compound 3 when crystallized from a hexane/thf solvent mixture shows two different conformers, 3′ and 3″, in the crystal structure, 3′ has two equivalent Sn⋯O interactions, while 3″ has two non-equivalent Sn⋯O interactions. Upon recrystallization of 3 from hexane only a single structural form is observed, 3′. The Sn⋯E distances in 3′, 3″, and 6 are 71.3; 73.5, 72.9; and 76.3% of the ΣvdW radii, respectively. The meta and para-substituted isomers of 3 (10, 11) exhibit a distortion at the tin atom due to self-association via intermolecular Sn⋯Cl interactions resulting in polymeric structures. 119Sn NMR spectroscopy suggests that the intramolecular Sn⋯E interactions persist in solution for the dichloride compounds 3 and 6. PMID:20047301

Autorefraction, Retinoscopy, Javal's Rule, and Grosvenor's Modified Javal's Rule: The Best Predictor of Refractive Astigmatism

PubMed Central

Asiedu, Kofi; Ampiah, Emmanuel Ekow

2016-01-01

The aim of the study was to determine the level of agreement between Javal's rule, autorefraction, retinoscopy, and refractive astigmatism and to determine which technique is the most suitable substitute when subjective refraction is not applicable using a clinical sample. A total of 36 subjects, 14 males and 22 females, were involved in this study. The intraclass correlation coefficients between subjective refraction, autorefraction, and retinoscopy were 0.895 and 0.989, respectively, for the spherical equivalent. The Bland-Altman 95% limits of agreement between subjective refraction and autorefraction; subjective refraction and retinoscopy; and autorefraction and retinoscopy were −2.84 to 3.58, −0.88 to 1.12, and −3.01 to 3.53, respectively, for the spherical equivalent. The intraclass correlation coefficients between spectacle total astigmatism and the following techniques were as follows: retinoscopy (0.85); autorefraction (0.92); Javal's rule (0.82); and Grosvenor et al. version (0.85). The Bland-Altman 95% limits of agreement between subjective refraction and autorefraction; subjective refraction and retinoscopy; subjective refraction and Javal's rule; and subjective refraction and Grosvenor et al. version were −0.87 to 1.25, −1.49 to 1.99, −0.73 to 1.93, and −0.89 to 1.7, respectively, for the total astigmatism. The study showed that autorefraction and Javal's rule may provide a starting point for subjective refraction cylinder power determination but only retinoscopy may satisfactorily replace subjective refraction total astigmatism when subjective refraction is not applicable. PMID:27803811

Trial Frame Refraction versus Autorefraction among New Patients in a Low-Vision Clinic

PubMed Central

DeCarlo, Dawn K.; McGwin, Gerald; Searcey, Karen; Gao, Liyan; Snow, Marsha; Waterbor, John; Owsley, Cynthia

2013-01-01

Purpose. To determine the relationship between refractive error as measured by autorefraction and that measured by trial frame refraction among a sample of adults with vision impairment seen in a university-based low-vision clinic and to determine if autorefraction might be a suitable replacement for trial frame refraction. Methods. A retrospective chart review of all new patients 19 years or older seen over an 18-month period was conducted and the following data collected: age, sex, primary ocular diagnosis, entering distance visual acuity, habitual correction, trial frame refraction, autorefraction, and distance visual acuity measured after trial frame refraction. Trial frame refraction and autorefraction were compared using paired t-tests, intraclass correlations, and Bland-Altman plots. Results. Final analyses included 440 patients for whom both trial frame refraction and autorefraction data were available for the better eye. Participants were mostly female (59%) with a mean age of 68 years (SD = 20). Age-related macular degeneration was the most common etiology for vision impairment (44%). Values for autorefraction and trial frame refraction were statistically different, but highly correlated for the spherical equivalent power (r = 0.92), the cylinder power (r = 0.80) and overall blurring strength (0.89). Although the values of the cross-cylinders J0 and J45 were similar, they were poorly correlated (0.08 and 0.15, respectively). The range of differences in spherical equivalent power was large (−8.6 to 4.9). Conclusions. Autorefraction is highly correlated with trial frame refraction. Differences are sometimes substantial, making autorefraction an unsuitable substitute for trial frame refraction. PMID:23188726

Effect of Diets Containing Sucrose vs. D-tagatose in Hypercholesterolemic Mice

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

Police, S.; Harris, J; Lodder, R

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr-/-) mice. LDLr-/- male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measuredmore » food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.« less

Can Propensity Score Analysis Approximate Randomized Experiments Using Pretest and Demographic Information in Pre-K Intervention Research?

PubMed

Dong, Nianbo; Lipsey, Mark W

2017-01-01

It is unclear whether propensity score analysis (PSA) based on pretest and demographic covariates will meet the ignorability assumption for replicating the results of randomized experiments. This study applies within-study comparisons to assess whether pre-Kindergarten (pre-K) treatment effects on achievement outcomes estimated using PSA based on a pretest and demographic covariates can approximate those found in a randomized experiment. Data-Four studies with samples of pre-K children each provided data on two math achievement outcome measures with baseline pretests and child demographic variables that included race, gender, age, language spoken at home, and mother's highest education. Research Design and Data Analysis-A randomized study of a pre-K math curriculum provided benchmark estimates of effects on achievement measures. Comparison samples from other pre-K studies were then substituted for the original randomized control and the effects were reestimated using PSA. The correspondence was evaluated using multiple criteria. The effect estimates using PSA were in the same direction as the benchmark estimates, had similar but not identical statistical significance, and did not differ from the benchmarks at statistically significant levels. However, the magnitude of the effect sizes differed and displayed both absolute and relative bias larger than required to show statistical equivalence with formal tests, but those results were not definitive because of the limited statistical power. We conclude that treatment effect estimates based on a single pretest and demographic covariates in PSA correspond to those from a randomized experiment on the most general criteria for equivalence.

Comparison of endothelial changes and power settings between torsional and longitudinal phacoemulsification.

PubMed

Reuschel, Anna; Bogatsch, Holger; Barth, Thomas; Wiedemann, Renate

2010-11-01

To compare the intraoperative and postoperative outcomes of conventional longitudinal phacoemulsification and torsional phacoemulsification. Department of Ophthalmology, University of Leipzig, Germany. Randomized single-center clinical trial. Eyes with senile cataract were randomized to have phacoemulsification using the Infiniti Vision System and the torsional mode (OZil) or conventional longitudinal mode. Primary outcomes were corrected distance visual acuity (CDVA) and central endothelial cell density (ECD), calculated according to the Conference on Harmonisation-E9 Guidelines in which missing values were substituted by the median in each group (primary analysis) and the loss was then calculated using actual data (secondary analysis). Secondary outcomes were ultrasound (US) time, cumulative dissipated energy (CDE), and percentage total equivalent power in position 3. Postoperative follow-up was at 3 months. The mean preoperative CDVA was 0.41 logMAR in the torsional group and 0.38 logMAR in the longitudinal group, improving to 0.07 logMAR postoperatively in both groups. The mean ECD loss was 7.2% ± 4.6% in the torsional group (72 patients) and 7.1% ± 4.4% in the longitudinal group (76 patients), with no statistically significant differences in the primary analysis (P = .342) or secondary analysis (P = .906). The mean US time, CDE, and percentage total equivalent power in position 3 were statistically significantly lower in the torsional group (98 patients) than in the longitudinal group (94 patients) (P<.001). The torsional mode was as safe as the longitudinal mode in phacoemulsification for age-related cataract. Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Effect of Diets Containing Sucrose vs. D-tagatose in Hypercholesterolemic Mice

PubMed Central

Police, Sara B.; Harris, J. Clay; Lodder, Robert A.; Cassis, Lisa A.

2010-01-01

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr−/−) mice. LDLr−/− male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis. PMID:19008872

Effect of diets containing sucrose vs. D-tagatose in hypercholesterolemic mice.

PubMed

Police, Sara B; Harris, J Clay; Lodder, Robert A; Cassis, Lisa A

2009-02-01

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr(-/-)) mice. LDLr(-/-) male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

Comparison of three officinal species of Callicarpa based on a biochemome profiling strategy with UHPLC-IT-MS and chemometrics analysis.

PubMed

Chen, Meng-Lu; Chang, Wen-Qi; Zhou, Jian-Liang; Yin, Ying-Hao; Xia, Wen-Rui; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

2017-10-25

Traditional Chinese medicine (TCM) materials with closely related species are frequently fungible in clinical use. Therefore, holistic comparison of the composition in bioactive compounds is essential to evaluate whether they are equivalent in efficacy. Taking three officinal species of Callicarpa as a case, we proposed and validated a standardized strategy for the discrimination of closely related TCM materials, which focused on the extraction, profiling and multivariate statistical analysis of their biochemome. Firstly, serial liquid-liquid extractions were utilized to prepare different batches of Callicarpa biochemome, and the preparation yields were utilized for the normalization of sampling quantity prior to UHPLC-IT-MS analysis. Secondly, 34 compounds, including 19 phenylethanoid glycosides, 10 flavonoids and 5 terpenoids, were identified based on an untargeted UHPLC-IT-MS method. Thirdly, method validation of linearity, precision and stability showed that the UHPLC-IT-MS system was qualified (R 2 >0.995, RSD<15%) for subsequent biochemome profiling. After PCA and PLS-DA analysis, 30 marker compounds were screened and demonstrated to be of good predictability using genetic algorithm optimized support vector machines. Finally, a heatmap visualization was employed for clarifying the distribution of marker compounds, which could be helpful to determine whether the three Callicarpa species are, in fact, equivalent substitutes. This study provides a standardized biochemome profiling strategy for systemic comparison analysis of closely related TCM materials, which shows promising perspectives in tracking the supply chain of pharmaceutical suppliers. Copyright © 2017 Elsevier B.V. All rights reserved.

A reduced amino acid alphabet for understanding and designing protein adaptation to mutation.

PubMed

Etchebest, C; Benros, C; Bornot, A; Camproux, A-C; de Brevern, A G

2007-11-01

Protein sequence world is considerably larger than structure world. In consequence, numerous non-related sequences may adopt similar 3D folds and different kinds of amino acids may thus be found in similar 3D structures. By grouping together the 20 amino acids into a smaller number of representative residues with similar features, sequence world simplification may be achieved. This clustering hence defines a reduced amino acid alphabet (reduced AAA). Numerous works have shown that protein 3D structures are composed of a limited number of building blocks, defining a structural alphabet. We previously identified such an alphabet composed of 16 representative structural motifs (5-residues length) called Protein Blocks (PBs). This alphabet permits to translate the structure (3D) in sequence of PBs (1D). Based on these two concepts, reduced AAA and PBs, we analyzed the distributions of the different kinds of amino acids and their equivalences in the structural context. Different reduced sets were considered. Recurrent amino acid associations were found in all the local structures while other were specific of some local structures (PBs) (e.g Cysteine, Histidine, Threonine and Serine for the alpha-helix Ncap). Some similar associations are found in other reduced AAAs, e.g Ile with Val, or hydrophobic aromatic residues Trp with Phe and Tyr. We put into evidence interesting alternative associations. This highlights the dependence on the information considered (sequence or structure). This approach, equivalent to a substitution matrix, could be useful for designing protein sequence with different features (for instance adaptation to environment) while preserving mainly the 3D fold.

The activity of CouR, a MarR family transcriptional regulator, is modulated through a novel molecular mechanism

DOE PAGES

Otani, Hiroshi; Stogios, Peter J.; Xu, Xiaohui; ...

2015-09-22

CouR, a MarR-type transcriptional repressor, regulates the cou genes, encoding p-hydroxycinnamate catabolism in the soil bacterium Rhodococcus jostii RHA1. The CouR dimer bound two molecules of the catabolite p-coumaroyl–CoA (K d = 11 ± 1 μM). The presence of p-coumaroyl–CoA, but neither p-coumarate nor CoASH, abrogated CouR's binding to its operator DNA in vitro. The crystal structures of ligand-free CouR and its p-coumaroyl–CoA-bound form showed no significant conformational differences, in contrast to other MarR regulators. The CouR– p-coumaroyl–CoA structure revealed two ligand molecules bound to the CouR dimer with their phenolic moieties occupying equivalent hydrophobic pockets in each protomer andmore » their CoA moieties adopting non-equivalent positions to mask the regulator's predicted DNA-binding surface. More specifically, the CoA phosphates formed salt bridges with predicted DNA-binding residues Arg36 and Arg38, changing the overall charge of the DNA-binding surface. The substitution of either arginine with alanine completely abrogated the ability of CouR to bind DNA. By contrast, the R36A/R38A double variant retained a relatively high affinity for p-coumaroyl–CoA (K d = 89 ± 6 μM). Altogether, our data point to a novel mechanism of action in which the ligand abrogates the repressor's ability to bind DNA by steric occlusion of key DNA-binding residues and charge repulsion of the DNA backbone.« less

Trial frame refraction versus autorefraction among new patients in a low-vision clinic.

PubMed

DeCarlo, Dawn K; McGwin, Gerald; Searcey, Karen; Gao, Liyan; Snow, Marsha; Waterbor, John; Owsley, Cynthia

2013-01-02

To determine the relationship between refractive error as measured by autorefraction and that measured by trial frame refraction among a sample of adults with vision impairment seen in a university-based low-vision clinic and to determine if autorefraction might be a suitable replacement for trial frame refraction. A retrospective chart review of all new patients 19 years or older seen over an 18-month period was conducted and the following data collected: age, sex, primary ocular diagnosis, entering distance visual acuity, habitual correction, trial frame refraction, autorefraction, and distance visual acuity measured after trial frame refraction. Trial frame refraction and autorefraction were compared using paired t-tests, intraclass correlations, and Bland-Altman plots. Final analyses included 440 patients for whom both trial frame refraction and autorefraction data were available for the better eye. Participants were mostly female (59%) with a mean age of 68 years (SD = 20). Age-related macular degeneration was the most common etiology for vision impairment (44%). Values for autorefraction and trial frame refraction were statistically different, but highly correlated for the spherical equivalent power (r = 0.92), the cylinder power (r = 0.80) and overall blurring strength (0.89). Although the values of the cross-cylinders J(0) and J(45) were similar, they were poorly correlated (0.08 and 0.15, respectively). The range of differences in spherical equivalent power was large (-8.6 to 4.9). Autorefraction is highly correlated with trial frame refraction. Differences are sometimes substantial, making autorefraction an unsuitable substitute for trial frame refraction.

Co(II) derivatives of Cu,Zn-superoxide dismutase with the cobalt bound in the place of copper. A new spectroscopic tool for the study of the active site.

PubMed

Desideri, A; Cocco, D; Calabrese, L; Rotilio, G

1984-03-29

Co(II) derivatives of Cu,Zn-superoxide dismutase having cobalt substituted for the copper (Co,Zn-superoxide dismutase and Co,Co-superoxide dismutase) were studied by optical and EPR spectroscopy. EPR and electronic absorption spectra of Co,Zn-superoxide dismutase are sensitive to solvent perturbation, and in particular to the presence of phosphate. This behaviour suggests that cobalt in Co,Zn-superoxide dismutase is open to solvent access, at variance with the Co(II) of the Cu,Co-superoxide dismutase, which is substituted for the Zn. Phosphate binding as monitored by optical titration is dependent on pH with an apparent pKa = 8.2. The absorption spectrum of Co,Zn-superoxide dismutase in water has three weak bands in the visible region (epsilon = 75 M-1 X cm-1 at 456 nm; epsilon = 90 M-1 X cm-1 at 520 nm; epsilon = 70 M-1 X cm-1 at 600 nm) and three bands in the near infrared region, at 790 nm (epsilon = 18 M-1 X cm-1), 916 nm (epsilon = 27 M-1 X cm-1) and 1045 nm (epsilon = 25 M-1 X cm-1). This spectrum is indicative of five-coordinate geometry. In the presence of phosphate, three bands are still present in the visible region but they have higher intensity (epsilon = 225 M-1 X cm-1 at 544 nm; epsilon = 315 M-1 X cm-1 at 575 nm; epsilon = 330 M-1 X cm-1 at 603 nm), whilst the lowest wavelength band in the near infrared region is at much lower energy, 1060 nm (epsilon = 44 M-1 X cm-1). The latter property suggests a tetrahedral coordination around the Co(II) centre. Addition of 1 equivalent of CN- gives rise to a stable Co(II) low-spin intermediate, which is characterized by an EPR spectrum with a highly rhombic line shape. Formation of this CN- complex was found to require more cyanide equivalents in the case of the phosphate adduct, suggesting that binding of phosphate may inhibit binding of other anions. Titration of the Co,Co-derivative with CN- provided evidence for magnetic interaction between the two metal centres. These results substantiate the contention that Co(II) can replace the copper of Cu,Zn-superoxide dismutase in a way that reproduces the properties of the native copper-binding site.

NMR Spectroscopy and Structural Characterization of Dithiophosphinates Relevant to Minor Actinide Extraction Processes

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

Scott R. Daly; Kevin S. Boland; John R. Klaehn

2012-02-01

Synthetic routes to alkyl and aryl substituted dithiophosphinate salts that contain non-coordinating PPh{sub 4}{sup 1+} counter cations are reported. In general, these compounds can be prepared via a multi-step procedure that starts with reacting secondary phosphines, i.e. HPR{sub 2}, with two equivalents elemental S. This transformation proceeds in two steps - first oxidation of the phosphine and second insertion of S into the H-P bond - and has been used to synthesize a series of dithiophoshinic acids, which were fully characterized, namely HS{sub 2}P(p-CF{sub 3}C{sub 6}H{sub 4}){sub 2}, HS{sub 2}P(m-CF{sub 3}C{sub 6}H{sub 4}){sub 2}, HS{sub 2}P(o-MeC{sub 6}H{sub 4}){sub 2}, andmore » HS{sub 2}P(o-MeOC{sub 6}H{sub 4}){sub 2}. Although the insertion step was found to be much slower than the oxidation reaction, the formation of (NH{sub 4})S{sub 2}PR{sub 2} from HPSR{sub 2} occurs almost instantaneous upon addition of NH{sub 4}OH. Subsequent cation exchange reactions proceed readily with PPh{sub 4}Cl in water, under air, and at ambient conditions to provide analytically pure samples of [PPh{sub 4}][S{sub 2}PR{sub 2}] (R = p-CF{sub 3}C{sub 6}H{sub 4}, m-CF{sub 3}C{sub 6}H{sub 4}, o-CF{sub 3}C{sub 6}H{sub 4}, o-MeC{sub 6}H{sub 4}, o-MeOC{sub 6}H{sub 4}, Ph, and Me, 1b-7b, respectively), which were characterized by elemental analysis, multinuclear NMR, and IR spectroscopy. In addition the S{sub 2}PMe{sub 2}{sup 1-}, S{sub 2}PPh{sub 2}{sup 1-}, and dithiophosphinates with ortho-substituted arene rings were characterized by X-ray crystallography. Structural analysis show that, as opposed to the acids which have short P=S double bonds and long P-SH single bonds, the metric parameters for the S atoms in S{sub 2}PR{sub 2}{sup 1-} are equivalent. In addition, the presence of large non-coordinating PPh{sub 4}{sup 1+} cations guard against intermolecular P-S {hor_ellipsis} X interactions and insure that the P-S bond is isolated. Overall, this synthetic procedure provides high-purity S{sub 2}PR{sub 2}{sup 1-} compounds necessary for subsequent spectroscopic and theoretical studies.« less

Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution.

PubMed

Gumbs, Pearl D; Verschuren, W M Monique; Souverein, Patrick C; Mantel-Teeuwisse, Aukje K; de Wit, G Ardine; de Boer, Anthonius; Klungel, Olaf H

2007-11-01

To assess the potential annual savings due to generic and therapeutic substitution of statin therapy for the general Dutch population, taking the patients medical history into account. We conducted a population-based costing study using the PHARMO Record Linkage System (RLS). PHARMO RLS contains drug dispensing records from a representative sample of pharmacies located in more than 50 regions in the Netherlands. We selected all statin users in the database since 2003. The cost-savings of generic substitution of statin therapy for all simvastatin and pravastatin users, and of therapeutic substitution of statin therapy for other statin users were calculated. Substituting current users and new users of statins were considered separately. Therapeutic substitution was based on the medical history of the individual patient. Patients were only substituted if there was an appropriate substitute available. The appropriateness of substitution was based on drug-drug interactions between statins and possible comedication and the availability of an equipotent alternative. Substituting (generic and therapeutic) statin therapy for all current users would lead to potential annual savings of approximately 87 million euros. Substituting (generic and therapeutic) all starters on statin therapy would lead to potential annual savings of around 51 million euros. In the case of generic substitution only, the potential annual savings for all current simvastatin and pravastatin users would be 2.4 million euros and for the new users about 1.8 million euros. From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution.

Functionalized polyfluorenes for use in optoelectronic devices

DOEpatents

Chichak, Kelly Scott [Clifton Park, NY; Lewis, Larry Neil [Scotia, NY; Cella, James Anthony [Clifton Park, NY; Shiang, Joseph John [Niskayuna, NY

2011-11-08

The present invention relates to process comprising reacting a polyfluorenes comprising at least one structural group of formula I ##STR00001## with an iridium (III) compound of formula II ##STR00002## wherein R.sup.1 and R.sup.2 are independently alkyl, substituted alkyl, aryl, substituted aryl or a combination thereof; R.sup.5is H or CHO; R.sup.3 and R.sup.4 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl or a combination thereof; R.sup.11 and R.sup.12 taken together form a substituted or unsubstituted monocyclic or bicyclic heteroaromatic ring; R.sup.13 is independently at each occurrence halo, nitro, hydroxy, amino, alkyl, aryl, arylalkyl, alkoxy, substituted alkoxy, substituted alkyl, substituted aryl, or substituted arylalkyl; Ar is aryl, heteroaryl, substituted aryl, substituted heteroaryl, or a combination thereof; X is selected from a direct bond, alky, substituted alkyl, and combinations thereof; Y is CHO or NH.sub.2; Z is CHO or NH.sub.2 where Z does not equal Y; and p is 0, 1 or 2. The invention also relates to the polyfluorenes, which are products of the reaction, and the use of the polyfluorenes in optoelectronic devices.

Biologic and synthetic skin substitutes: An overview

PubMed Central

Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd. Yussof, Shah Jumaat

2010-01-01

The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing. PMID:21321652

Secretion of wound healing mediators by single and bi-layer skin substitutes.

PubMed

Maarof, Manira; Law, Jia Xian; Chowdhury, Shiplu Roy; Khairoji, Khairul Anuar; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

2016-10-01

Limitations of current treatments for skin loss caused by major injuries leads to the use of skin substitutes. It is assumed that secretion of wound healing mediators by these skin substitutes plays a role in treating skin loss. In our previous study, single layer keratinocytes (SK), single layer fibroblast (SF) and bilayer (BL; containing keratinocytes and fibroblasts layers) skin substitutes were fabricated using fibrin that had shown potential to heal wounds in preclinical studies. This study aimed to quantify the secretion of wound healing mediators, and compare between single and bi-layer skin substitutes. Skin samples were digested to harvest fibroblasts and keratinocytes, and expanded to obtain sufficient cells for the construction of skin substitutes. Acellular fibrin (AF) construct was used as control. Substitutes i.e. AF, SK, SF and BL were cultured for 2 days, and culture supernatant was collected to analyze secretion of wound healing mediators via multiplex ELISA. Among 19 wound healing mediators tested, BL substitute secreted significantly higher amounts of CXCL1 and GCSF compared to SF and AF substitute but this was not significant with respect to SK substitute. The BL substitute also secreted significantly higher amounts of CXCL5 and IL-6 compared to other substitutes. In contrast, the SK substitute secreted significantly higher amounts of VCAM-1 compared to other substitutes. However, all three skin substitutes also secreted CCL2, CCL5, CCL11, GM-CSF, IL8, IL-1α, TNF-α, ICAM-1, FGF-β, TGF-β, HGF, VEGF-α and PDGF-BB factors, but no significant difference was seen. Secretion of these mediators after transplantation may play a significant role in promoting wound healing process for the treatment of skin loss.

[Physician versus 'off-label" ordinance].

PubMed

Kordus, Katarzyna; Spiewak, Radosław

2015-01-01

Polish physicians are obliged by legislation to prescribe drugs authorized for the sale in the Republic of Poland, based on registration documentation, including the Summaries of Product Characteristics (SPC). So called 'off label' treatment occurs in case of the conflict between prescription and information contained in the SPC, which may be considered as a 'medical experiment'. In case of adverse drug reactions, such classification excludes the responsibility of the marketing authorization holders, and damages are not covered by obligatory third party insurance, which can pose financial and legal consequences to the doctor. Deviations from SPC-compliant prescription may include a different way of drug administration, drug administration compliant with the indications yet in patients for whom there is no specified drug dosage, or in case of an indication not contained in the SPC. Medicinal products with equivalent active component, form and dose can have different registration indications in the SPC, and the actively promoted dispensation of less expensive substitutes by the pharmacists may, against doctor's will, result in the use that is non-compliant with registration of the substitute drug. Pharmacotherapy of 'orphan diseases', for which there are no registered medicinal products, also becomes an essential issue as it forces doctors into 'off-label' prescriptions. Moreover, the reimbursement of drugs in most cases is limited to medicinal products that are prescribed according to the registration indications. The pleas by medical professionals to make ordination and reimbursement of drugs depend on active pharmaceutical ingredient and evidence of efficacy, as well as to introduce Evidence Based Medicine (EBM) standards for the treatment of diseases, did not receive proper attention from the governing bodies. Therefore, a fundamental question remains unanswered as to what should be the principal gauge for physicians' therapeutic decision: the ethics, conscience, recent scientific evidence or legal and administrative regulations?

Prescription Omega-3 Fatty Acid Products and Dietary Supplements Are Not Interchangeable.

PubMed

Hilleman, Daniel; Smer, Aiman

2016-01-01

To provide an overview of prescription and dietary supplement omega-3 fatty acid (OM3-FA) products and considerations for clinical use. Narrative review. The PubMed database was searched for cardiovascular-related investigations focused on eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) (limit: English-only articles). Additional regulatory information on prescription and dietary supplements was obtained from United States Food and Drug Administration online sources. Prescription QM3-FA products are supported by robust clinical development and safety monitoring programs, whereas dietary supplements are not required to demonstrate safety or efficacy prior to marketing. There are no over-the-counter OM3-FA products available in the United States. Investigations of OM3-FA dietary supplements show that quantities of EPA and DHA are highly variable within and between brands. Dietary supplements also may contain potentially harmful components, including oxidized OM3-FA, other lipids, cholesterol, and toxins. Prescription OM3-FA products may contain DHA and EPA or EPA alone. All prescription OM3-FA products have demonstrated statistically significant triglyceride reduction as monotherapy or in combination with statins in patients with hypertriglyceridemia. Differential effects between products containing EPA and DHA compared with a high-purity EPA product (icosapent ethyl) have clinical implications: Increases in low-density lipoprotein cholesterol associated with DHA have the potential to confound strategies for managing patients with dyslipidemia. Cardiovascular outcomes studies of prescription CM3-FA products are ongoing. OM3-FA dietary supplements should not be substituted for prescription products, and prescription OM3-FA products that contain DHA are not equivalent to or interchangeable with high-purity EPA (icosapent ethyl) and should not be substituted for it.

Patterns of use for brand-name versus generic oral bisphosphonate drugs in Ontario over a 13-year period: a descriptive study.

PubMed

Fraser, Lisa-Ann; Albaum, Jordan M; Tadrous, Mina; Burden, Andrea M; Shariff, Salimah Z; Cadarette, Suzanne M

2015-01-01

Bisphosphonates are the first-line therapy for the treatment of osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds medications for patients aged 65 years and older. The Ontario Drug Benefit Program has a generic substitution policy that requires lower-cost generic drugs to be dispensed when they are available. However, there is controversy surrounding the efficacy and tolerability of generic bisphosphonates. The objective of this study was to describe patterns in the use of brand-name versus generic formulations when dispensing oral bisphosphonate over a 13-year period. We identified all osteoporotic preparations for alendronate and risedronate that were dispensed through the Ontario Drug Benefit Program from 2001 to 2014. We stratified our sample into community-dwelling residents and residents in long-term care facilities. The number of prescriptions dispensed per month were plotted to illustrate trends over time. We found a rapid switch from brand-name to generic bisphosphonate equivalents immediately after the generic became available on the Ontario Drug Benefit formulary, with generics accounting for > 88% of dispensed drug within 2 months. We also observed a reduction in the number of generic drugs dispensed each time a new brand-name alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was introduced to the formulary. The dispensing trends were similar in the community and long-term care settings. The Ontario Drug Benefit Program generic substitution policy resulted in rapid uptake of generic oral bisphosphonates among seniors in Ontario. However, there was a switch away from generic medications to new brand-name alternatives whenever they were introduced to the formulary. Therefore, some patients continued to use brand-name bisphosphonate despite the availability of generic options.

Interspecies protein substitution to investigate the role of the lyssavirus glycoprotein.

PubMed

Marston, Denise A; McElhinney, Lorraine M; Banyard, Ashley C; Horton, Daniel L; Núñez, Alejandro; Koser, Martin L; Schnell, Matthias J; Fooks, Anthony R

2013-02-01

European bat lyssaviruses type 1 (EBLV-1) and type 2 (EBLV-2) circulate within bat populations throughout Europe and are capable of causing disease indistinguishable from that caused by classical rabies virus (RABV). However, the determinants of viral fitness and pathogenicity are poorly understood. Full-length genome clones based on the highly attenuated, non-neuroinvasive, RABV vaccine strain (SAD-B19) were constructed with the glycoprotein (G) of either SAD-B19 (SN), of EBLV-1 (SN-1) or EBLV-2 (SN-2). In vitro characterization of SN-1 and SN-2 in comparison to wild-type EBLVs demonstrated that the substitution of G affected the final virus titre and antigenicity. In vivo, following peripheral infection with a high viral dose (10(4) f.f.u.), animals infected with SN-1 had reduced survivorship relative to infection with SN, resulting in survivorship similar to animals infected with EBLV-1. The histopathological changes and antigen distribution observed for SN-1 were more representative of those observed with SN than with EBLV-1. EBLV-2 was unable to achieve a titre equivalent to that of the other viruses. Therefore, a reduced-dose experiment (10(3) f.f.u.) was undertaken in vivo to compare EBLV-2 and SN-2, which resulted in 100 % survivorship for all recombinant viruses (SN, SN-1 and SN-2) while clinical disease developed in mice infected with the EBLVs. These data indicate that interspecies replacement of G has an effect on virus titre in vitro, probably as a result of suboptimal G-matrix protein interactions, and influences the survival outcome following a peripheral challenge with a high virus titre in mice.

Estimating Whether Replacing Time in Active Outdoor Play and Sedentary Video Games With Active Video Games Influences Youth's Mental Health.

PubMed

Janssen, Ian

2016-11-01

The primary objective was to use isotemporal substitution models to estimate whether replacing time spent in sedentary video games (SVGs) and active outdoor play (AOP) with active video games (AVGs) would be associated with changes in youth's mental health. A representative sample of 20,122 Canadian youth in Grades 6-10 was studied. The exposure variables were average hours/day spent playing AVGs, SVGs, and AOP. The outcomes consisted of a negative and internalizing mental health indicator (emotional problems), a positive and internalizing mental health indicator (life satisfaction), and a positive and externalizing mental health indicator (prosocial behavior). Isotemporal substitution models estimated the extent to which replacing time spent in SVGs and AOP with an equivalent amount of time in AVGs had on the mental health indicators. Replacing 1 hour/day of SVGs with 1 hour/day of AVGs was associated with a 6% (95% confidence interval: 3%-9%) reduced probability of high emotional problems, a 4% (2%-7%) increased probability of high life satisfaction, and a 13% (9%-16%) increased probability of high prosocial behavior. Replacing 1 hour/day of AOP with 1 hour/day of AVGs was associated with a 7% (3%-11%) increased probability of high emotional problems, a 3% (1%-5%) reduced probability of high life satisfaction, and a 6% (2%-9%) reduced probability of high prosocial behavior. Replacing SVGs with AVGs was associated with more preferable mental health indicators. Conversely, replacing AOP with AVGs was associated with more deleterious mental health indicators. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Logistics, Costs, and GHG Impacts of Utility-Scale Co-Firing with 20% Biomass

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

Nichol, Corrie Ian

This study analyzes the possibility that biopower in the U.S. is a cost-competitive option to significantly reduce greenhouse gas emissions. In 2009, net greenhouse gas (GHG) emitted in the United States was equivalent to 5,618 million metric tons CO 2, up 5.6% from 1990 (EPA 2011). Coal-fired power generation accounted for 1,748 million metric tons of this total. Intuitively, life-cycle CO 2 emissions in the power sector could be reduced by substituting renewable biomass for coal. If just 20% of the coal combusted in 2009 had been replaced with biomass, CO 2 emissions would have been reduced by 350 millionmore » metric tons, or about 6% of net annual GHG emission. This would have required approximately 225 million tons of dry biomass. Such an ambitious fuel substitution would require development of a biomass feedstock production and supply system tantamount to coal. This material would need to meet stringent specifications to ensure reliable conveyance to boiler burners, efficient combustion, and no adverse impact on heat transfer surfaces and flue gas cleanup operations. Therefore, this report addresses the potential cost/benefit tradeoffs of co-firing 20% specification-qualified biomass (on an energy content basis) in large U.S. coal-fired power plants. The dependence and sensitivity of feedstock cost on source of material, location, supply distance, and demand pressure was established. Subsequently, the dependence of levelized cost of electricity (LCOE) on feedstock costs, power plant feed system retrofit, and impact on boiler performance was determined. Overall life-cycle assessment (LCA) of greenhouse gas emissions saving were next evaluated and compared to wind and solar energy to benchmark the leading alternatives for meeting renewable portfolio standards (or RPS).« less

Conjugated Fatty Acid Synthesis

PubMed Central

Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

2012-01-01

Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

Intended and unintended consequences of the gabapentin off-label marketing lawsuit among patients with bipolar disorder.

PubMed

Chace, Meredith J; Zhang, Fang; Fullerton, Catherine A; Huskamp, Haiden A; Gilden, Daniel; Soumerai, Stephen B

2012-11-01

The number of lawsuits accusing pharmaceutical companies of off-label marketing has risen in recent years. The impact of such lawsuits on drug prescribing and spending has not been examined. We evaluated a nationwide sample to determine whether the $430 million gabapentin off-label marketing lawsuit and accompanying media coverage affected gabapentin market share, substitution of other scientifically substantiated and unsubstantiated anticonvulsants, and anticonvulsant spending of Medicare/Medicaid patients diagnosed with bipolar disorder. Using a national 5% sample of Medicare recipients linked to Medicaid claims, we used an interrupted times series design to evaluate the impact of the lawsuit on monthly market share, utilization, and spending from January 1, 2001, to December 31, 2005. The start of the lawsuit was associated with a 28% relative reduction in gabapentin market share (from ∼ 21% to ∼ 15%) and a reduction in the rate of prescribing from 108 prescriptions per 1,000 patients per month before the start of the lawsuit to 90 by the end of follow-up (P < .001). We also observed increases in market share for 3 other anticonvulsants. Total anticonvulsant use and spending per 1,000 patients increased by 13% and 74%, respectively, after the intervention. The increase in anticonvulsant spending was equivalent to $7,554 per 1,000 patients per year higher than expected compared with the baseline trend (P = .01). We conclude that the lawsuit resulted in a reduction in gabapentin market share, increased market share for other anticonvulsants, and substantially increased total anticonvulsant spending to approximately half of the settlement amount, not counting substitutions of newer drugs for other illnesses affected by the lawsuit. These findings support the need for further study of the effects of current lawsuits regarding off-label drug marketing. © Copyright 2012 Physicians Postgraduate Press, Inc.

Ecosystem Services in Conservation Planning: Targeted Benefits vs. Co-Benefits or Costs?

PubMed Central

Chan, Kai M. A.; Hoshizaki, Lara; Klinkenberg, Brian

2011-01-01

There is growing support for characterizing ecosystem services in order to link conservation and human well-being. However, few studies have explicitly included ecosystem services within systematic conservation planning, and those that have follow two fundamentally different approaches: ecosystem services as intrinsically-important targeted benefits vs. substitutable co-benefits. We present a first comparison of these two approaches in a case study in the Central Interior of British Columbia. We calculated and mapped economic values for carbon storage, timber production, and recreational angling using a geographical information system (GIS). These ‘marginal’ values represent the difference in service-provision between conservation and managed forestry as land uses. We compared two approaches to including ecosystem services in the site-selection software Marxan: as Targeted Benefits, and as Co-Benefits/Costs (in Marxan's cost function); we also compared these approaches with a Hybrid approach (carbon and angling as targeted benefits, timber as an opportunity cost). For this analysis, the Co-Benefit/Cost approach yielded a less costly reserve network than the Hybrid approach (1.6% cheaper). Including timber harvest as an opportunity cost in the cost function resulted in a reserve network that achieved targets equivalently, but at 15% lower total cost. We found counter-intuitive results for conservation: conservation-compatible services (carbon, angling) were positively correlated with each other and biodiversity, whereas the conservation-incompatible service (timber) was negatively correlated with all other networks. Our findings suggest that including ecosystem services within a conservation plan may be most cost-effective when they are represented as substitutable co-benefits/costs, rather than as targeted benefits. By explicitly valuing the costs and benefits associated with services, we may be able to achieve meaningful biodiversity conservation at lower cost and with greater co-benefits. PMID:21915318

The Ectodomain of Glycoprotein from the Candid#1 Vaccine Strain of Junin Virus Rendered Machupo Virus Partially Attenuated in Mice Lacking IFN-αβ/γ Receptor

PubMed Central

Koma, Takaaki; Huang, Cheng; Aronson, Judith F.; Walker, Aida G.; Miller, Milagros; Smith, Jeanon N.; Patterson, Michael; Paessler, Slobodan

2016-01-01

Machupo virus (MACV), a New World arenavirus, is the etiological agent of Bolivian hemorrhagic fever (BHF). Junin virus (JUNV), a close relative, causes Argentine hemorrhagic fever (AHF). Previously, we reported that a recombinant, chimeric MACV (rMACV/Cd#1-GPC) expressing glycoprotein from the Candid#1 (Cd#1) vaccine strain of JUNV is completely attenuated in a murine model and protects animals from lethal challenge with MACV. A rMACV with a single F438I substitution in the transmembrane domain (TMD) of GPC, which is equivalent to the F427I attenuating mutation in Cd#1 GPC, was attenuated in a murine model but genetically unstable. In addition, the TMD mutation alone was not sufficient to fully attenuate JUNV, indicating that other domains of the GPC may also contribute to the attenuation. To investigate the requirement of different domains of Cd#1 GPC for successful attenuation of MACV, we rescued several rMACVs expressing the ectodomain of GPC from Cd#1 either alone (MCg1), along with the TMD F438I substitution (MCg2), or with the TMD of Cd#1 (MCg3). All rMACVs exhibited similar growth curves in cultured cells. In mice, the MCg1 displayed significant reduction in lethality as compared with rMACV. The MCg1 was detected in brains and spleens of MCg1-infected mice and the infection was associated with tissue inflammation. On the other hand, all animals survived MCg2 and MCg3 infection without detectable levels of virus in various organs while producing neutralizing antibody against Cd#1. Overall our data suggest the indispensable role of each GPC domain in the full attenuation and immunogenicity of rMACV/Cd#1 GPC. PMID:27580122

An experimental and modeling study of the autoignition of 3-methylheptane

DOE PAGES

Wang, Weijing; Li, Zhenhua; Oehlschlaeger, Matthew A.; ...

2013-01-01

An experimental and kinetic modeling study of the autoignition of 3-methylheptane, a compound representative of the high molecular weight lightly branched alkanes found in large quantities in conventional and synthetic aviation kerosene and diesel fuels, is reported. Shock tube and rapid compression machine ignition delay time measurements are reported over a wide range of conditions of relevance to combustion engine applications: temperatures from 678 to 1356 K; pressures of 6.5, 10, 20, and 50 atm; and equivalence ratios of 0.5, 1.0, and 2.0. The wide range of temperatures examined provides observation of autoignition in three reactivity regimes, including the negativemore » temperature coefficient (NTC) regime characteristic of paraffinic fuels. Comparisons made between the current ignition delay measurements for 3-methylheptane and previous results for n-octane and 2-methylheptane quantifies the influence of a single methyl substitution and its location on the reactivity of alkanes. It is found that the three C8 alkane isomers have indistinguishable high-temperature ignition delay but their ignition delay times deviate in the NTC and low-temperature regimes in correlation with their research octane numbers. The experimental results are compared with the predictions of a proposed kinetic model that includes both high- and low-temperature oxidation chemistry. The model mechanistically explains the differences in reactivity for n-octane, 2-methylheptane, and 3-methylheptane in the NTC through the influence of the methyl substitution on the rates of isomerization reactions in the low-temperature chain branching pathway, that ultimately leads to ketohydroperoxide species, and the competition between low-temperature chain branching and the formation of cyclic ethers, in a chain propagating pathway.« less

Synthesis and structural characterization of lithium, sodium and potassium complexes supported by a tridentate amino-bisphenolate ligand

NASA Astrophysics Data System (ADS)

Durango-García, Clara J.; Rufino-Felipe, Ernesto; López-Cardoso, Marcela; Muñoz-Hernández, Miguel-Ángel; Montiel-Palma, Virginia

2018-07-01

Reactions of methylamino-N,N-bis(2-methylene-4,6-di-tert-butylphenol) (1) with one or two equivalents of bulk Li, Na or K metals in THF or DMSO render mono or dialkali metal complexes depending on the stoichiometric ratio of the reactants. The metal-methylamino-N-(2-methylene-4,6-tert-butylphenol)sbnd N-(2-methylene-4,6-tert-butylphenolate) complexes, 2Li, 2Na and 2K, are generated upon the substitution of a single phenol hydrogen of 1. In the solid state, complex 2Na is a dimer due to the establishment of two symmetric hydrogen bonds between two adjacent molecules. The Na center also engages into the formation of a ten-membered metallacycle ring with a butterfly-like structure. Due to dimerization, an intermolecular six-membered core is formed involving two sodium and four oxygen atoms. The weakly coordinated nitrogen atom from the ligand is nearly perpendicular to the hexagonal core. The dimetal-methylamino-N,N‧-bis(2-methylene-4,6-di-tert-butylphenolate) complexes, 3Li, 3Na and 3K result from metal substitution of the two phenol hydrogens from ligand 1. The SC-XRD structures of 3Li and 3Na are discreet, each incorporating two metal atoms in different coordination environments. Ten-membered rings with boat-boat conformations are also observed as are rhombic central M2O2 cores. The molecular structure of 3K in DMSO shows a higher degree of aggregation. It effectively comprises four K atoms, two ligand backbones and seven solvent molecules forming a central four-membered K2O2 ring perpendicular to an eight-membered structure formed also by K and O atoms spanning over the two ligand moieties.

Co-operative actions and degradation analysis of purified xylan-degrading enzymes from Thermomonospora fusca BD25 on oat-spelt xylan.

PubMed

Tuncer, M; Ball, A S

2003-01-01

To determine and quantify the products from the degradation of xylan by a range of purified xylan-degrading enzymes, endoxylanase, beta-xylosidase and alpha-l-arabinofuranosidase produced extracellularly by Thermomonospora fusca BD25. The amounts of reducing sugars released from oat-spelt xylan by the actions of endoxylanase, beta-xylosidase and alpha-l-arabinofuranosidase were equal to 28.1, 4.6 and 7% hydrolysis (as xylose equivalents) of the substrate used, respectively. However, addition of beta-xylosidase and alpha-l-arabinofuranosidase preparation to endoxylanase significantly enhanced (70 and 20% respectively) the action of endoxylanase on the substrate. The combination of purified endoxylanase, beta-xylosidase and alpha-l-arabinofuranosidase preparations produced a greater sugar yield (58.6% hydrolysis) and enhanced the total reducing sugar yield by around 50%. The main xylooligosaccharide products released using the action of endoxylanase alone on oat-spelt xylan were identified as xylobiose and xylopentose. alpha-l-Arabinofuranosidase was able to release arabinose and xylobiose from oat-spelt xylan. In the presence of all three purified enzymes the hydrolysis products of oat-spelt xylan were mainly xylose, arabinose and substituted xylotetrose with lesser amount of substituted xylotriose. The addition of the beta-xylosidase and alpha-l-arabinofuranosidase enzymes to purified xylanases more than doubled the degradation of xylan from 28 to 58% of the total substrate with xylose and arabinose being the major sugars produced. The results highlight the role of xylan de-branching enzymes in the degradation of xylan and suggest that the use of enzyme cocktails may significantly improve the hydrolysis of xylan in industrial processes.

The changing roles of dietary carbohydrates: from simple to complex.

PubMed

Griel, Amy E; Ruder, Elizabeth H; Kris-Etherton, Penny M

2006-09-01

The dietary recommendations made for carbohydrate intake by many organizations/agencies have changed over time. Early recommendations were based on the need to ensure dietary sufficiency and focused on meeting micronutrient intake requirements. Because carbohydrate-containing foods are a rich source of micronutrients, starches, grains, fruits, and vegetables became the foundation of dietary guidance, including the base of the US Department of Agriculture's Food Guide Pyramid. Dietary sufficiency recommendations were followed by recommendations to reduce cholesterol levels and the risk for cardiovascular disease; reduction in total fat (and hence saturated fat) predominated. Beginning in the 1970s, carbohydrates were recommended as the preferred substitute for fat by the American Heart Association and others to achieve the recommended successive reductions in total fat and low-density lipoprotein cholesterol (LDL-C). Additional research on fats and fatty acids found that monounsaturated fatty acids could serve as an alternative substitution for saturated fats, providing equivalent lowering of LDL-C without concomitant reductions in high-density lipoprotein cholesterol and increases in triglycerides witnessed when carbohydrates replace saturated fat. This research led to a sharper focus in the guidelines in the 1990s toward restricting saturated fat and liberalizing a range of intake of total fat. Higher-fat diets, still low in saturated fatty acids, became alternative strategies to lower-fat diets. As the population has become increasingly overweight and obese, the emergence of the metabolic syndrome and its associated disruptions in glucose and lipid metabolism has led to reconsiderations of the role of carbohydrate-containing foods in the American diet. Consequently, a review of the evidence for and against high-carbohydrate diets is important to put this controversy into perspective. The current dietary recommendations for carbohydrate intake are supported by the evidence.

Strategic Design of an Effective beta-Lactamase Inhibitor

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

Pattanaik, P.; Bethel, C; Hujer, A

In an effort to devise strategies for overcoming bacterial beta-lactamases, we studied LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone inhibitor. By possessing a catecholic functionality that resembles a natural bacterial siderophore, LN-1-255 is unique among beta-lactamase inhibitors. LN-1-255 combined with piperacillin was more potent against Escherichia coli DH10B strains bearing bla(SHV) extended-spectrum and inhibitor-resistant beta-lactamases than an equivalent amount of tazobactam and piperacillin. In addition, LN-1-255 significantly enhanced the activity of ceftazidime and cefpirome against extended-spectrum cephalosporin and Sme-1 containing carbapenem-resistant clinical strains. LN-1-255 inhibited SHV-1 and SHV-2 beta-lactamases with nm affinity (K(I) = 110 +/- 10 and 100 +/- 10 nm,more » respectively). When LN-1-255 inactivated SHV beta-lactamases, a single intermediate was detected by mass spectrometry. The crystal structure of LN-1-255 in complex with SHV-1 was determined at 1.55A resolution. Interestingly, this novel inhibitor forms a bicyclic aromatic intermediate with its carbonyl oxygen pointing out of the oxyanion hole and forming hydrogen bonds with Lys-234 and Ser-130 in the active site. Electron density for the 'tail' of LN-1-255 is less ordered and modeled in two conformations. Both conformations have the LN-1-255 carboxyl group interacting with Arg-244, yet the remaining tails of the two conformations diverge. The observed presence of the bicyclic aromatic intermediate with its carbonyl oxygen positioned outside of the oxyanion hole provides a rationale for the stability of this inhibitory intermediate. The 2'-substituted penicillin sulfone, LN-1-255, is proving to be an important lead compound for novel beta-lactamase inhibitor design.« less

[Industrial exploitation of renewable resources: from ethanol production to bioproducts development].

PubMed

Lopes Ferreira, Nicolas

2008-01-01

Plants, which are one of major groups of life forms, are constituted of an amazing number of molecules such as sugars, proteins, phenolic compounds etc. These molecules display multiple and complementary properties involved in various compartments of plants (structure, storage, biological activity etc.). The first uses of plants in industry were for food and feed, paper manufacturing or combustion. In the coming decades, these renewable biological materials will be the basis of a new concept: the "biorefiner" i.e. the chemical conversion of the whole plant to various products and uses. This concept, born in the 90ies, is analogous to today's petroleum refinery, which produces multiple fuels and derivative products from petroleum. Agriculture generates lots of co-products which were most often wasted. The rational use of these wasted products, which can be considered as valuable renewable materials, is now economically interesting and will contribute to the reduction of greenhouse has emissions by partially substituting for fossil fuels. Such substructures from biological waste products and transforming them into biofuels and new industrial products named "bioproducts". These compounds, such as bioplastics or biosurfactants, can replace equivalent petroleum derivatives. Towards that goal, lots of filamentous fungi, growing on a broad range of vegetable species, are able to produce enzymes adapted to the modification of these type of substrates. The best example, at least the more industrially developed to date, is the second generation biofuel technology using cellulose as a raw material. The process includes an enzymatic hydrolysis step which requires cellulases secreted from Trichoderma fungal species. This industrial development of a renewable energy will contribute to the diversification of energy sources used to transport and to the development of green chemistry which will partially substitute petrochemicals.

14 CFR 1260.55 - Reports substitution.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Reports substitution. 1260.55 Section 1260...

14 CFR 1260.55 - Reports substitution.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Reports substitution. 1260.55 Section 1260...

14 CFR 1260.55 - Reports substitution.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Reports substitution. 1260.55 Section 1260...

14 CFR 1260.55 - Reports substitution.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Reports substitution. 1260.55 Section 1260...

How much could be saved in Chinese hospitals in procurement of anti-hypertensives and anti-diabetics?

PubMed

Sun, Jing; Ren, Luo; Wirtz, Veronika

2016-09-01

Efficient use of government funding has been increasingly relevant for the success and sustainability of ongoing health-system reform in China; however, as there is no generic substitution policy, patients and basic health-insurance programs pay more for public-preferred brand originators. Such phenomenon is especially typical in public hospitals. The objective of this study is to estimate the potential cost savings in procurement by Chinese public hospitals when switching from brand originators of anti-hypertensive and anti-diabetic medications to their generic equivalents between 2012-2014. IMS Health volume and value consumption data (IMS China Hospitals Audit system 2012-2014) were used, which covered all Chinese hospitals with 100 beds and above. The top 60% IMS volume consumption of respective anti-hypertensive and anti-diabetic medication with unique dosage form and strength were included. The potential cost savings were calculated from a switch of brand originators with their generic equivalents on the Chinese and international market. An independent sample t-test was conducted to compare the difference of proportion of cost savings in value between the Chinese and international market. An average of 44% (US$44 million) and 87% (US$90 million) and a total of US$1.4 and 2.8 billion (2014 US$) could be saved from a switch from originator brand anti-hypertensives and anti-diabetics to domestically and internationally available generic equivalents, respectively. The differences of cost savings (in proportion) between domestic and international market were statistically significant (α = 0.005, p = 0.003, p = 0.002, p = 0.000). Expensive brand originators dominated the anti-hypertensive and anti-diabetic market in Chinese hospitals between 2012-2014. Preference of brand originators wastes a huge amount of health resources in China and these limited resources could have been used more efficiently. As one of the world's key generic suppliers, if China wants to use its health resource more efficiently on medicines, comprehensive measures are needed to address both demand-side (consumers' low trust in the quality of local generics) and supply-side barriers (health professionals' preference of brand originators).

26 CFR 601.505 - Revocation, change in representation and substitution or delegation of representative.

Code of Federal Regulations, 2010 CFR

2010-04-01

... authorizes the substitution or delegation. An employee of a recognized representative may not be substituted... substitution or delegation of representative. 601.505 Section 601.505 Internal Revenue INTERNAL REVENUE SERVICE... Practice Requirements § 601.505 Revocation, change in representation and substitution or delegation of...

14 CFR § 1260.55 - Reports substitution.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of such reports... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Reports substitution. § 1260.55 Section Â...

Ionic liquids comprising heteraromatic anions

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

Schneider, William F.; Brennecke, Joan F.; Maginn, Edward J.

2018-04-24

Some embodiments described herein relate to ionic liquids comprising an anion of a heteraromatic compound such as optionally substituted pyrrolide, optionally substituted pyrazolide, optionally substituted indolide, optionally substituted phospholide, or optionally substituted imidazolide. Methods and devices for gas separation or gas absorption related to these ionic liquids are also described herein.

Potential savings associated with drug substitution in Medicare Part D: the Translating Research into Action for Diabetes (TRIAD) study.

PubMed

Duru, O Kenrik; Ettner, Susan L; Turk, Norman; Mangione, Carol M; Brown, Arleen F; Fu, Jeffery; Simien, Leslie; Tseng, Chien-Wen

2014-01-01

Drug substitution is a promising approach to reducing medication costs. To calculate the potential savings in a Medicare Part D plan from generic or therapeutic substitution for commonly prescribed drugs. Cross-sectional, simulation analysis. Low-income subsidy (LIS) beneficiaries (n = 145,056) and non low-income subsidy (non-LIS) beneficiaries (n = 1,040,030) enrolled in a large, national Part D health insurer in 2007 and eligible for a possible substitution. Using administrative data from 2007, we identified claims filled for brand-name drugs for which a direct generic substitute was available. We also identified the 50 highest cost drugs separately for LIS and non-LIS beneficiaries, and reached consensus on which drugs had possible therapeutic substitutes (27 for LIS, 30 for non-LIS). For each possible substitution, we used average daily costs of the original and substitute drugs to calculate the potential out-of-pocket savings, health plan savings, and when applicable, savings for the government/LIS subsidy. Overall, 39 % of LIS beneficiaries and 51 % of non-LIS beneficiaries were eligible for a generic and/or therapeutic substitution. Generic substitutions resulted in an average annual savings of $160 in the case of LIS beneficiaries and $127 in the case of non-LIS beneficiaries. Therapeutic substitutions resulted in an average annual savings of $452 in the case of LIS beneficiaries and $389 in the case of non-LIS beneficiaries. Our findings indicate that drug substitution, particularly therapeutic substitution, could result in significant cost savings. There is a need for additional studies evaluating the acceptability of therapeutic substitution interventions within Medicare Part D.

Analyzing generic and branded substitution patterns in the Netherlands using prescription data.

PubMed

Pechlivanoglou, Petros; van der Veen, Willem Jan; Bos, Jens H; Postma, Maarten J

2011-04-27

As in other societies, pharmaceutical expenditures in the Netherlands are rising every year. As a consequence, needs for cost control are often expressed. One possible solution for cost control could come through increasing generic substitution by pharmacists. We aim to analyse the extent and nature of substitution in recent years and estimate the likelihood of generic or branded substitution in Dutch pharmacies in relation to various characteristics. We utilized a linked prescription dataset originating from a general practitioner (GP) and a pharmacy database, both from the northern Netherlands. We selected specific drugs of interest, containing about 55,000 prescriptions from 15 different classes. We used a crossed generalized linear mixed model to estimate the effects that certain patient and pharmacy characteristics as well as timing have on the likelihood that a prescription will eventually be substituted by the pharmacist. Generic substitution occurred at 25% of the branded prescriptions. Generic substitution was more likely to occur earlier in time after patent expiry and to patients that were older and more experienced in their drug use. Individually owned pharmacies had a lower probability of generic substitution compared to chain pharmacies. Oppositely, branded substitution occurred in 10% of generic prescriptions and was positively related to the patients' experience in branded use. Individually owned pharmacies were more likely to substitute a generic drug to a branded compared to other pharmacies. Antidepressant and PPI prescriptions were less prone to generic and more prone to branded substitution. Analysis of prescription substitution by the pharmacist revealed strong relations between substitution and patient experience on drug use, pharmacy status and timing. These findings can be utilised to design further strategies to enhance generic substitution.

40 CFR 721.9798 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenesulfonic acid, 2,2â²-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl]amino]-, sodium salt (generic). 721.9798... Substances § 721.9798 Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5...

40 CFR 721.9798 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenesulfonic acid, 2,2â²-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5-triazin-2-yl]amino]-, sodium salt (generic). 721.9798... Substances § 721.9798 Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-substituted-6-substituted-1,3,5...

Sugar Substitutes

MedlinePlus

... Substitutes Share Print Sugar substitutes are chemical or plant-based substances used to sweeten or enhance the ... made with saccharin. Stevia sweeteners Stevia is a plant-based sugar substitute that has no calories. The ...

How Do Substitute Teachers Substitute? An Empirical Study of Substitute-Teacher Labor Supply

ERIC Educational Resources Information Center

Gershenson, Seth

2012-01-01

This paper examines the daily labor supply of a potentially important, but often overlooked, source of instruction in U.S. public schools: substitute teachers. I estimate a sequential binary-choice model of substitute teachers' job-offer acceptance decisions using data on job offers made by a randomized automated calling system. Importantly, this…

Mono- and tetra-substituted zinc(II) phthalocyanines containing morpholinyl moieties: Synthesis, antifungal photodynamic activities, and structure-activity relationships.

PubMed

Zheng, Bi-Yuan; Ke, Mei-Rong; Lan, Wen-Liang; Hou, Lu; Guo, Jun; Wan, Dong-Hua; Cheong, Ling-Zhi; Huang, Jian-Dong

2016-05-23

A series of zinc(II) phthalocyanines (ZnPcs) mono-substituted and tetra-substituted with morpholinyl moieties and their quaternized derivatives have been synthesized and evaluated for their antifungal photodynamic activities toward Candida albicans. The α-substituted, quaternized, and mono-substituted ZnPcs are found to have higher antifungal photoactivity than β-substituted, neutral, and tetra-substituted counterparts. The cationic α-mono-substituted ZnPc (6a) exhibits the highest photocytotoxicity. Moreover, it is more potent than axially di-substituted analogue. The different photocytotoxicities of these compounds have also been rationalized by investigating their spectroscopic and photochemical properties, aggregation trend, partition coefficients, and cellular uptake. The IC90 value of 6a against C. albicans cells is as low as 3.3 μM with a light dose of 27 J cm(-2), meaning that 6a is a promising candidate as the antifungal photosensitizer for future investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

40 CFR Appendix B to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Code of Federal Regulations, 2010 CFR

2010-07-01

... Use Conditions Substitutes Application Substitute Decision Conditions Comments Electronics Cleaning w.... Electronics cleaning w/CFC-113 Dibromomethane Unacceptable High ODP; other alternatives exist. Electronics...

Zn-site Substitution Effect in YbCo2Zn20

NASA Astrophysics Data System (ADS)

Kobayashi, Riki; Takamura, Haruki; Higa, Yasuyuki; Ikeda, Yoichi; Matsubayashi, Kazuyuki; Uwatoko, Yoshiya; Yoshizawa, Hideki; Aso, Naofumi

2017-04-01

We have investigated the substitution effect of YbCo2(Zn1-xTx)20 (T = Cu, Ga, and Cd) systems by using the experiments of X-ray powder diffraction (XRPD), specific heat, magnetic susceptibility, magnetization, and electrical resistivity in order to find out a material that approaches a quantum critical point by chemical pressure. The XRPD and electrical resistivity measurements clarify that the Cu-substitution makes the lattice constants shrink and keeps the magnetic electrical resistivity high, while the Ga- and the Cd-substitution show opposite relation of the Cu-substitution. However, we could not detect clear substitution effect in the specific heat, magnetic susceptibility, and magnetization measurements of Cu-substitution system within our experiments. It is necessary that to study the Cu-substitution samples that have higher x value at lower temperature.

Advances in Skin Regeneration Using Tissue Engineering.

PubMed

Vig, Komal; Chaudhari, Atul; Tripathi, Shweta; Dixit, Saurabh; Sahu, Rajnish; Pillai, Shreekumar; Dennis, Vida A; Singh, Shree R

2017-04-07

Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.

Effect of Heating on DPPH Radical Scavenging Activity of Meat Substitute

PubMed Central

Song, Hyeun Sung; Bae, Jun Kyu; Park, Inshik

2013-01-01

This study was conducted to evaluate the increase of DPPH radical scavenging activity of meat substitute by heating. The meat substitute showed higher DPPH radical scavenging activity than those of other foods rich in protein such as beef, pork, chicken, and soybean curd. The DPPH radical scavenging activity of meat substitute was dependent upon concentration, heating temperature and heating time of meat substitute. The DPPH radical scavenging activity of meat substitute was enhanced with increasing heating temperature and time. The increase of DPPH radical scavenging activity was only applied to meat substitute without showing any activation in other foods rich in protein such as beef, pork, chicken, and soybean curd. PMID:24471114

Effect of Heating on DPPH Radical Scavenging Activity of Meat Substitute.

PubMed

Song, Hyeun Sung; Bae, Jun Kyu; Park, Inshik

2013-03-01

This study was conducted to evaluate the increase of DPPH radical scavenging activity of meat substitute by heating. The meat substitute showed higher DPPH radical scavenging activity than those of other foods rich in protein such as beef, pork, chicken, and soybean curd. The DPPH radical scavenging activity of meat substitute was dependent upon concentration, heating temperature and heating time of meat substitute. The DPPH radical scavenging activity of meat substitute was enhanced with increasing heating temperature and time. The increase of DPPH radical scavenging activity was only applied to meat substitute without showing any activation in other foods rich in protein such as beef, pork, chicken, and soybean curd.

Study on effects of powder and flake chemistry and morphology on the properties of Al-Cu-Mg-X-X-X powder metallurgy advanced aluminum alloys

NASA Technical Reports Server (NTRS)

Meschter, P. J.; Lederich, R. J.; Oneal, J. E.

1986-01-01

A study was conducted: (1) to develop rapid solidification processed (RSP) dispersoid-containing Al-3Cu-2Li-1Mg-0.2Zr alloys as substitutes for titanium alloys and commercial 2XXX aluminum alloys for service to at least 150 C; and (2) to develop RSP Al-4Li-Cu-Mg-Zr alloys as substitutes for high-strength commercial 7XXX alloys in ambient-temperature applications. RSP Al-3Cu-2Li-1Mg-0.2Zr alloys have density-normalized yield stresses at 150 C up to 52% larger than that of 2124-T851 and up to 30% larger than that of Ti-6Al-4V. Strength at 150 C in these alloys is provided by thermally stable delta' (Al3Li), T1 (Al2LiCu), and S' (Al2CuMg) precipitates. Density-normalized yield stresses of RSP Al-3Cu-2Li-1Mg-0.2Zr alloys are up to 100% larger than that of 2124-T851 and equivalent to that of Al-8Fe-4Ce at 260 C. Strength in the RSP alloys at 260 C is provided by incoherent dispersoids and subboundary constituent particles such as T1 and S. The RSP alloys are attractive substitutes in less than or = 100-h exposures for 2xxx and Al-4Fe-Ce alloys up to 260 C and for titanium alloys up to 150 C. RSP Al-4Li-Cu-Mg-Zr alloys have ambient-temperature yield and ultimate tensile stresses similar to that of 7050-T7651, and are 14% less dense. RSP Al-4Li-0.5Cu-1.5Mg-0.2Zr has a 20% higher specific yield stress, 40% higher specific elastic modulus, and superior corrosion resistance compared to the properties of 7050-T7651. Strength in the Al-4Li-Cu-Mg-Zr alloy class is primarily provided by the substructure and delta' precipitates and is independent of Cu:Mg ratio. Improvements in fracture toughness and transverse-orientation properties in both alloy classes depend on improved melt practices to eliminate oxide inclusions which are incorporated into the consolidated forms.

Mechanistic investigations of imine hydrogenation catalyzed by dinuclear iridium complexes.

PubMed

Martín, Marta; Sola, Eduardo; Tejero, Santiago; López, José A; Oro, Luis A

2006-05-15

Treatment of [Ir2(mu-H)(mu-Pz)2H3(NCMe)(PiPr3)2] (1) with one equivalent of HBF4 or [PhNH=CHPh]BF4 affords efficient catalysts for the homogeneous hydrogenation of N-benzylideneaniline. The reaction of 1 with HBF4 leads to the trihydride-dihydrogen complex [Ir2(mu-H)(mu-Pz)2H2(eta2-H2)(NCMe)(PiPr3)2]BF4 (2), which has been characterized by NMR spectroscopy and DFT calculations on a model complex. Complex 2 reacts with imines such as tBuN=CHPh or PhN=CHPh to afford amine complexes [Ir2(mu-H)(mu-Pz)2H2(NCMe){L}(PiPr3)2]BF4 (L = NH(tBu)CH2Ph, 3; NH(Ph)CH2Ph, 4) through a sequence of proton- and hydride-transfer steps. Dihydrogen partially displaces the amine ligand of 4 to form 2; this complements a possible catalytic cycle for the N-benzylideneaniline hydrogenation in which the amine-by-dihydrogen substitution is the turnover-determining step. The rates of ligand substitution in 4 and its analogues with labile ligands other than amine are dependent upon the nature of the leaving ligand and independent on the incoming ligand concentration, in agreement with dissociative substitutions. Water complex [Ir2(mu-H)(mu-Pz)2H2(NCMe)(OH2)(PiPr3)2]BF4 (7) hydrolyzes N-benzylideneaniline, which eventually affords the poor hydrogenation catalyst [Ir2(mu-H)(mu-Pz)2H2(NCMe)(NH2Ph)(PiPr3)2]BF4 (11). The rate law for the catalytic hydrogenation in 1,2-dichloroethane with complex [Ir2(mu-H)(mu-Pz)2H2(OSO2CF3)(NCMe)(PiPr3)2] (8) as catalyst precursor is rate = k[8]{p(H2)}; this is in agreement with the catalytic cycle deduced from the stochiometric experiments. The hydrogenation reaction takes place at a single iridium center of the dinuclear catalyst, although ligand modifications at the neighboring iridium center provoke changes in the hydrogenation rate. Even though this catalyst system is also capable of effectively hydrogenating alkenes, N-benzylideneaniline can be selectively hydrogenated in the presence of simple alkenes.