Sample records for acceptable tolerability profile

  1. How a tolerant past affects the present: historical tolerance and the acceptance of Muslim expressive rights.

    PubMed

    Smeekes, Anouk; Verkuyten, Maykel; Poppe, Edwin

    2012-11-01

    Three studies, conducted in The Netherlands, examined the relationship between a tolerant representation of national history and the acceptance of Muslim expressive rights. Following self-categorization theory, it was hypothesized that historical tolerance would be associated with greater acceptance of Muslim expressive rights, especially for natives who strongly identify with their national in-group. Furthermore, it was predicted that the positive effect of representations of historical tolerance on higher identifiers' acceptance could be explained by reduced perceptions of identity incompatibility. The results of Study 1 confirmed the first hypothesis, and the results of Study 2 and Study 3 supported the second hypothesis. These findings underline the importance of historical representations of the nation for understanding current reactions toward immigrants. Importantly, the results show that a tolerant representation of national history can elevate acceptance of immigrants, especially among natives who feel a relatively strong sense of belonging to their nation.

  2. Liver microRNA profile of induced allograft tolerance

    PubMed Central

    Vitalone, Matthew James; Wai, Liang; Fujiki, Masato; Lau, Audrey H.; Littau, Erik; Esquivel, Carlos; Martinez, Olivia M.; Krams, Sheri M.

    2016-01-01

    Introduction Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total Lymphoid Irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance. Methods To identify the miRNAs associated with TLI-induced tolerance we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (DA→Lewis) of orthotropic liver transplants that received post-transplant TLI, allogeneic recipients that were not treated post-transplantation and experienced acute rejection, and native DA livers. QPCR miRNA array cards were used to profile liver grafts. Results We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared to syngeneic livers, with 80% of the miRNAs increased. In established tolerance 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared to syngeneic livers. A principal component analysis of all miRNAs assayed, demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers. Conclusions The miRNA profile of established tolerant allografts is very similar to syngeneic grafts suggesting tolerance may be a return to an immunological state of quiescence. PMID:26950716

  3. Tolerance, Acceptance and the Virtue of Orthonomy: A Reply to Lawrence Blum and Brenda Almond

    ERIC Educational Resources Information Center

    Ciurria, Michelle

    2011-01-01

    In the "Journal of Moral Education," 39(2), Brenda Almond and Lawrence Blum debate the importance of tolerance versus acceptance in sex education. Blum defines acceptance as "positive regard", in contradistinction to mere tolerance, "a live and let live attitude toward others, an acceptance of coexistence, but with a…

  4. Multiparameter immune profiling of operational tolerance in liver transplantation.

    PubMed

    Martínez-Llordella, M; Puig-Pey, I; Orlando, G; Ramoni, M; Tisone, G; Rimola, A; Lerut, J; Latinne, D; Margarit, C; Bilbao, I; Brouard, S; Hernández-Fuentes, M; Soulillou, J-P; Sánchez-Fueyo, A

    2007-02-01

    Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter 'fingerprint' of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for gammadelta T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+ CD25+ T-cells and Vdelta1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.

  5. The Relation Between Death Attitude and Distress: Tolerance, Aggression, and Anger.

    PubMed

    Esnaashari, Fatemeh; Kargar, Flor Rezaei

    2018-06-01

    The aim of this research was to determine the relation between death attitude and distress tolerance and aggression and anger. For this, 135 subjects among 7,535 professional and specialist members of the Iran National Library were selected using convenience sampling method. They replied to Death Attitudes Profile-Revised, distress tolerance questionnaire, and aggression questionnaire. The results showed that the attitudes of approach acceptance, neutral acceptance, and escape acceptance had positive relation to distress tolerance and negative relation to aggression and anger while the attitudes of fear of death and death avoidance had negative relation to distress tolerance and positive relation to aggression and anger. Furthermore, all death attitudes predicted distress tolerance. But only the attitudes of approach acceptance, escape acceptance, fear of death, and death avoidance predicted aggression, and only approach acceptance, neutral acceptance, fear of death, and death avoidance predicted anger.

  6. Labeling Sexual Victimization Experiences: The Role of Sexism, Rape Myth Acceptance, and Tolerance for Sexual Harassment.

    PubMed

    LeMaire, Kelly L; Oswald, Debra L; Russell, Brenda L

    2016-01-01

    This study investigated whether attitudinal variables, such as benevolent and hostile sexism toward men and women, female rape myth acceptance, and tolerance of sexual harassment are related to women labeling their sexual assault experiences as rape. In a sample of 276 female college students, 71 (25.7%) reported at least one experience that met the operational definition of rape, although only 46.5% of those women labeled the experience "rape." Benevolent sexism, tolerance of sexual harassment, and rape myth acceptance, but not hostile sexism, significantly predicted labeling of previous sexual assault experiences by the victims. Specifically, those with more benevolent sexist attitudes toward both men and women, greater rape myth acceptance, and more tolerant attitudes of sexual harassment were less likely to label their past sexual assault experience as rape. The results are discussed for their clinical and theoretical implications.

  7. Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects

    PubMed Central

    Arya, Jaya; Henry, Sebastien; Kalluri, Haripriya; McAllister, Devin V.; Pewin, Winston P.; Prausnitz, Mark R.

    2017-01-01

    To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days. Microneedle patches could be administered by hand without the need of an applicator and delivery efficiencies were similar for investigator-administration and self-administration. Microneedle patch administration was not considered painful and the large majority of subjects were somewhat or fully confident that they self-administered patches correctly. Microneedle patches were overwhelmingly preferred over conventional needle and syringe injection. Altogether, these results demonstrate that dissolving microneedle patches were well tolerated, easily usable and strongly accepted by human subjects, which will facilitate further clinical translation of this technology. PMID:28285193

  8. The moderating and mediating roles of self-acceptance and tolerance to others in the relationship between mindfulness and subjective well-being.

    PubMed

    Xu, Wei; Oei, Tian Ps; Liu, Xinghua; Wang, Xiaoming; Ding, Chen

    2016-07-01

    This study explored the moderating and mediating influences of self-acceptance and tolerance to others in the relationship between mindfulness and subjective well-being. In total, 301 (130 males) university students completed the Five-Facet Mindfulness Questionnaire, Index of Well-being, Self-acceptance Questionnaire, and Tolerance Scale. The results showed that the positive link between mindfulness and subjective well-being was significantly mediated by self-acceptance only. Tolerance played a moderating role. The implications of the results for relevant research and mindfulness training were discussed. © The Author(s) 2014.

  9. Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation.

    PubMed

    Caprioli, Giovanni; Mammoli, Valerio; Ricciutelli, Massimo; Sagratini, Gianni; Ubaldi, Massimo; Domi, Esi; Mennuni, Laura; Sabatini, Chiara; Galimberti, Chiara; Ferrari, Flora; Milia, Chiara; Comi, Eleonora; Lanza, Marco; Giannella, Mario; Pigini, Maria; Del Bello, Fabio

    2015-12-15

    Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1, 2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1, 2, and 3 have been selected in that, although bearing a common scaffold, preferentially bind to α2-adrenoceptors, imidazoline I2 receptors, or both systems, respectively. Such compounds have been tested in vivo by measuring the paw withdrawal threshold to mechanical pressure after complete Freund's adjuvant injection. To determine the ligand levels in rat plasma, an HPLC-mass spectrometry method has been developed. All the compounds significantly reduced the induction of morphine tolerance, showing different potency and duration of action. Indeed, the selective imidazoline I2 receptor interaction (2) restored the analgesic response by maintaining the same time-dependent profile observed after a single morphine administration. Differently, the selective α2C-adrenoceptor activation (1) or the combination between α2C-adrenoceptor activation and imidazoline I2 receptor engagement (3) promoted a change in the temporal profile of morphine analgesia by maintaining a mild but long lasting analgesic effect. Interestingly, the kinetics of compounds in rat plasma supported the pharmacodynamic data. Therefore, this study highlights that both peculiar biological profile and bioavailability of such ligands complement each other to modulate the reduction of morphine tolerance. Based on these observations, 1-3 can be considered useful leads in the design of new drugs able to turn off the undesired tolerance induced by opioids. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Playing a Videogame with a Sexualized Female Character Increases Adolescents' Rape Myth Acceptance and Tolerance Toward Sexual Harassment.

    PubMed

    Driesmans, Karolien; Vandenbosch, Laura; Eggermont, Steven

    2015-04-01

    Prior research has documented favorable effects of active and educational videogames among adolescents. However, research on potential negative effects of such games is limited. Scholars have called attention to games portraying sexualized female characters. The purpose of the current study was to experimentally investigate the effect of playing a videogame with a sexualized female character on adolescents' acceptance of rape myths and tolerance for sexual harassment. Fifty-seven secondary school pupils, 12-15 years of age, participated in a 2 (gender: boys versus girls)×2 (game character: nonsexualized versus sexualized female) factorial design experiment. Participants played a game for 15 minutes and were randomly assigned to one of the two game characters. Afterward, they completed established scales to assess rape myth acceptance and tolerance for sexual harassment. Analyses of variance showed greater acceptance of rape myths (P=0.039) and greater tolerance of sexual harassment (P=0.046) in adolescents who played with the sexualized woman compared with adolescents in the control condition. We did not find significant differences between boys and girls or any interaction effect between gender and game character. Findings suggest that gameplaying with a sexualized woman may increase adolescents' acceptance of rape myths and tolerance for sexual harassment. These findings highlight attention to the use of sexualized female game characters in (educational and active) videogames that target adolescents.

  11. A new measurement method of profile tolerance for the LAMOST focal plane

    NASA Astrophysics Data System (ADS)

    Zhou, Zengxiang; Jin, Yi; Zhai, Chao; Xing, Xiaozheng

    2008-07-01

    There were a few methods taken in the profile tolerance measurement of the LAMOST Focal Plane Plate. One of the methods was to use CMM (Coordinate Measurement Machine) to measure the points on the small Focal Plane Plate and calculate the points whether or not in the tolerance zone. In this process there are some small shortcomings. The measuring point positions on the Focal Plane Plate are not the actual installation location of the optical fiber positioning system. In order to eliminate these principle errors, a measuring mandrel is inserted into the unit-holes, and the precision for the mandrel with the hole is controlled in the high level. Then measure the center of the precise target ball which is placed on the measuring mandrel by CMM. At last, fit a sphere surface with the measuring center points of the target ball and analyze the profile tolerance of the Focal Plane Plate. This process will be more in line with the actual installation location of the optical fiber positioning system. When use this method to judge the profile tolerance can provide the reference date for maintaining the ultra error unit-holes on the Focal Plane Plate. But when insert the measuring mandrel into the unit hole, there are manufacturing errors in the measuring mandrel, target ball and assembly errors. All these errors will bring the influence in the measurement. In the paper, an impact evaluation assesses the intermediate process with all these errors through experiments. And the experiment results show that there are little influence when use the target ball and the measuring mandrel in the measurement of the profile tolerance. Instead, there are more advantages than many past use of measuring methods.

  12. Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance.

    PubMed

    Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

    2015-03-01

    This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice.

  13. Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance

    PubMed Central

    Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

    2015-01-01

    This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. PMID:25838891

  14. VASCULARIZED COMPOSITE ALLOGRAFT TRANSPLANT SURVIVAL IN MINIATURE SWINE: IS MHC TOLERANCE SUFFICIENT FOR ACCEPTANCE OF EPIDERMIS?

    PubMed Central

    Cetrulo, Curtis L.; Torabi, Radbeh; Scalea, Joseph R.; Shimizu, Akira; Leto Barone, Angelo A.; Gillon, Brad C.; Tasaki, Masayuki; Leonard, David A.; Cormack, Taylor A.; Villani, Vincenzo; Randolph, Mark A.; Sachs, David H.; Yamada, Kazuhiko

    2014-01-01

    Background We have previously reported that MGH miniature swine which had accepted class-I mismatched kidneys long-term (LT) following 12 days of high dose Cyclosporine (CyA), uniformly accepted donor-MHC matched kidneys without immunosuppression but rejected donor-MHC matched split-thickness skin grafts (STSG) by day 25, without changes in renal graft function or anti-donor in vitro responses. We have now tested whether this “split tolerance” would also be observed for the primarily-vascularized skin of vascularized composite allografts (VCAs). Methods Group 1 animals (n=3) received donor-MHC matched VCAs <70 days following primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched t KTx followed by a donor-matched VCA >200 days after primary KTx. Results Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of 3 recipients of VCAs including epidermis in Group 2 accepted all components of the VCAs (>200 days). The other two recipients lost only the epidermis at day 45 and 85, with survival of the remainder of the VCA long-term. Conclusions All tissues of a VCA are accepted long-term on animals tolerant of class-I mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared to STSG, but not indefinite. Exposure of tolerant animals to second donor-matched kidneys prior to VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney. PMID:24056624

  15. Cereal bars produced with banana peel flour: evaluation of acceptability and sensory profile.

    PubMed

    Carvalho, Vania Silva; Conti-Silva, Ana Carolina

    2018-01-01

    A mixture design was used to investigate the effects of banana peel flour, rice flakes and oat flour on sensory acceptability of cereal bars, with subsequent evaluation of sensory profile of products identified as having high acceptability. Regions of greater response for acceptability of the cereal bars, which are dependent on the three investigated components, were found. Although having good acceptability, sensory profiles of cereal bars were different. A cereal bar with the lowest quantity of banana peel flour was described as having a higher amount of rice flakes, chewiness and crispness, while formulations with intermediate and highest quantities of banana peel flour were described by darker color, higher banana aroma and bitter taste. Contrary to expectations, banana flavor of cereal bar with highest quantity of banana peel flour was lower than cereal bars with intermediate quantities. Cereal bars were not different in terms of hardness and adhesiveness and they also had a similar sweet taste and oat flavor. The use of banana peel flour in production of cereal bars is feasible and, even with different sensory profiles, cereal bars with banana peel flour are acceptable, which may favor the development of new products for different market niches. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity

    PubMed Central

    Ravelli, A; van der Meulen, J H P; Osmond, C; Barker, D; Bleker, O

    2000-01-01

    BACKGROUND—It is generally accepted that breast feeding has a beneficial effect on the health of infants and young children. Recently, a few studies have shown that the method of infant feeding is also associated with cardiovascular disease and its risk factors in adult life.
AIMS—To examine the association between the method of infant feeding in the first weeks after birth and glucose tolerance, plasma lipid profile, blood pressure, and body mass in adults aged 48-53 years.
METHODS—Subjects born at term between 1 November 1943 and 28 February 1947 in the Wilhelmina Gasthuis in Amsterdam around the time of a severe period of famine (late November 1944 to early May 1945). For 625 subjects, information was available about infant feeding at the time of discharge from hospital (on average 10.4days after birth), and at least one blood sample after an overnight fast.
RESULTS—Subjects who were bottle fed had a higher mean 120 minute plasma glucose concentration after a standard oral glucose tolerance test than those who were exclusively breast fed. They also had a higher plasma low density lipoprotein (LDL) cholesterol concentration, a lower high density lipoprotein (HDL) cholesterol concentration, and a higher LDL/HDL ratio. Systolic blood pressure and body mass index were not affected by the method of infant feeding.
CONCLUSIONS—Exclusive breast feeding seems to have a protective effect against some risk factors for cardiovascular disease in later life.

 PMID:10685933

  17. Dietary live yeast alters metabolic profiles, protein biosynthesis and thermal stress tolerance of Drosophila melanogaster.

    PubMed

    Colinet, Hervé; Renault, David

    2014-04-01

    The impact of nutritional factors on insect's life-history traits such as reproduction and lifespan has been excessively examined; however, nutritional determinant of insect's thermal tolerance has not received a lot of attention. Dietary live yeast represents a prominent source of proteins and amino acids for laboratory-reared drosophilids. In this study, Drosophila melanogaster adults were fed on diets supplemented or not with live yeast. We hypothesized that manipulating nutritional conditions through live yeast supplementation would translate into altered physiology and stress tolerance. We verified how live yeast supplementation affected body mass characteristics, total lipids and proteins, metabolic profiles and cold tolerance (acute and chronic stress). Females fed with live yeast had increased body mass and contained more lipids and proteins. Using GC/MS profiling, we found distinct metabolic fingerprints according to nutritional conditions. Metabolite pathway enrichment analysis corroborated that live yeast supplementation was associated with amino acid and protein biosyntheses. The cold assays revealed that the presence of dietary live yeast greatly promoted cold tolerance. Hence, this study conclusively demonstrates a significant interaction between nutritional conditions and thermal tolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Students' Acceptance of Tablet PCs in Italian High Schools: Profiles and Differences

    ERIC Educational Resources Information Center

    Villani, Daniela; Morganti, Laura; Carissoli, Claudia; Gatti, Elena; Bonanomi, Andrea; Cacciamani, Stefano; Confalonieri, Emanuela; Riva, Giuseppe

    2018-01-01

    The tablet PC represents a very popular mobile computing device, and together with other technologies it is changing the world of education. This study aimed to explore the acceptance of tablet PC of Italian high school students in order to outline the typical students' profiles and to compare the acceptance conveyed in two types of use (learning…

  19. The perception of children's computer-imaged facial profiles by patients, mothers and clinicians.

    PubMed

    Miner, Robert M; Anderson, Nina K; Evans, Carla A; Giddon, Donald B

    2007-11-01

    To demonstrate the usefulness of a new imaging system for comparing the morphometric bases of children's self-perception of their facial profile with the perceptions of their mothers and treating clinicians. Rather than choosing among a series of static images, a computer imaging program was developed to elicit a range of acceptable responses or tolerance for change from which a midpoint of acceptability was derived. Using the method of Giddon et al, three profile features (upper and lower lips and mandible) from standardized images of 24 patients aged 8- 15 years were distorted and presented to patients, parents, and clinicians in random order as slowly moving images (four frames per second) from retrusive and protrusive extremes. Subjects clicked the mouse when the image became acceptable and released it when it was no longer acceptable. Subjects responded similarly to a neutral facial profile. Patients and their mothers overestimated the protrusiveness of the mandible of the actual pretreatment profile. Consistent with related studies, mothers had a smaller tolerance for change in the soft tissue profile than the children or clinicians. The magnitudes of the children's self-preference and preferred change in a neutral face were also significantly correlated. Both patients and mothers preferred a more protrusive profile than that of the actual or neutral face for the patient and neutral face. Imaging software can be used with children to compare their preferences with those of parents and clinicians to facilitate treatment planning and patient satisfaction.

  20. Evaluating the tolerability and acceptability of an alcohol-based hand rub - real-life experience with the WHO protocol.

    PubMed

    Wolfensberger, Aline; Durisch, Nina; Mertin, Juliane; Ajdler-Schaeffler, Evelyne; Sax, Hugo

    2015-01-01

    Optimizing user satisfaction with alcohol-based hand rubs (ABHR) may be vital to enhance hand hygiene performance. This study tested the tolerability and acceptability of a new ABHR (EVO9; Ecolab) in healthcare workers under daily working conditions and evaluated the practicability of the corresponding WHO protocol. We strictly applied the WHO single product ABHR evaluation protocol. A trained observer assessed hand skin conditions of healthy volunteers using at least 30 ml ABHR per day during their clinical work at baseline, day 3-5 and one month (visit 1-3). Participants rated ABHR tolerability and acceptability at visit 2 and 3. Additionally, we registered study time for participants and study team. Among 46 volunteers, 76% were female; 37% nurses, 28% physicians. Skin was observer-rated "not" or "incidentally" dry in 64.4%, 77.8%, and 90.9% participants at visit 1, 2, and 3, respectively. EVO9 was scored ≥5 (progressive scale, 1-7) for appearance, intactness, moisture content, and sensation by 95.7%, 97.7%, 88.9%, and 97.8% participants at visit 3, respectively. All WHO benchmarks were exceeded except for "speed of drying" at visit 2, and "texture" at visit 2 and 3. Cumulative study time expenditure was 14 days for the observer and four days for participants. EVO9 was well tolerated and accepted according to the WHO single ABHR evaluation protocol with the potential for improvement for stickiness. The WHO protocol is feasible but requires considerable time and logistics. It does not preclude bias, in this case especially due to the necessary switch to personal dispensers.

  1. Metabolic profiles of flooding-tolerant mechanism in early-stage soybean responding to initial stress.

    PubMed

    Wang, Xin; Zhu, Wei; Hashiguchi, Akiko; Nishimura, Minoru; Tian, Jingkui; Komatsu, Setsuko

    2017-08-01

    Metabolomic analysis of flooding-tolerant mutant and abscisic acid-treated soybeans suggests that accumulated fructose might play a role in initial flooding tolerance through regulation of hexokinase and phosphofructokinase. Soybean is sensitive to flooding stress, which markedly reduces plant growth. To explore the mechanism underlying initial-flooding tolerance in soybean, mass spectrometry-based metabolomic analysis was performed using flooding-tolerant mutant and abscisic-acid treated soybeans. Among the commonly-identified metabolites in both flooding-tolerant materials, metabolites involved in carbohydrate and organic acid displayed same profile at initial-flooding stress. Sugar metabolism was highlighted in both flooding-tolerant materials with the decreased and increased accumulation of sucrose and fructose, respectively, compared to flooded soybeans. Gene expression of hexokinase 1 was upregulated in flooded soybean; however, it was downregulated in both flooding-tolerant materials. Metabolites involved in carbohydrate/organic acid and proteins related to glycolysis/tricarboxylic acid cycle were integrated. Increased protein abundance of phosphofructokinase was identified in both flooding-tolerant materials, which was in agreement with its enzyme activity. Furthermore, sugar metabolism was pointed out as the tolerant-responsive process at initial-flooding stress with the integration of metabolomics, proteomics, and transcriptomics. Moreover, application of fructose declined the increased fresh weight of plant induced by flooding stress. These results suggest that fructose might be the critical metabolite through regulation of hexokinase and phosphofructokinase to confer initial-flooding stress in soybean.

  2. Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

    PubMed

    Gavin, Paul D; Simon, Lee S; Schlagheck, Thomas; Smith, Alisha J; Shakib, Sepehr

    2017-07-01

    To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM). Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h. Oxycodone was detected 8.0 ± 2.7-h postpatch administration, reaching a mean maximum plasma concentration of 3.41 ± 1.34 ng/ml at 49.3 ± 21.2 h. The safety profile was consistent with the application method and known side-effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation was observed. A 3-day application of the TPM/oxycodone patch demonstrated an acceptable safety profile and was well tolerated by healthy subjects, with limited dermal irritation following application.

  3. Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

    PubMed

    Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

    2017-04-16

    An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

  4. Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients.

    PubMed

    Martínez-Llordella, Marc; Lozano, Juan José; Puig-Pey, Isabel; Orlando, Giuseppe; Tisone, Giuseppe; Lerut, Jan; Benítez, Carlos; Pons, Jose Antonio; Parrilla, Pascual; Ramírez, Pablo; Bruguera, Miquel; Rimola, Antoni; Sánchez-Fueyo, Alberto

    2008-08-01

    A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.

  5. Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

    PubMed

    Guo, Lan; Ganguly, Abantika; Sun, Lingling; Suo, Fang; Du, Li-Lin; Russell, Paul

    2016-10-13

    Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron-sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5'-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms. Copyright © 2016 Guo et al.

  6. [HLA-G: from feto-maternal tolerance to organ acceptance].

    PubMed

    Carosella, Edgardo D

    2014-01-01

    HLA-G is a nonclassical class I molecule that differs from classical antigens by its restricted expression, very low polymorphism, expression of 7 different protein isoforms, and immune tolerance-inducing activity. HLA-G plays a key role in feto-maternal tolerance. Its interaction with three specific receptors expressed on immune cells (T, B, natural killer and antigen-presenting cells) allows it to act at all levels of the immune response. HLA-G can also be expressed by tumor cells and their microenvironment, endowing them with significant local tolerance. The same is true in some inflammatory and viral diseases.

  7. Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

    PubMed

    Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

    2017-01-01

    Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

  8. Tolerance of ambiguity, perfectionism and resilience are associated with personality profiles of medical students oriented to rural practice.

    PubMed

    Eley, Diann S; Leung, Janni K; Campbell, Narelle; Cloninger, C Robert

    2017-05-01

    Resilience, coping with uncertainty and learning from mistakes are vital characteristics for all medical disciplines - particularly rural practice. Levels of coping constructs were examined in medical students with and without a rural background or an interest in rural practice. Cross-sectional surveys identified two personality profiles, and their association with levels of Tolerance of Ambiguity, Resilience, Perfectionism-High Standards and Concern over mistakes as constructs indicative of coping. Medical students (N = 797) were stratified by rural background and degree of rural interest. Mediation analysis tested the effect of personality profile on levels of the coping constructs. More (72%) rural background students had Profile 1 which was associated with higher levels of Tolerance of Ambiguity, High standards, and Resilience, but lower Concern over mistakes. Non-rural background students reporting a strong rural interest also had Profile 1 (64%) and similar levels of coping constructs. Personality profile mediated the association between rural interest and levels of coping constructs regardless of background. Having a rural background or strong rural interest are associated with a personality profile that indicates a better capacity for coping. Personality may play a part in an individual's interest in rural practice. Rural workforce initiatives through education should encourage and nurture students with a genuine interest in rural practice - regardless of background.

  9. Galactinol synthase transcriptional profile in two genotypes of Coffea canephora with contrasting tolerance to drought.

    PubMed

    Santos, Tiago Benedito Dos; de Lima, Rogério Barbosa; Nagashima, Getúlio Takashi; Petkowicz, Carmen Lucia de Oliveira; Carpentieri-Pípolo, Valéria; Pereira, Luiz Filipe Protasio; Domingues, Douglas Silva; Vieira, Luiz Gonzaga Esteves

    2015-05-01

    Increased synthesis of galactinol and raffinose family oligosaccharides (RFOs) has been reported in vegetative tissues in response to a range of abiotic stresses. In this work, we evaluated the transcriptional profile of a Coffea canephora galactinol synthase gene (CcGolS1) in two clones that differed in tolerance to water deficit in order to assess the contribution of this gene to drought tolerance. The expression of CcGolS1 in leaves was differentially regulated by water deficit, depending on the intensity of stress and the genotype. In clone 109A (drought-susceptible), the abundance of CcGolS1 transcripts decreased upon exposure to drought, reaching minimum values during recovery from severe water deficit and stress. In contrast, CcGolS1 gene expression in clone 14 (drought-tolerant) was stimulated by water deficit. Changes in galactinol and RFO content did not correlate with variation in the steady-state transcript level. However, the magnitude of increase in RFO accumulation was higher in the tolerant cultivar, mainly under severe water deficit. The finding that the drought-tolerant coffee clone showed enhanced accumulation of CcGolS1 transcripts and RFOs under water deficit suggests the possibility of using this gene to improve drought tolerance in this important crop.

  10. Galactinol synthase transcriptional profile in two genotypes of Coffea canephora with contrasting tolerance to drought

    PubMed Central

    Santos, Tiago Benedito Dos; de Lima, Rogério Barbosa; Nagashima, Getúlio Takashi; Petkowicz, Carmen Lucia de Oliveira; Carpentieri-Pípolo, Valéria; Pereira, Luiz Filipe Protasio; Domingues, Douglas Silva; Vieira, Luiz Gonzaga Esteves

    2015-01-01

    Increased synthesis of galactinol and raffinose family oligosaccharides (RFOs) has been reported in vegetative tissues in response to a range of abiotic stresses. In this work, we evaluated the transcriptional profile of a Coffea canephora galactinol synthase gene (CcGolS1) in two clones that differed in tolerance to water deficit in order to assess the contribution of this gene to drought tolerance. The expression of CcGolS1 in leaves was differentially regulated by water deficit, depending on the intensity of stress and the genotype. In clone 109A (drought-susceptible), the abundance of CcGolS1 transcripts decreased upon exposure to drought, reaching minimum values during recovery from severe water deficit and stress. In contrast, CcGolS1 gene expression in clone 14 (drought-tolerant) was stimulated by water deficit. Changes in galactinol and RFO content did not correlate with variation in the steady-state transcript level. However, the magnitude of increase in RFO accumulation was higher in the tolerant cultivar, mainly under severe water deficit. The finding that the drought-tolerant coffee clone showed enhanced accumulation of CcGolS1 transcripts and RFOs under water deficit suggests the possibility of using this gene to improve drought tolerance in this important crop. PMID:26273221

  11. Sensory profile and acceptability for pitanga (Eugenia uniflora L.) nectar with different sweeteners.

    PubMed

    Freitas, Mírian Luisa Faria; Dutra, Mariana Borges de Lima; Bolini, Helena Maria André

    2016-12-01

    The objective of this study was to evaluate the sensory properties and acceptability of pitanga nectar samples prepared with sucrose and different sweeteners (sucralose, aspartame, stevia with 40% rebaudioside A, stevia with 95% rebaudioside A, neotame, and a 2:1 cyclamate/saccharin blend). A total of 13 assessors participated in a quantitative descriptive analysis and evaluated the samples in relation to the descriptor terms. The acceptability test was carried out by 120 fruit juice consumers. The results of the quantitative descriptive analysis of pitanga nectar showed that samples prepared with sucralose, aspartame, and the 2:1 cyclamate/saccharin blend had sensory profiles similar to that of the sample prepared with sucrose. Consumers' most accepted samples were prepared with sucrose, sucralose, aspartame, and neotame. The sweeteners that have the greatest potential to replace sucrose in pitanga nectar are sucralose and aspartame. © The Author(s) 2016.

  12. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

    PubMed

    Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

    2016-05-05

    In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. Published by Elsevier Ltd.

  13. Acceptance and commitment therapy improves exercise tolerance in sedentary women.

    PubMed

    Ivanova, Elena; Jensen, Dennis; Cassoff, Jamie; Gu, Fei; Knäuper, Bärbel

    2015-06-01

    To test the efficacy of an acute intervention derived from acceptance and commitment therapy (ACT) for increasing high-intensity constant work rate (CWR) cycle exercise tolerance in a group of low-active women age 18-45 yr. The secondary goals were to examine whether ACT would reduce perceived effort and improve in-task affect during exercise and increase postexercise enjoyment. In a randomized controlled trial, 39 women were randomized to either the experimental (using ACT-based cognitive techniques and listening to music during the CWR exercise tests) or a control group (listening to music during the CWR exercise tests). Before (CWR-1) and after the intervention (CWR-2), participants completed a CWR cycle exercise test at 80% of maximal incremental work rate (Wmax) until volitional exhaustion. On average, ACT (n = 18) and control (n = 21) groups were matched for age, body mass index, weekly leisure activity scores, and Wmax (all P > 0.05). Exercise tolerance time (ETT) increased by 15% from CWR-1 to CWR-2 for the ACT group (392.05 ± 146.4 vs 459.39 ± 209.3 s; mean ± SD) and decreased by 8% (384.71 ± 120.1 vs 353.86 ± 127.9 s) for the control group (P = 0.008). RPE were lower (e.g., by 1.5 Borg 6-20 scale units at 55% of ETT, P ≤ 0.01) during CWR-2 in the ACT versus that in the control group. By contrast, ACT had no effect on in-task affect. Exercise enjoyment was higher after CWR-2 in the ACT group versus that in the control group (P < 0.001). An acute ACT intervention increased high-intensity ETT and postexercise enjoyment and reduced perceived effort in low-active women. Further investigations of ACT as an effective intervention for enhancing the established health benefits of high-intensity exercise need to be provided.

  14. Acceptance, cognitive restructuring, and distraction as coping strategies for acute pain.

    PubMed

    Kohl, Annika; Rief, Winfried; Glombiewski, Julia Anna

    2013-03-01

    Little is known about treatment mechanisms underlying acceptance strategies. Acceptance is a strategy that is expected to increase pain tolerance more than distraction, while distraction should lead to lower pain intensity. The effect of cognitive restructuring on experimental pain has not yet been investigated. The present study aimed to explore differential short-term effects of acceptance, distraction, and cognitive restructuring on pain tolerance and intensity. Pain was induced in a sample of 109 female students using a thermode. We conducted analyses of covariance with instruction as the independent variable and posttest scores on pain variables as dependent variables, covarying for pretest scores. In addition, adherence to instructions and credibility of instructions were included as covariates. Acceptance led to a higher increase in pain tolerance than did cognitive restructuring of pain-related thoughts. No differences were detected between either acceptance and distraction or distraction and cognitive restructuring with respect to pain tolerance. Distraction led to lower pain intensity compared to acceptance. Cognitive restructuring did not differ from either acceptance or distraction with respect to pain intensity. As a short-term strategy, cognitive restructuring was not as useful as acceptance in increasing pain tolerance. Further studies should evaluate the preconditions under which different strategies are most effective. This study demonstrated that acceptance was superior to cognitive restructuring in increasing tolerance for experimentally induced pain, but was inferior to distraction with respect to decreasing pain intensity. Knowledge about the types of strategies that are useful in targeting diverse pain-related outcome measures is important for efforts to refine the treatment of chronic pain. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  15. KSC 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT) Report

    NASA Technical Reports Server (NTRS)

    Barbre, Robert E.

    2015-01-01

    This report documents analysis results of the Kennedy Space Center updated 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT). This test was designed to demonstrate that the new DRWP operates in a similar manner to the previous DRWP for use as a situational awareness asset for mission operations at the Eastern Range to identify rapid changes in the wind environment that weather balloons cannot depict. Data examination and two analyses showed that the updated DRWP meets the specifications in the OAT test plan and performs at least as well as the previous DRWP. Data examination verified that the DRWP provides complete profiles every five minutes from 1.8-19.5 km in vertical increments of 150 m. Analysis of 5,426 wind component reports from 49 concurrent DRWP and balloon profiles presented root mean square (RMS) wind component differences around 2.0 m/s. The DRWP's effective vertical resolution (EVR) was found to be 300 m for both the westerly and southerly wind component, which the best EVR possible given the DRWP's vertical sampling interval. A third analysis quantified the sensitivity to rejecting data that do not have adequate signal by assessing the number of first-guess propagations at each altitude. This report documents the data, quality control procedures, methodology, and results of each analysis. It also shows that analysis of the updated DRWP produced results that were at least as good as the previous DRWP with proper rationale. The report recommends acceptance of the updated DRWP for situational awareness usage as per the OAT's intent.

  16. Local tolerance testing under REACH: Accepted non-animal methods are not on equal footing with animal tests.

    PubMed

    Sauer, Ursula G; Hill, Erin H; Curren, Rodger D; Raabe, Hans A; Kolle, Susanne N; Teubner, Wera; Mehling, Annette; Landsiedel, Robert

    2016-07-01

    In general, no single non-animal method can cover the complexity of any given animal test. Therefore, fixed sets of in vitro (and in chemico) methods have been combined into testing strategies for skin and eye irritation and skin sensitisation testing, with pre-defined prediction models for substance classification. Many of these methods have been adopted as OECD test guidelines. Various testing strategies have been successfully validated in extensive in-house and inter-laboratory studies, but they have not yet received formal acceptance for substance classification. Therefore, under the European REACH Regulation, data from testing strategies can, in general, only be used in so-called weight-of-evidence approaches. While animal testing data generated under the specific REACH information requirements are per se sufficient, the sufficiency of weight-of-evidence approaches can be questioned under the REACH system, and further animal testing can be required. This constitutes an imbalance between the regulatory acceptance of data from approved non-animal methods and animal tests that is not justified on scientific grounds. To ensure that testing strategies for local tolerance testing truly serve to replace animal testing for the REACH registration 2018 deadline (when the majority of existing chemicals have to be registered), clarity on their regulatory acceptance as complete replacements is urgently required. 2016 FRAME.

  17. Sequence Tolerance of a Highly Stable Single Domain Antibody: Comparison of Computational and Experimental Profiles

    DTIC Science & Technology

    2016-09-09

    evaluating 18 mutants using either the A or B conformer is only r = ~ 0.2. Given the poor performance of approximating the observed experimental ...1    Sequence Tolerance of a Highly Stable Single Domain Antibody: Comparison of Computational and Experimental Profiles Mark A. Olson,1 Patricia...unusually high thermal stability is explored by a combined computational and experimental study. Starting with the crystallographic structure

  18. [Tolerance and chronic acceptability of lupine (Lupinus albus var. Multolupa) flour for feeding of young adults].

    PubMed

    Gattás Zaror, V; Barrera Acevedo, G; Yáñez Soto, E; Uauy-Dagach Imbarack, R

    1990-12-01

    Cookies enriched with sweet lupin flour were tested for their acceptability and tolerance in young adults, and compared with control cookies. A number of hematological, hepatic and renal tests were performed, as well as the measurement of allergic response, in order to detect possible changes induced by lupin. The study included 31 young adults assigned to two groups which comprised males and females, with mean ages of 26 +/- 6.5, and 27 +/- 5.9 years, respectively. The protein and energy intakes of the subjects were calculated, prior to the study, using the methods of dietary history and the 24-hr recall method. The subjects were free of any abnormalities detectable by medical history, physical examination, biochemical and hematological tests. Body weight and height were measured before the beginning of the study. The ratio weight/height of the individuals was calculated using the Jelliffe's standards. The mean values for the calorie and protein intakes were 1,919 kcal (SD +/- 655) and 59.3 g (SD +/- 22.7). The calorie contents of the control and experimental cookies were 507 and 610 kcal respectively, while the protein contents were 8.4 g and 24.1 g, respectively. The body weight of subjects in both groups increased significantly during the study (P less than 0.01 and P less than 0.02). No significant changes were recorded for other anthropometric parameters, except for the tricipital skinfold (P less than 0.01). Changes observed in hematological parameters were judged to be unrelated to lupin flour. The acceptability and tolerance to high levels of lupin flour were good. The above-mentioned results show that sweet lupin flour is a good and safe source of energy and protein for adults.

  19. Metabolite Profiling of Low-P Tolerant and Low-P Sensitive Maize Genotypes under Phosphorus Starvation and Restoration Conditions

    PubMed Central

    Ganie, Arshid Hussain; Ahmad, Altaf; Pandey, Renu; Aref, Ibrahim M.; Yousuf, Peerzada Yasir; Ahmad, Sayeed; Iqbal, Muhammad

    2015-01-01

    Background Maize (Zea mays L.) is one of the most widely cultivated crop plants. Unavoidable economic and environmental problems associated with the excessive use of phosphatic fertilizers demands its better management. The solution lies in improving the phosphorus (P) use efficiency to sustain productivity even at low P levels. Untargeted metabolomic profiling of contrasting genotypes provides a snap shot of whole metabolome which differs under specific conditions. This information provides an understanding of the mechanisms underlying tolerance to P stress and the approach for increasing P-use-efficiency. Methodology/Principal Findings A comparative metabolite-profiling approach based on gas chromatography-mass spectrometry (GC/MS) was applied to investigate the effect of P starvation and its restoration in low-P sensitive (HM-4) and low-P tolerant (PEHM-2) maize genotypes. A comparison of the metabolite profiles of contrasting genotypes in response to P-deficiency revealed distinct differences among low-P sensitive and tolerant genotypes. Another set of these genotypes were grown under P-restoration condition and sampled at different time intervals (3, 5 and 10 days) to investigate if the changes in metabolite profile under P-deficiency was restored. Significant variations in the metabolite pools of these genotypes were observed under P-deficiency which were genotype specific. Out of 180 distinct analytes, 91 were identified. Phosphorus-starvation resulted in accumulation of di- and trisaccharides and metabolites of ammonium metabolism, specifically in leaves, but decreased the levels of phosphate-containing metabolites and organic acids. A sharp increase in the concentrations of glutamine, asparagine, serine and glycine was observed in both shoots and roots under low-P condition. Conclusion The new insights generated on the maize metabolome in resposne to P-starvation and restoration would be useful towards improvement of the P-use efficiency in maize. PMID

  20. Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers.

    PubMed

    Rice, David; Heil, Justin W; Biernat, Lukasz

    2017-03-01

    Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max ) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. NCT02210247.

  1. Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.

    PubMed

    Ahrendt, Hans-Joachim; Nisand, Israel; Bastianelli, Carlo; Gómez, Maria Angeles; Gemzell-Danielsson, Kristina; Urdl, Wolfgang; Karskov, Birgit; Oeyen, Luc; Bitzer, Johannes; Page, Geert; Milsom, Ian

    2006-12-01

    This randomized multicenter, open-label, trial compared efficacy, acceptability, tolerability and compliance of NuvaRing with a combined oral contraceptive (COC), containing 30 microg of ethinyl estradiol (EE) and 3 mg of drospirenone. In this 13-cycle study, 983 women were randomized and treated (intent-to-treat population) with NuvaRing or COC. One in-treatment pregnancy occurred with NuvaRing (Pearl Index=0.25) (95% confidence interval [CI]: 0.006, 1.363) and four with the COC (Pearl Index=0.99) (95% CI: 0.269, 2.530). For both groups, compliance (89.2% NuvaRing, 85.5% COC) and satisfaction (84% NuvaRing; 87% COC) were high; the vast majority of women found NuvaRing easy to insert (96%) and remove (97%). Tolerability was similar; the most frequent adverse events with NuvaRing were related to ring use, whereas estrogen-related events were more common with the COC. NuvaRing has comparable efficacy and tolerability to a COC containing 30 microg of EE and 3 mg drospirenone. User acceptability of both methods was high.

  2. The affective profiles, psychological well-being, and harmony: environmental mastery and self-acceptance predict the sense of a harmonious life

    PubMed Central

    Al Nima, Ali; Kjell, Oscar N.E.

    2014-01-01

    Background. An important outcome from the debate on whether wellness equals happiness, is the need of research focusing on how psychological well-being might influence humans’ ability to adapt to the changing environment and live in harmony. To get a detailed picture of the influence of positive and negative affect, the current study employed the affective profiles model in which individuals are categorised into groups based on either high positive and low negative affect (self-fulfilling); high positive and high negative affect (high affective); low positive and low negative affect (low affective); and high negative and low positive affect (self-destructive). The aims were to (1) investigate differences between affective profiles in psychological well-being and harmony and (2) how psychological well-being and its dimensions relate to harmony within the four affective profiles. Method. 500 participants (mean age = 34.14 years, SD. = ±12.75 years; 187 males and 313 females) were recruited online and required to answer three self-report measures: The Positive Affect and Negative Affect Schedule; The Scales of Psychological Well-Being (short version) and The Harmony in Life Scale. We conducted a Multivariate Analysis of Variance where the affective profiles and gender were the independent factors and psychological well-being composite score, its six dimensions as well as the harmony in life score were the dependent factors. In addition, we conducted four multi-group (i.e., the four affective profiles) moderation analyses with the psychological well-being dimensions as predictors and harmony in life as the dependent variables. Results. Individuals categorised as self-fulfilling, as compared to the other profiles, tended to score higher on the psychological well-being dimensions: positive relations, environmental mastery, self-acceptance, autonomy, personal growth, and purpose in life. In addition, 47% to 66% of the variance of the harmony in life was explained by

  3. Efficacy, acceptability and tolerability of Zelesse® for the treatment of non-specific vulvovaginitis in paediatric patients: The NINESSE Study.

    PubMed

    García, Fátima; Rodríguez, Carmen-Amparo; Palomo, María-Lourdes; Català, Pere; Fernández, Santiago; Huerta, Ibone; Velasco, Syra; Nieto, Concepción

    2018-01-01

    Objective To evaluate the efficacy, tolerability and acceptability of Zelesse®, an intimate hygiene wash solution, in the relief of the symptoms and signs of non-specific vulvovaginitis in paediatric patients. Methods The NINESSE Study was a prospective, observational, multicentre study involving females aged 2-8 years who attended paediatric offices with symptoms suggestive of non-specific vulvovaginitis. They were administered Zelesse® as a single treatment for 15 ± 5 days. Pruritus, burning, dysuria, erythema, leucorrhoea and oedema were evaluated before and after treatment. Results A total of 71 paediatric patients were enrolled in the study (mean ± SD age, 4.5 ± 1.9 years). The most significant effects were observed for pruritus and burning, where 98.4% (62 of 63) and 96.9% (63 of 65) of the patients improved after treatment, respectively. Zelesse® demonstrated a beneficial effect on dysuria, erythema, leucorrhoea and oedema. The effects on the symptoms and signs were observed within the first week of treatment; although 44.9% (31 of 69) of patients experienced improvements after 2-3 days. Zelesse® was well accepted and tolerated by most patients. No serious adverse events were reported. Conclusions Zelesse® was very effective for the relief of the symptoms and signs of non-specific vulvovaginitis, in particular pruritus, burning and erythema, in females aged 2-8 years.

  4. Unpredictability of fighter pilots' g duration tolerance by anthropometric and physiological characteristics.

    PubMed

    Park, Myunghwan; Yoo, Seunghoon; Seol, Hyeongju; Kim, Cheonyoung; Hong, Youngseok

    2015-04-01

    While the factors affecting fighter pilots' G level tolerance have been widely accepted, the factors affecting fighter pilots' G duration tolerance have not been well understood. Thirty-eight subjects wearing anti-G suits were exposed to sustained high G forces using a centrifuge. The subjects exerted AGSM and decelerated the centrifuge when they reached the point of loss of peripheral vision. The G profile consisted of a +2.3 G onset rate, +7.3 G single plateau, and -1.6 G offset rate. Each subject's G tolerance time was recorded and the relationship between the tolerance time and the subject's anthropometric and physiological factors were analyzed. The mean tolerance time of the 38 subjects was 31.6 s, and the min and max tolerance times were 20 s and 58 s, respectively. The correlation analysis indicated that none of the factors had statistically significant correlations with the subjects' G duration tolerance. Stepwise multiple regression analysis showed that G duration tolerance was not dependent on any personal factors of the subjects. After the values of personal factors were simplified into 0 or 1, the t-test analysis showed that subjects' heights were inversely correlated with G duration tolerance at a statistically significant level. However, a logistic regression analysis suggested that the effect of the height factor to a pilot's G duration tolerance was too weak to be used as a predictor of a pilot's G tolerance. Fighter pilots' G duration tolerance could not be predicted by pilots' anthropometric and physiological factors.

  5. Sensory profiling and consumer acceptability of new dark cocoa bars containing Tuscan autochthonous food products.

    PubMed

    Cantini, Claudio; Salusti, Patrizia; Romi, Marco; Francini, Alessandra; Sebastiani, Luca

    2018-03-01

    A new set of cocoa bars named Toscolata ® were developed containing top-quality extra virgin olive oil, dried apples cultivars, and chestnut flour. The present work has been conducted to define the sensory profile of these products through tasting by trained experts and consumers to study the acceptability, preference, and quality perception. The four sensorial profiles of the bars differed in the level of persistence, bitterness, aromaticity, acidity, astringency, and tastiness. In particular, the sour attribute could be traced to the presence of dried apple. Bars containing apple and chestnut flour obtained higher acceptance ratings, compared to those with extra virgin olive oil. The bar with chestnut flour was preferred by consumers who considered it to be sweeter due to the presence of natural sugars, which lowered the bitter sensation of cocoa. These results showed that the selection of the preferred bar by consumers was mainly based on the level of bitterness and, in particular, elderly consumers expressed a strong preference for the sweetest product. As far as we know, this is the first study comparing the results of a panel of expert tasters with that of consumers in the tasting of dark chocolate.

  6. De novo transcriptome characterization and gene expression profiling of the desiccation tolerant moss Bryum argenteum following rehydration.

    PubMed

    Gao, Bei; Zhang, Daoyuan; Li, Xiaoshuang; Yang, Honglan; Zhang, Yuanming; Wood, Andrew J

    2015-05-28

    The desiccation-tolerant moss Bryum argenteum is an important component of the Biological Soil Crusts (BSCs) found in the Gurbantunggut desert. Desiccation tolerance is defined as the ability to revive from the air dried state. To elucidate the molecular mechanisms related to desiccation tolerance, we employed RNA-Seq and digital gene expression (DGE) technologies to study the genome-wide expression profiles of the dehydration and rehydration processes in this important desert plant. We applied a two-step approach to investigate the gene expression profile upon rehydration in the moss Bryum argenteum using Illumina HiSeq2000 sequencing platform. First, a total of 57,247 transcript assembly contigs (TACs) were obtained from 54.79 million reads by de novo assembly, with an average length of 863 bp and N50 of 1,372 bp. Among the reconstructed TACs, 36,916 (64.5%) revealed similarity with existing protein sequences in the public databases. 23,509 and 21,607 TACs were assigned GO and KEGG annotation information, respectively. Second, samples were taken from 3 hydration stages: desiccated (Dry), rehydrated 2 h (R2) and rehydrated 24 h (R24), and DEG libraries were constructed for Differentially Expressed Genes (DEGs) discovery. 4,081 and 6,709 DEGs were identified in R2 and R24, compared with Dry, respectively. Compared to the desiccated sample, up-regulated genes after two hours of hydration are primarily related to stress responses. GO function enrichment network, EKGG metabolic pathway and MapMan analysis supports the idea of the rapid recovery of photosynthesis after 24 h of rehydration. We identified 770 transcription factors (TFs) which were classified into 50 TF families. 142 TF transcripts were up-regulated upon rehydration including 23 members of the ERF family. In this study, we constructed a pioneering, high-quality reference transcriptome in B. argenteum and generated three DGE libraries to elucidate the changes of gene expression upon rehydration. Expression

  7. Tolerance, effectiveness, and acceptability of sulfate-free electrolyte lavage solution for colon cleaning before colonoscopy.

    PubMed

    Raymond, J M; Beyssac, R; Capdenat, E; Pineau, C H; Kerjean, A; Saux, M C; Couzigou, P; Amouretti, M

    1996-09-01

    The unpleasant taste of the solution used for preparation before colonoscopy may limit patients' compliance with the procedure. However, the published results concerning the acceptability of sulfate-free electrolyte lavage solution (SF-ELS) for colon cleansing before colonoscopy are conflicting. The aim of this study was to compare SF-ELS with the standard polyethylene glycol (PEG) solution with regard to tolerance, effectiveness, and acceptability. In the first part of the study, 24 patients were assigned to receive either one liter of SF-ELS or one liter of the standard PEG solution. After two hours, the patients had to choose two further liters (of either the first or second solution), and preparation for colonoscopy was completed. In the second part, fifty further patients were randomized into two groups: 25 patients received four liters of standard solution, and 25 patients received four liters of SF-ELS. The patients' opinions regarding the preparation and their willingness to repeat the use of the same preparation were recorded by questionnaire. The quality of the colon preparation was assessed by the endoscopists. Seventeen patients (71%; P < 0.05) preferred SF-ELS. The compliance rate in the two groups was 96%, and the frequency of occurrence of adverse effects was also similar. Colonoscopy was completed in 24 of the 25 patients in the SF-ELS group and 22 of the 25 patients in the standard PEG group (the difference was not significant). Visualization of the mucosa in the areas explored was perfect in 20 of the 25 patients in the SF-ELS group and in 17 of the 25 patients in the PEG group (not significant). Patients had a significant preference for SF-ELS. Eighteen of the 25 patients in the SF-ELS group were willing to accept the same preparation for a further colonoscopy, compared with 11 of the 25 in the other group (P < 0.05). Improving the acceptability of colonic preparation before colonoscopy could improve patients' compliance and the quality of the

  8. Sensory Profile and Consumer Acceptability of Prebiotic White Chocolate with Sucrose Substitutes and the Addition of Goji Berry (Lycium barbarum).

    PubMed

    Morais Ferreira, Janaína Madruga; Azevedo, Bruna Marcacini; Luccas, Valdecir; Bolini, Helena Maria André

    2017-03-01

    Functional food is a product containing nutrients that provide health benefits beyond basic nutrition. The objective of the present study was to evaluate the descriptive sensory profile and consumers' acceptance of functional (prebiotic) white chocolates with and without the addition of an antioxidant source (goji berry [GB]) and sucrose replacement. The descriptive sensory profile was determined by quantitative descriptive analysis (QDA) with trained assessors (n = 12), and the acceptance test was performed with 120 consumers. The correlation of descriptive and hedonic data was determined by partial least squares (PLS). The results of QDA indicated that GB reduces the perception of most aroma and flavor attributes, and enhances the bitter taste, bitter aftertaste, astringency, and most of the texture attributes. The consumers' acceptance of the chocolates was positive for all sensory characteristics, with acceptance scores above 6 on a 9-point scale. According to the PLS regression analysis, the descriptors cream color and cocoa butter flavor contributed positively to the acceptance of functional white chocolates. Therefore, prebiotic white chocolate with or without the addition of GB is innovative and can attract consumers, due to its functional properties, being a promising alternative for the food industry. © 2017 Institute of Food Technologists®.

  9. Identification of genes and pathways associated with aluminum stress and tolerance using transcriptome profiling of wheat near-isogenic lines.

    PubMed

    Houde, Mario; Diallo, Amadou Oury

    2008-08-27

    Aluminum is considered the most limiting factor for plant productivity in acidic soils, which cover large areas of the world's potential arable lands. The inhibition of root growth is recognized as the primary effect of Al toxicity. To identify genes associated with Al stress and tolerance, transcriptome analyses of four different wheat lines (2 Al-tolerant and 2 Al sensitive) that differ in their response to Al were performed. Microarray expression profiling revealed that 83 candidate genes are associated with Al stress and 25 are associated with tolerance. The stress-associated genes include important enzymes such as pyruvate dehydrogenase, alternative oxidase, and galactonolactone oxidase, ABC transporter and ascorbate oxido-reducatase. The Al tolerance-associated genes include the ALMT-1 malate transporter, glutathione S-transferase, germin/oxalate oxidase, fructose 1,6-bisphosphatase, cysteine-rich proteins, cytochrome P450 monooxygenase, cellulose synthase, zinc finger transcription factor, disease resistance response protein and F-box containing domain protein. In this survey, we identified stress- and tolerance-associated genes that may be involved in the detoxification of Al and reactive oxygen species. Alternative pathways could help maintain the supply of important metabolites (H2O2, ascorbate, NADH, and phosphate) needed for Al tolerance and root growth. The Al tolerance-associated genes may be key factors that regulate these pathways.

  10. Effect of saturated fatty acid-rich dietary vegetable oils on lipid profile, antioxidant enzymes and glucose tolerance in diabetic rats

    PubMed Central

    Kochikuzhyil, Benson Mathai; Devi, Kshama; Fattepur, Santosh Raghunandan

    2010-01-01

    Objective: To study the effect of saturated fatty acid (SFA)-rich dietary vegetable oils on the lipid profile, endogenous antioxidant enzymes and glucose tolerance in type 2 diabetic rats. Materials and Methods: Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rats. Twenty-eight-day-old normal (N) and diabetic (D) male Wistar rats were fed for 45 days with a fat-enriched special diet (10%) prepared with coconut oil (CO) – lauric acid-rich SFA, palm oil (PO) – palmitic acid-rich SFA and groundnut oil (GNO) – control (N and D). Lipid profile, endogenous antioxidant enzymes and oral glucose tolerance tests were monitored. Results: D rats fed with CO (D + CO) exhibited a significant decrease in the total cholesterol and non-high-density lipoprotein cholesterol. Besides, they also showed a trend toward improving antioxidant enzymes and glucose tolerance as compared to the D + GNO group, whereas D + PO treatment aggravated the dyslipidemic condition while causing a significant decrease in the superoxide dismutase levels when compared to N rats fed with GNO (N + GNO). D + PO treatment also impaired the glucose tolerance when compared to N + GNO and D + GNO. Conclusion: The type of FA in the dietary oil determines its deleterious or beneficial effects. Lauric acid present in CO may protect against diabetes-induced dyslipidemia. PMID:20871763

  11. Do fibromyalgia patients benefit from cognitive restructuring and acceptance? An experimental study.

    PubMed

    Kohl, Annika; Rief, Winfried; Glombiewski, Julia Anna

    2014-12-01

    The aim of this study was to clarify mechanisms of psychological fibromyalgia treatment by experimentally examining the effectiveness of its core elements. We assessed the effects of cognitive restructuring and acceptance on experimentally-induced heat and cold pain tolerance and pain intensity in fibromyalgia patients. Cold and heat pain were induced in a sample of 60 fibromyalgia patients using a thermode. We conducted ANCOVAs to examine group differences in posttest scores, co-varying for pretest scores. The between-groups factor was the type of instruction provided (acceptance, cognitive restructuring, and a control condition). In addition, we controlled for pain sensitivity, age, and depression. We found that acceptance and cognitive restructuring were superior to the control condition in increasing heat pain tolerance, but did not differ from one another. With respect to cold pain tolerance, cognitive restructuring was associated with increases in cold pain tolerance compared to the control condition, while acceptance did not differ either from the control condition or from cognitive restructuring. Further experimental research on chronic pain treatment mechanisms is needed, particularly research on individually tailoring treatment strategies according to patients characteristics. Results show that both, cognitive restructuring and acceptance instructions, enhance pain tolerance in fibromyalgia patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Quantification of uncertainty in machining operations for on-machine acceptance.

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

    Claudet, Andre A.; Tran, Hy D.; Su, Jiann-Chemg

    2008-09-01

    Manufactured parts are designed with acceptance tolerances, i.e. deviations from ideal design conditions, due to unavoidable errors in the manufacturing process. It is necessary to measure and evaluate the manufactured part, compared to the nominal design, to determine whether the part meets design specifications. The scope of this research project is dimensional acceptance of machined parts; specifically, parts machined using numerically controlled (NC, or also CNC for Computer Numerically Controlled) machines. In the design/build/accept cycle, the designer will specify both a nominal value, and an acceptable tolerance. As part of the typical design/build/accept business practice, it is required to verifymore » that the part did meet acceptable values prior to acceptance. Manufacturing cost must include not only raw materials and added labor, but also the cost of ensuring conformance to specifications. Ensuring conformance is a substantial portion of the cost of manufacturing. In this project, the costs of measurements were approximately 50% of the cost of the machined part. In production, cost of measurement would be smaller, but still a substantial proportion of manufacturing cost. The results of this research project will point to a science-based approach to reducing the cost of ensuring conformance to specifications. The approach that we take is to determine, a priori, how well a CNC machine can manufacture a particular geometry from stock. Based on the knowledge of the manufacturing process, we are then able to decide features which need further measurements from features which can be accepted 'as is' from the CNC. By calibration of the machine tool, and establishing a machining accuracy ratio, we can validate the ability of CNC to fabricate to a particular level of tolerance. This will eliminate the costs of checking for conformance for relatively large tolerances.« less

  13. Identification of a B cell signature associated with renal transplant tolerance in humans

    PubMed Central

    Newell, Kenneth A.; Asare, Adam; Kirk, Allan D.; Gisler, Trang D.; Bourcier, Kasia; Suthanthiran, Manikkam; Burlingham, William J.; Marks, William H.; Sanz, Ignacio; Lechler, Robert I.; Hernandez-Fuentes, Maria P.; Turka, Laurence A.; Seyfert-Margolis, Vicki L.

    2010-01-01

    Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients. PMID:20501946

  14. Acceptance- versus Change-Based Pain Management: The Role of Psychological Acceptance

    ERIC Educational Resources Information Center

    Blacker, Kara J.; Herbert, James D.; Forman, Evan M.; Kounios, John

    2012-01-01

    This study compared two theoretically opposed strategies for acute pain management: an acceptance-based and a change-based approach. These two strategies were compared in a within-subjects design using the cold pressor test as an acute pain induction method. Participants completed a baseline pain tolerance assessment followed by one of the two…

  15. Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management.

    PubMed

    Johnson, F Reed; Hauber, Brett; Özdemir, Semra; Siegel, Corey A; Hass, Steven; Sands, Bruce E

    2010-10-01

    improvement from moderate symptoms to remission. On average, gastroenterologists and patients disagreed about how much risk is tolerable for improvements in efficacy. In exchange for improvements from severe to moderate symptoms for the middle-aged patient profile, gastroenterologists were significantly more tolerant than patients of treatment risks of PML (P < 0.001) and serious infection (P = 0.001) but not lymphoma (P = 0.230). In contrast, in exchange for improvements from moderate symptoms to remission for the same patient profile, patients were significantly more tolerant than gastroenterologists of treatment risks for serious infection (P < 0.001) and lymphoma (P < 0.001) but not PML (P = 0.158). Gastroenterologists and patients have well-defined preferences among treatment attributes and are willing to accept tradeoffs between efficacy and treatment risks. However, risk tolerance varies depending on the type of patient for whom gastroenterologists are being asked to consider treatment. In rating treatment preferences for patients with a middle-aged profile, gastroenterologists are less tolerant of SAE risks than patients in exchange for improvement from moderate symptoms to remission.

  16. Prediction of tolerance in children with IgE mediated cow's milk allergy by microarray profiling and chemometric approach.

    PubMed

    Wulfert, F; Sanyasi, G; Tongen, L; Watanabe, L A; Wang, X; Renault, N K; Falcone, F H; Jacob, C M A; Alcocer, M J C

    2012-08-31

    The sera of a retrospective cohort (n=41) composed of children with well characterized cow's milk allergy collected from multiple visits were analyzed using a protein microarray system measuring four classes of immunoglobulins. The frequency of the visits, age and gender distribution reflected real situation faced by the clinicians at a pediatric reference center for food allergy in São Paulo, Brazil. The profiling array results have shown that total IgG and IgA share similar specificity whilst IgM and in particular IgE are distantly related. The correlation of specificity of IgE and IgA is variable amongst the patients and this relationship cannot be used to predict atopy or the onset of tolerance to milk. The array profiling technique has corroborated the clinical selection criteria for this cohort albeit it clearly suggested that 4 out of the 41 patients might have allergies other than milk origin. There was also a good correlation between the array data and ImmunoCAP results, casein in particular. By using qualitative and quantitative multivariate analysis routines it was possible to produce validated statistical models to predict with reasonable accuracy the onset of tolerance to milk proteins. If expanded to larger study groups, the array profiling in combination with the multivariate techniques show potential to improve the prognostic of milk allergic patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. 40 CFR 180.40 - Tolerances for crop groups.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.40 Tolerances... representative crops are given as an indication of the minimum residue chemistry data base acceptable to the...

  18. 40 CFR 180.40 - Tolerances for crop groups.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.40 Tolerances... representative crops are given as an indication of the minimum residue chemistry data base acceptable to the...

  19. 40 CFR 180.40 - Tolerances for crop groups.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.40 Tolerances... representative crops are given as an indication of the minimum residue chemistry data base acceptable to the...

  20. 40 CFR 180.40 - Tolerances for crop groups.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.40 Tolerances... representative crops are given as an indication of the minimum residue chemistry data base acceptable to the...

  1. 40 CFR 180.40 - Tolerances for crop groups.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Procedural Regulations § 180.40 Tolerances... representative crops are given as an indication of the minimum residue chemistry data base acceptable to the...

  2. A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials.

    PubMed

    Aparício, Luana V M; Guarienti, Fabiana; Razza, Lais Boralli; Carvalho, André F; Fregni, Felipe; Brunoni, André Russowsky

    2016-01-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies. To investigate the tolerability (rate of AEs) and acceptability (rate of dropouts) of tDCS. Systematic review and meta-analysis of tDCS randomized, sham-controlled trials in healthy or neuropsychiatric adult samples from the first date available to March 9, 2016. We only included parallel studies performing at least 5 tDCS sessions. An adapted version of CONSORT guidelines for reporting harms outcomes was used to evaluate AE reporting. Sixty-four studies (2262 participants) were included. They had a low risk of publication bias and methodological bias for the items assessed. Dropout rates in active and sham tDCS groups were, respectively, 6% and 7.2% (OR = 0.82 [0.59-1.14]). However, almost half of studies reported no dropouts and only 23.4% reported its reasons; when reported, the most frequent reasons were AEs and protocol violation. A tolerability meta-analysis was not performed, as most studies did not report AEs. The quality of AEs reporting was also limited, particularly in smaller studies and stroke studies. Although overall dropout rate was low and similar in active and sham groups, studies did not adequately describe AEs. An updated questionnaire and guidelines for assessment of AEs in tDCS trials are proposed in order to standardize the reporting of AE in the field. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Physiological Basis and Transcriptional Profiling of Three Salt-Tolerant Mutant Lines of Rice

    PubMed Central

    Domingo, Concha; Lalanne, Eric; Catalá, María M.; Pla, Eva; Reig-Valiente, Juan L.; Talón, Manuel

    2016-01-01

    Salinity is a complex trait that affects growth and productivity in many crops, including rice. Mutation induction, a useful tool to generate salt tolerant plants, enables the analysis of plants with similar genetic background, facilitating the understanding of the salt tolerance mechanisms. In this work, we generated three salt tolerant mutant lines by irradiation of a salt-sensitive cultivar plants and screened M2 plants at seedling stage in the presence of high salinity. These three lines, SaT20, SaS62, and SaT58, showed different responses to salinity, but exhibited similar phenotype to wild type plants, except SaT20 that displayed shorter height when grown in the absence of salt. Under salt conditions, all three mutants and the parental line showed similar reduction in yield, although relevant differences in other physiological parameters, such as Na+ accumulation in healthy leaves of SaT20, were registered. Microarray analyses of gene expression profiles in roots revealed the occurrence of common and specific responses in the mutants. The three mutants showed up-regulation of responsive genes, the activation of oxido-reduction process and the inhibition of ion transport. The participation of jasmonate in the plant response to salt was evident by down-regulation of a gene coding for a jasmonate O-methyltransferase. Genes dealing with lipid transport and metabolism were, in general, up-regulated except in SaS62, that also exhibited down-regulation of genes involved in ion transport and Ca2+ signal transduction. The two most tolerant varieties, SaS62 and SaT20, displayed lower levels of transcripts involved in K+ uptake. The physiological study and the description of the expression analysis evidenced that the three lines showed different responses to salt: SaT20 showed a high Na+ content in leaves, SaS62 presented an inhibition of lipid metabolism and ion transport and SaT58 differs in both features in the response to salinity. The analysis of these salt

  4. Profiling modifications for glioblastoma proteome using ultra-tolerant database search: Are the peptide mass shifts biologically relevant or chemically induced?

    PubMed

    Tarasova, Irina A; Chumakov, Peter M; Moshkovskii, Sergei A; Gorshkov, Mikhail V

    2018-05-17

    Peptide mass shifts were profiled using ultra-tolerant database search strategy for shotgun proteomics data sets of human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The main objective of this profiling was revealing the cell response to IFN treatment at the level of protein modifications. To achieve this objective, statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples were analyzed. Detailed analysis of MS/MS spectra allowed further interpretation of the observed mass shifts and differentiation between post-translational and artifact modifications. Malignant cells typically acquire increased sensitivity to viruses due to the deregulated antiviral mechanisms. Therefore, a viral therapy is considered as one of the promising approaches to treat cancer. However, recent studies have demonstrated that malignant cells can preserve intact antiviral mechanisms, e.g. interferon signaling, and develop resistance to virus infection in response to interferon treatment. Post translational modifications, e.g. tyrosine phosphorylation, are the interferon signaling drivers. Thus, comprehensive characterization of modifications is crucially important, yet, most challenging problem in cancer proteomics. Here, we report on the application of the recently introduced ultra-tolerant search strategy for profiling peptide modifications in the human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The specific aim of the study was identification of statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples, as well as determination of whether these shifts represent the biologically relevant modification. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Eigenstructure Assignment for Fault Tolerant Flight Control Design

    NASA Technical Reports Server (NTRS)

    Sobel, Kenneth; Joshi, Suresh (Technical Monitor)

    2002-01-01

    In recent years, fault tolerant flight control systems have gained an increased interest for high performance military aircraft as well as civil aircraft. Fault tolerant control systems can be described as either active or passive. An active fault tolerant control system has to either reconfigure or adapt the controller in response to a failure. One approach is to reconfigure the controller based upon detection and identification of the failure. Another approach is to use direct adaptive control to adjust the controller without explicitly identifying the failure. In contrast, a passive fault tolerant control system uses a fixed controller which achieves acceptable performance for a presumed set of failures. We have obtained a passive fault tolerant flight control law for the F/A-18 aircraft which achieves acceptable handling qualities for a class of control surface failures. The class of failures includes the symmetric failure of any one control surface being stuck at its trim value. A comparison was made of an eigenstructure assignment gain designed for the unfailed aircraft with a fault tolerant multiobjective optimization gain. We have shown that time responses for the unfailed aircraft using the eigenstructure assignment gain and the fault tolerant gain are identical. Furthermore, the fault tolerant gain achieves MIL-F-8785C specifications for all failure conditions.

  6. Profile preferences of Korean American orthodontic patients and orthodontists.

    PubMed

    Park, Yoon S; Evans, Carla A; Viana, Grace; Anderson, Nina K; Giddon, Donald B

    2006-01-01

    The purpose of this study was to determine differences in preference for Korean American facial profiles among Korean American orthodontic patients with 2 levels of acculturation, Asian American orthodontists, and Caucasian orthodontists. Images of 1 male and 1 female Korean American adult were animated to move parts of the faces from an extreme retrusive position to an extreme protrusive position by using the Perceptometrics computer program. Three movies were created of the nose, lips, and chin for each image. Three groups of judges, ie, 18 Korean American orthodontic patients, 17 Asian orthodontists, and 18 Caucasian orthodontists selected the most pleasing position and the zone of acceptability as a measure of tolerance. Statistically significant differences were found between Caucasian orthodontists and Korean American orthodontic patients for the most pleasing and midpoint of acceptability positions of female nose and male chin, with no differences in the zone of acceptability position among the groups. In general, the Korean American orthodontic patients preferred a more protrusive nose on the female image and more retrusive chin on the male image than Caucasian orthodontists for the most pleasing and midpoint of acceptability positions, with similar zone of acceptability for all 3 groups.

  7. Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

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

    Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com; Flagella, Kelly; Beyer, Joseph

    2013-12-01

    Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeysmore » and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and

  8. Tolerability of a Skin Care Regimen Formulated for Acne-Prone Skin in Children.

    PubMed

    Hensley, David; Meckfessel, Matthew H

    2015-01-01

    The epidemiology and demographic profile of acne vulgaris has evolved over the past several decades, with a noted earlier onset occurring in patients as young as 7 years of age. The combination of a foaming facial wash and a facial moisturizer with a sun protection factor (SPF) of 30 is an over-the-counter cleansing and moisturizing regimen for acne-prone skin that has been shown to be safe and tolerable in subjects 12 years of age and older. To assess the tolerability of this skin care regimen in children ages 7 to 11 years with acne-prone skin. This was an open-label, single-center study that investigated the safety and tolerability of these products in subjects 7 to 11 years of age (ClinicalTrials.gov, NCT01909713). Subjects used the foaming wash twice daily and the SPF 30 moisturizer once daily. Subjects were assessed for cutaneous tolerability, and satisfaction at baseline and weeks 1 and 3. Thirty-five subjects enrolled and completed the study. The cutaneous tolerability score of most subjects was none when assessed by the investigator and subject or legally authorized representative at weeks 1 and 3. The products were well tolerated and a positive impression for cosmetic acceptability was reported for both products by the study population on the questionnaire. This study supports the use of a skin care regimen comprising a wash and a moisturizer in acne-prone patients as young as 7 years old since these products were safe, well tolerated, and liked by subjects. © 2015 Wiley Periodicals, Inc.

  9. Intolerant tolerance.

    PubMed

    Khushf, G

    1994-04-01

    The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights.

  10. ACCEPT 2: A public library of cluster properties

    NASA Astrophysics Data System (ADS)

    Donahue, Megan

    2012-09-01

    The current public ACCEPT database of cluster properties includes radial profiles of Tx, n_elec, entropy, and cooling time. We propose to more than double the current number of clusters in ACCEPT and to expand the current suite of properties to include uniformly measured profiles of gas mass and hydrostatic equilibrium mass along with signatures of dynamical relaxation (centroid shift, power ratios, surface brightness concentration, temperature ratios) and global quantities such as core-excised Tx, Lx, and metallicities. We will explore the relationship between cool cores and dynamical relaxation, the reliability of hydrostatic mass profiles, and the dependence of the gas mass fraction on halo mass, redshift, and the degree of relaxation. ACCEPT2 will enable further community science.

  11. Results of the Updated NASA Kennedy Space Center 50-MHz Doppler Radar Wind Profiler Operational Acceptance Test

    NASA Technical Reports Server (NTRS)

    Barbre', Robert E., Jr.; Deker, Ryan K.; Leahy, Frank B.; Huddleston, Lisa

    2016-01-01

    We present here the methodology and results of the Operational Acceptance Test (OAT) performed on the new Kennedy Space Center (KSC) 50-MHz Doppler Radar Wind Profiler (DRWP). On day-of-launch (DOL), space launch vehicle operators have used data from the DRWP to invalidate winds in prelaunch loads and trajectory assessments due to the DRWP's capability to quickly identify changes in the wind profile within a rapidly-changing wind environment. The previous DRWP has been replaced with a completely new system, which needs to undergo certification testing before being accepted for use in range operations. The new DRWP replaces the previous three-beam system made of coaxial cables and a copper wire ground plane with a four-beam system that uses Yagi antennae with enhanced beam steering capability. In addition, the new system contains updated user interface software while maintaining the same general capability as the previous system. The new DRWP continues to use the Median Filter First Guess (MFFG) algorithm to generate a wind profile from Doppler spectra at each range gate. DeTect (2015) contains further details on the upgrade. The OAT is a short-term test designed so that end users can utilize the new DRWP in a similar manner to the previous DRWP during mission operations at the Eastern Range in the midst of a long-term certification process. This paper describes the Marshall Space Flight Center Natural Environments Branch's (MSFC NE's) analyses to verify the quality and accuracy of the DRWP's meteorological data output as compared to the previous DRWP. Ultimately, each launch vehicle program has the responsibility to certify the system for their own use.

  12. Network Candidate Genes in Breeding for Drought Tolerant Crops

    PubMed Central

    Krannich, Christoph Tim; Maletzki, Lisa; Kurowsky, Christina; Horn, Renate

    2015-01-01

    Climate change leading to increased periods of low water availability as well as increasing demands for food in the coming years makes breeding for drought tolerant crops a high priority. Plants have developed diverse strategies and mechanisms to survive drought stress. However, most of these represent drought escape or avoidance strategies like early flowering or low stomatal conductance that are not applicable in breeding for crops with high yields under drought conditions. Even though a great deal of research is ongoing, especially in cereals, in this regard, not all mechanisms involved in drought tolerance are yet understood. The identification of candidate genes for drought tolerance that have a high potential to be used for breeding drought tolerant crops represents a challenge. Breeding for drought tolerant crops has to focus on acceptable yields under water-limited conditions and not on survival. However, as more and more knowledge about the complex networks and the cross talk during drought is available, more options are revealed. In addition, it has to be considered that conditioning a crop for drought tolerance might require the production of metabolites and might cost the plants energy and resources that cannot be used in terms of yield. Recent research indicates that yield penalty exists and efficient breeding for drought tolerant crops with acceptable yields under well-watered and drought conditions might require uncoupling yield penalty from drought tolerance. PMID:26193269

  13. Network Candidate Genes in Breeding for Drought Tolerant Crops.

    PubMed

    Krannich, Christoph Tim; Maletzki, Lisa; Kurowsky, Christina; Horn, Renate

    2015-07-17

    Climate change leading to increased periods of low water availability as well as increasing demands for food in the coming years makes breeding for drought tolerant crops a high priority. Plants have developed diverse strategies and mechanisms to survive drought stress. However, most of these represent drought escape or avoidance strategies like early flowering or low stomatal conductance that are not applicable in breeding for crops with high yields under drought conditions. Even though a great deal of research is ongoing, especially in cereals, in this regard, not all mechanisms involved in drought tolerance are yet understood. The identification of candidate genes for drought tolerance that have a high potential to be used for breeding drought tolerant crops represents a challenge. Breeding for drought tolerant crops has to focus on acceptable yields under water-limited conditions and not on survival. However, as more and more knowledge about the complex networks and the cross talk during drought is available, more options are revealed. In addition, it has to be considered that conditioning a crop for drought tolerance might require the production of metabolites and might cost the plants energy and resources that cannot be used in terms of yield. Recent research indicates that yield penalty exists and efficient breeding for drought tolerant crops with acceptable yields under well-watered and drought conditions might require uncoupling yield penalty from drought tolerance.

  14. Transcriptome profiling of fully open flowers in a frost-tolerant almond genotype in response to freezing stress.

    PubMed

    Hosseinpour, Batool; Sepahvand, Sadegh; Kamali Aliabad, Kazem; Bakhtiarizadeh, MohammadReza; Imani, Ali; Assareh, Reza; Salami, Seyed Alireza

    2018-02-01

    Spring frost is a major limiting abiotic stress for the cultivation of almonds [Prunus dulcis (Mill.)] in Mediterranean areas or the Middle East. Spring frost, in particular, damages almond fully open flowers, resulting to significant reduction in yield. Little is known about the genetic factors expressed after frost stress in Prunus spp. as well as in almond fully open flowers. Here, we provide the molecular signature of pistils of fully open flowers from a frost-tolerant almond genotype. The level of frost tolerance in this genotype was determined for all three flowering stages and was confirmed by comparing it to two other cultivars using several physiological analyses. Afterwards, comprehensive expression profiling of genes expressed in fully open flowers was performed after being exposed to frost temperatures (during post-thaw period). Clean reads, 27,104,070 and 32,730,772, were obtained for non-frost-treated and frost-treated (FT) libraries, respectively. A total of 62.24 Mb was assembled, generating 50,896 unigenes and 66,906 transcripts. Therefore, 863 upregulated genes and 555 downregulated genes were identified in the FT library. Functional annotation showed that most of the upregulated genes were related to various biological processes involved in responding to abiotic stress. For the first time, a highly expressed cold-shock protein was identified in the reproductive organ of fruit trees. The expression of six genes was validated by RT-PCR. As the first comprehensive analysis of open flowers in a frost-tolerant almond genotype, this study represents a key step toward the molecular breeding of fruit tree species for frost tolerance.

  15. Serum lipid profiles, total tract nutrient digestibility, and gastrointestinal tolerance by dogs of α-cyclodextrin.

    PubMed

    Guevara, M A; Bauer, L L; Garleb, K A; Fahey, G C; de Godoy, M R C

    2015-05-01

    The objectives were to quantify gastrointestinal tolerance, total tract nutrient digestibility, and serum lipid profiles of dogs as affected by α-cyclodextrin (ACD) supplementation and to validate the accuracy of fat analyses techniques using novel ACD-fat complexes. The ACD was hydrolyzed and free sugars and hydrolyzed monosaccharides were quantified using high performance liquid chromatography. Known amount of fats were complexed with ACD, and fat content of complexes were determined using the ether extraction and acid-hydrolyzed fat methods. Nine mixed-breed hounds were used in a crossover design with 3 periods of 10 d each, including 6 d for diet adaptation and 4 d for fecal collection. Dogs were fed twice daily a diet with poultry byproduct meal and brewer's rice as the main ingredients, and chromic oxide (0.2%) was included as a digestion marker. Dogs were supplemented with either 0, 3, or 6 g of ACD diluted in 15 mL of water twice per day for a total of 0, 6, and 12 g ACD per day. The ACD had a very low free sugar concentration and, once hydrolyzed, released only glucose, as expected. Average daily food intake, fecal output (DM basis), and fecal scores were not significantly different among treatments. Body weight and condition score and serum triglycerides and cholesterol concentrations remained unaltered throughout the duration of the experiment. Dry matter, OM, and fat digestibility coefficients were lower (P < 0.05) for both treatment groups compared to the control. The acid-hydrolyzed fat method was valid to measure fat that was bound to ACD. Intake of ACD lowered fat digestibility somewhat but not to the extent previously reported, without affecting serum lipid concentrations or outcomes related to tolerance. Therefore, ACD supplementation resulted in a small decrease in fat digestibility, but ACD supplementation might have potential in modifying serum lipid profiles.

  16. Sensory Profile, Drivers of Liking, and Influence of Information on the Acceptance of Low-Calorie Synbiotic and Probiotic Chocolate Ice Cream.

    PubMed

    Peres, Juliana; Esmerino, Erick; da Silva, Alessandra Lins; Racowski, Ilana; Bolini, Helena

    2018-05-01

    The objective of this study was to evaluate the sensory profile and the influence of the information on the acceptance of the symbiotic chocolate ice cream made with sucrose and different sweeteners (aspartame, sucralose, neotame, Stevia with 60%, 85%, 95%, and 97% of rebaudioside A) through analysis of variance (ANOVA), Tukey's test, and partial least of square (PLS) regression. Quantitative descriptive analysis (QDA) was carried out by 18 assessors, who evaluated the samples in relation to the raised descriptors. Additionally, two acceptance tests (blind/informed) were performed with 120 consumers. The samples sweetened with sucralose and rebaudioside 97% presented similar profile to the control sample, thus having a better potential to replace sucrose in chocolate ice cream. The acceptance test carried out with information had higher scores for the attributes appearance, aroma, flavor, texture, and overall impression. The correlation between data from the acceptance tests and QDA showed that the descriptors "low-energy" and "natural sweetener" claims interfered negatively in the drivers of liking of chocolate ice cream. Therefore, we can conclude that some characteristics unnoticed by consumers were highlighted after providing the information about the product's characteristics. This research is important and contributes to the manufacture and development of low-calorie chocolate ice cream with functional properties, guiding, through suitable sensory and statistical tools, the application of stevia and other artificial sweeteners in products with reduction or total absence of sucrose and highlighting the impact of the labeling of these products on consumer perception. © 2018 Institute of Food Technologists®.

  17. Global transcriptome profiling reveals molecular mechanisms of metal tolerance in a chronically exposed wild population of brown trout.

    PubMed

    Uren Webster, T M; Bury, N; van Aerle, R; Santos, E M

    2013-08-06

    Worldwide, a number of viable populations of fish are found in environments heavily contaminated with metals, including brown trout (Salmo trutta) inhabiting the River Hayle in South-West of England. This population is chronically exposed to a water-borne mixture of metals, including copper and zinc, at concentrations lethal to naïve fish. We aimed to investigate the molecular mechanisms employed by the River Hayle brown trout to tolerate high metal concentrations. To achieve this, we combined tissue metal analysis with whole-transcriptome profiling using RNA-seq on an Illumina platform. Metal concentrations in the Hayle trout, compared to fish from a relatively unimpacted river, were significantly increased in the gills, liver and kidney (63-, 34- and 19-fold respectively), but not the gut. This confirms that these fish can tolerate considerable metal accumulation, highlighting the importance of these tissues in metal uptake (gill), storage and detoxification (liver, kidney). We sequenced, assembled and annotated the brown trout transcriptome using a de novo approach. Subsequent gene expression analysis identified 998 differentially expressed transcripts and functional analysis revealed that metal- and ion-homeostasis pathways are likely to be the most important mechanisms contributing to the metal tolerance exhibited by this population.

  18. Global Transcriptome Profiling Reveals Molecular Mechanisms of Metal Tolerance in a Chronically Exposed Wild Population of Brown Trout

    PubMed Central

    2013-01-01

    Worldwide, a number of viable populations of fish are found in environments heavily contaminated with metals, including brown trout (Salmo trutta) inhabiting the River Hayle in South-West of England. This population is chronically exposed to a water-borne mixture of metals, including copper and zinc, at concentrations lethal to naïve fish. We aimed to investigate the molecular mechanisms employed by the River Hayle brown trout to tolerate high metal concentrations. To achieve this, we combined tissue metal analysis with whole-transcriptome profiling using RNA-seq on an Illumina platform. Metal concentrations in the Hayle trout, compared to fish from a relatively unimpacted river, were significantly increased in the gills, liver and kidney (63-, 34- and 19-fold respectively), but not the gut. This confirms that these fish can tolerate considerable metal accumulation, highlighting the importance of these tissues in metal uptake (gill), storage and detoxification (liver, kidney). We sequenced, assembled and annotated the brown trout transcriptome using a de novo approach. Subsequent gene expression analysis identified 998 differentially expressed transcripts and functional analysis revealed that metal- and ion-homeostasis pathways are likely to be the most important mechanisms contributing to the metal tolerance exhibited by this population. PMID:23834071

  19. Organic and conventional nonflavored yogurts from the Italian market: study on sensory profiles and consumer acceptability.

    PubMed

    Toschi, Tullia Gallina; Bendini, Alessandra; Barbieri, Sara; Valli, Enrico; Cezanne, Marie Louise; Buchecker, Kirsten; Canavari, Maurizio

    2012-11-01

    The sensory properties of food products are an important success factor, especially in the organic market, where many producers and distributors of organic food claim superior taste for their products compared to the conventional alternative. For this reason consumer expectations and preferences, as well as the sensory properties of conventional and organic yogurt, have to be investigated in depth. In this work, the sensory profiling and consumer data of six nonflavored organic and conventional Italian yogurts were elaborated. Some results on the data segmentation (heavy and light users of organic food) and on the effect of information on liking (blind and labeled test) were obtained. Multivariate analysis was carried out to study how the sensory characteristics of 'natural yogurts' drive consumer liking. Consumers' preferences were oriented towards a creamy mouthfeel and smooth visual appearance and for a less acid and fresh taste. In particular, a conventional yogurt was the least accepted, because it was not creamy enough. This paper shows there is room to improve unflavored yogurt to better meet consumer expectations. Sensory profiling did not allow a distinction in odor/taste/texture between organic and conventional samples. However, three of four organic samples were in the region of highest consumer acceptability, fitting well consumers' preference. There was no clear tendency that heavy or light users scored differently in the blind and labeled tests regarding overall liking but, for all, the most liked conventional yogurt scored higher when labeled as organic. Copyright © 2012 Society of Chemical Industry.

  20. Comparison of intradialytic hemodynamic tolerance between on-line hemodiafiltration and acetate-free biofiltration with profiled potassium dialysate concentration.

    PubMed

    Kosmadakis, George; Correia, Enrique Da Costa; Somda, Frederic; Aguilera, Didier

    2017-01-01

    Intradialytic hypotensive episodes are deleterious for hemodialysis (HD) patients. Acetate-free biofiltration with profiled potassium (AFBK) dialysate concentration may improve their cardiovascular stability. The aim of the present crossover study was to compare intradialytic hemodynamic tolerance and biological parameters between online hemodiafiltration (olHDF) and AFBK. Ten frail HD patients (8 males) with a mean age of 66.71- ± 12.31 years were studied for three months on olHDF and AFBK. There was a significant reduction of the hypotensive episodes during the AFBK period compared to the olHDF period. Mean intradialytic systolic and diastolic blood pressures were significantly higher during the AFBK period. There was a significant postdialytic increase in serum sodium concentration with the AFBK compared to olHDF. The dry weight and ultrafiltration indices were significantly higher, and the Kt/V was significantly lower during the AFBK period. Serum albumin concentration significantly increased during the AFBK period. AFBK leads to a significantly improved intradialytic tolerance in hemodynamically instable HD patients.

  1. Hand to Hand: Teaching Tolerance and Social Justice One Child at a Time

    ERIC Educational Resources Information Center

    Zakin, Andrea

    2012-01-01

    Tolerance connotes patience, forbearance, and impartiality, as well as open-mindedness. In early childhood, possessing tolerance would refer to children's burgeoning awareness of themselves in relation to others, and the capability to accept appearance and behavior different from one's own. But is teaching tolerance, additionally considered the…

  2. Induction of transplantation tolerance to fully mismatched cardiac allografts by T cell mediated delivery of alloantigen

    PubMed Central

    Tian, Chaorui; Yuan, Xueli; Jindra, Peter T.; Bagley, Jessamyn; Sayegh, Mohamed H.; Iacomini, John

    2010-01-01

    Induction of transplantation tolerance has the potential to allow for allograft acceptance without the need for life-long immunosuppression. Here we describe a novel approach that uses delivery of alloantigen by mature T cells to induce tolerance to fully allogeneic cardiac grafts. Adoptive transfer of mature alloantigen-expressing T cells into myeloablatively conditioned mice results in long-term acceptance of fully allogeneic heart transplants without evidence of chronic rejection. Since myeloablative conditioning is clinically undesirable we further demonstrated that adoptive transfer of mature alloantigen-expressing T cells alone into mice receiving non-myeloablative conditioning resulted in long-term acceptance of fully allogeneic heart allografts with minimal evidence of chronic rejection. Mechanistically, tolerance induction involved both deletion of donor-reactive host T cells and the development of regulatory T cells. Thus, delivery of alloantigen by mature T cells induces tolerance to fully allogeneic organ allografts in non-myeloablatively conditioned recipients, representing a novel approach for tolerance induction in transplantation. PMID:20452826

  3. Safety profile of levetiracetam.

    PubMed

    Arroyo, Santiago; Crawford, Pamela

    2003-05-01

    A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

  4. Altering impulsive decision making with an acceptance-based procedure.

    PubMed

    Morrison, Kate L; Madden, Gregory J; Odum, Amy L; Friedel, Jonathan E; Twohig, Michael P

    2014-09-01

    Delay discounting is one facet of impulsive decision making and involves subjectively devaluing a delayed outcome. Steeply discounting delayed rewards is correlated with substance abuse and other problematic behaviors. To the extent that steep delay discounting underlies these clinical disorders, it would be advantageous to find psychosocial avenues for reducing delay discounting. Acceptance-based interventions may prove useful as they may help to decrease the distress that arises while waiting for a delayed outcome. The current study was conducted to determine if a 60-90 minute acceptance-based training would change delay discounting rates among 30 undergraduate university students in comparison to a waitlist control. Measures given at pre- and posttraining included a hypothetical monetary delay discounting task, the Acceptance and Action Questionnaire-II (AAQ-II), and the Distress Tolerance Scale. Those assigned to the treatment group decreased their discounting of delayed money, but not distress intolerance or psychological inflexibility when compared to the waitlist control group. After the waiting period, the control group received the intervention. Combining all participants' pre- to posttreatment data, the acceptance-based treatment significantly decreased discounting of monetary rewards and increased distress tolerance. The difference in AAQ-II approached significance. Acceptance-based treatments may be a worthwhile option for decreasing delay discounting rates and, consequently, affecting the choices that underlie addiction and other problematic behaviors. Copyright © 2014. Published by Elsevier Ltd.

  5. Social Acceptance of Wind: A Brief Overview (Presentation)

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

    Lantz, E.

    This presentation discusses concepts and trends in social acceptance of wind energy, profiles recent research findings, and discussions mitigation strategies intended to resolve wind power social acceptance challenges as informed by published research and the experiences of individuals participating in the International Energy Agencies Working Group on Social Acceptance of Wind Energy

  6. B cells in operational tolerance.

    PubMed

    Chesneau, M; Danger, R; Soulillou, J-P; Brouard, S

    2018-05-01

    Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunosuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal. This review summarizes studies that suggest a role for B cells as biomarkers of operational tolerance and discusses the use of B cells as a predictive tool for immunologic risk. Copyright © 2018. Published by Elsevier Inc.

  7. Use of Fatty Acid Methyl Ester Profiles to Compare Copper-Tolerant and Copper-Sensitive Strains of Pantoea ananatis.

    PubMed

    Nischwitz, C; Gitaitis, R; Sanders, H; Langston, D; Mullinix, B; Torrance, R; Boyhan, G; Zolobowska, L

    2007-10-01

    ABSTRACT A survey was conducted to evaluate differences in fatty acid methyl ester (FAME) profiles among strains of Pantoea ananatis, causal agent of center rot of onion (Allium cepa), isolated from 15 different onion cultivars in three different sites in Georgia. Differences in FAME composition were determined by plotting principal components (PCs) in two-dimensional plots. Euclidean distance squared (ED(2)) values indicated a high degree of similarity among strains. Plotting of PCs calculated from P. ananatis strains capable of growing on media amended with copper sulfate pentahydrate (200 mug/ml) indicated that copper-tolerant strains grouped into tight clusters separate from clusters formed by wild-type strains. However, unlike copper-sensitive strains, the copper-tolerant strains tended to cluster by location. A total of 80, 60, and 73% of the strains from Tift1, Tift2, and Tattnall, respectively, exhibited either confluent growth or partial growth on copper-amended medium. However, all strains were sensitive to a mixture of copper sulfate pentahydrate (200 mug/ml) and maneb (40 mug/ml). When copper-tolerant clones were analyzed and compared with their wild-type parents, in all cases the plotting of PCs developed from copper-tolerant clones formed tight clusters separate from clusters formed by the parents. Eigenvalues generated from these tests indicated that two components provided a good summary of the data, accounting for 98, 98, and 96% of the standardized variance for strains Pna 1-15B, Pna 1-12B, and Pna 2-5A, respectively. Furthermore, feature 4 (cis-9-hexadecenoic acid/2-hydroxy-13-methyltetradecanoic acid) and feature 7 (cis-9/trans-12/cis-7-octadecenoic acid) were the highest or second highest absolute values for PC1 in all three strains of the parents versus copper-tolerant clones, and hexadecanoic acid was the highest absolute value for PC2 in all three strains. Along with those fatty acids, dodecanoic acid and feature 3 (3-hydroxytetradecanoic

  8. Damage-Tolerance and Fatigue Evaluation of Structure

    DOT National Transportation Integrated Search

    1997-02-18

    This advisory circular (AC) sets forth an acceptable means of compliance : with the provisions of Part 25 of the Federal Aviation Regulations (FAR) dealing with the damage-tolerance and fatigue evaluation requirements of transport category aircraft s...

  9. Results of the NASA Kennedy Space Center 50-MHz Doppler Radar Wind Profiler Operational Acceptance Test

    NASA Technical Reports Server (NTRS)

    Barbre', Robert E., Jr.; Decker, Ryan K.; Leahy, Frank B.; Huddleston, Lisa

    2016-01-01

    This paper presents results of the new Kennedy Space Center (KSC) 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT). The goal of the OAT was to verify the data quality of the new DRWP against the performance of the previous DRWP in order to use wind data derived by the new DRWP for space launch vehicle operations support at the Eastern Range. The previous DRWP was used as a situational awareness asset for mission operations to identify rapid changes in the wind environment that weather balloons cannot depict. The Marshall Space Flight Center's Natural Environments Branch assessed data from the new DRWP collected during Jan-Feb 2015 against a specified set of test criteria. Data examination verified that the DRWP provides complete profiles every five minutes from 1.8-19.5 km in vertical increments of 150 m. Analysis of 49 concurrent DRWP and balloon profiles presented root mean square wind component differences around 2.0 m/s. Evaluation of the DRWP's coherence between five-minute wind pairs found the effective vertical resolution to be Nyquist-limited at 300 m for both wind components. In addition, the sensitivity to rejecting data that do not have adequate signal was quantified. This paper documents the data, quality control procedures, methodology, and results of each analysis.

  10. Longitudinal Stability of Social Competence Indicators in a Portuguese Sample: Q-Sort Profiles of Social Competence, Measures of Social Engagement, and Peer Sociometric Acceptance

    ERIC Educational Resources Information Center

    Santos, António J.; Vaughn, Brian E.; Peceguina, Inês; Daniel, João R.

    2014-01-01

    This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple…

  11. A centrifuge simulated push-pull manoeuvre with subsequent reduced +Gz tolerance.

    PubMed

    Xu, Yan; Li, Bao-Hui; Zhang, Li-Hui; Jin, Zhao; Wei, Xiao-Yang; Wang, Hong; Wu, San-Yuan; Wang, Hai-Xia; Wang, Quan; Yan, Gui-Ding; Deng, Lue; Geng, Xi-Chen

    2012-07-01

    The push-pull effect (PPE) has been recognized as a deleterious contributor to fatal flight accidents. The purpose of the study was to establish a push-pull manoeuvre (PPM) simulation with a tri-axes centrifuge, studying the effect of this PPM on the +Gz tolerance, and to make this simulation suitable for pilot centrifuge training. The PPM was realized through pre-programmed acceleration profiles consisting of -1 Gz for 5 s followed by a +Gz plateau for 10 s. Relaxed +Gz tolerance recordings were obtained from 20 healthy male fighter aircraft pilots and 6 healthy male volunteers through exposure to pre-programmed profiles with and without previous -1 Gz exposure. A statistically significant decrease in +Gz tolerance was seen in all subjects after -1 Gz for 5 s exposure, 0.87 ± 0.13 G in the volunteer group and 0.95 ± 0.25 G in the pilot group. The ear opacity pulse as a +Gz tolerance endpoint criterion was sometimes found to be unreliable during the PPM experiments. The simulated PPM in this study elicited a PPE, which was obvious from the significant reduction in +Gz tolerance. The PPM profile appears useful to be included in centrifuge training.

  12. Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies.

    PubMed

    Giovannoni, Gavin; Kappos, Ludwig; Gold, Ralf; Khatri, Bhupendra O; Selmaj, Krzysztof; Umans, Kimberly; Greenberg, Steven J; Sweetser, Marianne; Elkins, Jacob; McCroskery, Peter

    2016-09-01

    Daclizumab has been evaluated in multicentre, randomised, double-blind studies for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). Safety and tolerability are key considerations in MS treatment selection, as they influence adherence to medication. Evaluate the safety of daclizumab in patients with RRMS from an integrated analysis of six clinical studies. Patients treated with at least one dose of subcutaneous daclizumab 150mg or 300mg monthly in three completed and three ongoing clinical studies were included in this integrated analysis. Cumulative incidence of treatment-emergent adverse events (AEs) was the primary endpoint. This analysis included 2236 patients with 5214 patient-years of exposure to daclizumab. The cumulative incidence of any AE was 84% and of any serious AE excluding MS relapse was 16%. The incidences of AEs when evaluated by 6-month intervals remained stable over the 6.5 years of maximum follow-up. Most AEs were mild or moderate in severity. An important safety concern associated with daclizumab therapy involved hepatic AEs (16%) and serum transaminase elevations at least three times the upper limit of normal (10%), most of which were asymptomatic, self-limiting, and non-recurring. Cumulative incidences of cutaneous, infectious, and gastrointestinal AEs were 33%, 59%, and 25%, respectively; most events either resolved spontaneously or were treated successfully with standard medical interventions and did not result in discontinuation of treatment. This integrated analysis demonstrates that treatment of RRMS with daclizumab for periods of up to 6.5 years is associated with an acceptable safety profile with no evidence of cumulative toxicity over time. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. All roads lead to Rome: Towards understanding different avenues of tolerance to huanglongbing in citrus cultivars.

    PubMed

    Killiny, Nabil; Jones, Shelley E; Nehela, Yasser; Hijaz, Faraj; Dutt, Manjul; Gmitter, Frederick G; Grosser, Jude W

    2018-05-18

    Citrus tolerance to huanglongbing could result from tolerance to the pathogen Candidatus Liberibacter asiaticus (CLas) and/or to its vector Diaphorina citri. Field observations and greenhouse-controlled studies showed that some citrus cultivars were more tolerant than others. However, the mechanism(s) behind the tolerance has not been determined yet. Using GC-MS, we investigated the volatile organic compounds (VOCs) and the non-volatile metabolite profiles of two tolerant citrus cultivars- Australian finger lime, 'LB8-9' Sugar Belle ® mandarin hybrid, and a recently released mandarin hybrid 'Bingo'. The three were grafted onto the rootstock, Carrizo citrange. Our findings showed that the metabolomic profiles of Australian finger lime were different from that of 'LB8-9'. Finger lime was high in many amino acids and tricarboxylic acid intermediates, whereas 'LB8-9' was high in several amino acids, sugars, and sugar alcohols. 'LB8-9' was high in thymol, which is known for its strong antimicrobial activity against a panel of pathogenic bacteria. The metabolomic profiles of 'Bingo' were intensely different from the other mandarin hybrid, 'LB8-9', including a reduced thymol biosynthetic pathway and low amounts of most of the amino acids and sugar alcohols. Remarkably, 1,8-cineole (eucalyptol) was only detected in 'Bingo', indicating that eucalyptol could have feeding and ovipositional repellency against D. citri. The metabolite profiles generated for HLB-tolerant citrus species will improve the ability of citrus breeders and will allow them to take more informed decisions. Metabolomic profiling of HLB-tolerant citrus species could identify tolerance specific markers that can be introduced to other commercial citrus cultivars to improve their tolerance to HLB disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Children acceptance of laser dental treatment

    NASA Astrophysics Data System (ADS)

    Lazea, Andreea; Todea, Carmen

    2016-03-01

    Objectives: To evaluate the dental anxiety level and the degree of acceptance of laser assisted pedodontic treatments from the children part. Also, we want to underline the advantages of laser use in pediatric dentistry, to make this technology widely used in treating dental problems of our children patients. Methods: Thirty pediatric dental patients presented in the Department of Pedodontics, University of Medicine and Pharmacy "Victor Babeş", Timişoara were evaluated using the Wong-Baker pain rating scale, wich was administered postoperatory to all patients, to assess their level of laser therapy acceptance. Results: Wong-Baker faces pain rating scale (WBFPS) has good validity and high specificity; generally it's easy for children to use, easy to compare and has good feasibility. Laser treatment has been accepted and tolerated by pediatric patients for its ability to reduce or eliminate pain. Around 70% of the total sample showed an excellent acceptance of laser dental treatment. Conclusions: Laser technology is useful and effective in many clinical situations encountered in pediatric dentistry and a good level of pacient acceptance is reported during all laser procedures on hard and soft tissues.

  15. Differing disintegration and dissolution rates, pharmacokinetic profiles and gastrointestinal tolerability of over the counter ibuprofen formulations.

    PubMed

    Bjarnason, Ingvar; Sancak, Ozgur; Crossley, Anne; Penrose, Andrew; Lanas, Angel

    2018-02-01

    Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter t max and a higher C max for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in C max . © 2017 Royal Pharmaceutical Society.

  16. "Would you accept having your DNA profile inserted in the National Forensic DNA database? Why?" Results of a questionnaire applied in Portugal.

    PubMed

    Machado, Helena; Silva, Susana

    2014-01-01

    The creation and expansion of forensic DNA databases might involve potential threats to the protection of a range of human rights. At the same time, such databases have social benefits. Based on data collected through an online questionnaire applied to 628 individuals in Portugal, this paper aims to analyze the citizens' willingness to donate voluntarily a sample for profiling and inclusion in the National Forensic DNA Database and the views underpinning such a decision. Nearly one-quarter of the respondents would indicate 'no', and this negative response increased significantly with age and education. The overriding willingness to accept the inclusion of the individual genetic profile indicates an acknowledgement of the investigative potential of forensic DNA technologies and a relegation of civil liberties and human rights to the background, owing to the perceived benefits of protecting both society and the individual from crime. This rationale is mostly expressed by the idea that all citizens should contribute to the expansion of the National Forensic DNA Database for reasons that range from the more abstract assumption that donating a sample for profiling would be helpful in fighting crime to the more concrete suggestion that everyone (criminals and non-criminals) should be in the database. The concerns with the risks of accepting the donation of a sample for genetic profiling and inclusion in the National Forensic DNA Database are mostly related to lack of control and insufficient or unclear regulations concerning safeguarding individuals' data and supervising the access and uses of genetic data. By providing an empirically-grounded understanding of the attitudes regarding willingness to donate voluntary a sample for profiling and inclusion in a National Forensic DNA Database, this study also considers the citizens' perceived benefits and risks of operating forensic DNA databases. These collective views might be useful for the formation of international common

  17. The Tolerability Profile of Clindamycin 1%/Benzoyl Peroxide 5% Gel vs. Adapalene 0.1%/Benzoyl Peroxide 2.5% Gel for Facial Acne

    PubMed Central

    Cirigliano, Marcela; Gwazdauskas, Jennifer A; Gonzalez, Pablo

    2012-01-01

    Objective: To compare the first two weeks of tolerability of clindamycin/benzoyl peroxide gel versus adapalene/benzoyl peroxide gel followed by six weeks of open-label clindamycin/benzoyl peroxide gel therapy in subjects with mild-to-moderate acne who participated in two eight-week, identically designed, clinical studies. Methods: Using a split-face method, patients received both clindamycin/benzoyl peroxide gel and adapalene/benzoyl peroxide gel once daily for two weeks (allocation to the right or left side of the face was randomized) in an investigator-blinded fashion. Patients then went on to receive a further six weeks of open-label, full-face clindamycin/benzoyl peroxide gel. The primary outcome was to compare signs and symptoms of tolerability during the first two weeks of treatment using an investigator-assessed 4-point rating scale. Secondary endpoints included assessment of acne severity (Investigator Static Global Assessment and lesion counts), quality of life, product acceptability/preference, and patient assessments of tolerability and safety. Results: Of the 76 subjects enrolled in the two studies, 72 completed them. Overall both products were well tolerated, but mean scores for erythema, dryness, and peeling were significantly higher with adapalene/benzoyl peroxide gel than with clindamycin/benzoyl peroxide gel at both Weeks 1 and 2 (p<0.03). Patients also rated clindamycin/benzoyl peroxide gel significantly more tolerable than adapalene/benzoyl peroxide gel for redness, dryness, burning, itching, and scaling at Weeks 1 and 2 (p 0.0073). Mean Investigator Static Global Assessment score improved with both products during the first two weeks of treatment and continued to show significant improvement versus baseline when treatment with clindamycin/benzoyl peroxide gel was continued for a further six weeks (p<0.001 at Week 8). Lesion counts improved throughout the study with significant reductions from baseline occurring at Weeks 5 and 8 (p<0.0001 for

  18. Concordance and acceptability of electric stimulation therapy: a randomised controlled trial.

    PubMed

    Miller, C; McGuiness, W; Wilson, S; Cooper, K; Swanson, T; Rooney, D; Piller, N; Woodward, M

    2017-08-02

    A pilot single-blinded randomised controlled trial (RCT) was conducted to examine concordance with and acceptability of electric stimulation therapy (EST) in patients with venous leg ulcers (VLUs) who had not tolerated moderate to high compression. Participants were randomised to the intervention group (n=15) or a placebo control group (n=8) in which EST was used four times daily for 20 minutes per session. Participants were monitored for eight weeks during which time concordance with the treatment and perceptions of the treatment were assessed. Concordance with the total recommended treatment time was 71.4% for the intervention group and 82.9% for the control group; a difference that was not statistically significant. Participants rated EST as acceptable (84.6% intervention; 83.3% control), only two participants, both from the placebo control group, would not be willing to use EST again. The majority considered EST easier to use than compression (68.4%). EST was a practical and acceptable treatment among people who have been unable to tolerate moderate to high compression therapy.

  19. Acceptance Equipment System Data Acquisition and Processing Utility

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

    Fakhro, Rowan

    2015-02-01

    My internship at Sandia National Laboratories took place in the Department of Sensors and Embedded Systems, which is tasked with, among many things, the non-destructive testing of thermal batteries. The Acceptance Equipment System (AES) is a flexible rack system designed to electrically test thermal batteries individually for internal defects before they are stored in the battery stock pile. Aside from individual testing, data acquired by the AES is used for many things including trending and catching outliers within the tolerance levels of a particular battery type, allowing for the development of more refined acceptance requirements and testing procedures.

  20. [Acceptance and rejection of vasectomy in rural males].

    PubMed

    García Moreno, Juan; Solano Sainos, Luis Miguel

    2005-01-01

    One problem in rural population is the gap between coverage of contraception and scant masculine participation, which could be due to lack of information of to other sociocultural factors. We investigated, in two stages, the characteristics or the profile of the sexual and reproductive behavior of males in an exploratory study by means of focus groups to determine their relevant motivations and characteristics and subsequently, a structured questionnaire to ascertain the magnitude of the factors explored. The population corresponded to zones of rural hospital medical services zones of medical services in seven ethnic groups of the Mexican Republic and included men who accepted and who rejected vasectomy. The profile of males who accepted vasectomy allowed to determine that there exist a unsatisfied demand for contraceptive protection and the desire of not having additional children; in addition, we found that the decision to accept vasectomy is determined to a greater extent for reasons different from that of information on the contraceptive method. The important proportion of males who were non-users of contraceptive methods who accepted vasectomy supposed information on contraception to be the most consistent reason; nonetheless, this information was not considered sufficient and timely; thus, adverse economic situation, a certain condition related with the couple such as health or love for the female partner are the more weighty reasons for deciding to accept vasectomy, while the fear of poor sexual performance is the most powerful factor for rejection of vasectomy. Masculine participation in family planning is a factor that conditions contraceptive coverage and its respective benefits. The profile of the male who accepts vasectomy aids in identifying candidates forthe procedure and in reducing unsatisfied demand. Greater diffusion of information of the contraceptive method of vasectomy, greater links between male needs and vasectomy, and maintaining or

  1. Rejection Triggers Liver Transplant Tolerance: Involvements of Mesenchyme-Mediated Immune Control Mechanisms

    PubMed Central

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J.; Lu, Lina; Qian, Shiguang

    2015-01-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allograft in many species. The underlying mechanisms are not completely understood. We have been inspired by an unexpected phenomenon that the liver transplant tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigate the rejection of liver allografts deficient in IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effectors (Tef) cell-derived IFN-γ to drive the expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in liver transplant tolerance. Comparable elevations of T regulatory cells and myeloid-derived suppressor cells are seen in both rejection and tolerance groups, and are not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, as spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMCI may represent an important homeostatic mechanism that supports peripheral tolerance, and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is actively participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. PMID:25998530

  2. Assessing tolerance for wildlife: Clarifying relations between concepts and measures

    USGS Publications Warehouse

    Bruskotter, Jeremy T.; Singh, Ajay; Fulton, David C.; Slagle, Kristina

    2015-01-01

    Two parallel lines of inquiry, tolerance for and acceptance of wildlife populations, have arisen in the applied literature on wildlife conservation to assess probability of successfully establishing or increasing populations of controversial species. Neither of these lines is well grounded in social science theory, and diverse measures have been employed to assess tolerance, which inhibits comparability across studies. We empirically tested behavioral measures of tolerance against self-reports of previous policy-relevant behavior and behavioral intentions. Both composite behavioral measures were strongly correlated (r > .70) with two attitudinal measures of tolerance commonly employed in the literature. The strong correlation between attitudinal and behavioral measures suggests existing attitudinal measures represent valid, parsimonious measures of tolerance that may be useful when behavioral measures are too cumbersome or misreporting of behavior is anticipated. Our results demonstrate how behavioral measures of tolerance provide additional, useful information beyond general attitudinal measures.

  3. The Impact of Religiosity on Midshipman Adjustment and Feelings of Acceptance

    DTIC Science & Technology

    2006-06-01

    the military nature , if a midshipman is accepting of homosexuals he is often looked on as strange. Like if you have a gay friend it is looked on...grown exponentially over the past fifty years. Significant growth of religious diversity and religious media support the growing nature of popular...however, is still limited in scope and depth. The covert or personal nature of an individual’s beliefs makes acceptance and tolerance issues more

  4. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

    PubMed

    Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

    2015-01-01

    In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin

  5. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples - A pilot study

    PubMed Central

    Vodstrcil, Lenka A.; Danielewski, Jennifer A.; Murray, Gerald L.; Fairley, Christopher K.; Garland, Suzanne M.; Hocking, Jane S.; Tabrizi, Sepehr N.; Bradshaw, Catriona S.

    2018-01-01

    Objectives Recurrence following recommended treatment for bacterial vaginosis is unacceptably high. While the pathogenesis of recurrence is not well understood, recent evidence indicates re-infection from sexual partners is likely to play a role. The aim of this study was to assess the acceptability and tolerability of topical and oral antimicrobial therapy in male partners of women with bacterial vaginosis (BV), and to investigate the impact of dual-partner treatment on the vaginal and penile microbiota. Methods Women with symptomatic BV (Nugent Score of 4–10 and ≥3 Amsel criteria) and their regular male sexual partner were recruited from Melbourne Sexual Health Centre, Melbourne, Australia. Women received oral metronidazole 400mg twice daily (or intra-vaginal 2% clindamycin cream, if contraindicated) for 7-days. Male partners received oral metronidazole 400mg twice daily and 2% clindamycin cream topically to the penile skin twice daily for 7-days. Couples provided self-collected genital specimens and completed questionnaires at enrolment and then weekly for 4-weeks. Genital microbiota composition was determined by 16S rRNA gene sequencing. Changes in genital microbiota composition were assessed by Bray-Curtis index. Bacterial diversity was measured by the Shannon Diversity Index. Results Twenty-two couples were recruited. Sixteen couples (76%) completed all study procedures. Adherence was high; most participants took >90% of prescribed medication. Medication, and particularly topical clindamycin in males, was well tolerated. Dual-partner treatment had an immediate and sustained effect on the composition of vaginal microbiota (median Bray-Curtis score day 0 versus day 8 = 0.03 [IQR 0–0.15], day 0 vs day 28 = 0.03 [0.02–0.11]). We observed a reduction in bacterial diversity of the vaginal microbiota and a decrease in the prevalence and abundance of BV-associated bacteria following treatment. Treatment had an immediate effect on the composition of the

  6. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples - A pilot study.

    PubMed

    Plummer, Erica L; Vodstrcil, Lenka A; Danielewski, Jennifer A; Murray, Gerald L; Fairley, Christopher K; Garland, Suzanne M; Hocking, Jane S; Tabrizi, Sepehr N; Bradshaw, Catriona S

    2018-01-01

    Recurrence following recommended treatment for bacterial vaginosis is unacceptably high. While the pathogenesis of recurrence is not well understood, recent evidence indicates re-infection from sexual partners is likely to play a role. The aim of this study was to assess the acceptability and tolerability of topical and oral antimicrobial therapy in male partners of women with bacterial vaginosis (BV), and to investigate the impact of dual-partner treatment on the vaginal and penile microbiota. Women with symptomatic BV (Nugent Score of 4-10 and ≥3 Amsel criteria) and their regular male sexual partner were recruited from Melbourne Sexual Health Centre, Melbourne, Australia. Women received oral metronidazole 400mg twice daily (or intra-vaginal 2% clindamycin cream, if contraindicated) for 7-days. Male partners received oral metronidazole 400mg twice daily and 2% clindamycin cream topically to the penile skin twice daily for 7-days. Couples provided self-collected genital specimens and completed questionnaires at enrolment and then weekly for 4-weeks. Genital microbiota composition was determined by 16S rRNA gene sequencing. Changes in genital microbiota composition were assessed by Bray-Curtis index. Bacterial diversity was measured by the Shannon Diversity Index. Twenty-two couples were recruited. Sixteen couples (76%) completed all study procedures. Adherence was high; most participants took >90% of prescribed medication. Medication, and particularly topical clindamycin in males, was well tolerated. Dual-partner treatment had an immediate and sustained effect on the composition of vaginal microbiota (median Bray-Curtis score day 0 versus day 8 = 0.03 [IQR 0-0.15], day 0 vs day 28 = 0.03 [0.02-0.11]). We observed a reduction in bacterial diversity of the vaginal microbiota and a decrease in the prevalence and abundance of BV-associated bacteria following treatment. Treatment had an immediate effect on the composition of the cutaneous penile microbiota (median

  7. The failure-tolerant leader.

    PubMed

    Farson, Richard; Keyes, Ralph

    2002-08-01

    "The fastest way to succeed," IBM's Thomas Watson, Sr., once said, "is to double your failure rate." In recent years, more and more executives have embraced Watson's point of view, coming to understand what innovators have always known: Failure is a prerequisite to invention. But while companies may grasp the value of making mistakes at the level of corporate practices, they have a harder time accepting the idea at the personal level. People are afraid to fail, and corporate culture reinforces that fear. In this article, psychologist and former Harvard Business School professor Richard Farson and coauthor Ralph Keyes discuss how companies can reduce the fear of miscues. What's crucial is the presence of failure-tolerant leaders--executives who, through their words and actions, help employees overcome their anxieties about making mistakes and, in the process, create a culture of intelligent risk-taking that leads to sustained innovation. Such leaders don't just accept productive failure, they promote it. Drawing from their research in business, politics, sports, and science, the authors identify common practices among failure-tolerant leaders. These leaders break down the social and bureaucratic barriers that separate them from their followers. They engage at a personal level with the people they lead. They avoid giving either praise or criticism, preferring to take a nonjudgmental, analytical posture as they interact with staff. They openly admit their own mistakes rather than trying to cover them up or shifting the blame. And they try to root out the destructive competitiveness built into most organizations. Above all else, failure-tolerant leaders push people to see beyond traditional definitions of success and failure. They know that as long as a person views failure as the opposite of success, rather than its complement, he or she will never be able to take the risks necessary for innovation.

  8. Possible role of plant volatiles in tolerance against huanglongbing in citrus

    PubMed Central

    Hijaz, Faraj; Nehela, Yasser; Killiny, Nabil

    2016-01-01

    abstract Volatile organic compounds (VOC) play an important role in protecting plants from insect and pathogen attack. In this study, we investigated the leaf volatile profiles of 14 citrus varieties. The VOC in citrus leaves were extracted with n-hexane and analyzed using gas chromatography-mass spectrometry (GC-MS). Overall, 4six volatile compounds were identified in the n-hexane extract from citrus leaves. Most of the detected compounds belonged to 3 main groups (monoterpenes, sesquiterpenes, and aliphatic aldehydes). Principle component analysis was used to examine the relative distribution of the studied varieties to each other. Interestingly, volatile profiles of varieties that are tolerant to Candidatus Liberibacter asiaticus (CLas) were different from those of the susceptible ones. Tolerant and moderately-tolerant cultivars contained relatively higher amounts of volatiles than susceptible varieties. In addition, tolerant varieties were also higher in specific compounds which are known for their antimicrobial activities. These compounds include Aldehydes (undecanal, neral, geranial, and citronellal) and some monoterpenes such as linalool, d-limonene, myrcene, α- and β- phellandrene. In addition, some sesquiterpene compounds including t-caryophellene, γ-elemene, β-elemene, germacrene D, and geranyl acetate were higher in tolerant and moderately tolerant cultivars. Severinia buxifolia which is known for its tolerance to CLas and many other pathogens contained higher levels of santalenes and coumarins. Our results indicated that citrus leaf volatiles might play a role in citrus tolerance to CLas. The results of this study may help in understanding of the mechanism of citrus tolerance against CLas. PMID:26829496

  9. Possible role of plant volatiles in tolerance against huanglongbing in citrus.

    PubMed

    Hijaz, Faraj; Nehela, Yasser; Killiny, Nabil

    2016-01-01

    Volatile organic compounds (VOC) play an important role in protecting plants from insect and pathogen attack. In this study, we investigated the leaf volatile profiles of 14 citrus varieties. The VOC in citrus leaves were extracted with n-hexane and analyzed using gas chromatography-mass spectrometry (GC-MS). Overall, 4six volatile compounds were identified in the n-hexane extract from citrus leaves. Most of the detected compounds belonged to 3 main groups (monoterpenes, sesquiterpenes, and aliphatic aldehydes). Principle component analysis was used to examine the relative distribution of the studied varieties to each other. Interestingly, volatile profiles of varieties that are tolerant to Candidatus Liberibacter asiaticus (CLas) were different from those of the susceptible ones. Tolerant and moderately-tolerant cultivars contained relatively higher amounts of volatiles than susceptible varieties. In addition, tolerant varieties were also higher in specific compounds which are known for their antimicrobial activities. These compounds include Aldehydes (undecanal, neral, geranial, and citronellal) and some monoterpenes such as linalool, d-limonene, myrcene, α- and β- phellandrene. In addition, some sesquiterpene compounds including t-caryophellene, γ-elemene, β-elemene, germacrene D, and geranyl acetate were higher in tolerant and moderately tolerant cultivars. Severinia buxifolia which is known for its tolerance to CLas and many other pathogens contained higher levels of santalenes and coumarins. Our results indicated that citrus leaf volatiles might play a role in citrus tolerance to CLas. The results of this study may help in understanding of the mechanism of citrus tolerance against CLas.

  10. Females in Law Enforcement: Femininity, Competence, Attraction, and Work Acceptance.

    ERIC Educational Resources Information Center

    Hernandez, Ernie, Jr.

    1982-01-01

    Used photographs and biographical descriptions of female deputy strangers to examine effects of femininity and competence on male deputy attraction to and work acceptance of female deputies. Findings included an attraction preference for feminine-competent female deputies, and greater tolerance of feminine-incompetent female deputies for staff…

  11. Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

    PubMed

    Bianchi, Cristina; Miccoli, Roberto; Trombetta, Maddalena; Giorgino, Francesco; Frontoni, Simona; Faloia, Emanuela; Marchesini, Giulio; Dolci, Maria A; Cavalot, Franco; Cavallo, Gisella; Leonetti, Frida; Bonadonna, Riccardo C; Del Prato, Stefano

    2013-05-01

    In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function. Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

  12. Genome-Wide Identification, Characterization, and Expression Profiling of Glutathione S-Transferase (GST) Family in Pumpkin Reveals Likely Role in Cold-Stress Tolerance

    PubMed Central

    Abdul Kayum, Md.; Nath, Ujjal Kumar; Park, Jong-In; Choi, Eung Kyoo; Song, Jae-Young; Kim, Hoy-Taek; Nou, Ill-Sup

    2018-01-01

    Plant growth and development can be adversely affected by cold stress, limiting productivity. The glutathione S-transferase (GST) family comprises important detoxifying enzymes, which play major roles in biotic and abiotic stress responses by reducing the oxidative damage caused by reactive oxygen species. Pumpkins (Cucurbita maxima) are widely grown, economically important, and nutritious; however, their yield can be severely affected by cold stress. The identification of putative candidate genes responsible for cold-stress tolerance, including the GST family genes, is therefore vital. For the first time, we identified 32 C. maxima GST (CmaGST) genes using a combination of bioinformatics approaches and characterized them by expression profiling. These CmaGST genes represent seven of the 14 known classes of plant GSTs, with 18 CmaGSTs categorized into the tau class. The CmaGSTs were distributed across 13 of pumpkin’s 20 chromosomes, with the highest numbers found on chromosomes 4 and 6. The large number of CmaGST genes resulted from gene duplication; 11 and 5 pairs of CmaGST genes were segmental- and tandem-duplicated, respectively. In addition, all CmaGST genes showed organ-specific expression. The expression of the putative GST genes in pumpkin was examined under cold stress in two lines with contrasting cold tolerance: cold-tolerant CP-1 (C. maxima) and cold-susceptible EP-1 (Cucurbita moschata). Seven genes (CmaGSTU3, CmaGSTU7, CmaGSTU8, CmaGSTU9, CmaGSTU11, CmaGSTU12, and CmaGSTU14) were highly expressed in the cold-tolerant line and are putative candidates for use in breeding cold-tolerant crop varieties. These results increase our understanding of the cold-stress-related functions of the GST family, as well as potentially enhancing pumpkin breeding programs. PMID:29439434

  13. [Difference in target antigens between central tolerance and peripheral tolerance deficiencies].

    PubMed

    Chida, Natsuko; Kobayashi, Ichiro

    2015-01-01

    Failure of the immunotolerance mechanisms causes multiple organ-specific autoimmune disorders. Mutations of autoimmune regulator (AIRE) gene result in central immunotolerance deficiency named autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED). Mutations of FOXP3 genes cause regulatory T cell (Treg) deficiency named immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Because T cell tolerance influences B cell tolerance, autoantibodies seem to reflect the presence of autoreactive T cells with the same antigen specificity. To date many differences in both clinical features and autoantibody profiles have been described between APECED and IPEX syndrome. In addition to the differences in target organs, we have found differences in the target antigens in the same organ, small intestine, between both disorders; anti-autoimmune enteropathy-related 75 kDa antigen (AIE-75) antibodies are specific to IPEX syndrome, whereas anti-tryptophan hydroxylase-1 (TPH-1) antibodies are specific to APECED. These facts suggest that immunotolerance to AIE-75 depends on the Treg, whereas the tolerance to TPH-1 depends on the central mechanisms. Furthermore, given the earlier onset and more serious clinical features of IPEX syndrome than APECED, physiological roles of Aire on the selection of Treg may be, if present, limited.

  14. BIOMARKERS OF OPERATIONAL TOLERANCE IN SOLID ORGAN TRANSPLANTATION

    PubMed Central

    Heidt, Sebastiaan; Wood, Kathryn J.

    2012-01-01

    Introduction Long-term immunosuppressive therapy represents a huge burden on transplant recipients, but currently cannot be omitted. Improving long-term transplant outcome by immunosuppressive drug withdrawal may be achieved in patients who have developed (partial) immunological unresponsiveness towards their graft, either spontaneously or through tolerance induction. Reliable biomarkers are essential to define such immunological unresponsiveness and will facilitate controlled immunosuppressive drug weaning as well as provide surrogate end-points for tolerance induction trials. Areas covered Tolerance biomarkers have been defined for both liver and kidney transplantation and can accurately identify operationally tolerant transplant recipients retrospectively. These two tolerance fingerprints are remarkably different, indicating the involvement of distinct mechanisms. Limited data suggest that tolerance biomarkers can be detected in immunosuppressed transplant recipients. Whether these patients can safely have their immunosuppressive drugs withdrawn needs to be established. Expert opinion Mechanistic interpretation of the kidney transplant tolerance biomarker profile dominated by B cell markers remains a challenge in light of experimental evidence suggesting the pivotal involvement of regulatory T cells. Therefore, defining animal models that resemble human transplant tolerance is crucial in understanding the underlying mechanisms. Additionally, to ensure patient safety while monitoring for tolerance, it is essential to develop biomarkers to non-invasively detect early signs of rejection as well. PMID:22988481

  15. Nut-enriched bread is an effective and acceptable vehicle to improve regular nut consumption.

    PubMed

    Devi, Asika; Chisholm, Alexandra; Gray, Andrew; Tey, Siew Ling; Williamson-Poutama, Destynee; Cameron, Sonya L; Brown, Rachel C

    2016-10-01

    Consuming 30 g of nuts/day is recommended to reduce chronic disease. However, nut consumption appears far from ideal among several populations. A potential strategy to increase consumption is to add nuts to a staple, for example, bread. Whether the health benefits and acceptability of nuts persist in this form is currently unknown. Thus, we examined the effects of consuming three nut-enriched breads on postprandial glycaemia, satiety, gastrointestinal tolerance, dietary intakes, and acceptance. In this controlled, crossover study, 32 participants were randomly allocated to receive one of four breads for 8 days each. Three breads contained either 30 g of finely sliced hazelnuts, 30 g semi-defatted hazelnut flour, or 15 g of each (amounts per 120 g bread) and were compared with a control nut-free bread. Blood glucose response was measured over 120 min, along with ratings of gastrointestinal discomfort. Appetite ratings and diet diaries were completed during each treatment period. Area under the blood glucose curve was significantly lower for the nut breads compared to the control bread (all P < 0.001), with no significant differences between the nut breads (all P ≥ 0.130). There were no significant differences in satiety (all P ≥ 0.135) or gastrointestinal symptoms (all P ≥ 0.102) between the breads. Acceptance was highest for the finely sliced hazelnut bread. Furthermore, consuming hazelnut-enriched bread improved diet quality, increasing monounsaturated fat, vitamin E, and dietary fibre intakes. Bread appears to be an effective and acceptable vehicle for increasing nut consumption, resulting in improved postprandial glycaemia and diet profiles. Long-term studies are now required.

  16. Bully/Victim Profiles’ Differential Risk for Worsening Peer Acceptance: The Role of Friendship

    PubMed Central

    Kochel, Karen P.; Ladd, Gary W.; Bagwell, Catherine L.; Yabko, Brandon A.

    2015-01-01

    Study aims were to: (1) evaluate the association between bully/victim profiles, derived via latent profile analysis (LPA), and changes in peer acceptance from the fall to spring of 7th grade, and (2) investigate the likelihood of friendlessness, and the protective function of mutual friendship, among identified profiles. Participants were 2,587 7th graders; peer nomination and rating-scale data were collected in the fall and spring. Four profiles, including bullies, victims, bully-victims, and uninvolved adolescents, were identified at each time point. Findings showed that for victims, more so than for bullies and uninvolved profiles, acceptance scores worsened over time. Results further revealed that bully-victim and victim profiles included a greater proportion of friendless youth relative to the bully profile, which, in turn, contained a greater proportion of friendless adolescents than the uninvolved profile. Findings also provided evidence for the buffering role of friendship among all bully/victim profiles and among bully-victims especially. PMID:26309346

  17. Directionality between Tolerance of Deviance and Deviant Behavior Is Age-Moderated in Chronically Stressed Youth

    ERIC Educational Resources Information Center

    Ridenour, Ty A.; Caldwell, Linda L.; Coatsworth, J. Douglas; Gold, Melanie A.

    2011-01-01

    Problem behavior theory posits that tolerance of deviance is an antecedent to antisocial behavior and substance use. In contrast, cognitive dissonance theory implies that acceptability of a behavior may increase after experiencing the behavior. Using structural equation modeling, this investigation tested whether changes in tolerance of deviance…

  18. "Zones of Tolerance" in Perceptions of Library Service Quality: A LibQUAL+[TM] Study.

    ERIC Educational Resources Information Center

    Cook, Colleen; Heath, Fred M.; Thompson, Bruce

    2003-01-01

    One of the two major ways of interpreting LibQUAL+[TM] data involves placing perceived service quality ratings within "zones of tolerance" defined as the distances between minimally-acceptable and desired service quality levels. This study compared zones of tolerance on the 25 LibQUAL+[TM] items across undergraduate, graduate student and…

  19. Tolerant compressed sensing with partially coherent sensing matrices

    NASA Astrophysics Data System (ADS)

    Birnbaum, Tobias; Eldar, Yonina C.; Needell, Deanna

    2017-08-01

    Most of compressed sensing (CS) theory to date is focused on incoherent sensing, that is, columns from the sensing matrix are highly uncorrelated. However, sensing systems with naturally occurring correlations arise in many applications, such as signal detection, motion detection and radar. Moreover, in these applications it is often not necessary to know the support of the signal exactly, but instead small errors in the support and signal are tolerable. Despite the abundance of work utilizing incoherent sensing matrices, for this type of tolerant recovery we suggest that coherence is actually beneficial . We promote the use of coherent sampling when tolerant support recovery is acceptable, and demonstrate its advantages empirically. In addition, we provide a first step towards theoretical analysis by considering a specific reconstruction method for selected signal classes.

  20. Natural genetic variation of freezing tolerance in Arabidopsis.

    PubMed

    Hannah, Matthew A; Wiese, Dana; Freund, Susanne; Fiehn, Oliver; Heyer, Arnd G; Hincha, Dirk K

    2006-09-01

    Low temperature is a primary determinant of plant growth and survival. Using accessions of Arabidopsis (Arabidopsis thaliana) originating from Scandinavia to the Cape Verde Islands, we show that freezing tolerance of natural accessions correlates with habitat winter temperatures, identifying low temperature as an important selective pressure for Arabidopsis. Combined metabolite and transcript profiling show that during cold exposure, global changes of transcripts, but not of metabolites, correlate with the ability of Arabidopsis to cold acclimate. There are, however, metabolites and transcripts, including several transcription factors, that correlate with freezing tolerance, indicating regulatory pathways that may be of primary importance for this trait. These data identify that enhanced freezing tolerance is associated with the down-regulation of photosynthesis and hormonal responses and the induction of flavonoid metabolism, provide evidence for naturally increased nonacclimated freezing tolerance due to the constitutive activation of the C-repeat binding factors pathway, and identify candidate transcriptional regulators that correlate with freezing tolerance.

  1. Steam pressure treatment of defective Coffea canephora beans improves the volatile profile and sensory acceptance of roasted coffee blends.

    PubMed

    Kalschne, Daneysa Lahis; Viegas, Marcelo Caldeira; De Conti, Antonio José; Corso, Marinês Paula; Benassi, Marta de Toledo

    2018-03-01

    Between 15 and 20% of Brazilian coffee production corresponds to defective beans (PVA), which decreases the quality of the coffee brew. Steam treatment has been reported as an alternative to improve the volatile profile and cup quality of coffee. The aim of this study was to propose a steam treatment of defective Coffea canephora beans to improve the volatile profile of the roasted coffee. The sensory impacts of adding steamed coffee (SC) in Coffea arabica blends were evaluated. The steam treatments studied modified the volatile profile of roasted SCs, increasing the contents of acetoin, benzyl alcohol, maltol, 2,6-dimethylpyrazine, 2-furfurylthiol, and 5-methylfurfural and decreasing the contents of 4-ethylguaiacol, isovaleric acid, methional, 2,3-diethyl-5-methylpyrazine, and 3-methoxy-3-methylpyrazine. Among the evaluated parameters, the best condition to maximized the content of the volatiles with a potential positive impact and minimize those with a potential negative impact was 5bar/16min (SC 5). The thresholds of consumer rejection and of detection indicate that up to 30% SC 5 can be added to a high cup quality Coffea arabica coffee without perception or rejection of the coffee brew. A blend of 30% of SC 5 and 70% of Coffea arabica was well accepted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Multi-version software reliability through fault-avoidance and fault-tolerance

    NASA Technical Reports Server (NTRS)

    Vouk, Mladen A.; Mcallister, David F.

    1989-01-01

    A number of experimental and theoretical issues associated with the practical use of multi-version software to provide run-time tolerance to software faults were investigated. A specialized tool was developed and evaluated for measuring testing coverage for a variety of metrics. The tool was used to collect information on the relationships between software faults and coverage provided by the testing process as measured by different metrics (including data flow metrics). Considerable correlation was found between coverage provided by some higher metrics and the elimination of faults in the code. Back-to-back testing was continued as an efficient mechanism for removal of un-correlated faults, and common-cause faults of variable span. Software reliability estimation methods was also continued based on non-random sampling, and the relationship between software reliability and code coverage provided through testing. New fault tolerance models were formulated. Simulation studies of the Acceptance Voting and Multi-stage Voting algorithms were finished and it was found that these two schemes for software fault tolerance are superior in many respects to some commonly used schemes. Particularly encouraging are the safety properties of the Acceptance testing scheme.

  3. Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh.

    PubMed

    Inskip, Chloe; Carter, Neil; Riley, Shawn; Roberts, Thomas; MacMillan, Douglas

    2016-01-01

    Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the 'Wildlife Stakeholder Acceptance Capacity' concept, to explore villagers' tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers' beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide.

  4. Distress Tolerance Treatment for Early-Lapse Smokers

    PubMed Central

    Brown, Richard A.; Palm, Kathleen M.; Strong, David R.; Lejuez, Carl W.; Kahler, Christopher W.; Zvolensky, Michael J.; Hayes, Steven C.; Wilson, Kelly G.; Gifford, Elizabeth V.

    2008-01-01

    A significant percentage of individuals attempting smoking cessation lapse within a matter of days, and very few are able to recover to achieve long-term abstinence. This observation suggests that many smokers may have quit-attempt histories characterized exclusively by early lapses to smoking following quit attempts. Recent negative-reinforcement conceptualizations of early lapse to smoking suggest that individuals' reactions to withdrawal and inability to tolerate the experience of these symptoms, rather than withdrawal severity itself, may represent an important treatment target in the development of new behavioral interventions for this subpopulation of smokers. This article presents the theoretical rationale and describes a novel, multicomponent distress-tolerance treatment for early-lapse smokers that incorporates behavioral and pharmacological elements of standard smoking-cessation treatment, whereas drawing distress-tolerance elements from exposure-based and Acceptance and Commitment Therapy–based treatment approaches. Preliminary data from a pilot study (N = 16) are presented, and clinical implications are discussed. PMID:18391050

  5. Opioid tolerance and dependence -- do they matter?

    PubMed

    Jage, Jürgen

    2005-04-01

    The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization.

  6. Effect of flax addition on the flavor profile and acceptability of bagels.

    PubMed

    Aliani, Michel; Ryland, Donna; Pierce, Grant N

    2012-01-01

    Bakery products containing flaxseed, a rich source of alpha linolenic acid (ALA), may provide health benefits. However, the effect of adding flaxseed, especially in the high amounts required for use as the food supplement in clinical trials (23% by weight of the raw ingredients), may affect the flavor characteristics and consumer acceptability. Sensory attributes of bagels containing 30 g of milled flaxseed were evaluated by a 9 member trained panel using a descriptive test and by 89 participants using a consumer test. Grain/flax aroma and flavor were significantly higher for the flax bagels compared to the nonflax bagels. The cinnamon raisin bagel had significantly lower grain/flax aroma and flavor and significantly higher sweet aroma and taste compared to the plain and sunflower sesame types. Older consumers rated the appearance, color, and flavor of the bagels significantly higher than the younger consumers possibly leading to higher compliance in clinical studies for this age group. Bagels with flax showed a significantly lower mean value for flavor acceptability, overall acceptability, and frequency of eating compared to bagels without flax. Appearance, color, and texture acceptability showed no significant differences. The cinnamon raisin bagel had significantly higher flavor acceptance compared to sunflower sesame and plain bagels. In conclusion, for bagels containing 6 g ALA in the form of milled flaxseed, cinnamon raisin appears to be a promising flavoring alternative for ALA fortification for use in clinical trials or as part of the daily diet. Consumers are seeking functional foods that contain omega-3 fatty acids. Bagels made with 23% milled flaxseed (approximately 2 times the amount in regular flax baked products) provided 6 g ALA, an amount high enough to test the efficacy of ALA in human subjects without causing gastrointestinal distress. This study showed that flaxseed aroma and flavor were detected in fortified compared to nonfortified bagels but

  7. Proteome profiling reveals insights into cold-tolerant growth in sea buckthorn.

    PubMed

    He, Caiyun; Gao, Guori; Zhang, Jianguo; Duan, Aiguo; Luo, Hongmei

    2016-01-01

    Low temperature is one of the crucial environmental factors limiting the productivity and distribution of plants. Sea buckthorn ( Hippophae rhamnoides L.), a well recognized multipurpose plant species, live successfully in in cold desert regions. But their molecular mechanisms underlying cold tolerance are not well understood. Physiological and biochemical responses to low-temperature stress were studied in seedlings of sea buckthorn. Differentially expressed protein spots were analyzed using multiplexing fluorescent two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry (MS), the concentration of phytohormone was measured using enzyme-linked immunosorbent assay, and a spectrophotometric assay was used to measure enzymatic reactions. With the increase of cold stress intensity, the photosynthesis rate, transpiration rate, stomatal conductance in leaves and contents of abscisic acid (ABA) and indole acetic acid (IAA) in roots decreased significantly; however, water-use efficiency, ABA and zeatin riboside in leaves increased significantly, while cell membrane permeability, malondialdehyde and IAA in leaves increased at 7 d and then decreased at 14 d. DIGE and MS/MS analysis identified 32 of 39 differentially expressed protein spots under low-temperature stress, and their functions were mainly involved in metabolism, photosynthesis, signal transduction, antioxidative systems and post-translational modification. The changed protein abundance and corresponding physiological-biochemical response shed light on the molecular mechanisms related to cold tolerance in cold-tolerant plants and provide key candidate proteins for genetic improvement of plants.

  8. Transcript analysis in two alfalfa salt tolerance selected breeding populations relative to a non-tolerant population.

    PubMed

    Gruber, M Y; Xia, J; Yu, M; Steppuhn, H; Wall, K; Messer, D; Sharpe, A G; Acharya, S N; Wishart, D S; Johnson, D; Miller, D R; Taheri, A

    2017-02-01

    With the growing limitations on arable land, alfalfa (a widely cultivated, low-input forage) is now being selected to extend cultivation into saline lands for low-cost biofeedstock purposes. Here, minerals and transcriptome profiles were compared between two new salinity-tolerant North American alfalfa breeding populations and a more salinity-sensitive western Canadian alfalfa population grown under hydroponic saline conditions. All three populations accumulated two-fold higher sodium in roots than shoots as a function of increased electrical conductivity. At least 50% of differentially expressed genes (p < 0.05) were down-regulated in the salt-sensitive population growing under high salinity, while expression remained unchanged in the saline-tolerant populations. In particular, most reduction in transcript levels in the salt-sensitive population was observed in genes specifying cell wall structural components, lipids, secondary metabolism, auxin and ethylene hormones, development, transport, signalling, heat shock, proteolysis, pathogenesis-response, abiotic stress, RNA processing, and protein metabolism. Transcript diversity for transcription factors, protein modification, and protein degradation genes was also more strongly affected in salt-tolerant CW064027 than in salt-tolerant Bridgeview and salt-sensitive Rangelander, while both saline-tolerant populations showed more substantial up-regulation in redox-related genes and B-ZIP transcripts. The report highlights the first use of bulked genotypes as replicated samples to compare the transcriptomes of obligate out-cross breeding populations in alfalfa.

  9. Rejection triggers liver transplant tolerance: Involvement of mesenchyme-mediated immune control mechanisms in mice.

    PubMed

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J; Lu, Lina; Qian, Shiguang

    2015-09-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allografts in many species. The underlying mechanisms are not completely understood. However, liver transplant (LT) tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigated the rejection of liver allografts deficient in the IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effector (Tef) cell-derived IFN-γ that drives expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in LT tolerance. Comparable elevations of T-regulatory cells and myeloid-derived suppressor cells were observed in both rejection and tolerance groups and were not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, given that spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMIC may represent an important homeostatic mechanism that supports peripheral tolerance and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is an active participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. © 2015 by the American Association for the Study of Liver Diseases.

  10. Transcriptome profiling of Vitis amurensis, an extremely cold-tolerant Chinese wild Vitis species, reveals candidate genes and events that potentially connected to cold stress.

    PubMed

    Xu, Weirong; Li, Ruimin; Zhang, Ningbo; Ma, Fuli; Jiao, Yuntong; Wang, Zhenping

    2014-11-01

    Vitis amurensis Rupr. is an exceptional wild-growing Vitis (grape) species that can safely survive a wide range of cold conditions, but the underlying cold-adaptive mechanism associated with gene regulation is poorly investigated. We have analyzed the physiochemical and transcriptomic changes caused by cold stress in a cold-tolerant accession, 'Heilongjiang seedling', of Chinese wild V. amurensis. We statistically determined that a total of 6,850 cold-regulated transcripts were involved in cold regulation, including 3,676 up-regulated and 3,174 down-regulated transcripts. A global survey of messenger RNA revealed that skipped exon is the most prevalent form of alternative spicing event. Importantly, we found that the total splicing events increased with the prolonged cold stress. We also identified thirty-eight major TF families that were involved in cold regulation, some of which were previously unknown. Moreover, a large number of candidate pathways for the metabolism or biosynthesis of secondary metabolites were found to be regulated by cold, which is of potential importance in coordinating cold tolerance with growth and development. Several heat shock proteins and heat shock factors were also detected to be intensively cold-regulated. Furthermore, we validated the expression profiles of 16 candidates using qRT-PCR to further confirm the accuracy of the RNA-seq data. Our results provide a genome-wide view of the dynamic changes in the transcriptome of V. amurensis, in which it is evident that various structural and regulatory genes are crucial for cold tolerance/adaptation. Moreover, our robust dataset advances our knowledge of the genes involved in the complex regulatory networks of cold stress and leads to a better understanding of cold tolerance mechanisms in this extremely cold-tolerant Vitis species.

  11. Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh

    PubMed Central

    Inskip, Chloe; Roberts, Thomas; MacMillan, Douglas

    2016-01-01

    Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the ‘Wildlife Stakeholder Acceptance Capacity’ concept, to explore villagers’ tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers’ beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide. PMID:26760035

  12. Interrelating Behavioral Measures of Distress Tolerance with Self-Reported Experiential Avoidance.

    PubMed

    Schloss, Heather M; Haaga, David A F

    2011-03-01

    Experiential avoidance and distress intolerance play a central role in novel behavior therapies, yet they appear to overlap considerably the REBT concept of low frustration tolerance. Using baseline data from 100 adult cigarette smokers enrolled in a clinical trial of smoking cessation therapies, the present study evaluated the convergent validity of common questionnaire measures of experiential avoidance (Acceptance and Action Questionnaire; AAQ; Hayes et al. 2004, and Avoidance and Inflexibility Scale: AIS; Gifford et al. 2004) and behavioral measures of distress tolerance (computerized Mirror Tracing Persistence Task: MTPT-C: Strong et al. 2003; computerized Paced Auditory Serial Addition Task; PASAT-C; Lejuez et al. 2003). The distress tolerance measures correlated significantly (r = .29) with one another. However, the questionnaire measures of experiential avoidance did not correlate with each other, nor with the behavioral measures. Further research is needed on the validity of measuring experiential avoidance by self-report and of the overlap versus distinctiveness of seemingly similar constructs such as experiential avoidance, distress tolerance, and frustration tolerance.

  13. Acceptance of Prostitution and Its Social Determinants in Canada.

    PubMed

    Cao, Liqun; Lu, Ruibin; Mei, Xiaohan

    2017-08-01

    The nature of collective perception of prostitution is understudied in Canada. Except some rudimentary reports on the percentages of the key legal options, multivariate analysis has never been used to analyze the details of public opinion on prostitution. The current study explores the trend of public attitude toward prostitution acceptability in Canada over a 25-year span and examines the social determinants of the acceptability of prostitution, using structural equation modeling (SEM), which allows researchers to elaborate both direct and indirect effects (through mediating variables) on the outcome variable. Results show that the public has become more acceptant of prostitution over time. In addition, the less religious, less authoritarian, and more educated are more acceptant of prostitution than the more religious, more authoritarian, and less well educated. The effects of religiosity and authoritarianism mediate out the direct effects of age, gender, gender equality, marriage, marriage as an outdated institution, Quebec, race, and tolerance. The findings may serve as a reference point for the law reform regarding the regulation of prostitution in Canada.

  14. Acceptable Risk Analysis for Abrupt Environmental Pollution Accidents in Zhangjiakou City, China.

    PubMed

    Du, Xi; Zhang, Zhijiao; Dong, Lei; Liu, Jing; Borthwick, Alistair G L; Liu, Renzhi

    2017-04-20

    Abrupt environmental pollution accidents cause considerable damage worldwide to the ecological environment, human health, and property. The concept of acceptable risk aims to answer whether or not a given environmental pollution risk exceeds a societally determined criterion. This paper presents a case study on acceptable environmental pollution risk conducted through a questionnaire survey carried out between August and October 2014 in five representative districts and two counties of Zhangjiakou City, Hebei Province, China. Here, environmental risk primarily arises from accidental water pollution, accidental air pollution, and tailings dam failure. Based on 870 valid questionnaires, demographic and regional differences in public attitudes towards abrupt environmental pollution risks were analyzed, and risk acceptance impact factors determined. The results showed females, people between 21-40 years of age, people with higher levels of education, public servants, and people with higher income had lower risk tolerance. People with lower perceived risk, low-level risk knowledge, high-level familiarity and satisfaction with environmental management, and without experience of environmental accidents had higher risk tolerance. Multiple logistic regression analysis indicated that public satisfaction with environmental management was the most significant factor in risk acceptance, followed by perceived risk of abrupt air pollution, occupation, perceived risk of tailings dam failure, and sex. These findings should be helpful to local decision-makers concerned with environmental risk management (e.g., selecting target groups for effective risk communication) in the context of abrupt environmental accidents.

  15. Acceptable Risk Analysis for Abrupt Environmental Pollution Accidents in Zhangjiakou City, China

    PubMed Central

    Du, Xi; Zhang, Zhijiao; Dong, Lei; Liu, Jing; Borthwick, Alistair G. L.; Liu, Renzhi

    2017-01-01

    Abrupt environmental pollution accidents cause considerable damage worldwide to the ecological environment, human health, and property. The concept of acceptable risk aims to answer whether or not a given environmental pollution risk exceeds a societally determined criterion. This paper presents a case study on acceptable environmental pollution risk conducted through a questionnaire survey carried out between August and October 2014 in five representative districts and two counties of Zhangjiakou City, Hebei Province, China. Here, environmental risk primarily arises from accidental water pollution, accidental air pollution, and tailings dam failure. Based on 870 valid questionnaires, demographic and regional differences in public attitudes towards abrupt environmental pollution risks were analyzed, and risk acceptance impact factors determined. The results showed females, people between 21–40 years of age, people with higher levels of education, public servants, and people with higher income had lower risk tolerance. People with lower perceived risk, low-level risk knowledge, high-level familiarity and satisfaction with environmental management, and without experience of environmental accidents had higher risk tolerance. Multiple logistic regression analysis indicated that public satisfaction with environmental management was the most significant factor in risk acceptance, followed by perceived risk of abrupt air pollution, occupation, perceived risk of tailings dam failure, and sex. These findings should be helpful to local decision-makers concerned with environmental risk management (e.g., selecting target groups for effective risk communication) in the context of abrupt environmental accidents. PMID:28425956

  16. Arabidopsis Enhanced Drought Tolerance1/HOMEODOMAIN GLABROUS11 Confers Drought Tolerance in Transgenic Rice without Yield Penalty1[W][OA

    PubMed Central

    Yu, Linhui; Chen, Xi; Wang, Zhen; Wang, Shimei; Wang, Yuping; Zhu, Qisheng; Li, Shigui; Xiang, Chengbin

    2013-01-01

    Enhancing drought tolerance without yield decrease has been a great challenge in crop improvement. Here, we report the Arabidopsis (Arabidopsis thaliana) homodomain-leucine zipper transcription factor Enhanced Drought Tolerance/HOMEODOMAIN GLABROUS11 (EDT1/HDG11) was able to confer drought tolerance and increase grain yield in transgenic rice (Oryza sativa) plants. The improved drought tolerance was associated with a more extensive root system, reduced stomatal density, and higher water use efficiency. The transgenic rice plants also had higher levels of abscisic acid, proline, soluble sugar, and reactive oxygen species-scavenging enzyme activities during stress treatments. The increased grain yield of the transgenic rice was contributed by improved seed setting, larger panicle, and more tillers as well as increased photosynthetic capacity. Digital gene expression analysis indicated that AtEDT1/HDG11 had a significant influence on gene expression profile in rice, which was consistent with the observed phenotypes of transgenic rice plants. Our study shows that AtEDT1/HDG11 can improve both stress tolerance and grain yield in rice, demonstrating the efficacy of AtEDT1/HDG11 in crop improvement. PMID:23735506

  17. Progesterone promotes maternal–fetal tolerance by reducing human maternal T‐cell polyfunctionality and inducing a specific cytokine profile

    PubMed Central

    Eldershaw, Suzy A.; Inman, Charlotte F.; Coomarasamy, Aravinthan; Moss, Paul A. H.; Kilby, Mark D.

    2015-01-01

    Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4+ and CD8+ T cells, with reductions not only in potentially deleterious IFN‐γ and TNF‐α production but also in IL‐10 and IL‐5. Conversely, production of IL‐4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL‐4. This was accompanied by reduced T‐cell proliferation. Using fetal and viral antigen‐specific CD8+ T‐cell clones, we confirmed that this as a direct, nonantigen‐specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4+ and CD8+ T cells responded to progesterone in a dose‐dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal–fetal interface. This characterization of how progesterone modulates T‐cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. PMID:26249148

  18. Salinity and High Temperature Tolerance in Mungbean [Vigna radiata (L.) Wilczek] from a Physiological Perspective

    PubMed Central

    HanumanthaRao, Bindumadhava; Nair, Ramakrishnan M.; Nayyar, Harsh

    2016-01-01

    Biotic and abiotic constraints seriously affect the productivity of agriculture worldwide. The broadly recognized benefits of legumes in cropping systems—biological nitrogen fixation, improving soil fertility and broadening cereal-based agro-ecologies, are desirable now more than ever. Legume production is affected by hostile environments, especially soil salinity and high temperatures (HTs). Among legumes, mungbean has acceptable intrinsic tolerance mechanisms, but many agro-physiological characteristics of the Vigna species remain to be explored. Mungbean has a distinct advantage of being short-duration and can grow in wide range of soils and environments (as mono or relay legume). This review focuses on salinity and HT stresses on mungbean grown as a fallow crop (mungbean-rice-wheat to replace fallow-rice-wheat) and/or a relay crop in cereal cropping systems. Salinity tolerance comprises multifaceted responses at the molecular, physiological and plant canopy levels. In HTs, adaptation of physiological and biochemical processes gradually may lead to improvement of heat tolerance in plants. At the field level, managing or manipulating cultural practices can mitigate adverse effects of salinity and HT. Greater understanding of physiological and biochemical mechanisms regulating these two stresses will contribute to an evolving profile of the genes, proteins, and metabolites responsible for mungbean survival. We focus on abiotic stresses in legumes in general and mungbean in particular, and highlight gaps that need to be bridged through future mungbean research. Recent findings largely from physiological and biochemical fronts are examined, along with a few agronomic and farm-based management strategies to mitigate stress under field conditions. PMID:27446183

  19. The metal tolerance profile of Thlaspi goesingense is mimicked in Arabidopsis thaliana heterologously expressing serine acetyl-transferase.

    PubMed

    Freeman, John L; Salt, David E

    2007-11-28

    The Ni hyperaccumulator Thlaspi goesingense is tolerant to Ni congruent with Zn, congruent with Co and slightly resistant to > Cd. We previously observed that elevated glutathione, driven by constitutive activation of serine acetyltransferase (SAT), plays a role in the Ni tolerance of T. goesingense. Here we show that the elevated shoot concentration of glutathione, previously shown to cause elevated Ni tolerance in Arabidopsis thaliana heterologously expressing T. goesingense mitochondrial serine acetyltransferase (SATm), also causes tolerance to Co and Zn while slightly enhancing resistance to Cd. The level of tolerance afforded to each metal is ranked Ni congruent with Co, > Zn > Cd. The Ni congruent with Co, > Zn tolerances are positively correlated with both the accumulation of glutathione (GSH) and the ability to resist the oxidative damage induced by these different metals. Based on the relative concentrations of each metal used a relatively low level of resistance to Cd was observed in both T. goesingense and TgSATm expressing lines and Cd resistance was least correlated to GSH accumulation. Such data supports the conclusion that elevated glutathione levels, driven by constitutively enhanced SAT activity in the hyperaccumulator T. goesingense, plays an important role in the Ni, Co and Zn tolerance of this and other Thlaspi species. The hyper-activation of S assimilation through SAT is an excellent strategy for engineering enhanced metal tolerance in transgenic plants potentially used for phytoremediation.

  20. The metal tolerance profile of Thlaspi goesingense is mimicked in Arabidopsis thaliana heterologously expressing serine acetyl-transferase

    PubMed Central

    Freeman, John L; Salt, David E

    2007-01-01

    Background The Ni hyperaccumulator Thlaspi goesingense is tolerant to Ni ≅ Zn, ≅ Co and slightly resistant to > Cd. We previously observed that elevated glutathione, driven by constitutive activation of serine acetyltransferase (SAT), plays a role in the Ni tolerance of T. goesingense. Results Here we show that the elevated shoot concentration of glutathione, previously shown to cause elevated Ni tolerance in Arabidopsis thaliana heterologously expressing T. goesingense mitochondrial serine acetyltransferase (SATm), also causes tolerance to Co and Zn while slightly enhancing resistance to Cd. The level of tolerance afforded to each metal is ranked Ni ≅ Co, > Zn > Cd. The Ni ≅ Co, > Zn tolerances are positively correlated with both the accumulation of glutathione (GSH) and the ability to resist the oxidative damage induced by these different metals. Based on the relative concentrations of each metal used a relatively low level of resistance to Cd was observed in both T. goesingense and TgSATm expressing lines and Cd resistance was least correlated to GSH accumulation. Conclusion Such data supports the conclusion that elevated glutathione levels, driven by constitutively enhanced SAT activity in the hyperaccumulator T. goesingense, plays an important role in the Ni, Co and Zn tolerance of this and other Thlaspi species. The hyper-activation of S assimilation through SAT is an excellent strategy for engineering enhanced metal tolerance in transgenic plants potentially used for phytoremediation. PMID:18045473

  1. Urine biomarkers informative of human kidney allograft rejection and tolerance.

    PubMed

    Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

    2018-05-01

    We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

  2. Simulation of aspheric tolerance with polynomial fitting

    NASA Astrophysics Data System (ADS)

    Li, Jing; Cen, Zhaofeng; Li, Xiaotong

    2018-01-01

    The shape of the aspheric lens changes caused by machining errors, resulting in a change in the optical transfer function, which affects the image quality. At present, there is no universally recognized tolerance criterion standard for aspheric surface. To study the influence of aspheric tolerances on the optical transfer function, the tolerances of polynomial fitting are allocated on the aspheric surface, and the imaging simulation is carried out by optical imaging software. Analysis is based on a set of aspheric imaging system. The error is generated in the range of a certain PV value, and expressed as a form of Zernike polynomial, which is added to the aspheric surface as a tolerance term. Through optical software analysis, the MTF of optical system can be obtained and used as the main evaluation index. Evaluate whether the effect of the added error on the MTF of the system meets the requirements of the current PV value. Change the PV value and repeat the operation until the acceptable maximum allowable PV value is obtained. According to the actual processing technology, consider the error of various shapes, such as M type, W type, random type error. The new method will provide a certain development for the actual free surface processing technology the reference value.

  3. Study of fault tolerant software technology for dynamic systems

    NASA Technical Reports Server (NTRS)

    Caglayan, A. K.; Zacharias, G. L.

    1985-01-01

    The major aim of this study is to investigate the feasibility of using systems-based failure detection isolation and compensation (FDIC) techniques in building fault-tolerant software and extending them, whenever possible, to the domain of software fault tolerance. First, it is shown that systems-based FDIC methods can be extended to develop software error detection techniques by using system models for software modules. In particular, it is demonstrated that systems-based FDIC techniques can yield consistency checks that are easier to implement than acceptance tests based on software specifications. Next, it is shown that systems-based failure compensation techniques can be generalized to the domain of software fault tolerance in developing software error recovery procedures. Finally, the feasibility of using fault-tolerant software in flight software is investigated. In particular, possible system and version instabilities, and functional performance degradation that may occur in N-Version programming applications to flight software are illustrated. Finally, a comparative analysis of N-Version and recovery block techniques in the context of generic blocks in flight software is presented.

  4. Acceptability of hypothetical dengue vaccines among travelers.

    PubMed

    Benoit, Christine M; MacLeod, William B; Hamer, Davidson H; Sanchez-Vegas, Carolina; Chen, Lin H; Wilson, Mary E; Karchmer, Adolf W; Yanni, Emad; Hochberg, Natasha S; Ooi, Winnie W; Kogelman, Laura; Barnett, Elizabeth D

    2013-01-01

    Dengue viruses have spread widely in recent decades and cause tens of millions of infections mostly in tropical and subtropical areas. Vaccine candidates are being studied aggressively and may be ready for licensure soon. We surveyed patients with past or upcoming travel to dengue-endemic countries to assess rates and determinants of acceptance for four hypothetical dengue vaccines with variable efficacy and adverse event (AE) profiles. Acceptance ratios were calculated for vaccines with varied efficacy and AE risk. Acceptance of the four hypothetical vaccines ranged from 54% for the vaccine with lower efficacy and serious AE risk to 95% for the vaccine with higher efficacy and minor AE risk. Given equal efficacy, vaccines with lower AE risk were better accepted than those with higher AE risk; given equivalent AE risk, vaccines with higher efficacy were better accepted than those with lower efficacy. History of Japanese encephalitis vaccination was associated with lower vaccine acceptance for one of the hypothetical vaccines. US-born travelers were more likely than non-US born travelers to accept a vaccine with 75% efficacy and a risk of minor AEs (p = 0.003). Compared with North American-born travelers, Asian- and African-born travelers were less likely to accept both vaccines with 75% efficacy. Most travelers would accept a safe and efficacious dengue vaccine if one were available. Travelers valued fewer potential AEs over increased vaccine efficacy. © 2013 International Society of Travel Medicine.

  5. Evaluating contribution of ionic, osmotic and oxidative stress components towards salinity tolerance in barley

    PubMed Central

    2014-01-01

    Background Salinity tolerance is a physiologically multi-faceted trait attributed to multiple mechanisms. Three barley (Hordeum vulgare) varieties contrasting in their salinity tolerance were used to assess the relative contribution of ionic, osmotic and oxidative stress components towards overall salinity stress tolerance in this species, both at the whole-plant and cellular levels. In addition, transcriptional changes in the gene expression profile were studied for key genes mediating plant ionic and oxidative homeostasis (NHX; RBOH; SOD; AHA and GORK), to compare a contribution of transcriptional and post-translational factors towards the specific components of salinity tolerance. Results Our major findings are two-fold. First, plant tissue tolerance was a dominating component that has determined the overall plant responses to salinity, with root K+ retention ability and reduced sensitivity to stress-induced hydroxyl radical production being the main contributing tolerance mechanisms. Second, it was not possible to infer which cultivars were salinity tolerant based solely on expression profiling of candidate genes at one specific time point. For the genes studied and the time point selected that transcriptional changes in the expression of these specific genes had a small role for barley’s adaptive responses to salinity. Conclusions For better tissue tolerance, sodium sequestration, K+ retention and resistance to oxidative stress all appeared to be crucial. Because these traits are highly interrelated, it is suggested that a major progress in crop breeding for salinity tolerance can be achieved only if these complementary traits are targeted at the same time. This study also highlights the essentiality of post translational modifications in plant adaptive responses to salinity. PMID:24774965

  6. Functional associations between the metabolome and manganese tolerance in Vigna unguiculata

    PubMed Central

    Führs, Hendrik; Specht, André; Erban, Alexander; Kopka, Joachim; Horst, Walter J.

    2012-01-01

    Genotypic- and silicon (Si)-mediated differences in manganese (Mn) tolerance of cowpea (Vigna unguiculata) arise from a combination of symplastic and apoplastic traits. A detailed metabolomic inspection could help to identify functional associations between genotype- and Si-mediated Mn tolerance and metabolism. Two cowpea genotypes differing in Mn tolerance (TVu 91, Mn sensitive; TVu 1987, Mn tolerant) were subjected to differential Mn and Si treatments. Gas chromatography–mass spectrometry (GC-MS)-based metabolite profiling of leaf material was performed. Detailed evaluation of the response of metabolites was combined with gene expression and physiological analyses. After 2 d of 50 μM Mn supply TVu 91 expressed toxicity symptoms first in the form of brown spots on the second oldest trifoliate leaves. Silicon treatment suppressed symptom development in TVu 91. Despite higher concentrations of Mn in leaves of TVu 1987 compared with TVu 91, the tolerant genotype did not show symptoms. From sample cluster formation as identified by independent component analysis (ICA) of metabolite profiles it is concluded that genotypic differences accounted for the highest impact on variation in metabolite pools, followed by Mn and Si treatments in one of two experiments. Analysis of individual metabolites corroborated a comparable minor role for Mn and Si treatments in the modulation of individual metabolites. Mapping individual metabolites differing significantly between genotypes onto biosynthetic pathways and gene expression studies on the corresponding pathways suggest that genotypic Mn tolerance is a consequence of differences (i) in the apoplastic binding capacity; (ii) in the capability to maintain a high antioxidative state; and (iii) in the activity of shikimate and phenylpropanoid metabolism. PMID:21934118

  7. A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

    PubMed Central

    Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W.; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M.

    2014-01-01

    Abstract Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be “very likely” to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug. PMID:24070431

  8. A randomized male tolerance study of dapivirine gel following multiple topical penile exposures (MTN 012/IPM 010).

    PubMed

    Cranston, Ross D; Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M

    2014-02-01

    Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be "very likely" to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug.

  9. Interrelating Behavioral Measures of Distress Tolerance with Self-Reported Experiential Avoidance

    PubMed Central

    Schloss, Heather M.

    2011-01-01

    Experiential avoidance and distress intolerance play a central role in novel behavior therapies, yet they appear to overlap considerably the REBT concept of low frustration tolerance. Using baseline data from 100 adult cigarette smokers enrolled in a clinical trial of smoking cessation therapies, the present study evaluated the convergent validity of common questionnaire measures of experiential avoidance (Acceptance and Action Questionnaire; AAQ; Hayes et al. 2004, and Avoidance and Inflexibility Scale: AIS; Gifford et al. 2004) and behavioral measures of distress tolerance (computerized Mirror Tracing Persistence Task: MTPT-C: Strong et al. 2003; computerized Paced Auditory Serial Addition Task; PASAT-C; Lejuez et al. 2003). The distress tolerance measures correlated significantly (r = .29) with one another. However, the questionnaire measures of experiential avoidance did not correlate with each other, nor with the behavioral measures. Further research is needed on the validity of measuring experiential avoidance by self-report and of the overlap versus distinctiveness of seemingly similar constructs such as experiential avoidance, distress tolerance, and frustration tolerance. PMID:21448252

  10. Tolerance to acetic acid is improved by mutations of the TATA-binding protein gene.

    PubMed

    An, Jieun; Kwon, Hyeji; Kim, Eunjung; Lee, Young Mi; Ko, Hyeok Jin; Park, Hongjae; Choi, In-Geol; Kim, Sooah; Kim, Kyoung Heon; Kim, Wankee; Choi, Wonja

    2015-03-01

    Screening a library of overexpressing mutant alleles of the TATA-binding gene SPT15 yielded two Saccharomyces cerevisiae strains (MRRC 3252 and 3253) with enhanced tolerance to acetic acid. They were also tolerant to propionic acid and hydrogen peroxide. Transcriptome profile analysis identified 58 upregulated genes and 106 downregulated genes in MRRC 3252. Stress- and protein synthesis-related transcription factors were predominantly enriched in the upregulated and downregulated genes respectively. Eight deletion mutants for some of the highly downregulated genes were acetic acid-tolerant. The level of intracellular reactive oxygen species was considerably lessened in MRRC 3252 and 3253 upon exposure to acetic acid. Metabolome profile analysis revealed that intracellular concentrations of 5 and 102 metabolites were increased and decreased, respectively, in MRRC 3252, featuring a large increase of urea and a significant decrease of amino acids. The dur1/2Δmutant, in which the urea degradation gene DUR1/2 is deleted, displayed enhanced tolerance to acetic acid. Enhanced tolerance to acetic acid was also observed on the medium containing a low concentration of amino acids. Taken together, this study identified two SPT15 alleles, nine gene deletions and low concentration of amino acids in the medium that confer enhanced tolerance to acetic acid. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Acceptability of robotic technology in neuro-rehabilitation: preliminary results on chronic stroke patients.

    PubMed

    Mazzoleni, Stefano; Turchetti, Giuseppe; Palla, Ilaria; Posteraro, Federico; Dario, Paolo

    2014-09-01

    During the last decade, different robotic devices have been developed for motor rehabilitation of stroke survivors. These devices have been shown to improve motor impairment and contribute to the understanding of mechanisms underlying motor recovery after a stroke. The assessment of the robotic technology for rehabilitation assumes great importance. The aim of this study is to present preliminary results on the assessment of the acceptability of the robotic technology for rehabilitation on a group of thirty-four chronic stroke patients. The results from questionnaires on the patients' acceptability of two different robot-assisted rehabilitation scenarios show that the robotic approach was well accepted and tolerated by the patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates

    PubMed Central

    Skerker, Jeffrey M; Leon, Dacia; Price, Morgan N; Mar, Jordan S; Tarjan, Daniel R; Wetmore, Kelly M; Deutschbauer, Adam M; Baumohl, Jason K; Bauer, Stefan; Ibáñez, Ana B; Mitchell, Valerie D; Wu, Cindy H; Hu, Ping; Hazen, Terry; Arkin, Adam P

    2013-01-01

    The efficient production of biofuels from cellulosic feedstocks will require the efficient fermentation of the sugars in hydrolyzed plant material. Unfortunately, plant hydrolysates also contain many compounds that inhibit microbial growth and fermentation. We used DNA-barcoded mutant libraries to identify genes that are important for hydrolysate tolerance in both Zymomonas mobilis (44 genes) and Saccharomyces cerevisiae (99 genes). Overexpression of a Z. mobilis tolerance gene of unknown function (ZMO1875) improved its specific ethanol productivity 2.4-fold in the presence of miscanthus hydrolysate. However, a mixture of 37 hydrolysate-derived inhibitors was not sufficient to explain the fitness profile of plant hydrolysate. To deconstruct the fitness profile of hydrolysate, we profiled the 37 inhibitors against a library of Z. mobilis mutants and we modeled fitness in hydrolysate as a mixture of fitness in its components. By examining outliers in this model, we identified methylglyoxal as a previously unknown component of hydrolysate. Our work provides a general strategy to dissect how microbes respond to a complex chemical stress and should enable further engineering of hydrolysate tolerance. PMID:23774757

  13. Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile.

    PubMed

    Lissauer, David; Eldershaw, Suzy A; Inman, Charlotte F; Coomarasamy, Aravinthan; Moss, Paul A H; Kilby, Mark D

    2015-10-01

    Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4(+) and CD8(+) T cells, with reductions not only in potentially deleterious IFN-γ and TNF-α production but also in IL-10 and IL-5. Conversely, production of IL-4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL-4. This was accompanied by reduced T-cell proliferation. Using fetal and viral antigen-specific CD8(+) T-cell clones, we confirmed that this as a direct, nonantigen-specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4(+) and CD8(+) T cells responded to progesterone in a dose-dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal-fetal interface. This characterization of how progesterone modulates T-cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Chemical genomic guided engineering of gamma-valerolactone tolerant yeast.

    PubMed

    Bottoms, Scott; Dickinson, Quinn; McGee, Mick; Hinchman, Li; Higbee, Alan; Hebert, Alex; Serate, Jose; Xie, Dan; Zhang, Yaoping; Coon, Joshua J; Myers, Chad L; Landick, Robert; Piotrowski, Jeff S

    2018-01-12

    Gamma valerolactone (GVL) treatment of lignocellulosic bomass is a promising technology for degradation of biomass for biofuel production; however, GVL is toxic to fermentative microbes. Using a combination of chemical genomics with the yeast (Saccharomyces cerevisiae) deletion collection to identify sensitive and resistant mutants, and chemical proteomics to monitor protein abundance in the presence of GVL, we sought to understand the mechanism toxicity and resistance to GVL with the goal of engineering a GVL-tolerant, xylose-fermenting yeast. Chemical genomic profiling of GVL predicted that this chemical affects membranes and membrane-bound processes. We show that GVL causes rapid, dose-dependent cell permeability, and is synergistic with ethanol. Chemical genomic profiling of GVL revealed that deletion of the functionally related enzymes Pad1p and Fdc1p, which act together to decarboxylate cinnamic acid and its derivatives to vinyl forms, increases yeast tolerance to GVL. Further, overexpression of Pad1p sensitizes cells to GVL toxicity. To improve GVL tolerance, we deleted PAD1 and FDC1 in a xylose-fermenting yeast strain. The modified strain exhibited increased anaerobic growth, sugar utilization, and ethanol production in synthetic hydrolysate with 1.5% GVL, and under other conditions. Chemical proteomic profiling of the engineered strain revealed that enzymes involved in ergosterol biosynthesis were more abundant in the presence of GVL compared to the background strain. The engineered GVL strain contained greater amounts of ergosterol than the background strain. We found that GVL exerts toxicity to yeast by compromising cellular membranes, and that this toxicity is synergistic with ethanol. Deletion of PAD1 and FDC1 conferred GVL resistance to a xylose-fermenting yeast strain by increasing ergosterol accumulation in aerobically grown cells. The GVL-tolerant strain fermented sugars in the presence of GVL levels that were inhibitory to the unmodified strain

  15. Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

    PubMed

    Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

    2016-01-01

    In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

  16. Software Fault Tolerance: A Tutorial

    NASA Technical Reports Server (NTRS)

    Torres-Pomales, Wilfredo

    2000-01-01

    Because of our present inability to produce error-free software, software fault tolerance is and will continue to be an important consideration in software systems. The root cause of software design errors is the complexity of the systems. Compounding the problems in building correct software is the difficulty in assessing the correctness of software for highly complex systems. After a brief overview of the software development processes, we note how hard-to-detect design faults are likely to be introduced during development and how software faults tend to be state-dependent and activated by particular input sequences. Although component reliability is an important quality measure for system level analysis, software reliability is hard to characterize and the use of post-verification reliability estimates remains a controversial issue. For some applications software safety is more important than reliability, and fault tolerance techniques used in those applications are aimed at preventing catastrophes. Single version software fault tolerance techniques discussed include system structuring and closure, atomic actions, inline fault detection, exception handling, and others. Multiversion techniques are based on the assumption that software built differently should fail differently and thus, if one of the redundant versions fails, it is expected that at least one of the other versions will provide an acceptable output. Recovery blocks, N-version programming, and other multiversion techniques are reviewed.

  17. Acceptance threshold hypothesis is supported by chemical similarity of cuticular hydrocarbons in a stingless bee, Melipona asilvai.

    PubMed

    Nascimento, D L; Nascimento, F S

    2012-11-01

    The ability to discriminate nestmates from non-nestmates in insect societies is essential to protect colonies from conspecific invaders. The acceptance threshold hypothesis predicts that organisms whose recognition systems classify recipients without errors should optimize the balance between acceptance and rejection. In this process, cuticular hydrocarbons play an important role as cues of recognition in social insects. The aims of this study were to determine whether guards exhibit a restrictive level of rejection towards chemically distinct individuals, becoming more permissive during the encounters with either nestmate or non-nestmate individuals bearing chemically similar profiles. The study demonstrates that Melipona asilvai (Hymenoptera: Apidae: Meliponini) guards exhibit a flexible system of nestmate recognition according to the degree of chemical similarity between the incoming forager and its own cuticular hydrocarbons profile. Guards became less restrictive in their acceptance rates when they encounter non-nestmates with highly similar chemical profiles, which they probably mistake for nestmates, hence broadening their acceptance level.

  18. Impact of intensive lipid lowering on lipid profiles over time and tolerability in stable coronary artery disease: insights from a subanalysis of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS).

    PubMed

    Kawashiri, Masa-Aki; Yamagishi, Masakazu; Sakamoto, Tomohiro; Takayama, Tadateru; Hiro, Takafumi; Daida, Hiroyuki; Hirayama, Atsushi; Saito, Satoshi; Yamaguchi, Tetsu; Matsuzaki, Masunori

    2013-12-01

    Previous studies have demonstrated that intensive lipid lowering using rosuvastatin results in regression of coronary plaques. However, few data exist regarding lipid profiles over time, drug tolerability, and the effects of prior use of lipid lowering agents in patients on rosuvastatin treatment. Therefore, we studied these matters in a subanalysis of the Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS). Rosuvastatin was titrated for 76 weeks to attain LDL-C < 80 mg/dL in 213 Japanese dyslipidemic patients with CAD. Clinic visits were scheduled for every 4 weeks during the 76-week study period. Changes over time in lipid parameters, changes in those according to prior lipid-lowering therapy, and changes in those according to baseline lipid levels were evaluated in this subanalysis. Overall, 126 patients completed the study. The mean rosuvastatin dose at the last observation carried forward was 16.9 mg (range, 2.5-20 mg). Rosuvastatin significantly increased HDL-C, lowered LDL-C, and improved the LDL-C/HDL-C ratio (all, P < 0.0001). Increases in serum HDL-C levels were significantly greater in patients with HDL-C < 40 mg/dL than in those with HDL-C ≥ 40 mg/dL at baseline (P = 0.0005). The estimated glomerular filtration rate increased significantly by 2.84 ± 9.01 mL/min/1.73 m(2) (P < 0.0001). Of 166 adverse events in 74 patients, 113 events in 54 patients were laboratory values beyond the normal range. Rosuvastatin significantly improved lipid profiles, with an acceptable safety profile, contributing to plaque regression in Japanese patients with CAD. © 2013 John Wiley & Sons Ltd.

  19. The CD8 T-cell response during tolerance induction in liver transplantation

    PubMed Central

    Wong, Yik Chun; McCaughan, Geoffrey W; Bowen, David G; Bertolino, Patrick

    2016-01-01

    Both experimental and clinical studies have shown that the liver possesses unique tolerogenic properties. Liver allografts can be spontaneously accepted across complete major histocompatibility mismatch in some animal models. In addition, some liver transplant patients can be successfully withdrawn from immunosuppressive medications, developing ‘operational tolerance'. Multiple mechanisms have been shown to be involved in inducing and maintaining alloimmune tolerance associated with liver transplantation. Here, we focus on CD8 T-cell tolerance in this setting. We first discuss how alloreactive cytotoxic T-cell responses are generated against allografts, before reviewing how the liver parenchyma, donor passenger leucocytes and the host immune system function together to attenuate alloreactive CD8 T-cell responses to promote the long-term survival of liver transplants. PMID:27867515

  20. Sensory characteristics and consumer acceptability of fermented soybean paste (Doenjang).

    PubMed

    Kim, H G; Hong, J H; Song, C K; Shin, H W; Kim, K O

    2010-09-01

    This study was conducted to examine the sensory profiles of fermented soybean paste (Doenjang), to understand consumers' acceptability of different types of Doenjang samples and to identify the sensory characteristics that drive consumer acceptability of Doenjang products. Descriptive analysis and consumer acceptability test were conducted for 7 different types of Doenjang samples. The samples included 2 types of Doenjang made by either traditional or commercially modified methods. For the descriptive analysis, 8 trained panelists developed and evaluated 31 descriptors. There were significant differences in all 31 attributes among the samples. Principal component analysis was also performed to summarize the sensory characteristics of the samples. In consumer testing, 200 consumers evaluated the acceptability of Doenjang samples. Significant differences in consumer acceptability were observed among the samples. The consumers preferred the Doenjang samples manufactured using a commercially modified method. In overall point of view, most consumers liked the Doenjang samples that had strong "sweet" and "MSG (monosodium glutamate)" tastes. It appears that "sweet" and "MSG" tastes are the drivers of liking for Doenjang. "Salty" taste, "meju,"traditional Korean soy sauce," and "fermented fish" odor/flavors seem to be the drivers of disliking for Doenjang. Cluster analysis identified 3 subconsumer segments sharing a common preference pattern for the 7 samples within a cluster. The results showed that each consumer cluster preferred different Doenjang samples. External preference mapping was performed to establish the relationships between the sensory attributes and consumer acceptability in each cluster. Consumption of the fermented soybean products is gradually expanding around the world, due to their various health benefits. Therefore, understanding sensory characteristics and consumer acceptability of Doenjang are becoming increasingly important. The intense and complex

  1. A comparison of cat-related risk perceptions and tolerance for outdoor cats in Florida and Hawaii.

    PubMed

    Wald, Dara M; Lohr, Cheryl A; Lepczyk, Christopher A; Jacobson, Susan K; Cox, Linda J

    2016-12-01

    Risk perceptions and attitudes toward animals often explain tolerance for wildlife and management preferences. However, little is understood about how these relationships vary across different geographic regions and stakeholder groups. To address this gap in knowledge, we compared differences in acceptance capacity, risk perceptions, perceived enjoyment from outdoor cats, and experiences with outdoor cats among 3 groups (general public, conservation community, and animal-welfare community) in Hawaii and Florida, two states with large conservation challenges. We combined independently collected data from Florida and Hawaii, to determine how perception of the risks presented by outdoor cats, group membership, and state of residence influenced people's tolerance for outdoor cats. Florida respondents were significantly more tolerant of outdoor cats and less concerned about cat-related risks than Hawaii respondents (p < 0.05). In both states, animal-welfare group members reported greater enjoyment seeing cats and perceived a smaller increase in the cat population and lower levels of risk than other groups (p < 0.05). All groups exhibited similar relationships between acceptance capacity and enjoyment and the perceived increase in the cat population. Our results suggest public tolerance for cats varied due to the influence of local or geographical concerns, but that strongly held beliefs, risk perceptions, and feelings about cats explained more of the variance in stakeholder tolerance. © 2016 Society for Conservation Biology.

  2. Size acceptance as a grief process: observations from psychotherapy with lesbian feminists.

    PubMed

    Courtney, Jeanne

    2008-01-01

    Based on observations from my psychotherapy practice, I apply Kubler-Ross' five stages of grief (denial, anger, bargaining, depression, and acceptance) to the process a woman goes through when she learns about size acceptance and lets go of the unrealistic wish to make her body size conform to fat-phobic societal ideals of female beauty. Clients' presentations, therapeutic interventions, and countertransference are discussed for each stage. Lesbian feminists are likely to embrace size acceptance politics but may retain negative feelings about their own body size. In the bargaining stage, they may confound health concerns with body image issues, and it is important in their therapy to provide a holding environment that can tolerate ambivalence. My own depression stage was marked by countertransference that caused me to avoid the topic of body image with my clients. Therapists can help women in the size acceptance grief process by exploring their own evolving feelings about body image, bringing up the topic, and providing a non-judgmental holding environment.

  3. [Safety profile of dolutegravir].

    PubMed

    Rivero, Antonio; Domingo, Pere

    2015-03-01

    Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  4. Expression profile of desiccation tolerance factors in intertidal seaweed species during the tidal cycle.

    PubMed

    Fierro, Camila; López-Cristoffanini, Camilo; Meynard, Andrés; Lovazzano, Carlos; Castañeda, Francisco; Guajardo, Eduardo; Contreras-Porcia, Loretto

    2017-06-01

    The transcriptional modulation of desiccation tolerance factors in P. orbicularis explains its successful recuperation after water deficit. Differential responses to air exposure clarify seaweed distribution along intertidal rocky zones. Desiccation-tolerant seaweed species, such as Pyropia orbicularis, can tolerate near 96% water loss during air exposure. To understand the phenotypic plasticity of P. orbicularis to desiccation, several tolerance factors were assessed by RT-qPCR, Western-blot analysis, and enzymatic assays during the natural desiccation-rehydration cycle. Comparative enzymatic analyses were used to evidence differential responses between P. orbicularis and desiccation-sensitive species. The results showed that during desiccation, the relative mRNA levels of genes associated with basal metabolism [trehalose phosphate synthase (tps) and pyruvate dehydrogenase (pdh)] were overexpressed in P. orbicularis. Transcript levels related to antioxidant metabolism [peroxiredoxin (prx); thioredoxin (trx); catalase (cat); lipoxygenase (lox); ferredoxin (fnr); glutathione S-transferase (gst)], cellular detoxification [ABC transporter (abc) and ubiquitin (ubq)], and signal transduction [calmodulin (cam)] increased approximately 15- to 20-fold, with the majority returning to basal levels during the final hours of rehydration. In contrast, actin (act) and transcription factor 1 (tf1) transcripts were down-regulated. ABC transporter protein levels increased in P. orbicularis during desiccation, whereas PRX transcripts decreased. The antioxidant enzymes showed higher specific activity in P. orbicularis under desiccation, and sensitive species exhibited enzymatic inactivation and scarce ABC and PRX protein detection following prolonged desiccation. In conclusion, the reported findings contribute towards understanding the ecological distribution of intertidal seaweeds at the molecular and functional levels.

  5. Host responses and metabolic profiles of wood components in Dutch elm hybrids with a contrasting tolerance to Dutch elm disease

    PubMed Central

    Ďurkovič, Jaroslav; Kačík, František; Olčák, Dušan; Kučerová, Veronika; Krajňáková, Jana

    2014-01-01

    Background and Aims Changes occurring in the macromolecular traits of cell wall components in elm wood following attack by Ophiostoma novo-ulmi, the causative agent of Dutch elm disease (DED), are poorly understood. The purpose of this study was to compare host responses and the metabolic profiles of wood components for two Dutch elm (Ulmus) hybrids, ‘Groeneveld’ (a susceptible clone) and ‘Dodoens’ (a tolerant clone), that have contrasting survival strategies upon infection with the current prevalent strain of DED. Methods Ten-year-old plants of the hybrid elms were inoculated with O. novo-ulmi ssp. americana × novo-ulmi. Measurements were made of the content of main cell wall components and extractives, lignin monomer composition, macromolecular traits of cellulose and neutral saccharide composition. Key Results Upon infection, medium molecular weight macromolecules of cellulose were degraded in both the susceptible and tolerant elm hybrids, resulting in the occurrence of secondary cell wall ruptures and cracks in the vessels, but rarely in the fibres. The 13C nuclear magnetic resonance spectra revealed that loss of crystalline and non-crystalline cellulose regions occurred in parallel. The rate of cellulose degradation was influenced by the syringyl:guaiacyl ratio in lignin. Both hybrids commonly responded to the medium molecular weight cellulose degradation with the biosynthesis of high molecular weight macromolecules of cellulose, resulting in a significant increase in values for the degree of polymerization and polydispersity. Other responses of the hybrids included an increase in lignin content, a decrease in relative proportions of d-glucose, and an increase in proportions of d-xylose. Differential responses between the hybrids were found in the syringyl:guaiacyl ratio in lignin. Conclusions In susceptible ‘Groeneveld’ plants, syringyl-rich lignin provided a far greater degree of protection from cellulose degradation than in ‘Dodoens’, but

  6. Facial profile preferences, self-awareness and perception among groups of people in the United Arab Emirates

    PubMed Central

    Al Taki, Amjad; Guidoum, Amina

    2014-01-01

    Objectives: The objective of this study is to assess the differences in facial profile preference among different layers of people in the United Arab Emirates. Facial profile self-awareness among the different groups was also evaluated. Materials and Methods: A total sample of 222 participants (mean [standard deviation] age = 25.71 [8.3] years, almost 80% of the participants were of Arab origin and 55% were males); consisting of 60 laypersons, 60 dental students, 60 general practitioners, 16 oral surgeons, and 26 orthodontists. Facial profile photographs of a male and female adult with straight profiles and a Class I skeletal relationship were used as a baseline template. Computerized photographic image modification was carried out on the templates to obtain seven different facial profile silhouettes for each gender. To assess differences in facial profile perception, participants were asked to rank the profiles of each gender on a scale from most to least attractive (1 [highest score] and 7 [least score]). Awareness and satisfaction with the facial appearance on a profile view was assessed using questionnaires completed by the non-expert groups. Results: The straight facial profile was perceived to be highly attractive by all five groups. The least attractive profiles were the bimaxillary protrusion and the mandibular retrusion for the male and the female profiles, respectively. Lip protrusion was more esthetically acceptable in females. Significant differences in perception existed among groups. The female profile esthetic perception was highly correlated between the expert groups (P > 0.05). Overall agreement between the non-expert group's perceptions of their own profiles and evaluation by the expert orthodontist was 51% (κ = 0.089). Candidates who perceived themselves as having a Class III facial profile were the least satisfied with their profile. Conclusions: Dental professionals, dental students, and laypersons had a similar perception trends in female and

  7. A Mixed-Methods Study on Acceptability, Tolerability, and Substitution of Brown Rice for White Rice to Lower Blood Glucose Levels among Nigerian Adults.

    PubMed

    Adebamowo, Sally N; Eseyin, Olabimpe; Yilme, Susan; Adeyemi, David; Willett, Walter C; Hu, Frank B; Spiegelman, Donna; Adebamowo, Clement A

    2017-01-01

    Whole-grain products such as brown rice have been associated with lower risk of metabolic disorders including diabetes. We examined the acceptability and tolerability of substituting brown rice for white rice and the feasibility of introducing brown rice into the diet through a long-term trial to lower the risk of type 2 diabetes. Fifty-one adults residing in Abuja, Nigeria, participated in this study. Using purposeful sampling for focus group discussions (FGDs), participants were enrolled based on their age (19-25 vs. 40-60 years) and body mass index (BMI) (normal weight vs. overweight/obese). Participants tasted four meals with different constitution of brown and white rice (25:75%, 50:50%, 75:25%, and 100% brown rice). Twelve FGDs were conducted, six before and six after the food tasting. Two-hour postprandial blood glucose was measured after consumption of each rice meal. The mean age of the participants was 39 (±14) years, their mean BMI was 25.6 (±5.2) and about half of them were male. Most of the participants (61%) reported that rice was their main source of carbohydrate and 67% consumed rice at least five times/week. Before the food tasting, participants considered white polished rice superior to brown rice with regard to quality, taste, and nutritional value. After the food tasting, most of the participants (49%) indicated a preference for the 100% brown rice, 19% preferred the 25% brown rice, 18% preferred the 50% brown rice, and 7% preferred the 75% brown rice meals. Factors that may affect the acceptability of brown rice include its appearance, longer cooking time, cost, limited availability, and poor appreciation of its nutritional value. In general, 2-h postprandial glucose levels were lower, after consumption of meals with higher proportion of brown rice. This study provides valuable insight into the acceptability of brown rice as a substitute for white rice in Nigeria. If confirmed in larger studies, these results highlight the importance of

  8. Differential gene expression by Moniliophthora roreri while overcoming cacao tolerance in the field.

    PubMed

    Bailey, Bryan A; Melnick, Rachel L; Strem, Mary D; Crozier, Jayne; Shao, Jonathan; Sicher, Richard; Phillips-Mora, Wilberth; Ali, Shahin S; Zhang, Dapeng; Meinhardt, Lyndel

    2014-09-01

    Frosty pod rot (FPR) of Theobroma cacao (cacao) is caused by the hemibiotrophic fungus Moniliophthora roreri. Cacao clones tolerant to FPR are being planted throughout Central America. To determine whether M. roreri shows a differential molecular response during successful infections of tolerant clones, we collected field-infected pods at all stages of symptomatology for two highly susceptible clones (Pound-7 and CATIE-1000) and three tolerant clones (UF-273, CATIE-R7 and CATIE-R4). Metabolite analysis was carried out on clones Pound-7, CATIE-1000, CATIE-R7 and CATIE-R4. As FPR progressed, the concentrations of sugars in pods dropped, whereas the levels of trehalose and mannitol increased. Associations between symptoms and fungal loads and some organic and amino acid concentrations varied depending on the clone. RNA-Seq analysis identified 873 M. roreri genes that were differentially expressed between clones, with the primary difference being whether the clone was susceptible or tolerant. Genes encoding transcription factors, heat shock proteins, transporters, enzymes modifying membranes or cell walls and metabolic enzymes, such as malate synthase and alternative oxidase, were differentially expressed. The differential expression between clones of 43 M. roreri genes was validated by real-time quantitative reverse transcription polymerase chain reaction. The expression profiles of some genes were similar in susceptible and tolerant clones (other than CATIE-R4) and varied with the biotrophic/necrotropic shift. Moniliophthora roreri genes associated with stress metabolism and responses to heat shock and anoxia were induced early in tolerant clones, their expression profiles resembling that of the necrotrophic phase. Moniliophthora roreri stress response genes, induced during the infection of tolerant clones, may benefit the fungus in overcoming cacao defense mechanisms. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  9. Autonomous Congestion Control in Delay-Tolerant Networks

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott C.; Jennings, Esther H.

    2005-01-01

    Congestion control is an important feature that directly affects network performance. Network congestion may cause loss of data or long delays. Although this problem has been studied extensively in the Internet, the solutions for Internet congestion control do not apply readily to challenged network environments such as Delay Tolerant Networks (DTN) where end-to-end connectivity may not exist continuously and latency can be high. In DTN, end-to-end rate control is not feasible. This calls for congestion control mechanisms where the decisions can be made autonomously with local information only. We use an economic pricing model and propose a rule-based congestion control mechanism where each router can autonomously decide on whether to accept a bundle (data) based on local information such as available storage and the value and risk of accepting the bundle (derived from historical statistics).

  10. Health-related behavior, profile of health locus of control and acceptance of illness in patients suffering from chronic somatic diseases.

    PubMed

    Janowski, Konrad; Kurpas, Donata; Kusz, Joanna; Mroczek, Bozena; Jedynak, Tomasz

    2013-01-01

    The purpose of the study was to determine health-related behaviors, profile of health locus of control (HLC), and to assess the relationships between these constructs among patients suffering from chronic somatic diseases. Three-hundred adult patients suffering from various chronic diseases participated in the study. The patients' mean age was 54.6 years (SD = 17.57). No statistically significant differences were found between the different clinical groups in health-related behavior, acceptance of illness, internal HLC or chance HLC. Patients with neurologic conditions showed slightly lower powerful others HLC than did some other clinical groups. Health-related behavior was significantly positively related to all three categories of HLC, with most prominent associations observed with powerful others HLC. Only one type of health-related behavior--preventive behavior--correlated significantly and negatively with acceptance of illness. Differences in the frequency of health-related behavior were also found due to gender (women showing more healthy nutritional habits than men), age (older subjects showing more frequent health-promoting behavior), education (higher education was associated with less frequent health-promoting behavior) and marital status (widowed subjects reporting more frequent health-promoting behavior). Health-related behavior in patients with chronic diseases seems to be unrelated to a specific diagnosis; however it shows associations with both internal and external HLC. Sociodemographic factors are also crucial factors determining frequency of health-related behavior in such patients.

  11. Safety and tolerability of new-generation anti-obesity medications: a narrative review.

    PubMed

    Patel, Dhiren K; Stanford, Fatima Cody

    2018-03-01

    The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk-benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk-benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk-benefit.

  12. An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial.

    PubMed

    Khanna, Dinesh; Albera, Carlo; Fischer, Aryeh; Khalidi, Nader; Raghu, Ganesh; Chung, Lorinda; Chen, Dan; Schiopu, Elena; Tagliaferri, Margit; Seibold, James R; Gorina, Eduard

    2016-09-01

    Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc. All patients received pirfenidone and were randomized 1:1 to either a 2- or 4-week titration starting at 801 mg/day and finishing at a maintenance dose of 2403 mg/day. Patients received pirfenidone for 16 weeks in total. Assessments included treatment-emergent AE (TEAE) and exploratory disease outcomes. Sixty-three patients were randomized; 96.8% experienced a TEAE and more patients reported TEAE during the titration versus the maintenance period. The most commonly reported TEAE were consistent with those observed for pirfenidone in IPF (nausea, headache, fatigue) and were similar regardless of titration schedule. More patients discontinued treatment because of TEAE in the 2- versus 4-week titration group (5 vs 1, respectively); all discontinuation events occurred > 3 weeks after reaching the full dose of pirfenidone. Mycophenolate mofetil (MMF), taken by 63.5% of patients in addition to pirfenidone, did not appear to affect tolerability. Exploratory disease outcomes remained largely unchanged. Pirfenidone showed an acceptable tolerability profile in SSc-ILD, although a longer titration may be associated with better tolerability. Tolerability was not affected by concomitant MMF. The present findings support further investigation of pirfenidone in future clinical trials in patients with SSc-ILD. ClinicalTrials.gov; www.clinicaltrials.gov NCT01933334.

  13. Damage Tolerant Design for Cold-Section Turbine Engine Disks

    DTIC Science & Technology

    1981-06-01

    Ti-6Al-4V Disks ......... .. 59 28. FIOO 2nd-Stage Fan Disk Designs ........ ................ .. 61 29. Fan Disk Tangential Stress Profile... 61 30. Life-Limiting Features of Damage-Tolerant Disk .......... ... 62 31. Disk Life Limits .... ...................... 62 32. Life Test...Stress Rati• Model ..... .......... .. 113 61 . Thick-Section Center-Notched Specimen ....... ............. .. 116 62. Bolthole Specimen

  14. Freeform solar concentrator with a highly asymmetric acceptance cone

    NASA Astrophysics Data System (ADS)

    Wheelwright, Brian; Angel, J. Roger P.; Coughenour, Blake; Hammer, Kimberly

    2014-10-01

    A solar concentrator with a highly asymmetric acceptance cone is investigated. Concentrating photovoltaic systems require dual-axis sun tracking to maintain nominal concentration throughout the day. In addition to collecting direct rays from the solar disk, which subtends ~0.53 degrees, concentrating optics must allow for in-field tracking errors due to mechanical misalignment of the module, wind loading, and control loop biases. The angular range over which the concentrator maintains <90% of on-axis throughput is defined as the optical acceptance angle. Concentrators with substantial rotational symmetry likewise exhibit rotationally symmetric acceptance angles. In the field, this is sometimes a poor match with azimuth-elevation trackers, which have inherently asymmetric tracking performance. Pedestal-mounted trackers with low torsional stiffness about the vertical axis have better elevation tracking than azimuthal tracking. Conversely, trackers which rotate on large-footprint circular tracks are often limited by elevation tracking performance. We show that a line-focus concentrator, composed of a parabolic trough primary reflector and freeform refractive secondary, can be tailored to have a highly asymmetric acceptance angle. The design is suitable for a tracker with excellent tracking accuracy in the elevation direction, and poor accuracy in the azimuthal direction. In the 1000X design given, when trough optical errors (2mrad rms slope deviation) are accounted for, the azimuthal acceptance angle is +/- 1.65°, while the elevation acceptance angle is only +/-0.29°. This acceptance angle does not include the angular width of the sun, which consumes nearly all of the elevation tolerance at this concentration level. By decreasing the average concentration, the elevation acceptance angle can be increased. This is well-suited for a pedestal alt-azimuth tracker with a low cost slew bearing (without anti-backlash features).

  15. Identification of Mild Freezing Shock Response Pathways in Barley Based on Transcriptome Profiling.

    PubMed

    Wang, Xiaolei; Wu, Dezhi; Yang, Qian; Zeng, Jianbin; Jin, Gulei; Chen, Zhong-Hua; Zhang, Guoping; Dai, Fei

    2016-01-01

    Low temperature is a major abiotic stress affecting crop growth and productivity. A better understanding of low temperature tolerance mechanisms is imperative for developing the crop cultivars with improved tolerance. We herein performed an Illumina RNA-sequencing experiment using two barley genotypes differing in freezing tolerance (Nure, tolerant and Tremois, sensitive), to determine the transcriptome profiling and genotypic difference under mild freezing shock treatment after a very short acclimation for gene induction. A total of 6474 differentially expressed genes, almost evenly distributed on the seven chromosomes, were identified. The key DEGs could be classified into six signaling pathways, i.e., Ca(2+) signaling, PtdOH signaling, CBFs pathway, ABA pathway, jasmonate pathway, and amylohydrolysis pathway. Expression values of DEGs in multiple signaling pathways were analyzed and a hypothetical model of mild freezing shock tolerance mechanism was proposed. Expression and sequence profile of HvCBFs cluster within Frost resistance-H2, a major quantitative trait locus on 5H being closely related to low temperature tolerance in barley, were further illustrated, considering the crucial role of HvCBFs on freezing tolerance. It may be concluded that multiple signaling pathways are activated in concert when barley is exposed to mild freezing shock. The pathway network we presented may provide a platform for further exploring the functions of genes involved in low temperature tolerance in barley.

  16. Lack of tolerable treatment options for patients with schizophrenia.

    PubMed

    Citrome, Leslie; Eramo, Anna; Francois, Clement; Duffy, Ruth; Legacy, Susan N; Offord, Steve J; Krasa, Holly B; Johnston, Stephen S; Guiraud-Diawara, Alice; Kamat, Siddhesh A; Rohman, Patricia

    2015-01-01

    combining patient risk profile with antipsychotic AE profile, physicians may quickly run out of tolerable treatment options for individual patients, despite the availability of many AAs, suggesting a need for additional treatment options with better tolerability and without compromising efficacy.

  17. Nesting and acoustic ecology, but not phylogeny, influence passerine urban tolerance.

    PubMed

    Cardoso, Gonçalo C

    2014-03-01

    Urbanization is one of the most extensive and ecologically significant changes happening to terrestrial environments, as it strongly affects the distribution of biodiversity. It is well established that native species richness is reduced in urban and suburban areas, but the species traits that predict tolerance to urbanization are yet little understood. In birds, one of the most studied groups in this respect, evidence is appearing that acoustic traits influence urban living, but it remains unknown how this compares to the effects of more obvious ecological traits that facilitate urban living. Therefore, it remains unclear whether acoustic communication is an important predictor of urban tolerance among species. Here, with a comparative study across 140 European and North American passerines, I show that high song frequency, which is less masked by the low-frequency anthropogenic noise, is associated with urban tolerance, with an effect size over half that of the most important ecological trait studied: off-ground nesting. Other nesting and foraging traits accepted to facilitate urban living did not differ for species occurring in urban environments. Thus, the contribution of acoustic traits for passerine urban tolerance approximates that of more obvious ecological traits. Nonetheless, effect sizes of the biological predictors of urban tolerance were low and the phylogenetic signal for urban tolerance was null, both of which suggest that factors other than phenotypic traits have major effects on urban tolerance. A simple possibility is exposure to urbanization, as there was a higher proportion of urban-tolerant species in Europe, which is more urbanized than North America. © 2013 John Wiley & Sons Ltd.

  18. Tolerating Zero Tolerance?

    ERIC Educational Resources Information Center

    Moore, Brian N.

    2010-01-01

    The concept of zero tolerance dates back to the mid-1990s when New Jersey was creating laws to address nuisance crimes in communities. The main goal of these neighborhood crime policies was to have zero tolerance for petty crime such as graffiti or littering so as to keep more serious crimes from occurring. Next came the war on drugs. In federal…

  19. A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

    PubMed Central

    Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

    2010-01-01

    Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

  20. Public tolerance to defoliation and flower distortion in a public horticulture garden.

    PubMed

    Sadof, Clifford S; Sclar, D Casey

    2002-04-01

    Surveys of visitor and grower perception of live potted plant quality were conducted in various locations in a large public display garden. Canna lily, Canna x generalis L.H.Bailey, was used to examine effects of defoliation by Japanese beetle, Popillia japonica Newman, on public perception. Chrysanthemums, Chrysanthemum x morifolium Ramat., were used to identify visitor and grower tolerance to flower distortion caused by western flower thrips, Frankliniella occidentalis (Pergande), on single and multiple flowered plants. On average, the maximum amount of defoliation or flower distortion tolerated by any respondent was low (< or = 10% for canna and < or = 25% for chrysanthemum). The level of acceptable injury was influenced by factors intrinsic to both the respondents and the plants themselves. Tolerance to injury was negatively associated with the risk aversion of the respondents. Visitors were less tolerant of injury on plants they considered for purchase than those that they would view at the garden. Similarly, grower tolerance was lower than that of visitors because producing substandard plants could put their professional reputation at risk. Factors that distracted visitor attention (e.g., presence of flowers and higher levels of background injury) increased their tolerance to plant injury. Visitors tolerated greater levels of flower distortion on multiple flowering chrysanthemum than on those with single flowers. We suggest that tolerance to insect pests can be increased by designing plantings that distract viewers from injured plant parts.

  1. Longitudinal Studies of a B Cell Derived Signature of Tolerance in Renal Transplant Recipients

    PubMed Central

    Newell, Kenneth A.; Asare, Adam; Sanz, Ignacio; Wei, Chungwen; Rosenberg, Alexander; Gao, Zhong; Kanaparthi, Sai; Asare, Smita; Lim, Noha; Stahly, Michael; Howell, Michael; Knechtle, Stuart; Kirk, Allan; Marks, William H.; Kawai, Tatsuo; Spitzer, Thomas; Tolkoff-Rubin, Nina; Sykes, Megan; Sachs, David H.; Cosimi, A. Benedict; Burlingham, William J.; Phippard, Deborah; Turka, Laurence A.

    2016-01-01

    Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transplant recipients and patients enrolled in two interventional tolerance trials using flow cytometry and gene expression profiling. Using a previously reported tolerant cohort as well as newly identified tolerant patients we confirmed our previous finding that tolerance was associated with increased expression of B cell-associated genes relative to immunosuppressed patients. This was not accounted for merely by an increase in total B cell numbers, but was associated with the increased frequencies of transitional and naïve B cells. Moreover, serial measurements of gene expression demonstrated that this pattern persisted over several years although patients receiving immunosuppression also displayed an increase in the two most dominant tolerance-related B cell genes, IGKV1D-13 and IGLL-1, over time. Importantly, patients rendered tolerant via induction of transient mixed chimerism, and those weaned to minimal immunosuppression, showed similar increases in IGKV1D-13 as did spontaneously tolerant individuals. Collectively, these findings support the notion that alterations in B cells may be a common theme for tolerant kidney transplant recipients, and a useful monitoring tool in prospective trials. PMID:26461968

  2. Tolerance at arm's length: the Dutch experience.

    PubMed

    Schuijer, J

    1990-01-01

    With respect to pedophilia and the age of consent, the Netherlands warrants special attention. Although pedophilia is not as widely accepted in the Netherlands as sometimes is supposed, developments in the judicial practice showed a growing reservedness. These developments are a spin-off of related developments in Dutch society. The tolerance in the Dutch society has roots that go far back in history and is also a consequence of the way this society is structured. The social changes of the sixties and seventies resulted in a "tolerance at arm's length" for pedophiles, which proved to be deceptive when the Dutch government proposed to lower the age of consent in 1985. It resulted in a vehement public outcry. The prevailing sex laws have been the prime target of protagonists of pedophile emancipation. Around 1960, organized as a group, they started to undertake several activities. In the course of their existence, they came to redefine the issue of pedophilia as one of youth emancipation.

  3. Metabolite profiling during cold acclimation of Lolium perenne genotypes distinct in the level of frost tolerance.

    PubMed

    Bocian, Aleksandra; Zwierzykowski, Zbigniew; Rapacz, Marcin; Koczyk, Grzegorz; Ciesiołka, Danuta; Kosmala, Arkadiusz

    2015-11-01

    Abiotic stresses, including low temperature, can significantly reduce plant yielding. The knowledge on the molecular basis of stress tolerance could help to improve its level in species of relatively high importance to agriculture. Unfortunately, the complex research performed so far mainly on model species and also, to some extent, on cereals does not fully cover the demands of other agricultural plants of temperate climate, including forage grasses. Two Lolium perenne (perennial ryegrass) genotypes with contrasting levels of frost tolerance, the high frost tolerant (HFT) and the low frost tolerant (LFT) genotypes, were selected for comparative metabolomic research. The work focused on the analysis of leaf metabolite accumulation before and after seven separate time points of cold acclimation. Gas chromatography-mass spectrometry (GC/MS) was used to identify amino acids (alanine, proline, glycine, glutamic and aspartic acid, serine, lysine and asparagine), carbohydrates (fructose, glucose, sucrose, raffinose and trehalose) and their derivatives (mannitol, sorbitol and inositol) accumulated in leaves in low temperature. The observed differences in the level of frost tolerance between the analysed genotypes could be partially due to the time point of cold acclimation at which the accumulation level of crucial metabolite started to increase. In the HFT genotype, earlier accumulation was observed for proline and asparagine. The increased amounts of alanine, glutamic and aspartic acids, and asparagine during cold acclimation could be involved in the regulation of photosynthesis intensity in L. perenne. Among the analysed carbohydrates, only raffinose revealed a significant association with the acclimation process in this species.

  4. More than visual literacy: art and the enhancement of tolerance for ambiguity and empathy.

    PubMed

    Bentwich, Miriam Ethel; Gilbey, Peter

    2017-11-10

    Comfort with ambiguity, mostly associated with the acceptance of multiple meanings, is a core characteristic of successful clinicians. Yet past studies indicate that medical students and junior physicians feel uncomfortable with ambiguity. Visual Thinking Strategies (VTS) is a pedagogic approach involving discussions of art works and deciphering the different possible meanings entailed in them. However, the contribution of art to the possible enhancement of the tolerance for ambiguity among medical students has not yet been adequately investigated. We aimed to offer a novel perspective on the effect of art, as it is experienced through VTS, on medical students' tolerance of ambiguity and its possible relation to empathy. Quantitative method utilizing a short survey administered after an interactive VTS session conducted within mandatory medical humanities course for first-year medical students. The intervention consisted of a 90-min session in the form of a combined lecture and interactive discussions about art images. The VTS session and survey were filled by 67 students in two consecutive rounds of first-year students. 67% of the respondents thought that the intervention contributed to their acceptance of multiple possible meanings, 52% thought their visual observation ability was enhanced and 34% thought that their ability to feel the sufferings of other was being enhanced. Statistically significant moderate-to-high correlations were found between the contribution to ambiguity tolerance and contribution to empathy (0.528-0.744; p ≤ 0.01). Art may contribute especially to the development of medical students' tolerance of ambiguity, also related to the enhancement of empathy. The potential contribution of visual art works used in VTS to the enhancement of tolerance for ambiguity and empathy is explained based on relevant literature regarding the embeddedness of ambiguity within art works, coupled with reference to John Dewey's theory of learning. Given the

  5. Discrete choice experiment produced estimates of acceptable risks of therapeutic options in cancer patients with febrile neutropenia.

    PubMed

    Sung, Lillian; Alibhai, Shabbir M; Ethier, Marie-Chantal; Teuffel, Oliver; Cheng, Sylvia; Fisman, David; Regier, Dean A

    2012-06-01

    To use a discrete choice experiment (DCE) to describe patient/proxy tolerance for the number of clinic visits, and chances of readmission, intensive care unit admission, and mortality to accept oral outpatient management of low-risk febrile neutropenia. Adults and children aged 12-18 years with cancer and parents of pediatric cancer patients were asked to choose between outpatient oral and inpatient intravenous management of low-risk febrile neutropenia. Using a DCE, we varied the attribute levels with the outpatient option and kept them constant for the inpatient option. Seventy-eight adults, 153 parents, and 43 children provided responses. All four attributes significantly affected choices. The mean tolerance (95% confidence interval) for the number of clinic visits per week was 3.6 (2.2-4.8), 2.1 (1.1-3.2), and 4.3 (2.5-6.0) to accept outpatient management among adults, parents, and children, respectively. With thrice weekly clinic visits and 7.5% chance of readmission, probabilities of accepting the outpatient strategy were 50% (44-54%) for adults, 43% (39-48%) for parents, and 53% (46-59%) for children. Using a DCE, we determined that a 7.5% chance of readmission and clinic visits more frequently than thrice weekly are unlikely to be acceptable. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation.

    PubMed

    Gallon, Lorenzo; Mathew, James M; Bontha, Sai Vineela; Dumur, Catherine I; Dalal, Pranav; Nadimpalli, Lakshmi; Maluf, Daniel G; Shetty, Aneesha A; Ildstad, Suzanne T; Leventhal, Joseph R; Mas, Valeria R

    2018-02-01

    The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways. Copyright © 2018 by the

  7. Global transcriptional profiling of a cold-tolerant rice variety under moderate cold stress reveals different cold stress response mechanisms.

    PubMed

    Zhao, Junliang; Zhang, Shaohong; Yang, Tifeng; Zeng, Zichong; Huang, Zhanghui; Liu, Qing; Wang, Xiaofei; Leach, Jan; Leung, Hei; Liu, Bin

    2015-07-01

    Gene expression profiling under severe cold stress (4°C) has been conducted in plants including rice. However, rice seedlings are frequently exposed to milder cold stresses under natural environments. To understand the responses of rice to milder cold stress, a moderately low temperature (8°C) was used for cold treatment prior to genome-wide profiling of gene expression in a cold-tolerant japonica variety, Lijiangxintuanheigu (LTH). A total of 5557 differentially expressed genes (DEGs) were found at four time points during moderate cold stress. Both the DEGs and differentially expressed transcription factor genes were clustered into two groups based on their expression, suggesting a two-phase response to cold stress and a determinative role of transcription factors in the regulation of stress response. The induction of OsDREB2A under cold stress is reported for the first time in this study. Among the anti-oxidant enzyme genes, glutathione peroxidase (GPX) and glutathione S-transferase (GST) were upregulated, suggesting that the glutathione system may serve as the main reactive oxygen species (ROS) scavenger in LTH. Changes in expression of genes in signal transduction pathways for auxin, abscisic acid (ABA) and salicylic acid (SA) imply their involvement in cold stress responses. The induction of ABA response genes and detection of enriched cis-elements in DEGs suggest that ABA signaling pathway plays a dominant role in the cold stress response. Our results suggest that rice responses to cold stress vary with the specific temperature imposed and the rice genotype. © 2014 Scandinavian Plant Physiology Society.

  8. Transcriptome Profiling of the Pineapple under Low Temperature to Facilitate Its Breeding for Cold Tolerance

    PubMed Central

    Chen, Chengjie; Zhang, Yafeng; Xu, Zhiqiang; Luan, Aiping; Mao, Qi; Feng, Junting; Xie, Tao; Gong, Xue; Wang, Xiaoshuang; Chen, Hao; He, Yehua

    2016-01-01

    The pineapple (Ananas comosus) is cold sensitive. Most cultivars are injured during winter periods, especially in sub-tropical regions. There is a lack of molecular information on the pineapple’s response to cold stress. In this study, high-throughput transcriptome sequencing and gene expression analysis were performed on plantlets of a cold-tolerant genotype of the pineapple cultivar ‘Shenwan’ before and after cold treatment. A total of 1,186 candidate cold responsive genes were identified, and their credibility was confirmed by RT-qPCR. Gene set functional enrichment analysis indicated that genes related to cell wall properties, stomatal closure and ABA and ROS signal transduction play important roles in pineapple cold tolerance. In addition, a protein association network of CORs (cold responsive genes) was predicted, which could serve as an entry point to dissect the complex cold response network. Our study found a series of candidate genes and their association network, which will be helpful to cold stress response studies and pineapple breeding for cold tolerance. PMID:27656892

  9. Effects of a Follow-On Formula Containing Isomaltulose (Palatinose™) on Metabolic Response, Acceptance, Tolerance and Safety in Infants: A Randomized-Controlled Trial

    PubMed Central

    Fleddermann, M.; Rauh-Pfeiffer, A.; Demmelmair, H.; Holdt, L.; Teupser, D.; Koletzko, B.

    2016-01-01

    Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50) were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™)/100mL) or an isocaloric conventional formula (CF) providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60min after start of feeding (primary outcome) was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60min after start of feeding was 122(105,140) mg/dL in IF (median, interquartile range) and 111(100,123) in CF (p = 0.01). Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0) vs. CF:56.8(37.5, 129),p = 0.43). Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045), protein (R = 0.42,p = 0.006) and fat (R = 0.40,p = 0.01) but not with carbohydrate intake (R = 0.22,p = 0.16). Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants. Trial registration: ClinicalTrials.gov NCT01627015 PMID:26987056

  10. Genetic variation in Southern USA rice genotypes for seedling salinity tolerance

    PubMed Central

    De Leon, Teresa B.; Linscombe, Steven; Gregorio, Glenn; Subudhi, Prasanta K.

    2015-01-01

    The success of a rice breeding program in developing salt tolerant varieties depends on genetic variation and the salt stress response of adapted and donor rice germplasm. In this study, we used a combination of morphological and physiological traits in multivariate analyses to elucidate the phenotypic and genetic variation in salinity tolerance of 30 Southern USA rice genotypes, along with 19 donor genotypes with varying degree of tolerance. Significant genotypic variation and correlations were found among the salt injury score (SIS), ion leakage, chlorophyll reduction, shoot length reduction, shoot K+ concentration, and shoot Na+/K+ ratio. Using these parameters, the combined methods of cluster analysis and discriminant analysis validated the salinity response of known genotypes and classified most of the USA varieties into sensitive groups, except for three and seven varieties placed in the tolerant and moderately tolerant groups, respectively. Discriminant function and MANOVA delineated the differences in tolerance and suggested no differences between sensitive and highly sensitive (HS) groups. DNA profiling using simple sequence repeat markers showed narrow genetic diversity among USA genotypes. However, the overall genetic clustering was mostly due to subspecies and grain type differentiation and not by varietal grouping based on salinity tolerance. Among the donor genotypes, Nona Bokra, Pokkali, and its derived breeding lines remained the donors of choice for improving salinity tolerance during the seedling stage. However, due to undesirable agronomic attributes and photosensitivity of these donors, alternative genotypes such as TCCP266, Geumgangbyeo, and R609 are recommended as useful and novel sources of salinity tolerance for USA rice breeding programs. PMID:26074937

  11. Distress tolerance and physiological reactivity to stress predict women's problematic alcohol use.

    PubMed

    Holzhauer, Cathryn Glanton; Wemm, Stephanie; Wulfert, Edelgard

    2017-06-01

    Research has shown that measures of reactivity to distress-including distress tolerance and physiological reactivity to stress-are dysregulated in women who misuse alcohol. These variables may interact and create a risk profile for young adult women, reflecting patterns of stress reactivity that confer a risk for alcohol misuse. The current study tested this hypothesis by examining the independent and interactive associations of subjective distress tolerance, behavioral distress tolerance, and physiological stress reactivity with women's alcohol misuse. The study was conducted with a sample of 91 college women recruited on a large northeastern university campus. Results showed that subjective levels of distress tolerance and physiological reactivity to stress (skin conductance reactivity, SCR), but not behavioral distress tolerance, were independently associated with alcohol misuse. In addition, subjective distress tolerance moderated the relationship between SCR and negative alcohol-related consequences. Specifically, women with low physiological reactivity (SCR) to a stressful task and greater urge to quickly rid themselves of distress (low subjective distress tolerance) endorsed a significantly greater number of adverse consequences from their alcohol use. These results extend prior findings by showing that, even among a nonclinical sample of women, lower stress reactivity in combination with low subjective distress tolerance is associated with increased risk for various drinking-related negative consequences. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation.

    PubMed

    Zheng, Shuang; Xu, Hua; Zhou, Huan; Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

    2017-01-01

    To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals.

  13. Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation

    PubMed Central

    Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

    2017-01-01

    Aims To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). Methods 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Results Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Conclusions Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals. PMID:28199386

  14. Impact of the lay-off length on +Gz tolerance.

    PubMed

    Mikuliszyn, Romuald; Kowalski, Wieslaw; Kowalczuk, Krzysztof

    2002-07-01

    There are many factors affecting pilots' +Gz-tolerance. Recently, attention of the aviation community has been focused on lay-off and it's impact on +Gz-tolerance. Pilots of the Polish Air Force (PAF) have dealt with that problem for several years now. The aim of the study was to provide insight on how lay-off periods with different duration impact +Gz-tolerance. 95 male jet pilots from the PAF participated in the study. Every one had at least two weeks lay-off period (non-medical reasons). Subjects were divided into four groups according to the length of lay-off period (2-4 weeks; 5-13 weeks; 14-26 weeks; 27-154 weeks), All pilots were subjected to a centrifuge exposure in GOR (0.1 G/s) or ROR (1.0 G/s) profiles, depending on the pre-lay-off exposure. Post-lay-off exposures were carried out directly after lay-off. 18 jet pilots without any lay-off constituted the control group. The difference between pre- and post-lay-off G-tolerance limit (-0,93 +/- 0,53) was statistically significant (p<0.01) only for one group, where lay-off period ranged between two and four weeks. No statistically significant differences were found where influence of other factors like total and yearly flight hours, heart rate gain (AHR) or physical activity measured as maximal oxygen intake were considered. 2-4 weeks of lay-off period decreases +Gz tolerance is statistically significant manner. Subsequent increase of lay-off period does not result in mean tolerance changes for group, however in certain individuals critical decrement of +Gz tolerance occurs. Total and last year flying hours, physical fitness does not modify impact of lay-off period on +Gz tolerance.

  15. Probability of Future Observations Exceeding One-Sided, Normal, Upper Tolerance Limits

    DOE PAGES

    Edwards, Timothy S.

    2014-10-29

    Normal tolerance limits are frequently used in dynamic environments specifications of aerospace systems as a method to account for aleatory variability in the environments. Upper tolerance limits, when used in this way, are computed from records of the environment and used to enforce conservatism in the specification by describing upper extreme values the environment may take in the future. Components and systems are designed to withstand these extreme loads to ensure they do not fail under normal use conditions. The degree of conservatism in the upper tolerance limits is controlled by specifying the coverage and confidence level (usually written inmore » “coverage/confidence” form). Moreover, in high-consequence systems it is common to specify tolerance limits at 95% or 99% coverage and confidence at the 50% or 90% level. Despite the ubiquity of upper tolerance limits in the aerospace community, analysts and decision-makers frequently misinterpret their meaning. The misinterpretation extends into the standards that govern much of the acceptance and qualification of commercial and government aerospace systems. As a result, the risk of a future observation of the environment exceeding the upper tolerance limit is sometimes significantly underestimated by decision makers. This note explains the meaning of upper tolerance limits and a related measure, the upper prediction limit. So, the objective of this work is to clarify the probability of exceeding these limits in flight so that decision-makers can better understand the risk associated with exceeding design and test levels during flight and balance the cost of design and development with that of mission failure.« less

  16. Statewide implementation of the total pavement acceptance device (TPAD) : final report.

    DOT National Transportation Integrated Search

    2016-07-01

    Construction and development of the Total Pavement Acceptance Device (TPAD) was completed at the end of August 2012 through TxDOT Research Project 0-6005-01. The TPAD is a multi-function pavement evaluation device used to profile continuously along p...

  17. Host responses and metabolic profiles of wood components in Dutch elm hybrids with a contrasting tolerance to Dutch elm disease.

    PubMed

    Durkovič, Jaroslav; Kačík, František; Olčák, Dušan; Kučerová, Veronika; Krajňáková, Jana

    2014-07-01

    Changes occurring in the macromolecular traits of cell wall components in elm wood following attack by Ophiostoma novo-ulmi, the causative agent of Dutch elm disease (DED), are poorly understood. The purpose of this study was to compare host responses and the metabolic profiles of wood components for two Dutch elm (Ulmus) hybrids, 'Groeneveld' (a susceptible clone) and 'Dodoens' (a tolerant clone), that have contrasting survival strategies upon infection with the current prevalent strain of DED. Ten-year-old plants of the hybrid elms were inoculated with O. novo-ulmi ssp. americana × novo-ulmi. Measurements were made of the content of main cell wall components and extractives, lignin monomer composition, macromolecular traits of cellulose and neutral saccharide composition. Upon infection, medium molecular weight macromolecules of cellulose were degraded in both the susceptible and tolerant elm hybrids, resulting in the occurrence of secondary cell wall ruptures and cracks in the vessels, but rarely in the fibres. The (13)C nuclear magnetic resonance spectra revealed that loss of crystalline and non-crystalline cellulose regions occurred in parallel. The rate of cellulose degradation was influenced by the syringyl:guaiacyl ratio in lignin. Both hybrids commonly responded to the medium molecular weight cellulose degradation with the biosynthesis of high molecular weight macromolecules of cellulose, resulting in a significant increase in values for the degree of polymerization and polydispersity. Other responses of the hybrids included an increase in lignin content, a decrease in relative proportions of d-glucose, and an increase in proportions of d-xylose. Differential responses between the hybrids were found in the syringyl:guaiacyl ratio in lignin. In susceptible 'Groeneveld' plants, syringyl-rich lignin provided a far greater degree of protection from cellulose degradation than in 'Dodoens', but only guaiacyl-rich lignin in 'Dodoens' plants was involved in

  18. Workplace violence: managing a culture of acceptance.

    PubMed

    Fredrick, Marie

    2014-01-01

    The cultural acceptance of workplace violence is changing. Management has become more educated on regulatory issues around its tolerance of workplace violence. Events around the country in a variety of settings have aided in raising awareness of this issue. Healthcare professionals are not immune to workplace violence, including those working in the imaging profession. Healthcare workers, historically, have given care despite the demeanor of patients, often putting up with aggressive behavior including sexual harassment and physical assault. Management needs to take all possible measures to ensure employees feel safe at work. It is essential to have well thought out policies and procedures to mitigate workplace violence; keeping in mind that a goal of eliminating workplace violence is unrealistic.

  19. Redirecting reproductive immunology research toward pregnancy as a period of temporary immune tolerance.

    PubMed

    Gleicher, Norbert; Kushnir, Vitaly A; Barad, David H

    2017-04-01

    Referring to two recent publications, we here propose that clinical reproductive immunology has for decades stagnated because reproductive medicine, including assisted reproduction (AR), has failed to accept embryo implantation as an immune system-driven process, dependent on establishment of maternal tolerance toward the implanting fetal semi-allograft (and complete allograft in cases of oocyte donation). Pregnancy represents a biologically unique period of temporary (to the period of gestation restricted) tolerance, otherwise only known in association with parasitic infections. Rather than investigating the immune pathways necessary to induce this rather unique state of tolerance toward the rapidly growing parasitic antigen load of the fetus, the field, instead, concentrated on irrelevant secondary immune phenomena (i.e., "immunological noise"). It, therefore, does not surprise that interesting recent research, offering new potential insights into maternal tolerance during pregnancy, was mostly published outside of the field of reproductive medicine. This research offers evidence for existence of inducible maternal tolerance pathways with the ability of improving maternal fecundity and, potentially, reducing such late pregnancy complications as premature labor and preeclampsia/eclampsia due to premature abatement of maternal tolerance. Increasing evidence also suggests that tolerance-inducing immune pathways are similar in successful pregnancy, successful organ transplantation and, likely also in the tolerance of "self" (i.e., prevention of autoimmunity). Identifying and isolating these pathways, therefore, may greatly benefit all three of these clinical areas, and research in reproductive immunology should be accordingly redirected.

  20. PRODUCTION OF IMMUNOLOGICAL TOLERANCE IN MICE AFTER REPEATED INJECTIONS OF DISRUPTED SPLEEN CELLS

    PubMed Central

    Martinez, C.; Smith, J. M.; Blaese, M.; Good, R. A.

    1963-01-01

    1. Tolerance of male skin isografts has been regularly produced in female mice of the C57B1 strain sublines 1, 4, and 6 during adult life by repeated injection of completely disrupted spleen cells derived from male donors. The tolerant state is long-lasting since such grafts have remained in place more than 9 months. 2. Prolonged survival of homotransplants of skin has regularly been produced in DBA/2 mice during adult life by repeated injections of completely disrupted spleen cells from Balb/C donors. When injections of disrupted spleen cell material are continued over a sufficiently long period, permanent acceptance of the skin homografts may be obtained between these strains. 3. Immunological tolerance across even the strong H-2 histocompatibility barrier was obtained in the neonatal period and during adult life by repeated injection of disrupted spleen cell preparations. The tolerant state has been revealed by both mammary adenocarcinoma and skin homografting across this strong histocompatibility barrier. 4. In contradistinction to the tolerant state produced by injection of intact spleen cells in neonatal animals or during adult life or that produced by parabiotic union, the tolerance produced by repeated injection of disrupted spleen cell preparations cannot be transferred to syngenic neonatal mice with spleen cells of the tolerant animal. 5. The implications of these findings in transplantation biology and in consideration of the basic nature of tolerance are discussed. PMID:14087619

  1. A theory of drug tolerance and dependence II: the mathematical model.

    PubMed

    Peper, Abraham

    2004-08-21

    The preceding paper presented a model of drug tolerance and dependence. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behaviour to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The present paper discusses the mathematical model in terms of its design. The model is a nonlinear, learning feedback system, fully satisfying control theoretical principles. It accepts any form of the stimulus-the drug intake-and describes how the physiological processes involved affect the distribution of the drug through the body and the stability of the regulation loop. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes.

  2. Genomic, transcriptomic, and proteomic approaches towards understanding the molecular mechanisms of salt tolerance in Frankia strains isolated from Casuarina trees.

    PubMed

    Oshone, Rediet; Ngom, Mariama; Chu, Feixia; Mansour, Samira; Sy, Mame Ourèye; Champion, Antony; Tisa, Louis S

    2017-08-18

    Soil salinization is a worldwide problem that is intensifying because of the effects of climate change. An effective method for the reclamation of salt-affected soils involves initiating plant succession using fast growing, nitrogen fixing actinorhizal trees such as the Casuarina. The salt tolerance of Casuarina is enhanced by the nitrogen-fixing symbiosis that they form with the actinobacterium Frankia. Identification and molecular characterization of salt-tolerant Casuarina species and associated Frankia is imperative for the successful utilization of Casuarina trees in saline soil reclamation efforts. In this study, salt-tolerant and salt-sensitive Casuarina associated Frankia strains were identified and comparative genomics, transcriptome profiling, and proteomics were employed to elucidate the molecular mechanisms of salt and osmotic stress tolerance. Salt-tolerant Frankia strains (CcI6 and Allo2) that could withstand up to 1000 mM NaCl and a salt-sensitive Frankia strain (CcI3) which could withstand only up to 475 mM NaCl were identified. The remaining isolates had intermediate levels of salt tolerance with MIC values ranging from 650 mM to 750 mM. Comparative genomic analysis showed that all of the Frankia isolates from Casuarina belonged to the same species (Frankia casuarinae). Pangenome analysis revealed a high abundance of singletons among all Casuarina isolates. The two salt-tolerant strains contained 153 shared single copy genes (most of which code for hypothetical proteins) that were not found in the salt-sensitive(CcI3) and moderately salt-tolerant (CeD) strains. RNA-seq analysis of one of the two salt-tolerant strains (Frankia sp. strain CcI6) revealed hundreds of genes differentially expressed under salt and/or osmotic stress. Among the 153 genes, 7 and 7 were responsive to salt and osmotic stress, respectively. Proteomic profiling confirmed the transcriptome results and identified 19 and 8 salt and/or osmotic stress-responsive proteins in the

  3. Evaluation of the safety and tolerability profile of Sativex: is it reassuring enough?

    PubMed

    Wade, Derick

    2012-04-01

    The adoption of new drug therapies involves an assessment of risk:benefit based upon the best clinical evidence, including clinical trials but also everyday clinical practice data collection. However, in the case of Sativex, a cannabinoid medicine containing the two main active ingredients of cannabis, δ-9-tetrahydrocannabinol and cannabidiol, the picture is somewhat clouded by preconceived views regarding the world's most widely used illicit drug, herbal cannabis. In this review, I aim to look beyond these preconceptions and evaluate the body of published data concerning this medicine currently approved in different countries for the management of one of the most frequent and disabling symptoms associated with multiple sclerosis, spasticity. In particular, data relevant to areas of concern such as tolerability, safety, psychoactivity, effects on withdrawal (including possible drug tolerance) and finally the potential for abuse/dependence are evaluated. Balancing these risk factors, the main positive clinical data published over the years by the Oxford Centre for Enablement, following on from the first pilot study in 2004, are presented. Based upon our experience, the benefits that are seen initially with Sativex when treating multiple sclerosis spasticity patients are generally maintained during long-term treatment. Furthermore, following withdrawal of Sativex, symptoms often return, but, beyond this, sudden cessation is generally safe with no evidence of physiological or psychological dependence. Dose escalation has not usually been observed in clinical trials or clinical practice after the first titration weeks. Adverse effects occur relatively frequently, but they are usually mild to moderate in intensity and rarely require drug discontinuation. Overall, Sativex appears to be well-tolerated and a useful addition for patients who have failed treatment with traditional antispastic agents.

  4. Autonomous Congestion Control in Delay-Tolerant Networks

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott; Jennings, Esther; Schoolcraft, Joshua

    2006-01-01

    Congestion control is an important feature that directly affects network performance. Network congestion may cause loss of data or long delays. Although this problem has been studied extensively in the Internet, the solutions for Internet congestion control do not apply readily to challenged network environments such as Delay Tolerant Networks (DTN) where end-to-end connectivity may not exist continuously and latency can be high. In DTN, end-to-end rate control is not feasible. This calls for congestion control mechanisms where the decisions can be made autonomously with local information only. We use an economic pricing model and propose a rule-based congestion control mechanism where each router can autonomously decide on whether to accept a bundle (data) based on local information such as available storage and the value and risk of accepting the bundle (derived from historical statistics). Preliminary experimental results show that this congestion control mechanism can protect routers from resource depletion without loss of data.

  5. Global Expression Profiling of Low Temperature Induced Genes in the Chilling Tolerant Japonica Rice Jumli Marshi

    PubMed Central

    Chawade, Aakash; Lindlöf, Angelica; Olsson, Björn; Olsson, Olof

    2013-01-01

    Low temperature is a key factor that limits growth and productivity of many important agronomical crops worldwide. Rice (Oryza sativa L.) is negatively affected already at temperatures below +10°C and is therefore denoted as chilling sensitive. However, chilling tolerant rice cultivars exist and can be commercially cultivated at altitudes up to 3,050 meters with temperatures reaching as low as +4°C. In this work, the global transcriptional response to cold stress (+4°C) was studied in the Nepalese highland variety Jumli Marshi (spp. japonica) and 4,636 genes were identified as significantly differentially expressed within 24 hours of cold stress. Comparison with previously published microarray data from one chilling tolerant and two sensitive rice cultivars identified 182 genes differentially expressed (DE) upon cold stress in all four rice cultivars and 511 genes DE only in the chilling tolerant rice. Promoter analysis of the 182 genes suggests a complex cross-talk between ABRE and CBF regulons. Promoter analysis of the 511 genes identified over-represented ABRE motifs but not DRE motifs, suggesting a role for ABA signaling in cold tolerance. Moreover, 2,101 genes were DE in Jumli Marshi alone. By chromosomal localization analysis, 473 of these cold responsive genes were located within 13 different QTLs previously identified as cold associated. PMID:24349120

  6. Involvement of an ABI-like protein and a Ca2+-ATPase in drought tolerance as revealed by transcript profiling of a sweetpotato somatic hybrid and its parents Ipomoea batatas (L.) Lam. and I. triloba L.

    PubMed

    Yang, Yufeng; Wang, Yannan; Jia, Licong; Yang, Guohong; Xu, Xinzhi; Zhai, Hong; He, Shaozhen; Li, Junxia; Dai, Xiaodong; Qin, Na; Zhu, Cancan; Liu, Qingchang

    2018-01-01

    Previously, we obtained the sweetpotato somatic hybrid KT1 from a cross between sweetpotato (Ipomoea batatas (L.) Lam.) cv. Kokei No. 14 and its drought-tolerant wild relative I. triloba L. KT1 not only inherited the thick storage root characteristic of Kokei No. 14 but also the drought-tolerance trait of I. triloba L. The aim of this study was to explore the molecular mechanism of the drought tolerance of KT1. Four-week-old in vitro-grown plants of KT1, Kokei No. 14, and I. triloba L. were subjected to a simulated drought stress treatment (30% PEG6000) for 0, 6, 12 and 24 h. Total RNA was extracted from samples at each time point, and then used for transcriptome sequencing. The gene transcript profiles of KT1 and its parents were compared to identify differentially expressed genes, and drought-related modules were screened by a weighted gene co-expression network analysis. The functions of ABI-like protein and Ca2+-ATPase, two proteins screened from the cyan and light yellow modules, were analyzed in terms of their potential roles in drought tolerance in KT1 and its parents. These analyses of the drought responses of KT1 and its somatic donors at the transcriptional level provide new annotations for the molecular mechanism of drought tolerance in the somatic hybrid KT1 and its parents.

  7. Involvement of an ABI-like protein and a Ca2+-ATPase in drought tolerance as revealed by transcript profiling of a sweetpotato somatic hybrid and its parents Ipomoea batatas (L.) Lam. and I. triloba L.

    PubMed Central

    Jia, Licong; Yang, Guohong; Xu, Xinzhi; Zhai, Hong; He, Shaozhen; Li, Junxia; Dai, Xiaodong; Qin, Na; Zhu, Cancan

    2018-01-01

    Previously, we obtained the sweetpotato somatic hybrid KT1 from a cross between sweetpotato (Ipomoea batatas (L.) Lam.) cv. Kokei No. 14 and its drought-tolerant wild relative I. triloba L. KT1 not only inherited the thick storage root characteristic of Kokei No. 14 but also the drought-tolerance trait of I. triloba L. The aim of this study was to explore the molecular mechanism of the drought tolerance of KT1. Four-week-old in vitro-grown plants of KT1, Kokei No. 14, and I. triloba L. were subjected to a simulated drought stress treatment (30% PEG6000) for 0, 6, 12 and 24 h. Total RNA was extracted from samples at each time point, and then used for transcriptome sequencing. The gene transcript profiles of KT1 and its parents were compared to identify differentially expressed genes, and drought-related modules were screened by a weighted gene co-expression network analysis. The functions of ABI-like protein and Ca2+-ATPase, two proteins screened from the cyan and light yellow modules, were analyzed in terms of their potential roles in drought tolerance in KT1 and its parents. These analyses of the drought responses of KT1 and its somatic donors at the transcriptional level provide new annotations for the molecular mechanism of drought tolerance in the somatic hybrid KT1 and its parents. PMID:29466419

  8. Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis.

    PubMed

    Chen, Jian-Jun; Zhao, Li-Bo; Liu, Yi-Yun; Fan, Song-Hua; Xie, Peng

    2017-03-01

    The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD. The literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates. Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non -significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate. ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues

    PubMed Central

    Kant, Cavit D.; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2014-01-01

    In this study, we show that aly/aly mice, which are devoid of lymph nodes and Peyer’s patches, rejected acutely fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts were also rejected acutely by splenectomized aly/aly mice (aly/aly-spl−) devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8+ T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected in aly/aly-spl− mice. Actually, aly/aly-spl− mice having spontaneously accepted a heart allotransplant displayed donor-specific tolerance also accepted skin grafts from the same but not a third-party donor via a mechanism involving CD4+ regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs. PMID:25535285

  10. Rotor with Flattened Exit Pressure Profile

    NASA Technical Reports Server (NTRS)

    Baltas, Constantine (Inventor); Prasad, Dilip (Inventor); Gallagher, Edward J. (Inventor)

    2015-01-01

    A rotor blade comprises an airfoil extending radially from a root section to a tip section and axially from a leading edge to a trailing edge, the leading and trailing edges defining a curvature therebetween. The curvature determines a relative exit angle at a relative span height between the root section and the tip section, based on an incident flow velocity at the leading edge of the airfoil and a rotational velocity at the relative span height. In operation of the rotor blade, the relative exit angle determines a substantially flat exit pressure ratio profile for relative span heights from 75% to 95%, wherein the exit pressure ratio profile is constant within a tolerance of 10% of a maximum value of the exit pressure ratio profile.

  11. Tolerance assignment in optical design

    NASA Astrophysics Data System (ADS)

    Youngworth, Richard Neil

    2002-09-01

    Tolerance assignment is necessary in any engineering endeavor because fabricated systems---due to the stochastic nature of manufacturing and assembly processes---necessarily deviate from the nominal design. This thesis addresses the problem of optical tolerancing. The work can logically be split into three different components that all play an essential role. The first part addresses the modeling of manufacturing errors in contemporary fabrication and assembly methods. The second component is derived from the design aspect---the development of a cost-based tolerancing procedure. The third part addresses the modeling of image quality in an efficient manner that is conducive to the tolerance assignment process. The purpose of the first component, modeling manufacturing errors, is twofold---to determine the most critical tolerancing parameters and to understand better the effects of fabrication errors. Specifically, mid-spatial-frequency errors, typically introduced in sub-aperture grinding and polishing fabrication processes, are modeled. The implication is that improving process control and understanding better the effects of the errors makes the task of tolerance assignment more manageable. Conventional tolerancing methods do not directly incorporate cost. Consequently, tolerancing approaches tend to focus more on image quality. The goal of the second part of the thesis is to develop cost-based tolerancing procedures that facilitate optimum system fabrication by generating the loosest acceptable tolerances. This work has the potential to impact a wide range of optical designs. The third element, efficient modeling of image quality, is directly related to the cost-based optical tolerancing method. Cost-based tolerancing requires efficient and accurate modeling of the effects of errors on the performance of optical systems. Thus it is important to be able to compute the gradient and the Hessian, with respect to the parameters that need to be toleranced, of the figure

  12. Tolerability and cosmetic acceptability of liquor carbonis distillate (coal tar) solution 15% as topical therapy for plaque psoriasis.

    PubMed

    Brouda, Irina; Edison, Brenda; Van Cott, Alicia; Green, Barbara A

    2010-04-01

    Although generally recognized as an effective therapy for psoriasis, coal tar therapy lost appeal in modern clinical practice due to poor patient acceptability of its aesthetic properties. A new liquor carbonis distillate (LCD) solution 15% (equivalent to coal tar 2.3%) that uses an evaporative and transparent vehicle, fragrance, and a dab-on applicator was developed. Cosmetic acceptability of the LCD solution was compared to calcipotriene cream 0.005% during a randomized, active-controlled, investigator-blinded clinical trial. Participants with moderate plaque psoriasis applied LCD solution or calcipotriene cream twice daily to body lesions for 12 weeks and then were followed for 6 additional weeks without treatment. Participants completed a cosmetic acceptability survey about their medications after starting therapy. Mean ratings for aesthetic and product performance attributes were high in both groups; however, more participants treated with LCD solution versus calcipotriene cream rated their product as more convenient and beneficial compared to prior psoriasis therapies. Ratings of the scent, staining, drying time, and dab-on applicator for the LCD solution were favorable. Participant experience with LCD solution in this study suggests that it is a cosmetically acceptable psoriasis treatment that is comparable to calcipotriene cream.

  13. Reconfigurable fault tolerant avionics system

    NASA Astrophysics Data System (ADS)

    Ibrahim, M. M.; Asami, K.; Cho, Mengu

    This paper presents the design of a reconfigurable avionics system based on modern Static Random Access Memory (SRAM)-based Field Programmable Gate Array (FPGA) to be used in future generations of nano satellites. A major concern in satellite systems and especially nano satellites is to build robust systems with low-power consumption profiles. The system is designed to be flexible by providing the capability of reconfiguring itself based on its orbital position. As Single Event Upsets (SEU) do not have the same severity and intensity in all orbital locations, having the maximum at the South Atlantic Anomaly (SAA) and the polar cusps, the system does not have to be fully protected all the time in its orbit. An acceptable level of protection against high-energy cosmic rays and charged particles roaming in space is provided within the majority of the orbit through software fault tolerance. Check pointing and roll back, besides control flow assertions, is used for that level of protection. In the minority part of the orbit where severe SEUs are expected to exist, a reconfiguration for the system FPGA is initiated where the processor systems are triplicated and protection through Triple Modular Redundancy (TMR) with feedback is provided. This technique of reconfiguring the system as per the level of the threat expected from SEU-induced faults helps in reducing the average dynamic power consumption of the system to one-third of its maximum. This technique can be viewed as a smart protection through system reconfiguration. The system is built on the commercial version of the (XC5VLX50) Xilinx Virtex5 FPGA on bulk silicon with 324 IO. Simulations of orbit SEU rates were carried out using the SPENVIS web-based software package.

  14. (E)-Propyl α-Cyano-4-Hydroxyl Cinnamylate: A High Sensitive and Salt Tolerant Matrix for Intact Protein Profiling by MALDI Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Wang, Sheng; Xiao, Zhaohui; Xiao, Chunsheng; Wang, Huixin; Wang, Bing; Li, Ying; Chen, Xuesi; Guo, Xinhua

    2016-04-01

    Low-abundance samples and salt interference are always of great challenges for the practical protein profiling by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Herein, a series of carboxyl-esterified derivatives of α-cyano-4-hydroxycinnamic acid (CHCA) were synthesized and evaluated as matrices for MALDI-MS analysis of protein. Among them, (E)-propyl α-cyano-4-hydroxyl cinnamylate (CHCA-C3) was found to exhibit excellent assay performance for intact proteins by improving the detection sensitivity 10 folds compared with the traditional matrices [i.e., super2,5-dihydroxybenzoic acid (superDHB), sinapic acid (SA), and CHCA]. In addition, CHCA-C3 was shown to have high tolerance to salts, the ion signal of myoglobin was readily detected even in the presence of urea (8 M), NH4HCO3 (2 M), and KH2PO4 (500 mM), meanwhile sample washability was robust. These achievements were mainly attributed to improved ablation ability and increased hydrophobicity or affinity of CHCA-C3 to proteins in comparison with hydrophilic matrixes, leading to more efficient ionization of analyte. Furthermore, direct analysis of proteins from crude egg white demonstrated that CHCA-C3 was a highly efficient matrix for the analysis of low-abundance proteins in complex biological samples. These outstanding performances indicate the tremendous potential use of CHCA-C3 in protein profiling by MALDI-MS.

  15. Comparative Metabolomic Analyses of Ipomoea lacunosa Biotypes with Contrasting Glyphosate Tolerance Captures Herbicide-Induced Differential Perturbations in Cellular Physiology.

    PubMed

    Maroli, Amith S; Nandula, Vijay K; Duke, Stephen O; Gerard, Patrick; Tharayil, Nishanth

    2018-02-28

    Glyphosate-tolerant Ipomoea lacunosa is emerging as a problematic weed in the southeastern United States. Metabolomic profiling was conducted to examine the innate physiology and the glyphosate induced perturbations in two biotypes of I. lacunosa (WAS and QUI) that had contrasting glyphosate tolerance. Compared to the less tolerant QUI-biotype, the innate metabolism of the more tolerant WAS-biotype was characterized by a higher abundance of amino acids, and pyruvate; whereas the sugar profile of the QUI biotype was dominated by the transport sugar sucrose. Glyphosate application (80 g ae/ha) caused similar shikimate accumulation in both biotypes. Compared to QUI, in WAS, the content of aromatic amino acids was less affected by glyphosate treatment, and the content of Ala, Val, Ile, and Pro increased. However, the total sugars decreased by ∼75% in WAS, compared to ∼50% decrease in QUI. The innate, higher proportional abundance, of the transport-sugar sucrose in QUI coud partly explain the higher translocation and greater sensitivity of this biotype to glyphosate. The decrease in sugars, accompanied by an increase in amino acids could delay feedback regulation of upstream enzymes of the shikimate acid pathway in WAS, which could contribute to a greater glyphosate tolerance. Our study, through a metabolomics approach, provides complementary data that elucidates the cellular physiology of herbicide tolerance in Ipomoea lacunosa biotypes.

  16. Gene profiling-based phenotyping for identification of cellular parameters that contribute to fitness, stress-tolerance and virulence of Listeria monocytogenes variants.

    PubMed

    Koomen, Jeroen; den Besten, Heidy M W; Metselaar, Karin I; Tempelaars, Marcel H; Wijnands, Lucas M; Zwietering, Marcel H; Abee, Tjakko

    2018-06-07

    Microbial population heterogeneity allows for a differential microbial response to environmental stresses and can lead to the selection of stress resistant variants. In this study, we have used two different stress resistant variants of Listeria monocytogenes LO28 with mutations in the rpsU gene encoding ribosomal protein S21, to elucidate features that can contribute to fitness, stress-tolerance and host interaction using a comparative gene profiling and phenotyping approach. Transcriptome analysis showed that 116 genes were upregulated and 114 genes were downregulated in both rpsU variants. Upregulated genes included a major contribution of SigB-controlled genes such as intracellular acid resistance-associated glutamate decarboxylase (GAD) (gad3), genes involved in compatible solute uptake (opuC), glycerol metabolism (glpF, glpK, glpD), and virulence (inlA, inlB). Downregulated genes in the two variants involved mainly genes involved in flagella synthesis and motility. Phenotyping results of the two rpsU variants matched the gene profiling data including enhanced freezing resistance conceivably linked to compatible solute accumulation, higher glycerol utilisation rates, and better adhesion to Caco 2 cells presumably linked to higher expression of internalins. Also, bright field and electron microscopy analysis confirmed reduced flagellation of the variants. The activation of SigB-mediated stress defence offers an explanation for the multiple-stress resistant phenotype in rpsU variants. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Study of tolerance and acceptance of a high energy density enteral formula in patients coronary unit study

    PubMed

    Izaola, Olatz; De la Fuente, Beatriz; Gómez Hoyos, Emilia; López Gómez, Juan José; Torres, Beatriz; Ortola, Ana; De Luis, Daniel A

    2017-02-01

    Objective: The aim of our study was to evaluate the tolerance of enteral formula with high energetic density in patients hospitalized in a coronary care unit requering enteral support for at least five days. Methods: Opened, non-comparative, nonrandomized, descriptive study, evaluating the tolerance of enteral formula with high energy density in patients admitted to a coronary care unit. Results: 31 patients were included with a mean age of 67.32 ± 13.8 years, 66.7% were male. The average prescribed final volume Nutrison Energy® was 928.5 ± 278.5 mL/day (range: 800-1,500 mL/day). The average duration of enteral nutrition was 11.2 ± 3.2 days. The average calorie intake was 1,392 ± 417 cal/day, with 169.9 ± 50.9 g/day of carbohydrates, 53.8 ± 16.1 g/day of fat and 55.7 ± 16.9 g/day of protein. After administration there was a significant increased levels of transferrin. A total of 3 patients had an episode of diarrhea (9.7%). The number of patients experiencing at least one episode of gastric residue was 5 (16.1%) not forced in any way to withdra wing enteral nutrition, forcing in 2 patients to diminish the nutritional intake volume for 24 hours. During nutritional support, in only 3 patients it was required to decrease the volume made the previous day energy formula. With regard to vomiting, in 1 patient this situation (3.2%) was verified. No patient in the study presented any digestive complications associated with the administration of the enteral nutrition formula. Finally, no adverse events related to the administered formulation were recorded. Conclusions: The results show that enteral formula with high energy density is a well-tolerated formula with a very low frequency of gastrointestinal symptoms, which favors compliance.

  18. CD40 ligand blockade induces CD4+ T cell tolerance and linked suppression.

    PubMed

    Honey, K; Cobbold, S P; Waldmann, H

    1999-11-01

    The CD40-CD40 ligand (CD40L) interaction is a key event in the initiation of an adaptive immune response, and as such the therapeutic value of CD40L blockade has been studied in many experimental models of tissue transplantation and autoimmune disease. In rodents, transplantation of allogeneic tissues under the cover of anti-CD40L Abs has resulted in prolonged graft survival but not tolerance. In this report, we show that failure to induce tolerance probably results from the inability of anti-CD40L Abs to prevent graft rejection elicited by the CD8+ T cell subset. When the CD8+ T cell population is controlled independently, using anti-CD8 Abs, then tolerance is possible. Transplantation tolerance induced by anti-CD4 mAbs can often be associated with dominant regulation, manifested as infectious tolerance and linked suppression, both of which are mediated by CD4+ T cells. We show here that CD4+ T cells rendered tolerant using anti-CD40L therapy exhibit the same regulatory property of linked suppression, as demonstrated by their ability to accept grafts expressing third party Ags only if they are expressed in conjunction with the tolerated Ags. This observation of linked suppression reveals a hitherto undocumented consequence of CD40L blockade that suggests the tolerant state is maintained by a dominant regulatory mechanism. Our results suggest that, although anti-CD40L Abs are attractive clinical immunotherapeutic agents, additional therapies to control aggressive CD8+ T cell responses may be required.

  19. Need for Tolerances and Tolerance Exemptions for Minimum Risk Pesticides

    EPA Pesticide Factsheets

    The ingredients used in minimum risk products used on food, food crops, food contact surfaces, or animal feed commodities generally have a tolerance or tolerance exemption. Learn about tolerances and tolerance exemptions for minimum risk ingredients.

  20. Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans

    PubMed Central

    Sagoo, Pervinder; Perucha, Esperanza; Sawitzki, Birgit; Tomiuk, Stefan; Stephens, David A.; Miqueu, Patrick; Chapman, Stephanie; Craciun, Ligia; Sergeant, Ruhena; Brouard, Sophie; Rovis, Flavia; Jimenez, Elvira; Ballow, Amany; Giral, Magali; Rebollo-Mesa, Irene; Le Moine, Alain; Braudeau, Cecile; Hilton, Rachel; Gerstmayer, Bernhard; Bourcier, Katarzyna; Sharif, Adnan; Krajewska, Magdalena; Lord, Graham M.; Roberts, Ian; Goldman, Michel; Wood, Kathryn J.; Newell, Kenneth; Seyfert-Margolis, Vicki; Warrens, Anthony N.; Janssen, Uwe; Volk, Hans-Dieter; Soulillou, Jean-Paul; Hernandez-Fuentes, Maria P.; Lechler, Robert I.

    2010-01-01

    Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to α-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell–related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients. PMID:20501943

  1. Adherence to balance tolerance limits at the Upper Mississippi Science Center, La Crosse, Wisconsin.

    USGS Publications Warehouse

    Myers, C.T.; Kennedy, D.M.

    1998-01-01

    Verification of balance accuracy entails applying a series of standard masses to a balance prior to use and recording the measured values. The recorded values for each standard should have lower and upper weight limits or tolerances that are accepted as verification of balance accuracy under normal operating conditions. Balance logbooks for seven analytical balances at the Upper Mississippi Science Center were checked over a 3.5-year period to determine if the recorded weights were within the established tolerance limits. A total of 9435 measurements were checked. There were 14 instances in which the balance malfunctioned and operators recorded a rationale in the balance logbook. Sixty-three recording errors were found. Twenty-eight operators were responsible for two types of recording errors: Measurements of weights were recorded outside of the tolerance limit but not acknowledged as an error by the operator (n = 40); and measurements were recorded with the wrong number of decimal places (n = 23). The adherence rate for following tolerance limits was 99.3%. To ensure the continued adherence to tolerance limits, the quality-assurance unit revised standard operating procedures to require more frequent review of balance logbooks.

  2. Impact of essential oils on the taste acceptance of tomato juice, vegetable soup, or poultry burgers.

    PubMed

    Espina, Laura; García-Gonzalo, Diego; Pagán, Rafael

    2014-08-01

    Despite the vast body of available literature on the possibilities of essential oils (EOs) as food preservatives or functional ingredients, the sensory impact of their addition to foods has barely been approached. This work focuses on the hedonic taste acceptance of 3 food products (tomato juice, vegetable soup, and poultry burgers) when they are incorporated with potentially antimicrobial concentrations (20 to 200 μL/L) of 6 selected EOs (lemon, pennyroyal mint, thyme, and rosemary) and individual compounds (carvacrol, p-cymene). Although addition of 20 μL/L of pennyroyal mint or lemon EO did not change the taste acceptance of tomato juice, higher concentrations of these compounds or any concentration of the other 4 compounds did. In vegetable soup, the tolerance limit for rosemary EO, thyme EO, carvacrol, or p-cymene was 20 μL/L, while the addition of 200 μL/L of lemon EO was accepted. Tolerance limits in poultry burgers were established in 20 μL/L for carvacrol and thyme EOs, 100 μL/L for pennyroyal mint EO and p-cymene, and 200 μL/L for lemon and rosemary EOs. Moreover, incorporation of pennyroyal mint EO to tomato juice or poultry burgers, and enrichment of vegetable soup with lemon EO, could contribute to the development of food products with an improved sensory appeal. © 2014 Institute of Food Technologists®

  3. Using certification trails to achieve software fault tolerance

    NASA Technical Reports Server (NTRS)

    Sullivan, Gregory F.; Masson, Gerald M.

    1993-01-01

    A conceptually novel and powerful technique to achieve fault tolerance in hardware and software systems is introduced. When used for software fault tolerance, this new technique uses time and software redundancy and can be outlined as follows. In the initial phase, a program is run to solve a problem and store the result. In addition, this program leaves behind a trail of data called a certification trail. In the second phase, another program is run which solves the original problem again. This program, however, has access to the certification trail left by the first program. Because of the availability of the certification trail, the second phase can be performed by a less complex program and can execute more quickly. In the final phase, the two results are accepted as correct; otherwise an error is indicated. An essential aspect of this approach is that the second program must always generate either an error indication or a correct output even when the certification trail it receives from the first program is incorrect. The certification trail approach to fault tolerance was formalized and it was illustrated by applying it to the fundamental problem of finding a minimum spanning tree. Cases in which the second phase can be run concorrectly with the first and act as a monitor are discussed. The certification trail approach was compared to other approaches to fault tolerance. Because of space limitations we have omitted examples of our technique applied to the Huffman tree, and convex hull problems. These can be found in the full version of this paper.

  4. (In)Tolerable Zero Tolerance Policy

    ERIC Educational Resources Information Center

    Dickerson, Sean L.

    2014-01-01

    The spread of zero tolerance policies for school-based scenarios flourished under President William J. Clinton who wanted to close a loophole in the Guns-Free School Zones Act of 1990. Expansion in the coverage of zero tolerance policy to offenses outside the initial scope of weapon and drug offenses has led to a disproportional ratio of African…

  5. Pesticide tolerance in amphibians: induced tolerance in susceptible populations, constitutive tolerance in tolerant populations

    PubMed Central

    Hua, Jessica; Morehouse, Nathan I; Relyea, Rick

    2013-01-01

    The role of plasticity in shaping adaptations is important to understanding the expression of traits within individuals and the evolution of populations. With increasing human impacts on the environment, one challenge is to consider how plasticity shapes responses to anthropogenic stressors such as contaminants. To our knowledge, only one study (using mosquitoes) has considered the possibility of induced insecticide tolerance. Using populations of wood frogs (Lithobates sylvaticus) located close to and far from agricultural fields, we discovered that exposing some populations of embryos and hatchlings to sublethal concentrations of the insecticide carbaryl induced higher tolerance to a subsequent lethal concentration later in life. Interestingly, the inducible populations were located >800 m from agricultural areas and were the most susceptible to the insecticide. In contrast, the noninducible populations were located close to agricultural areas and were the least susceptible. We also found that sublethal concentrations of carbaryl induced higher tadpole AChE concentrations in several cases. This is the first study to demonstrate inducible tolerance in a vertebrate species and the pattern of inducible and constitutive tolerance among populations suggests the process of genetic assimilation. PMID:24187585

  6. Acceptability of smoke from prescribed forest burning in the northern inland west: a focus group approach

    Treesearch

    Brad R. Weisshaupt; Matthew S. Carroll; Keith A. Blatner; William D. Robinson; Pamela J. Jakes

    2005-01-01

    Focus groups were used to gauge tolerance of smoke from broadcast prescribed forest burning in the wildland-urban interface of the northern Inland West. Focus group participants worked through issues surrounding prescribed burning as a management tool to determine if the origin of smoke made a difference in the acceptance of that smoke. Participant responses across...

  7. Transcriptomic Profiling and Physiological Responses of Halophyte Kochia sieversiana Provide Insights into Salt Tolerance

    PubMed Central

    Zhao, Long; Yang, Zongze; Guo, Qiaobing; Mao, Shun; Li, Shaoqiang; Sun, Fasheng; Wang, Huan; Yang, Chunwu

    2017-01-01

    Halophytes are remarkable plants that can tolerate extremely high-salinity conditions, and have different salinity tolerance mechanisms from those of glycophytic plants. In this work, we investigated the mechanisms of salinity tolerance of an extreme halophyte, Kochia sieversiana (Pall.) C. A. M, using RNA sequencing and physiological tests. The results showed that moderate salinity stimulated the growth and water uptake of K. sieversiana and, even under 480-mM salinity condition, K. sieversiana maintained an extremely high water content. This high water content may be a specific adaptive strategy of K. sieversiana to high salinity. The physiological analysis indicated that increasing succulence and great accumulations of sodium, alanine, sucrose, and maltose may be favorable to the water uptake and osmotic regulation of K. sieversiana under high-salinity stress. Transcriptome data indicated that some aquaporin genes and potassium (K+) transporter genes may be important for water uptake and ion balance, respectively, while different members of those gene families were employed under low- and high-salinity stresses. In addition, several aquaporin genes were up-regulated in low- but not high-salinity stressed roots. The highly expressed aquaporin genes may allow low-salinity stressed K. sieversiana plants to uptake more water than control plants. The leaf K+/root K+ ratio was enhanced under low- but not high-salinity stress, which suggested that low salinity might promote K+ transport from the roots to the shoots. Hence, we speculated that low salinity might allow K. sieversiana to uptake more water and transport more K+ from roots to shoots, increasing the growth rate of K. sieversiana. PMID:29225608

  8. Assessing Children's Perceptions of Academic Interventions: The Kids Intervention Profile

    ERIC Educational Resources Information Center

    Eckert, Tanya L.; Hier, Bridget O.; Hamsho, Narmene F.; Malandrino, Rigby D.

    2017-01-01

    The psychometric properties of the Kids Intervention Profile (KIP), a rating scale designed to measure academic intervention acceptability from the perspective of students, were examined as well as the influence of background factors on students' acceptability ratings. Data were extracted from 4 randomized controlled trials investigating the…

  9. Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants: preferential localization of chimerism in donor bone

    PubMed Central

    Rahhal, Dina N.; Xu, Hong; Huang, Wei-Chao; Wu, Shengli; Wen, Yujie; Huang, Yiming; Ildstad, Suzanne T.

    2009-01-01

    Background Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTA). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. Methods WF (RT1Au) rats were conditioned with 600-300 cGy total body irradiation (TBI, day-1), 100 × 106 T cell-depleted ACI (RT1Aabl) bone marrow cells were transplanted day 0, followed by a 11-day course of tacrolimus and one dose of anti-lymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4-6 weeks after bone marrow transplantation. Results Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-αβ-TCR mAb (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-αβ-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving ≥ 300 cGy TBI plus anti-αβ-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap-acceptors lost peripheral blood (PB) chimerism within 6 months. However, donor chimerism persisted in transplanted bone at significantly higher levels compared to other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of PB chimerism. Conclusions Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA which is associated with persistent chimerism preferentially in transplanted donor bone. PMID:19920776

  10. Noise tolerant dendritic lattice associative memories

    NASA Astrophysics Data System (ADS)

    Ritter, Gerhard X.; Schmalz, Mark S.; Hayden, Eric; Tucker, Marc

    2011-09-01

    Linear classifiers based on computation over the real numbers R (e.g., with operations of addition and multiplication) denoted by (R, +, x), have been represented extensively in the literature of pattern recognition. However, a different approach to pattern classification involves the use of addition, maximum, and minimum operations over the reals in the algebra (R, +, maximum, minimum) These pattern classifiers, based on lattice algebra, have been shown to exhibit superior information storage capacity, fast training and short convergence times, high pattern classification accuracy, and low computational cost. Such attributes are not always found, for example, in classical neural nets based on the linear inner product. In a special type of lattice associative memory (LAM), called a dendritic LAM or DLAM, it is possible to achieve noise-tolerant pattern classification by varying the design of noise or error acceptance bounds. This paper presents theory and algorithmic approaches for the computation of noise-tolerant lattice associative memories (LAMs) under a variety of input constraints. Of particular interest are the classification of nonergodic data in noise regimes with time-varying statistics. DLAMs, which are a specialization of LAMs derived from concepts of biological neural networks, have successfully been applied to pattern classification from hyperspectral remote sensing data, as well as spatial object recognition from digital imagery. The authors' recent research in the development of DLAMs is overviewed, with experimental results that show utility for a wide variety of pattern classification applications. Performance results are presented in terms of measured computational cost, noise tolerance, classification accuracy, and throughput for a variety of input data and noise levels.

  11. Transcriptome assembly, profiling and differential gene expression analysis of the halophyte Suaeda fruticosa provides insights into salt tolerance.

    PubMed

    Diray-Arce, Joann; Clement, Mark; Gul, Bilquees; Khan, M Ajmal; Nielsen, Brent L

    2015-05-06

    Improvement of crop production is needed to feed the growing world population as the amount and quality of agricultural land decreases and soil salinity increases. This has stimulated research on salt tolerance in plants. Most crops tolerate a limited amount of salt to survive and produce biomass, while halophytes (salt-tolerant plants) have the ability to grow with saline water utilizing specific biochemical mechanisms. However, little is known about the genes involved in salt tolerance. We have characterized the transcriptome of Suaeda fruticosa, a halophyte that has the ability to sequester salts in its leaves. Suaeda fruticosa is an annual shrub in the family Chenopodiaceae found in coastal and inland regions of Pakistan and Mediterranean shores. This plant is an obligate halophyte that grows optimally from 200-400 mM NaCl and can grow at up to 1000 mM NaCl. High throughput sequencing technology was performed to provide understanding of genes involved in the salt tolerance mechanism. De novo assembly of the transcriptome and analysis has allowed identification of differentially expressed and unique genes present in this non-conventional crop. Twelve sequencing libraries prepared from control (0 mM NaCl treated) and optimum (300 mM NaCl treated) plants were sequenced using Illumina Hiseq 2000 to investigate differential gene expression between shoots and roots of Suaeda fruticosa. The transcriptome was assembled de novo using Velvet and Oases k-45 and clustered using CDHIT-EST. There are 54,526 unigenes; among these 475 genes are downregulated and 44 are upregulated when samples from plants grown under optimal salt are compared with those grown without salt. BLAST analysis identified the differentially expressed genes, which were categorized in gene ontology terms and their pathways. This work has identified potential genes involved in salt tolerance in Suaeda fruticosa, and has provided an outline of tools to use for de novo transcriptome analysis. The

  12. Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.

    PubMed

    Azuma, H; Isaka, Y; Li, X; Hünig, T; Sakamoto, T; Nohmi, H; Takabatake, Y; Mizui, M; Kitazawa, Y; Ichimaru, N; Ibuki, N; Ubai, T; Inamoto, T; Katsuoka, Y; Takahara, S

    2008-10-01

    The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

  13. Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.

    PubMed

    Morgan, Michael M; Christie, MacDonald J

    2011-10-01

    Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  14. Risk-Factor Profile of Living Kidney Donors: The Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry 2004-2012.

    PubMed

    Clayton, Philip A; Saunders, John R; McDonald, Stephen P; Allen, Richard D M; Pilmore, Helen; Saunder, Alan; Boudville, Neil; Chadban, Steven J

    2016-06-01

    Recent literature suggests that living kidney donation may be associated with an excess risk of end-stage kidney disease and death. Efforts to maximize access to transplantation may result in acceptance of donors who do not fit within current guidelines, potentially placing them at risk of adverse long-term outcomes. We studied the risk profile of Australian and New Zealand living kidney donors using data from the Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry over 2004 to 2012. We compared their predonation profile against national guidelines for donor acceptance. The analysis included 2,932 donors (mean age 48.8 ± 11.2 years, range 18-81), 58% female and 87% Caucasian. Forty (1%) had measured glomerular filtration rate less than 80 mL/min; 32 (1%) had proteinuria >300 mg/day; 589 (20%) were hypertensive; 495 (18%) obese; 9 (0.3%) were diabetic while a further 55 (2%) had impaired glucose tolerance; and 218 (7%) were current smokers. Overall 767 donors (26%) had at least one relative contraindication to donation and 268 (9%) had at least one absolute contraindication according to national guidelines. Divergence of current clinical practice from national guidelines has occurred. In the context of recent evidence demonstrating elevated long-term donor risk, rigorous follow-up and reporting of outcomes are now mandated to ensure safety and document any change in risk associated with such a divergence.

  15. Learning Style Profile: Examiner's Manual.

    ERIC Educational Resources Information Center

    Keefe, James W.; Monk, John S.

    This examiner's manual accompanies the Learning Style Profile (LSP), which measures cognitive skills as well as affective and environmental preferences. Charles Letteri's General Operations Model was accepted as the prototype for relating learning styles to cognitive information processing. The LSP was developed from 1983 to 1986; several versions…

  16. Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure

    PubMed Central

    Ménard, Sandie; Ben Haddou, Tanila; Ramadani, Arba Pramundita; Ariey, Frédéric; Iriart, Xavier; Beghain, Johann; Bouchier, Christiane; Witkowski, Benoit; Berry, Antoine; Mercereau-Puijalon, Odile

    2015-01-01

    Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia threatens global malaria control strategies. Whether delayed parasite clearance, which exposes larger parasite numbers to artemisinins for longer times, selects higher-grade resistance remains unexplored. We investigated whether long-lasting artemisinin pressure selects a novel multidrug-tolerance profile. Although 50% inhibitory concentrations for 10 antimalarial drugs tested were unchanged, drug-tolerant parasites showed higher recrudescence rates for endoperoxides, quinolones, and an antifolate, including partner drugs of recommended combination therapies, but remained susceptible to atovaquone. Moreover, the age range of intraerythrocytic stages able to resist artemisinin was extended to older ring forms and trophozoites. Multidrug tolerance results from drug-induced quiescence, which enables parasites to survive exposure to unrelated antimalarial drugs that inhibit a variety of metabolic pathways. This novel resistance pattern should be urgently monitored in the field because this pattern is not detected by current assays and represents a major threat to antimalarial drug policy. PMID:26401601

  17. WE-AB-207B-01: Dose Tolerance for SBRT/SABR

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

    Grimm, J

    Purpose: Stereotactic body radiation therapy (SBRT) / stereotactic ablative body radiotherapy (SABR) is gaining popularity, but quantitative dose tolerance has still been lacking. To improve this, the April 2016 issue of Seminars in Radiation Oncology will have normal tissue complication probability (NTCP) models for 10 critical structures: optic pathway, cochlea, oral mucosa, esophagus, chestwall, aorta, bronchi, duodenum, small bowel, and spinal cord. Methods: The project included more than 1500 treatments in 1–5 fractions using CyberKnife, Gamma Knife, or LINAC, with 60 authors from 15 institutions. NTCP models were constructed from the 97 grade 2–3 complications, predominantly scored using the commonmore » terminology criteria for adverse events (CTCAEv4). Dose volume histogram (DVH) data from each institutional dataset was loaded into the DVH Evaluator software (DiversiLabs, LLC, Huntingdon Valley, Pa) for modeling. The current state of the literature for the critical structures was depicted using DVH Risk Maps: comparative graphs of dose tolerance limits that can include estimated risk levels, reported complications, DVH data for study patients, as well as high- and low-risk dose tolerance limits. Results: For relatively acceptable toxicity like grade 1–3 rib fractures and chestwall pain, the high-risk limits have 50% risk and the low-risk limits have 5% risk. Emami et al (IJROBP 1991 May 15;21(1):109–22) used 50% and 5% risk levels for all structures, whereas this effort used clinically acceptable ranges for each: in structures like aorta or spinal cord where complications must be avoided, the high- and low-risk limits have about 3% and 1% risk, respectively, in this issue of Seminars. These statistically based guidelines can help ensure plan quality for each patient. Conclusion: NTCP for SBRT is now becoming available. Hypofractionated dose tolerance can be dramatically different than extrapolations of conventional fractionation so NTCP analysis

  18. Psoriasis patients' willingness to accept side-effect risks for improved treatment efficacy.

    PubMed

    Kauf, Teresa L; Yang, Jui-Chen; Kimball, Alexa B; Sundaram, Murali; Bao, Yanjun; Okun, Martin; Mulani, Parvez; Hauber, A Brett; Johnson, F Reed

    2015-01-01

    Previous studies suggest that efficacy is more important than side-effect risks to psoriasis patients. However, those studies did not consider potentially fatal risks of biologic treatments. To quantify the risks patients are willing to accept for improvements in psoriasis symptoms. Adults with a self-reported physician diagnosis of psoriasis were recruited through the National Psoriasis Foundation. Using a discrete-choice experiment, patients completed a series of nine choice questions, each including a pair of hypothetical treatments. Treatments were defined by severity of plaques, body surface area (BSA), and 10-year risks of tuberculosis, serious infection and lymphoma. For complete clearance of 25% BSA with mild plaques, respondents (n = 1608) were willing to accept a 20% (95% confidence interval: 9-26%) risk of serious infection, 10% (5-15%) risk of tuberculosis and 2% (1-3%) risk of lymphoma. For complete clearance of 25% BSA with severe plaques, respondents were willing to accept a 54% (48-62%) risk of serious infection, 36% (28-49%) risk of tuberculosis and 8% (7-9%) risk of lymphoma. Respondents were asked to evaluate hypothetical scenarios. Actual treatment choices may differ. Respondents were willing to accept risks above likely clinical exposures for improvements in psoriasis symptoms. Individual risk tolerances may vary.

  19. An environmental tolerance index for ostracodes as indicators of physical and chemical factors in aquatic habitats

    USGS Publications Warehouse

    Curry, B. Brandon

    1999-01-01

    Continental ostracode occurrences reflect salinity, solute composition, temperature, flow conditions, and other environmental properties of the water they inhabit. Their occurrences also reflect the variability of many of these environmental parameters. Environmental tolerance indices (ETIs) offer a new way to express the nature of an ostracode's environment. As defined herein, ETIs range in value from zero to one, and may be calculated for continuous and binary variables. For continuous variables such as salinity, the ETI is the ratio of the range of values of salinity tolerated by an ostracode to the total range of salinity values from a representative database. In this investigation, the database of continuous variables consists of information from 341 sites located throughout the United States. Binary ETIs indicate whether an environmental variable such as flowing water affects ostracode presence or absence. The binary database consists of information from 784 sites primarily from Illinois, USA. ETIs were developed in this investigation to interpret paleohydrological changes implied by fossil ostracode successions. ETI profiles may be cast in terms of a weighted average, or on presence/absence. The profiles express ostracode tolerance of environmental parameters such as salinity or currents. Tolerance of a wide range of values is taken to indicate shallow water because shallow environments are conducive to thermal variability, short-term water residence, and the development of currents from wind-driven waves.

  20. The cost of tolerance for violence.

    PubMed

    Sigler, R T

    1995-01-01

    Our society evinces a high tolerance for violence. This acceptance of certain forms of violent behavior is ingrained in the American value system, established through our history in the simple struggle to survive. Beginning with the colonial era, through the settlement of the western frontier, and during the wave of immigrant arrivals, Americans often used violence to establish basic rights. Sociobiological explanations of individual violent tendencies focus on genetic predisposition established through natural selection--or survival of the fittest--while psychoanalytical perspectives define extreme violence as a deviant form of natural aggression. On the other hand, criminologists define all violence as deviant. In today's society, physical force is considered to be justifiable when expressing political dissent and protecting self and property, and less so during domestic disputes.

  1. Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants: preferential localization of chimerism in donor bone.

    PubMed

    Rahhal, Dina N; Xu, Hong; Huang, Wei-Chao; Wu, Shengli; Wen, Yujie; Huang, Yiming; Ildstad, Suzanne T

    2009-09-27

    Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6) T-cell-depleted ACI (RT1A(abl)) bone marrow cells were transplanted on day 0, followed by a 11-day course of tacrolimus and one dose of antilymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4 to 6 weeks after bone marrow transplantation. Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-alphabeta-T-cell receptor (TCR) monoclonal antibody (mAb) (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-alphabeta-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving more than or equal to 300 cGy TBI plus anti-alphabeta-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap acceptors lost peripheral blood chimerism within 6 months. However, donor chimerism persisted in the transplanted bone at significantly higher levels compared with other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of peripheral blood chimerism. Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.

  2. Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

    PubMed

    Schmied, Julie; Rupa, Prithy; Garvie, Sarah; Wilkie, Bruce

    2013-07-15

    The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Analytical modeling and tolerance analysis of a linear variable filter for spectral order sorting.

    PubMed

    Ko, Cheng-Hao; Chang, Kuei-Ying; Huang, You-Min

    2015-02-23

    This paper proposes an innovative method to overcome the low production rate of current linear variable filter (LVF) fabrication. During the fabrication process, a commercial coater is combined with a local mask on a substrate. The proposed analytical thin film thickness model, which is based on the geometry of the commercial coater, is developed to more effectively calculate the profiles of LVFs. Thickness tolerance, LVF zone width, thin film layer structure, transmission spectrum and the effects of variations in critical parameters of the coater are analyzed. Profile measurements demonstrate the efficacy of local mask theory in the prediction of evaporation profiles with a high degree of accuracy.

  4. Borderline Personality Disorder and the Effects of Instructed Emotional Avoidance or Acceptance in Daily Life.

    PubMed

    Chapman, Alexander L; Rosenthal, M Zachary; Dixon-Gordon, Katherine L; Turner, Brianna J; Kuppens, Peter

    2017-08-01

    This study examined the effects of avoidance- versus acceptance-oriented emotion regulation instructions among individuals with borderline personality disorder (BPD; n = 48), major depressive disorder (MDD; n = 54), and non-psychiatric controls (NPC; n = 50) using ecological momentary assessment. Participants were randomly assigned to either accept or avoid negative emotions, and monitored their moods, urges, and distress tolerance several times per day over 6 days. Avoidance instructions resulted in reduced negative affect and urges for maladaptive behaviors uniquely among BPD participants. Together with past research, and consistent with treatment approaches emphasizing the short-term use of skills to avoid or distract from emotions (e.g., DBT; Linehan, 1993b, 2015), these findings suggest that avoidance of negative emotions may have temporary benefits for individuals with BPD. Acceptance-oriented strategies may take longer or may require more extensive training to be beneficial for emotional functioning in everyday life in BPD.

  5. Abundance of Plasma Antioxidant Proteins Confers Tolerance to Acute Hypobaric Hypoxia Exposure

    PubMed Central

    Padhy, Gayatri; Sethy, Niroj Kumar; Ganju, Lilly

    2013-01-01

    Abstract Padhy, Gayatri, Niroj Kumar Sethy, Lilly Ganju, and Kalpana Bhargava. Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure. High Alt Med Biol 14:289–297, 2013—Systematic identification of molecular signatures for hypobaric hypoxia can aid in better understanding of human adaptation to high altitude. In an attempt to identify proteins promoting hypoxia tolerance during acute exposure to high altitude, we screened and identified hypoxia tolerant and susceptible rats based on hyperventilation time to a simulated altitude of 32,000 ft (9754 m). The hypoxia tolerance was further validated by estimating 8-isoprotane levels and protein carbonyls, which revealed that hypoxia tolerant rats possessed significant lower plasma levels as compared to susceptible rats. We used a comparative plasma proteome profiling approach using 2-dimensional gel electrophoresis (2-DGE) combined with MALDI TOF/TOF for both groups, along with an hypoxic control group. This resulted in the identification of 19 differentially expressed proteins. Seven proteins (TTR, GPx-3, PON1, Rab-3D, CLC11, CRP, and Hp) were upregulated in hypoxia tolerant rats, while apolipoprotein A-I (APOA1) was upregulated in hypoxia susceptible rats. We further confirmed the consistent higher expression levels of three antioxidant proteins (PON1, TTR, and GPx-3) in hypoxia-tolerant animals using ELISA and immunoblotting. Collectively, these proteomics-based results highlight the role of antioxidant enzymes in conferring hypoxia tolerance during acute hypobaric hypoxia. The expression of these antioxidant enzymes could be used as putative biomarkers for screening altitude adaptation as well as aiding in better management of altered oxygen pathophysiologies. PMID:24067188

  6. Anastatica hierochuntica, an Arabidopsis Desert Relative, Is Tolerant to Multiple Abiotic Stresses and Exhibits Species-Specific and Common Stress Tolerance Strategies with Its Halophytic Relative, Eutrema (Thellungiella) salsugineum

    PubMed Central

    Eshel, Gil; Shaked, Ruth; Kazachkova, Yana; Khan, Asif; Eppel, Amir; Cisneros, Aroldo; Acuna, Tania; Gutterman, Yitzhak; Tel-Zur, Noemi; Rachmilevitch, Shimon; Fait, Aaron; Barak, Simon

    2017-01-01

    The search for novel stress tolerance determinants has led to increasing interest in plants native to extreme environments – so called “extremophytes.” One successful strategy has been comparative studies between Arabidopsis thaliana and extremophyte Brassicaceae relatives such as the halophyte Eutrema salsugineum located in areas including cold, salty coastal regions of China. Here, we investigate stress tolerance in the desert species, Anastatica hierochuntica (True Rose of Jericho), a member of the poorly investigated lineage III Brassicaceae. We show that A. hierochuntica has a genome approximately 4.5-fold larger than Arabidopsis, divided into 22 diploid chromosomes, and demonstrate that A. hierochuntica exhibits tolerance to heat, low N and salt stresses that are characteristic of its habitat. Taking salt tolerance as a case study, we show that A. hierochuntica shares common salt tolerance mechanisms with E. salsugineum such as tight control of shoot Na+ accumulation and resilient photochemistry features. Furthermore, metabolic profiling of E. salsugineum and A. hierochuntica shoots demonstrates that the extremophytes exhibit both species-specific and common metabolic strategies to cope with salt stress including constitutive up-regulation (under control and salt stress conditions) of ascorbate and dehydroascorbate, two metabolites involved in ROS scavenging. Accordingly, A. hierochuntica displays tolerance to methyl viologen-induced oxidative stress suggesting that a highly active antioxidant system is essential to cope with multiple abiotic stresses. We suggest that A. hierochuntica presents an excellent extremophyte Arabidopsis relative model system for understanding plant survival in harsh desert conditions. PMID:28144244

  7. Simulation studies on the effect of positioning tolerances on optical coupling efficiency

    NASA Astrophysics Data System (ADS)

    Pamidighantam, Ramana V.; Yeo, Yongkee; Sudharsanam, Krishnamachari; Lee, Sik Pong; Iyer, Mahadevan K.

    2002-08-01

    The development of Optoelectronic components for communications is converging towards access networks where device cost makes a significant impact on the market acceptance. Thus, the device design engineer needs to input assembly, fabrication and process constraints into the design at an early stage. The present study is part of a Project on Packaging of Optical Components that IME, Singapore has initiated as part of an ongoing Electronics Packaging Research Consortium with industry partnership. In the present study, the coupling of optical radiation from a laser diode to optical fiber is simulated for a fiber optic transmitter component development project. Different optical configurations based on direct coupling, spherical ball lenses, integral lensed fibers and thermally expanded fibers are created within the commercially available transmitter package space. The effect of optical element variables on the placement tolerance is analyzed and will be reported. The effect of alignment tolerances on the optical coupling is analyzed. Simulation results are presented recommending realizable alignment and placement tolerances to develop a low cost short range link distance transmitter.

  8. Establishment of an equivalence acceptance criterion for accelerated stability studies.

    PubMed

    Burdick, Richard K; Sidor, Leslie

    2013-01-01

    In this article, the use of statistical equivalence testing for providing evidence of process comparability in an accelerated stability study is advocated over the use of a test of differences. The objective of such a study is to demonstrate comparability by showing that the stability profiles under nonrecommended storage conditions of two processes are equivalent. Because it is difficult at accelerated conditions to find a direct link to product specifications, and hence product safety and efficacy, an equivalence acceptance criterion is proposed that is based on the statistical concept of effect size. As with all statistical tests of equivalence, it is important to collect input from appropriate subject-matter experts when defining the acceptance criterion.

  9. Systemic nature of drought-tolerance in common bean.

    PubMed

    Montero-Tavera, Víctor; Ruiz-Medrano, Roberto; Xoconostle-Cázares, Beatriz

    2008-09-01

    The response to drought at the physiological and molecular levels was studied in two common bean varieties with contrasting susceptibility to drought stress. A number of genes were found to be upregulated in the tolerant variety Pinto Villa relative to the susceptible cultivar, Carioca. The products of these genes fell in different functional categories. Further analyses of selected genes, consisting of their spatial differential expression and in situ mRNA accumulation patterns displayed interesting profiles. The drought-tolerant variety displayed a more developed root vasculature in drought conditions, when compared to the susceptible tropical bean Carioca. The in situ localization of three selected genes indicated the accumulation of their corresponding mRNAs in companion cells, sieve tubes and in developing phloem, suggesting that these, and/or the encoded proteins could constitute phloem-mobile signals. Indeed, a number of transcripts that are induced in response to water deficit accumulate in the phloem in other plant species, suggesting a general phenomenon. Moreover, the analysis of drought stress in plant varieties with contrasting tolerance to such stimulus will help to determine the role of differential expression of specific genes in response to such phenomenon, as well as other biochemical, morphological and physiological features in both cultivars.Drought-tolerant plants likely evolved a system that would allow them to maintain its vascular tissue integrity under stress. A functional phloem would then still function in the transmission of long-range signals, important for the systemic adaptation to the stress. It is expected that plants showing increased tolerance to abiotic stress, such as drought, are able to better protect their conductive tissues. This general strategy might help such plants evolve under stress conditions and colonize successfully new habitats.

  10. [Tolerance in transplantation: potential contribution of haematopoietic transplantation and cell therapy].

    PubMed

    Kleinclauss, François; Bittard, Hugues; Perruche, Sylvain; de Carvalho-Bittencourt, Marcello; Chalopin, Jean-Marc; Hervé, Patrick; Tiberghien, Pierre; Saas, Philippe

    2003-12-01

    The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.

  11. Directionality Between Tolerance of Deviance and Deviant Behavior is Age-Moderated in Chronically Stressed Youth

    PubMed Central

    Ridenour, TY A.; Caldwell, Linda L.; Coatsworth, J. Douglas; Gold, Melanie A.

    2011-01-01

    Problem behavior theory posits that tolerance of deviance is an antecedent to antisocial behavior and substance use. In contrast, cognitive dissonance theory implies that acceptability of a behavior may increase after experiencing the behavior. Using structural equation modeling, this investigation tested whether changes in tolerance of deviance precede changes in conduct disorder criteria or substance use or vice versa, or if they change concomitantly. Two-year longitudinal data from 246 8- to 16-year-olds suggested that tolerance of deviance increases after conduct disorder criteria or substance use in 8-to-10- and 11-to-12-year-olds. These results were consistent with cognitive dissonance theory. In 13-to-16- year-olds, no directionality was suggested, consistent with neither theory. These results were replicated in boys and girls and for different types of conduct disorder criteria aggression (covert behavior), deceitfulness and vandalism (overt behavior), and serious rule-breaking (authority conflict). The age-specific directionality between tolerance of deviance and conduct disorder criteria or substance use is consistent with unique etiologies between early onset versus adolescent-onset subtypes of behavior problems. PMID:22180721

  12. Directionality Between Tolerance of Deviance and Deviant Behavior is Age-Moderated in Chronically Stressed Youth.

    PubMed

    Ridenour, Ty A; Caldwell, Linda L; Coatsworth, J Douglas; Gold, Melanie A

    2011-03-20

    Problem behavior theory posits that tolerance of deviance is an antecedent to antisocial behavior and substance use. In contrast, cognitive dissonance theory implies that acceptability of a behavior may increase after experiencing the behavior. Using structural equation modeling, this investigation tested whether changes in tolerance of deviance precede changes in conduct disorder criteria or substance use or vice versa, or if they change concomitantly. Two-year longitudinal data from 246 8- to 16-year-olds suggested that tolerance of deviance increases after conduct disorder criteria or substance use in 8-to-10- and 11-to-12-year-olds. These results were consistent with cognitive dissonance theory. In 13-to-16- year-olds, no directionality was suggested, consistent with neither theory. These results were replicated in boys and girls and for different types of conduct disorder criteria aggression (covert behavior), deceitfulness and vandalism (overt behavior), and serious rule-breaking (authority conflict). The age-specific directionality between tolerance of deviance and conduct disorder criteria or substance use is consistent with unique etiologies between early onset versus adolescent-onset subtypes of behavior problems.

  13. Risk perception and public acceptance toward a highly protested Waste-to-Energy facility.

    PubMed

    Ren, Xiangyu; Che, Yue; Yang, Kai; Tao, Yun

    2016-02-01

    The application of Waste-to-Energy treatment in Municipal Solid Waste faces strong protest by local communities, especially in cities with high population densities. This study introduces insight into the public awareness, acceptance and risk perception toward Waste-to-Energy through a structured questionnaire survey around a Waste-to-Energy facility in Shanghai, China. The Dichotomous-Choice contingent valuation method was applied to study the willingness to accept of residents as an indicator of risk perception and tolerance. The factors influencing risk perception and the protest response choice were analyzed. The geographical distributions of the acceptance of Waste-to-Energy facility and protest response were explored using geographical information systems. The findings of the research indicated an encouraging vision of promoting Waste-to-Energy, considering its benefits of renewable energy and the conservation of land. A high percentage of protest willingness to accept (50.94%) was highlighted with the effect of income, opinion about Waste-to-Energy, gender and perceived impact. The fuzzy classification among people with different opinions on compensation (valid 0, positive or protest willingness to accept) revealed the existing yet rejected demand of compensation among protesters. Geographical distribution in the public attitude can also be observed. Finally significant statistical relation between knowledge and risk perception indicates the need of risk communication, as well as involving public into whole management process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A first-line nurse manager's goal-profile.

    PubMed

    Johansson, Gunilla; Pörn, Ingmar; Theorell, Töres; Gustafsson, Barbro

    2007-01-01

    The aim of this case study was to acquire understanding concerning the first-line nurse manager's goal-profile, i.e. prioritization of goals in her work as a first-line nurse manager, through use of an action-theoretic and confirmatory theory. The first-line nurse manager's pivotal role regarding quality of care and development in relation to on-going changes in the health care sector is stressed by many researchers and the transition from nurse to manager is described as a demanding challenge for the first-line nurse manager. The case study described in this paper concerns a first-line nurse manager in an actual working environment in care of older people. Data collection comprised interviews, observations, a job description and policy documents. A hermeneutic interpretation was used for data analysis. The results showed that the first-line nurse manager had three goals in her goal-profile, in the following order of priority: (i) a nurse goal that she had strongly accepted and in which she had excellent control, (ii) an administrator goal that she had accepted and in which she had control, (iii) a leadership goal that she had not accepted and in which she did not have control. Both the administrator and leadership goals were based on her job description, but the nurse goal was a personally chosen goal based on her own self-relation/goal-fulfillment. The first-line nurse manager's prioritized self-identity, based on successful realization of goals in her goal-profile, was decisive in the manifestation of her work. This study contributes to a new understanding of the first-line nurse manager's self-identity related to work in terms of goal acceptance and goal control of prioritized goals. This action-theoretic approach could be a valuable 'key' for understanding leadership (or lack of leadership) in clinical practice.

  15. Long-Term Tolerance Towards Haploidentical Vascularized Composite Allograft Transplantation in a Canine Model Using Bone Marrow or Mobilized Stem Cells

    PubMed Central

    Chang, Jeff; Graves, Scott S.; Butts-Miwongtum, Tiffany; Sale, George E.; Storb, Rainer; Mathes, David W.

    2017-01-01

    Background The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen (DLA) identical donor. In the present study, we extend those findings across a DLA mismatched barrier. Methods Eight Recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n=4) or granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (n=4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days). Results In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5–7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease (GVHD) while 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance towards its VCA (>90 weeks). Conclusion The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance towards the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared to marrow HCT and an increase in the incidence of GVHD. PMID:27861292

  16. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    PubMed Central

    Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

    2017-01-01

    Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

  17. Genotypes Associated with Listeria monocytogenes Isolates Displaying Impaired or Enhanced Tolerances to Cold, Salt, Acid, or Desiccation Stress

    PubMed Central

    Hingston, Patricia; Chen, Jessica; Dhillon, Bhavjinder K.; Laing, Chad; Bertelli, Claire; Gannon, Victor; Tasara, Taurai; Allen, Kevin; Brinkman, Fiona S. L.; Truelstrup Hansen, Lisbeth; Wang, Siyun

    2017-01-01

    The human pathogen Listeria monocytogenes is a large concern in the food industry where its continuous detection in food products has caused a string of recalls in North America and Europe. Most recognized for its ability to grow in foods during refrigerated storage, L. monocytogenes can also tolerate several other food-related stresses with some strains possessing higher levels of tolerances than others. The objective of this study was to use a combination of phenotypic analyses and whole genome sequencing to elucidate potential relationships between L. monocytogenes genotypes and food-related stress tolerance phenotypes. To accomplish this, 166 L. monocytogenes isolates were sequenced and evaluated for their ability to grow in cold (4°C), salt (6% NaCl, 25°C), and acid (pH 5, 25°C) stress conditions as well as survive desiccation (33% RH, 20°C). The results revealed that the stress tolerance of L. monocytogenes is associated with serotype, clonal complex (CC), full length inlA profiles, and the presence of a plasmid which was identified in 55% of isolates. Isolates with full length inlA exhibited significantly (p < 0.001) enhanced cold tolerance relative to those harboring a premature stop codon (PMSC) in this gene. Similarly, isolates possessing a plasmid demonstrated significantly (p = 0.013) enhanced acid tolerance. We also identified nine new L. monocytogenes sequence types, a new inlA PMSC, and several connections between CCs and the presence/absence or variations of specific genetic elements. A whole genome single-nucleotide-variants phylogeny revealed sporadic distribution of tolerant isolates and closely related sensitive and tolerant isolates, highlighting that minor genetic differences can influence the stress tolerance of L. monocytogenes. Specifically, a number of cold and desiccation sensitive isolates contained PMSCs in σB regulator genes (rsbS, rsbU, rsbV). Collectively, the results suggest that knowing the sequence type of an isolate in

  18. Bridging the Gap between Social Acceptance and Ethical Acceptability.

    PubMed

    Taebi, Behnam

    2017-10-01

    New technology brings great benefits, but it can also create new and significant risks. When evaluating those risks in policymaking, there is a tendency to focus on social acceptance. By solely focusing on social acceptance, we could, however, overlook important ethical aspects of technological risk, particularly when we evaluate technologies with transnational and intergenerational risks. I argue that good governance of risky technology requires analyzing both social acceptance and ethical acceptability. Conceptually, these two notions are mostly complementary. Social acceptance studies are not capable of sufficiently capturing all the morally relevant features of risky technologies; ethical analyses do not typically include stakeholders' opinions, and they therefore lack the relevant empirical input for a thorough ethical evaluation. Only when carried out in conjunction are these two types of analysis relevant to national and international governance of risky technology. I discuss the Rawlsian wide reflective equilibrium as a method for marrying social acceptance and ethical acceptability. Although the rationale of my argument is broadly applicable, I will examine the case of multinational nuclear waste repositories in particular. This example will show how ethical issues may be overlooked if we focus only on social acceptance, and will provide a test case for demonstrating how the wide reflective equilibrium can help to bridge the proverbial acceptance-acceptability gap. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

  19. Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

    PubMed

    Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

    2014-10-01

    Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation

    PubMed Central

    Mahr, Benedikt; Granofszky, Nicolas; Muckenhuber, Moritz; Wekerle, Thomas

    2017-01-01

    The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing graft-vs.-host disease (GVHD) constitute the most prohibitive hurdles. However, several approaches have recently been developed at the experimental level to reduce or even overcome the necessity for cytoreductive conditioning, such as costimulation blockade, pro-apoptotic drugs, or Treg therapy. But even in the absence of any hazardous pretreatment, the recipients are exposed to the risk of developing GVHD as long as non-tolerant donor T cells are present. Total lymphoid irradiation and enriching the stem cell graft with facilitating cells emerged as potential strategies to reduce this peril. On the other hand, the long-lasting survival of kidney allografts, seen with transient chimerism in some clinical series, questions the need for durable chimerism for robust tolerance. From a safety point of view, loss of chimerism would indeed be favorable as it eliminates the risk of GVHD, but also complicates the assessment of tolerance. Therefore, other biomarkers are warranted to monitor tolerance and to identify those patients who can safely be weaned off immunosuppression. In addition to these safety concerns, the limited efficacy of the current pilot trials with approximately 40–60% patients becoming tolerant remains an important issue that needs to be resolved. Overall, the road ahead to clinical routine may still be rocky but the first successful long-term patients and progress

  1. Profitability and acceptability of fat- and sodium-modified hot entrees in a worksite cafeteria.

    PubMed

    Perlmutter, C A; Canter, D D; Gregoire, M B

    1997-04-01

    To compare the acceptability of fat- and sodium-modified entrees before and after implementation of a marketing program and to determine the effect offering and marketing these healthful entrees had on total cafeteria and entree sales in a worksite cafeteria. The research was conducted in five phases, including sales data collection, acceptance testing of unmodified hot entrees, acceptance testing of modified entrees, and implementation of a marketing campaign for promoting low-fat, sodium-controlled food selections. The Kansas Farm Bureau and Affiliated Services (KFB) employee cafeteria. KFB employees who ate lunch in the employee cafeteria and were willing to participate in the study. Sales data (percent of customers purchasing a modified entree and sales of modified entree as a percent of total sales); nutrient analysis data (energy, grams of total fat, percent of energy from fat, milligrams of cholesterol, and milligrams of sodium); and acceptability data (11 characteristics were measured using a seven-point hedonic scale). General linear model analysis of variance was used to compare sales data from phases 1 to 5 and to compare acceptability data from phases 2 to 4. No significant differences in sales data were observed during the 7-month study. No significant changes in overall acceptability were found for any entree. However, customers tended to rate overall acceptability higher when entrees were marketed as lower in fat and sodium. Customers in worksite cafeterias may be more willing to tolerate changes in flavor attributes when modified entrees are marketed as "healthful" and nutrition information is available.

  2. A Log-Scaling Fault Tolerant Agreement Algorithm for a Fault Tolerant MPI

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

    Hursey, Joshua J; Naughton, III, Thomas J; Vallee, Geoffroy R

    The lack of fault tolerance is becoming a limiting factor for application scalability in HPC systems. The MPI does not provide standardized fault tolerance interfaces and semantics. The MPI Forum's Fault Tolerance Working Group is proposing a collective fault tolerant agreement algorithm for the next MPI standard. Such algorithms play a central role in many fault tolerant applications. This paper combines a log-scaling two-phase commit agreement algorithm with a reduction operation to provide the necessary functionality for the new collective without any additional messages. Error handling mechanisms are described that preserve the fault tolerance properties while maintaining overall scalability.

  3. Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing.

    PubMed

    Lee, Mei-Chong Wendy; Lopez-Diaz, Fernando J; Khan, Shahid Yar; Tariq, Muhammad Akram; Dayn, Yelena; Vaske, Charles Joseph; Radenbaugh, Amie J; Kim, Hyunsung John; Emerson, Beverly M; Pourmand, Nader

    2014-11-04

    The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy.

  4. Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing

    PubMed Central

    Lee, Mei-Chong Wendy; Lopez-Diaz, Fernando J.; Khan, Shahid Yar; Tariq, Muhammad Akram; Dayn, Yelena; Vaske, Charles Joseph; Radenbaugh, Amie J.; Kim, Hyunsung John; Emerson, Beverly M.; Pourmand, Nader

    2014-01-01

    The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy. PMID:25339441

  5. Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

    PubMed Central

    Smarr, Charles B.; Bryce, Paul J.; Miller, Stephen D.

    2013-01-01

    Allergic diseases are an increasing health concern, particularly in the developed world. The standard clinical approach to treatment of allergic disease focuses on allergen avoidance and symptom control but does little to address the underlying Th2 bias of disease. Specific immunotherapy (SIT) consisting of controlled administration of allergen, however, has been demonstrated to successfully induce desensitization and tolerance in an antigen-specific manner for a variety of Th2-mediated diseases. This review focuses on the mechanisms by which current SIT approaches induce tolerance as well as discussing attempts to modify the safety and efficacy of SIT. These refinements focus on three major aspects of SIT: the route of antigen administration, modification of the antigen to remove allergenic epitopes and reduce adverse events and choice of adjuvant used to induce tolerance and/or immune deviation from Th2 to Th1 and regulatory T cell (Treg) phenotypes. Synthesis of these recent developments in SIT provides considerable promise for more robust therapies with improved safety profiles to improve resolution of allergic disease and its associated costs. PMID:24099300

  6. Facial profile esthetics in operated children with bilateral cleft lip and palate

    PubMed Central

    Lauris, Rita de Cássia Moura Carvalho; Capelozza, Leopoldino; Calil, Louise Resti; Lauris, José Roberto Pereira; Janson, Guilherme; Garib, Daniela Gamba

    2017-01-01

    ABSTRACT Objective: The aim of this study was to evaluate the facial profile esthetics of rehabilitated children with complete bilateral cleft lip and palate (BCLP), comparing the judgment of professionals related and not related to cleft rehabilitation and laypersons. Methods: Thirty children in the mixed dentition (24 male; 6 female) with a mean age of 7.8 years were evaluated using facial profile photographs by 25 examiners: 5 orthodontists and 5 plastic surgeons with experience in cleft care, 5 orthodontists and 5 plastic surgeons without experience in oral cleft rehabilitation and 5 graduated laymen. Their facial profiles were classified into esthetically unpleasant (grade 1 to 3), esthetically acceptable (grade 4 to 6), and esthetically pleasant (grade 7 to 9). Intraexaminer and interexaminer errors were evaluated using Spearman correlation coefficient and Kendall’s test, respectively. Inter-rater differences were analyzed using Friedman test and Student-Newman-Keuls test for multiple comparisons. Results: Orthodontists dealing with oral clefts rehabilitation considered the majority of the sample as esthetically pleasant. Plastic surgeons of the cleft team and laypersons classified most of the sample as esthetically acceptable. Most of the orthodontists and plastic surgeons not related to cleft care evaluated the facial profile as esthetically unpleasant. The structures associated to unpleasant profiles were the nose, the midface and the upper lip. Conclusions: The facial profile of children with BCLP was classified as esthetically acceptable by laypersons. Professionals related to cleft rehabilitation were more lenient and those not related to cleft care were stricter to facial esthetics than laypersons. PMID:28902248

  7. Transcriptome profiling of Kentucky bluegrass (Poa pratensis L.) accessions in response to salt stress.

    PubMed

    Bushman, B Shaun; Amundsen, Keenan L; Warnke, Scott E; Robins, Joseph G; Johnson, Paul G

    2016-01-13

    Kentucky bluegrass (Poa pratensis L.) is a prominent turfgrass in the cool-season regions, but it is sensitive to salt stress. Previously, a relatively salt tolerant Kentucky bluegrass accession was identified that maintained green colour under consistent salt applications. In this study, a transcriptome study between the tolerant (PI 372742) accession and a salt susceptible (PI 368233) accession was conducted, under control and salt treatments, and in shoot and root tissues. Sample replicates grouped tightly by tissue and treatment, and fewer differentially expressed transcripts were detected in the tolerant PI 372742 samples compared to the susceptible PI 368233 samples, and in root tissues compared to shoot tissues. A de novo assembly resulted in 388,764 transcripts, with 36,587 detected as differentially expressed. Approximately 75 % of transcripts had homology based annotations, with several differences in GO terms enriched between the PI 368233 and PI 372742 samples. Gene expression profiling identified salt-responsive gene families that were consistently down-regulated in PI 372742 and unlikely to contribute to salt tolerance in Kentucky bluegrass. Gene expression profiling also identified sets of transcripts relating to transcription factors, ion and water transport genes, and oxidation-reduction process genes with likely roles in salt tolerance. The transcript assembly represents the first such assembly in the highly polyploidy, facultative apomictic Kentucky bluegrass. The transcripts identified provide genetic information on how this plant responds to and tolerates salt stress in both shoot and root tissues, and can be used for further genetic testing and introgression.

  8. Resiliency Scales for Children and Adolescents: Profiles of Juvenile Offenders

    ERIC Educational Resources Information Center

    Mowder, Melissa H.; Cummings, Jack A.; McKinney, Robert

    2010-01-01

    An exploratory study of resiliency profiles of male and female juvenile offenders committed to a juvenile correctional facility was conducted. The goal of the present study was to examine juvenile offenders' positive characteristics (e.g., adaptability, optimism, self-efficacy, tolerance of differences). To assess positive characteristics and…

  9. Radiation tolerant 1 micron CMOS technology

    NASA Astrophysics Data System (ADS)

    Crevel, P.; Rodde, K.

    1991-03-01

    Starting from a standard one micron Complementary Metal Oxide Semiconductor (CMOS) for high density, low power memory applications, the degree of radiation tolerance of the baseline process is evaluated. Implemented process modifications to improve latchup sensitivity under heavy ion irradiation as well as total dose effects without changing layout rules are described. By changing doping profiles in Metal Nitride Oxide Semiconductors (MNOS) and P-channel MOS (PMOS) device regions, it is possible to guarantee data sheet specification of a 64 K low power static RAM for total gamma dose up to 35 krad (Si) (and even higher values for the gate array family) without latch up for Linear Energy Transfer LET up to 115 MeV/(mg/cm squared).

  10. Persistence of antigen is required to maintain transplantation tolerance induced by genetic modification of bone marrow stem cells.

    PubMed

    Tian, C; Bagley, J; Iacomini, J

    2006-09-01

    Genetic modification of hematopoietic stem cells (HSCs) resulting in a state of molecular chimerism can be used to induce donor-specific tolerance to allografts. However, the requirements for maintaining tolerance in molecular chimeras remain unknown. Here, we examined whether long-term expression of a retrovirally encoded alloantigen in hematopoietic cells is required to maintain donor-specific tolerance in molecular chimeras. To this end, mice were reconstituted with syngeneic bone marrow transduced with retroviruses carrying the gene encoding the allogeneic MHC class I molecule Kb. Following induction of molecular chimerism, mice were depleted of cells expressing Kb by administration of the anti-Kb monoclonal antibody Y-3. Mice that were effectively depleted of cells expressing the retrovirally encoded MHC class I antigen rejected Kb disparate skin allografts. In contrast, control molecular chimeras accepted Kb disparate skin allografts indefinitely. These data suggest maintenance of tolerance in molecular chimeras requires long-term expression of retrovirally transduced alloantigen on the progeny of retrovirally transduced HSCs.

  11. Coping with Pain in the Motivational Context of Values: Comparison between an Acceptance-Based and a Cognitive Control-Based Protocol

    ERIC Educational Resources Information Center

    Paez-Blarrina, Marisa; Luciano, Carmen; Gutierrez-Martinez, Olga; Valdivia, Sonsoles; Rodriguez-Valverde, Miguel; Ortega, Jose

    2008-01-01

    This study compares the effect of an acceptance-based protocol (ACT) and a cognitive control-based (CONT) protocol on three measures of pain coping: tolerance, self-report, and believability. Specific methodological controls were employed to further isolate the role of the value of participating in a pain task, compared to previous investigations…

  12. Stress tolerant virulent strains of Cronobacter sakazakii from food.

    PubMed

    Fakruddin, Md; Rahaman, Mizanur; Ahmed, Monzur Morshed; Hoque, Md Mahfuzul

    2014-11-25

    Cronobacter sakazakii is considered as an emerging foodborne pathogen. The aim of this study was to isolate and characterize virulent strains of Cronobacter sakazakii from food samples of Bangladesh. Six (6) Cronobacter sakazakii was isolated and identified from 54 food samples on the basis of biochemical characteristics, sugar fermentation, SDS-PAGE of whole cell protein, plasmid profile and PCR of Cronobacter spp. specific genes (esak, gluA, zpx, ompA, ERIC, BOX-AIR) and sequencing. These strains were found to have moderately high antibiotic resistance against common antibiotics and some are ESBL producer. Most of the C. sakazakii isolates were capable of producing biofilm (strong biofilm producer), extracellular protease and siderophores, curli expression, haemolysin, haemagglutinin, mannose resistant haemagglutinin, had high cell surface hydrophobicity, significant resistance to human serum, can tolerate high concentration of salt, bile and DNase production. Most of them produced enterotoxins of different molecular weight. The isolates pose significant serological cross-reactivity with other gram negative pathogens such as serotypes of Salmonella spp., Shigella boydii, Shigella sonnei, Shigella flexneri and Vibrio cholerae. They had significant tolerance to high temperature, low pH, dryness and osmotic stress. Special attention should be given in ensuring hygiene in production and post-processing to prevent contamination of food with such stress-tolerant virulent Cronobacter sakazakii.

  13. Network-Based Identification of Adaptive Pathways in Evolved Ethanol-Tolerant Bacterial Populations

    PubMed Central

    Swings, Toon; Weytjens, Bram; Schalck, Thomas; Bonte, Camille; Verstraeten, Natalie; Michiels, Jan

    2017-01-01

    Abstract Efficient production of ethanol for use as a renewable fuel requires organisms with a high level of ethanol tolerance. However, this trait is complex and increased tolerance therefore requires mutations in multiple genes and pathways. Here, we use experimental evolution for a system-level analysis of adaptation of Escherichia coli to high ethanol stress. As adaptation to extreme stress often results in complex mutational data sets consisting of both causal and noncausal passenger mutations, identifying the true adaptive mutations in these settings is not trivial. Therefore, we developed a novel method named IAMBEE (Identification of Adaptive Mutations in Bacterial Evolution Experiments). IAMBEE exploits the temporal profile of the acquisition of mutations during evolution in combination with the functional implications of each mutation at the protein level. These data are mapped to a genome-wide interaction network to search for adaptive mutations at the level of pathways. The 16 evolved populations in our data set together harbored 2,286 mutated genes with 4,470 unique mutations. Analysis by IAMBEE significantly reduced this number and resulted in identification of 90 mutated genes and 345 unique mutations that are most likely to be adaptive. Moreover, IAMBEE not only enabled the identification of previously known pathways involved in ethanol tolerance, but also identified novel systems such as the AcrAB-TolC efflux pump and fatty acids biosynthesis and even allowed to gain insight into the temporal profile of adaptation to ethanol stress. Furthermore, this method offers a solid framework for identifying the molecular underpinnings of other complex traits as well. PMID:28961727

  14. Microarray-assisted fine-mapping of quantitative trait loci for cold tolerance in rice.

    PubMed

    Liu, Fengxia; Xu, Wenying; Song, Qian; Tan, Lubin; Liu, Jiayong; Zhu, Zuofeng; Fu, Yongcai; Su, Zhen; Sun, Chuanqing

    2013-05-01

    Many important agronomic traits, including cold stress resistance, are complex and controlled by quantitative trait loci (QTLs). Isolation of these QTLs will greatly benefit the agricultural industry but it is a challenging task. This study explored an integrated strategy by combining microarray with QTL-mapping in order to identify cold-tolerant QTLs from a cold-tolerant variety IL112 at early-seedling stage. All the early seedlings of IL112 survived normally for 9 d at 4-5°C, while Guichao2 (GC2), an indica cultivar, died after 4 d under the same conditions. Using the F2:3 population derived from the progeny of GC2 and IL112, we identified seven QTLs for cold tolerance. Furthermore, we performed Affymetrix rice whole-genome array hybridization and obtained the expression profiles of IL112 and GC2 under both low-temperature and normal conditions. Four genes were selected as cold QTL-related candidates, based on microarray data mining and QTL-mapping. One candidate gene, LOC_Os07g22494, was shown to be highly associated with cold tolerance in a number of rice varieties and in the F2:3 population, and its overexpression transgenic rice plants displayed strong tolerance to low temperature at early-seedling stage. The results indicated that overexpression of this gene (LOC_Os07g22494) could increase cold tolerance in rice seedlings. Therefore, this study provides a promising strategy for identifying candidate genes in defined QTL regions.

  15. Enhancing expression of SSU1 genes in Saccharomyces uvarum leads to an increase in sulfite tolerance and a transcriptome profile change.

    PubMed

    Liu, X Z; Sang, M; Zhang, X A; Zhang, T K; Zhang, H Y; He, X; Li, S X; Sun, X D; Zhang, Z M

    2017-05-01

    Saccharomyces uvarum is a good wine yeast species that may have great potential for the future. However, sulfur tolerance of most S. uvarum strains is very poor. In addition there is still little information about the SSU1 gene of S. uvarum, which encodes a putative transporter conferring sulfite tolerance. In order to analyze the function of the SSU1 gene, two expression vectors that contained different SSU1 genes were constructed and transferred into a sulfite-tolerant S. uvarum strain, A9. Then sulfite tolerance, SO2 production, and PCR, sequencing, RT-qPCR and transcriptome analyses were used to access the function of the S. uvarum SSU1 gene. Our results illustrated that enhancing expression of the SSU1 gene can promote sulfite resistance in S. uvarum, and an insertion fragment ahead of the additional SSU1 gene, as seen in some alleles, could affect the expression of other genes and the sulfite tolerance level of S. uvarum. This is the first report on enhancing the expression of the SSU1 gene of S. uvarum. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Physiological performance and differential expression profiling of genes associated with drought tolerance in contrasting varieties of two Gossypium species.

    PubMed

    Singh, Ruchi; Pandey, Neha; Naskar, Jishnu; Shirke, Pramod A

    2015-03-01

    Cotton is mostly cultivated under rain-fed conditions in India, thus faces frequent drought conditions during its life cycle. Drought being a major stress factor responsible for yield penalty, there has always been a high priority to generate knowledge on adaptation and tolerance of cotton. In the present study, four cotton varieties, JKC-770 and KC-2 (Gossypium hirsutum), and JKC-717 and RAHS-187(Gossypium herbaceum), were imposed to drought. Under drought condition, differential changes in physiological characters like net photosynthesis, transpiration, stomatal conductance, chlorophyll fluorescence, relative water content (RWC), and predawn water potential (ψ 0) showed a change. While proline, malondialdehyde (MDA), and glutathione-S-transferase (GST) content increased along with a concomitant change in the expression of their associated genes. Under moderate stress, tolerant varieties maintain lower ψ 0 probably due to higher proline content as compared to sensitive varieties. Cyclic electron flow (CEF) also plays an important role in tolerance under mild water stress in G. hirsutum varieties. CEF not only activates at high light but also initiates at a very low light intensity. Expression analysis of genes reveals that drought-tolerant varieties showed enhanced detoxifying mechanism by up-regulation of asparagine synthase (AS), glutathione-S-transferase (GST), and methyl glyoxalase (GlyI) genes under drought stress. Up-regulation of Δ(1)-pyrroline-5-carboxylase synthase (Δ(1)P5CS) enhanced accumulation of proline, an osmolyte, under drought in tolerant varieties. While the drought-sensitive varieties showed up-regulation of ethylene responsive factor (ERF) and down-regulation of WRKY70 responsible for senescence of the leaf which correlated well with the high rate of leaf fall in sensitive varieties under water stress.

  17. Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

    PubMed Central

    Morgan, Michael M; Christie, MacDonald J

    2011-01-01

    Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21434879

  18. Deception in medical and behavioral research: is it ever acceptable?

    PubMed

    Wendler, D

    1996-01-01

    Ethicists argue that deception is unacceptable, whereas researchers regard it as a necessary part of (certain kinds of) research. This impasse could be resolved by establishing the specific conditions under which deception in medical and behavioral research can be tolerated. An approach based on a consideration of the "Ethical Principles of Psychologists and Code of Conduct," one of the few writings on this topic, would satisfy the needs of both parties. It takes the form of a requirement that subjects be informed of the use of deception before enrolling in a deceptive study. This "second order consent" approach to acceptable deception represents our best chance for reconciling respect for subjects with the occasional scientific need for deceptive research.

  19. Adaptive evolution of Saccharomyces cerevisiae with enhanced ethanol tolerance for Chinese rice wine fermentation.

    PubMed

    Chen, Shuang; Xu, Yan

    2014-08-01

    High tolerance towards ethanol is a desirable property for the Saccharomyces cerevisiae strains used in the alcoholic beverage industry. To improve the ethanol tolerance of an industrial Chinese rice wine yeast, a sequential batch fermentation strategy was used to adaptively evolve a chemically mutagenized Chinese rice wine G85 strain. The high level of ethanol produced under Chinese rice wine-like fermentation conditions was used as the selective pressure. After adaptive evolution of approximately 200 generations, mutant G85X-8 was isolated and shown to have markedly increased ethanol tolerance. The evolved strain also showed higher osmotic and temperature tolerances than the parental strain. Laboratory Chinese rice wine fermentation showed that the evolved G85X-8 strain was able to catabolize sugars more completely than the parental G85 strain. A higher level of yeast cell activity was found in the fermentation mash produced by the evolved strain, but the aroma profiles were similar between the evolved and parental strains. The improved ethanol tolerance in the evolved strain might be ascribed to the altered fatty acids composition of the cell membrane and higher intracellular trehalose concentrations. These results suggest that adaptive evolution is an efficient approach for the non-recombinant modification of industrial yeast strains.

  20. The influence of surgeon personality factors on risk tolerance: a pilot study.

    PubMed

    Contessa, Jack; Suarez, Luis; Kyriakides, Tassos; Nadzam, Geoffrey

    2013-01-01

    This study attempts to assess the association between surgeon personality factors (measured by the Myers-Briggs Type Indicator personality inventory (MBTI(®))) and risk tolerance (measured by the Revised Physicians' Reactions to Uncertainty (PRU) and Physician Risk Attitude (PRA) scales). Instrument assessing surgeon personality profile (MBTI) and 2 questionnaires measuring surgeon risk tolerance and risk aversion (PRU and PRA). Saint Raphael campus of Yale New Haven Hospital in New Haven, Connecticut. Twenty categorical surgery residents and 7 surgical core faculty members. The following findings suggest there might be a relationship between surgeon personality factors and risk tolerance. In certain areas of risk assessment, it appears that surgeons with personality factors E (Extravert), T (Thinking), and P (Perception) demonstrated higher tolerance for risk. Conversely, as MBTI(®) dichotomies are complementary, surgeons with personality factors I (Introvert), F (Feeling), and J (Judgment) suggest risk aversion on these same measures. These findings are supported by at least 2 studies outside medicine demonstrating that personality factors E, N, T, and P are associated with risk taking. This preliminary research project represents an initial step in exploring what may be considered a fundamental component in a "successful" surgical personality. © 2013 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  1. Cold tolerance is unaffected by oxygen availability despite changes in anaerobic metabolism

    NASA Astrophysics Data System (ADS)

    Boardman, Leigh; Sørensen, Jesper G.; Koštál, Vladimír; Šimek, Petr; Terblanche, John S.

    2016-09-01

    Insect cold tolerance depends on their ability to withstand or repair perturbations in cellular homeostasis caused by low temperature stress. Decreased oxygen availability (hypoxia) can interact with low temperature tolerance, often improving insect survival. One mechanism proposed for such responses is that whole-animal cold tolerance is set by a transition to anaerobic metabolism. Here, we provide a test of this hypothesis in an insect model system (Thaumatotibia leucotreta) by experimental manipulation of oxygen availability while measuring metabolic rate, critical thermal minimum (CTmin), supercooling point and changes in 43 metabolites in moth larvae at three key timepoints (before, during and after chill coma). Furthermore, we determined the critical oxygen partial pressure below which metabolic rate was suppressed (c. 4.5 kPa). Results showed that altering oxygen availability did not affect (non-lethal) CTmin nor (lethal) supercooling point. Metabolomic profiling revealed the upregulation of anaerobic metabolites and alterations in concentrations of citric acid cycle intermediates during and after chill coma exposure. Hypoxia exacerbated the anaerobic metabolite responses induced by low temperatures. These results suggest that cold tolerance of T. leucotreta larvae is not set by oxygen limitation, and that anaerobic metabolism in these larvae may contribute to their ability to survive in necrotic fruit.

  2. Evaluation of the Sparton tight-tolerance AXBT

    NASA Technical Reports Server (NTRS)

    Boyd, Janice D.; Linzell, Robert S.

    1993-01-01

    Forty-six near-simultaneous pairs of conductivity - temperature - depth (CTD) and Sparton 'tight tolerance' air expendable bathythermograph (AXBT) temperature profiles were obtained in summer 1991 from a location in the Sargasso Sea. The data were analyzed to assess the temperature and depth accuracies of the Sparton AXBTs. The tight-tolerance criterion was not achieved using the manufacturer's equations but may have been achieved using customized equations computed from the CTD data. The temperature data from the customized equations had a one standard deviation error of 0.13 C. A customized elapsed fall time-to-depth conversion equation was found to be z = 1.620t - 2.2384 x 10(exp -4) t(exp 2) + 1.291 x 10(exp -7) t(exp 3), with z the depth in meters and t the elapsed fall time after probe release in seconds. The standard deviation of the depth error was about 5 m; a rule of thumb for estimating maximum bounds on the depth error below 100 m could be expressed as +/-2% of depth or +/- 10 m, whichever is greater. This equation gave greater depth accuracy than either the manufacturer's supplied equation or the navy standard equation.

  3. Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins.

    PubMed

    Gaeta, Francesco; Valluzzi, Rocco Luigi; Alonzi, Cristiana; Maggioletti, Michela; Caruso, Cristiano; Romano, Antonino

    2015-04-01

    Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

    PubMed Central

    Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

    2016-01-01

    Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

  5. A lignocellulosic hydrolysate-tolerant Aurantiochytrium sp. mutant strain for docosahexaenoic acid production.

    PubMed

    Qi, Feng; Zhang, Mingliang; Chen, Youwei; Jiang, Xianzhang; Lin, Jinxin; Cao, Xiao; Huang, Jianzhong

    2017-03-01

    To utilize lignocellulosic hydrolysate for docosahexaenoic acid (DHA) production, a novel mutant Aurantiochytrium sp. FN21 with strong tolerance against inhibitory lignocellulosic hydrolysate was obtained through continuous domestication processes from the parent strain Aurantiochytrium sp. FJU-512. Aurantiochytrium sp. FN21 can accumulate 21.3% and 30.7% more DHA compared to its parent strain cultured in fermentation medium and a medium with 50% (v/v) sugarcane bagasse hydrolysate (SBH), respectively. After optimization with different nitrogen sources, the highest lipid (11.84g/L) and DHA (3.15g/L) production were achieved in SBH. The results demonstrated that Aurantiochytrium sp. FN21 has the commercial applications for DHA production using lignocellulosic hydrolysate. In order to elucidate the tolerance mechanism, transcriptomic profiling of the two strains was studied. The highly up-regulated genes and corresponding cellular pathways (TCA cycle, amino acid biosynthesis, fatty acid metabolism and degradation of aromatic compounds) are considered to be associated with the hydrolysate-tolerance of Aurantiochytrium sp. FN21. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Orthodontic Bracket Manufacturing Tolerances and Dimensional Differences between Select Self-Ligating Brackets

    PubMed Central

    Major, Thomas W.; Carey, Jason P.; Nobes, David S.; Major, Paul W.

    2010-01-01

    In all manufacturing processes there are tolerances; however, orthodontic bracket manufacturers seldom state the slot dimensional tolerances. This experiment develops a novel method of analyzing slot profile dimensions using photographs of the slot. Five points are selected along each wall, and lines are fitted to define a trapezoidal slot shape. This investigation measures slot height at the slot's top and bottom, angles between walls, slot taper, and the linearity of each wall. Slot dimensions for 30 upper right central incisor self-ligating stainless steel brackets from three manufacturers were evaluated. Speed brackets have a slot height 2% smaller than the nominal 0.559 mm size and have a slightly convergent taper. In-Ovation brackets have a divergent taper at an average angle of 1.47 degrees. In-Ovation is closest to the nominal value of slot height at the slot base and has the smallest manufacturing tolerances. Damon Q brackets are the most rectangular in shape, with nearly 90-degree corners between the slot bottom and walls. Damon slot height is on average 3% oversized. PMID:20981299

  7. Correcting direct effects of ethanol on translation and transcription machinery confers ethanol tolerance in bacteria

    PubMed Central

    Haft, Rembrandt J. F.; Keating, David H.; Schwaegler, Tyler; Schwalbach, Michael S.; Vinokur, Jeffrey; Tremaine, Mary; Peters, Jason M.; Kotlajich, Matthew V.; Pohlmann, Edward L.; Ong, Irene M.; Grass, Jeffrey A.; Kiley, Patricia J.; Landick, Robert

    2014-01-01

    The molecular mechanisms of ethanol toxicity and tolerance in bacteria, although important for biotechnology and bioenergy applications, remain incompletely understood. Genetic studies have identified potential cellular targets for ethanol and have revealed multiple mechanisms of tolerance, but it remains difficult to separate the direct and indirect effects of ethanol. We used adaptive evolution to generate spontaneous ethanol-tolerant strains of Escherichia coli, and then characterized mechanisms of toxicity and resistance using genome-scale DNAseq, RNAseq, and ribosome profiling coupled with specific assays of ribosome and RNA polymerase function. Evolved alleles of metJ, rho, and rpsQ recapitulated most of the observed ethanol tolerance, implicating translation and transcription as key processes affected by ethanol. Ethanol induced miscoding errors during protein synthesis, from which the evolved rpsQ allele protected cells by increasing ribosome accuracy. Ribosome profiling and RNAseq analyses established that ethanol negatively affects transcriptional and translational processivity. Ethanol-stressed cells exhibited ribosomal stalling at internal AUG codons, which may be ameliorated by the adaptive inactivation of the MetJ repressor of methionine biosynthesis genes. Ethanol also caused aberrant intragenic transcription termination for mRNAs with low ribosome density, which was reduced in a strain with the adaptive rho mutation. Furthermore, ethanol inhibited transcript elongation by RNA polymerase in vitro. We propose that ethanol-induced inhibition and uncoupling of mRNA and protein synthesis through direct effects on ribosomes and RNA polymerase conformations are major contributors to ethanol toxicity in E. coli, and that adaptive mutations in metJ, rho, and rpsQ help protect these central dogma processes in the presence of ethanol. PMID:24927582

  8. Intelligent failure-tolerant control

    NASA Technical Reports Server (NTRS)

    Stengel, Robert F.

    1991-01-01

    An overview of failure-tolerant control is presented, beginning with robust control, progressing through parallel and analytical redundancy, and ending with rule-based systems and artificial neural networks. By design or implementation, failure-tolerant control systems are 'intelligent' systems. All failure-tolerant systems require some degrees of robustness to protect against catastrophic failure; failure tolerance often can be improved by adaptivity in decision-making and control, as well as by redundancy in measurement and actuation. Reliability, maintainability, and survivability can be enhanced by failure tolerance, although each objective poses different goals for control system design. Artificial intelligence concepts are helpful for integrating and codifying failure-tolerant control systems, not as alternatives but as adjuncts to conventional design methods.

  9. Improving Saccharomyces cerevisiae ethanol production and tolerance via RNA polymerase II subunit Rpb7.

    PubMed

    Qiu, Zilong; Jiang, Rongrong

    2017-01-01

    Classical strain engineering methods often have limitations in altering multigenetic cellular phenotypes. Here we try to improve Saccharomyces cerevisiae ethanol tolerance and productivity by reprogramming its transcription profile through rewiring its key transcription component RNA polymerase II (RNAP II), which plays a central role in synthesizing mRNAs. This is the first report on using directed evolution method to engineer RNAP II to alter S. cerevisiae strain phenotypes. Error-prone PCR was employed to engineer the subunit Rpb7 of RNAP II to improve yeast ethanol tolerance and production. Based on previous studies and the presumption that improved ethanol resistance would lead to enhanced ethanol production, we first isolated variant M1 with much improved resistance towards 8 and 10% ethanol. The ethanol titers of M1 was ~122 g/L (96.58% of the theoretical yield) under laboratory very high gravity (VHG) fermentation, 40% increase as compared to the control. DNA microarray assay showed that 369 genes had differential expression in M1 after 12 h VHG fermentation, which are involved in glycolysis, alcoholic fermentation, oxidative stress response, etc. This is the first study to demonstrate the possibility of engineering eukaryotic RNAP to alter global transcription profile and improve strain phenotypes. Targeting subunit Rpb7 of RNAP II was able to bring differential expression in hundreds of genes in S. cerevisiae , which finally led to improvement in yeast ethanol tolerance and production.

  10. Improving crop salt tolerance.

    PubMed

    Flowers, T J

    2004-02-01

    Salinity is an ever-present threat to crop yields, especially in countries where irrigation is an essential aid to agriculture. Although the tolerance of saline conditions by plants is variable, crop species are generally intolerant of one-third of the concentration of salts found in seawater. Attempts to improve the salt tolerance of crops through conventional breeding programmes have met with very limited success, due to the complexity of the trait: salt tolerance is complex genetically and physiologically. Tolerance often shows the characteristics of a multigenic trait, with quantitative trait loci (QTLs) associated with tolerance identified in barley, citrus, rice, and tomato and with ion transport under saline conditions in barley, citrus and rice. Physiologically salt tolerance is also complex, with halophytes and less tolerant plants showing a wide range of adaptations. Attempts to enhance tolerance have involved conventional breeding programmes, the use of in vitro selection, pooling physiological traits, interspecific hybridization, using halophytes as alternative crops, the use of marker-aided selection, and the use of transgenic plants. It is surprising that, in spite of the complexity of salt tolerance, there are commonly claims in the literature that the transfer of a single or a few genes can increase the tolerance of plants to saline conditions. Evaluation of such claims reveals that, of the 68 papers produced between 1993 and early 2003, only 19 report quantitative estimates of plant growth. Of these, four papers contain quantitative data on the response of transformants and wild-type of six species without and with salinity applied in an appropriate manner. About half of all the papers report data on experiments conducted under conditions where there is little or no transpiration: such experiments may provide insights into components of tolerance, but are not grounds for claims of enhanced tolerance at the whole plant level. Whether enhanced

  11. Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance.

    PubMed

    Li, Huan; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Lu, Yi-Bin; Chen, Li-Song

    2016-07-21

    Seedlings of aluminum-tolerant 'Xuegan' (Citrus sinensis) and Al-intolerant 'sour pummelo' (Citrus grandis) were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl₃·6H₂O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ), we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a) better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b) less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c) upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance.

  12. A Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio®) in cardiac surgery: the REVAKI‐1 study

    PubMed Central

    Ring, Arne; Morris, Tom; Wozniak, Marcin; Sullo, Nikol; Dott, William; Verheyden, Veerle; Kumar, Tracy; Brunskill, Nigel; Vaja, Rakesh

    2016-01-01

    Aims Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. There is no effective prevention or treatment. Sildenafil citrate (Revatio®, Pfizer Inc.), a phosphodiesterase type 5 inhibitor, prevents post cardiac surgery AKI in pre‐clinical studies, however its use is contraindicated in patients with symptomatic cardiovascular disease. The aim of this study is to assess the safety and pharmacokinetics of intravenous sildenafil in cardiac surgery patients. Methods We conducted an open label, dose escalation study with six patients per dose level. The six doses were 2.5 mg, 5 mg or 10 mg as a bolus, either alone or followed by an additional 2 h infusion of 2.5 mg sildenafil. Results Thirty‐six patients entered the trial, of which 33 completed it. The mean age was 69.9 years. One patient died during surgery, two others were removed from the trial before dosing (all at dose level 5 mg + 2.5 mg). The pharmacokinetic profile of sildenafil was similar to previously published studies. For a dose of 10 mg administered as a bolus followed by 2.5 mg administered over 2 h the results were AUC∞ 537 ng h ml−1, C max 189.4 ng ml−1 and t 1/2 10.5 h. The drug was well tolerated with no serious adverse events related to drug administration. Higher sildenafil doses stabilized post‐surgery nitric oxide bioavailability. Conclusions Pharmacokinetics of sildenafil during cardiopulmonary bypass were comparable to those of other patient groups. The drug was well tolerated at therapeutic plasma levels. These results support the further evaluation of sildenafil for the prevention of AKI in cardiac surgery. PMID:27779776

  13. Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

    PubMed

    Lousberg, Laurence; Jerusalem, Guy

    2016-01-01

    Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

  14. Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer

    PubMed Central

    Lousberg, Laurence; Jerusalem, Guy

    2016-01-01

    Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus–exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile. PMID:28096680

  15. Effects of Cadmium Exposure on Growth and Metabolic Profile of Bermudagrass [Cynodon dactylon (L.) Pers.

    PubMed Central

    Xie, Yan; Hu, Longxing; Du, Zhimin; Sun, Xiaoyan; Amombo, Erick; Fan, Jibiao; Fu, Jinmin

    2014-01-01

    Metabolic responses to cadmium (Cd) may be associated with variations in Cd tolerance in plants. The objectives of this study were to examine changes in metabolic profiles in bermudagrass in response to Cd stress and to identify predominant metabolites associated with differential Cd tolerance using gas chromatography-mass spectrometry. Two genotypes of bermudagrass with contrasting Cd tolerance were exposed to 0 and 1.5 mM CdSO4 for 14 days in hydroponics. Physiological responses to Cd were evaluated by determining turf quality, growth rate, chlorophyll content and normalized relative transpiration. All these parameters exhibited higher tolerance in WB242 than in WB144. Cd treated WB144 transported more Cd to the shoot than in WB242. The metabolite analysis of leaf polar extracts revealed 39 Cd responsive metabolites in both genotypes, mainly consisting of amino acids, organic acids, sugars, fatty acids and others. A difference in the metabolic profiles was observed between the two bermudagrass genotypes exposed to Cd stress. Seven amino acids (norvaline, glycine, proline, serine, threonine, glutamic acid and gulonic acid), four organic acids (glyceric acid, oxoglutaric acid, citric acid and malic acid,) and three sugars (xylulose, galactose and talose) accumulated more in WB242 than WB144. However, compared to the control, WB144 accumulated higher quantities of sugars than WB242 in the Cd regime. The differential accumulation of these metabolites could be associated with the differential Cd tolerance in bermudagrass. PMID:25545719

  16. Effects of cadmium exposure on growth and metabolic profile of bermudagrass [Cynodon dactylon (L.) Pers].

    PubMed

    Xie, Yan; Hu, Longxing; Du, Zhimin; Sun, Xiaoyan; Amombo, Erick; Fan, Jibiao; Fu, Jinmin

    2014-01-01

    Metabolic responses to cadmium (Cd) may be associated with variations in Cd tolerance in plants. The objectives of this study were to examine changes in metabolic profiles in bermudagrass in response to Cd stress and to identify predominant metabolites associated with differential Cd tolerance using gas chromatography-mass spectrometry. Two genotypes of bermudagrass with contrasting Cd tolerance were exposed to 0 and 1.5 mM CdSO4 for 14 days in hydroponics. Physiological responses to Cd were evaluated by determining turf quality, growth rate, chlorophyll content and normalized relative transpiration. All these parameters exhibited higher tolerance in WB242 than in WB144. Cd treated WB144 transported more Cd to the shoot than in WB242. The metabolite analysis of leaf polar extracts revealed 39 Cd responsive metabolites in both genotypes, mainly consisting of amino acids, organic acids, sugars, fatty acids and others. A difference in the metabolic profiles was observed between the two bermudagrass genotypes exposed to Cd stress. Seven amino acids (norvaline, glycine, proline, serine, threonine, glutamic acid and gulonic acid), four organic acids (glyceric acid, oxoglutaric acid, citric acid and malic acid,) and three sugars (xylulose, galactose and talose) accumulated more in WB242 than WB144. However, compared to the control, WB144 accumulated higher quantities of sugars than WB242 in the Cd regime. The differential accumulation of these metabolites could be associated with the differential Cd tolerance in bermudagrass.

  17. Implications of path tolerance and path characteristics on critical vehicle manoeuvres

    NASA Astrophysics Data System (ADS)

    Lundahl, K.; Frisk, E.; Nielsen, L.

    2017-12-01

    Path planning and path following are core components in safe autonomous driving. Typically, a path planner provides a path with some tolerance on how tightly the path should be followed. Based on that, and other path characteristics, for example, sharpness of curves, a speed profile needs to be assigned so that the vehicle can stay within the given tolerance without going unnecessarily slow. Here, such trajectory planning is based on optimal control formulations where critical cases arise as on-the-limit solutions. The study focuses on heavy commercial vehicles, causing rollover to be of a major concern, due to the relatively high centre of gravity. Several results are obtained on required model complexity depending on path characteristics, for example, quantification of required path tolerance for a simple model to be sufficient, quantification of when yaw inertia needs to be considered in more detail, and how the curvature rate of change interplays with available friction. Overall, in situations where the vehicle is subject to a wide range of driving conditions, from good transport roads to more tricky avoidance manoeuvres, the requirements on the path following will vary. For this, the provided results form a basis for real-time path following.

  18. Network-Based Identification of Adaptive Pathways in Evolved Ethanol-Tolerant Bacterial Populations.

    PubMed

    Swings, Toon; Weytjens, Bram; Schalck, Thomas; Bonte, Camille; Verstraeten, Natalie; Michiels, Jan; Marchal, Kathleen

    2017-11-01

    Efficient production of ethanol for use as a renewable fuel requires organisms with a high level of ethanol tolerance. However, this trait is complex and increased tolerance therefore requires mutations in multiple genes and pathways. Here, we use experimental evolution for a system-level analysis of adaptation of Escherichia coli to high ethanol stress. As adaptation to extreme stress often results in complex mutational data sets consisting of both causal and noncausal passenger mutations, identifying the true adaptive mutations in these settings is not trivial. Therefore, we developed a novel method named IAMBEE (Identification of Adaptive Mutations in Bacterial Evolution Experiments). IAMBEE exploits the temporal profile of the acquisition of mutations during evolution in combination with the functional implications of each mutation at the protein level. These data are mapped to a genome-wide interaction network to search for adaptive mutations at the level of pathways. The 16 evolved populations in our data set together harbored 2,286 mutated genes with 4,470 unique mutations. Analysis by IAMBEE significantly reduced this number and resulted in identification of 90 mutated genes and 345 unique mutations that are most likely to be adaptive. Moreover, IAMBEE not only enabled the identification of previously known pathways involved in ethanol tolerance, but also identified novel systems such as the AcrAB-TolC efflux pump and fatty acids biosynthesis and even allowed to gain insight into the temporal profile of adaptation to ethanol stress. Furthermore, this method offers a solid framework for identifying the molecular underpinnings of other complex traits as well. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Central memory CD8+ T lymphocytes mediate lung allograft acceptance

    PubMed Central

    Krupnick, Alexander Sasha; Lin, Xue; Li, Wenjun; Higashikubo, Ryuiji; Zinselmeyer, Bernd H.; Hartzler, Hollyce; Toth, Kelsey; Ritter, Jon H.; Berezin, Mikhail Y.; Wang, Steven T.; Miller, Mark J.; Gelman, Andrew E.; Kreisel, Daniel

    2014-01-01

    Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8+ T cells (CD44hiCD62LhiCCR7+). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8+ T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8+ central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung. PMID:24569377

  20. When is diagnostic testing inappropriate or irrational? Acceptable regret approach.

    PubMed

    Hozo, Iztok; Djulbegovic, Benjamin

    2008-01-01

    The authors provide a new model within the framework of theories of bounded rationality for the observed physicians' behavior that their ordering of diagnostic tests may not be rational. Contrary to the prevailing thinking, the authors find that physicians do not act irrationally or inappropriately when they order diagnostic tests in usual clinical practice. When acceptable regret (i.e., regret that a decision maker finds tolerable upon making a wrong decision) is taken into account, the authors show that physicians tend to order diagnostic tests at a higher level of pretest probability of disease than predicted by expected utility theory. They also show why physicians tend to overtest when regret about erroneous decisions is extremely small. Finally, they explain variations in the practice of medicine. They demonstrate that in the same clinical situation, different decision makers might have different acceptable regret thresholds for withholding treatment, for ordering a diagnostic test, or for administering treatment. This in turn means that for some decision makers, the most rational strategy is to do nothing, whereas for others, it may be to order a diagnostic test, and still for others, choosing treatment may be the most rational course of action.

  1. Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance.

    PubMed

    Fairbanks, C A; Wilcox, G L

    1997-09-01

    The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 degrees C) tail flick test in mice. Intrathecal pretreatment with morphine (40 nmol) produced a 9.6-fold rightward shift in the morphine dose-response curve. This shift confirmed the induction of acute spinal morphine tolerance. Intrathecal copretreatment with the receptor antagonists (competitive and noncompetitive, respectively) dizolcipine (MK801, 3 nmol) or LY235959 (4 pmol) and morphine [40 nmol, intrathecally (i.t.)] attenuated acute tolerance to morphine measured 8 hr later. A 60-min pretreatment of 7-nitroindazole (6 nmol, i.t.), a selective neuronal NOS inhibitor, followed by administration of morphine (40 nmol, i.t.) blocked the induction of morphine tolerance. Intrathecal copretreatment with morphine (40 nmol, i.t.) and agmatine (4 nmol, i.t.), an imidazoline, receptor agonist and putative nitric oxide synthase inhibitor, almost completely abolished acute spinal morphine tolerance. The results of these experiments agree with previous reports using models of chronically induced morphine tolerance. This evidence supports the proposal that the mechanisms responsible for acute morphine tolerance parallel those underlying chronic morphine tolerance. This study attests to the powerful predictive value of acute induction as a model for morphine tolerance.

  2. Genetic analysis of tolerance to boron toxicity in the legume Medicago truncatula.

    PubMed

    Bogacki, Paul; Peck, David M; Nair, Ramakrishnan M; Howie, Jake; Oldach, Klaus H

    2013-03-27

    Medicago truncatula Gaertn. (barrel medic) is cultivated as a pasture legume for its high protein content and ability to improve soils through nitrogen fixation. Toxic concentrations of the micronutrient Boron (B) in agricultural soils hamper the production of cereal and leguminous crops. In cereals, the genetic analysis of B tolerance has led to the development of molecular selection tools to introgress and maintain the B tolerance trait in breeding lines. There is a comparable need for selection tools in legumes that grow on these toxic soils, often in rotation with cereals. Genetic variation for B tolerance in Medicago truncatula was utilised to generate two F2 populations from crosses between tolerant and intolerant parents. Phenotyping under B stress revealed a close correlation between B tolerance and biomass production and a segregation ratio explained by a single dominant locus. M. truncatula homologues of the Arabidopsis major intrinsic protein (MIP) gene AtNIP5;1 and the efflux-type transporter gene AtBOR1, both known for B transport, were identified and nearby molecular markers screened across F2 lines to verify linkage with the B-tolerant phenotype. Most (95%) of the phenotypic variation could be explained by the SSR markers h2_6e22a and h2_21b19a, which flank a cluster of five predicted MIP genes on chromosome 4. Three CAPS markers (MtBtol-1,-2,-3) were developed to dissect the region further. Expression analysis of the five predicted MIPs indicated that only MtNIP3 was expressed when leaf tissue and roots were assessed. MtNIP3 showed low and equal expression in the roots of tolerant and intolerant lines but a 4-fold higher expression level in the leaves of B-tolerant cultivars. The expression profile correlates closely with the B concentration measured in the leaves and roots of tolerant and intolerant plants. Whereas no significant difference in B concentration exists between roots of tolerant and intolerant plants, the B concentration in the leaves

  3. Genetic analysis of tolerance to Boron toxicity in the legume Medicago truncatula

    PubMed Central

    2013-01-01

    Background Medicago truncatula Gaertn. (barrel medic) is cultivated as a pasture legume for its high protein content and ability to improve soils through nitrogen fixation. Toxic concentrations of the micronutrient Boron (B) in agricultural soils hamper the production of cereal and leguminous crops. In cereals, the genetic analysis of B tolerance has led to the development of molecular selection tools to introgress and maintain the B tolerance trait in breeding lines. There is a comparable need for selection tools in legumes that grow on these toxic soils, often in rotation with cereals. Results Genetic variation for B tolerance in Medicago truncatula was utilised to generate two F2 populations from crosses between tolerant and intolerant parents. Phenotyping under B stress revealed a close correlation between B tolerance and biomass production and a segregation ratio explained by a single dominant locus. M. truncatula homologues of the Arabidopsis major intrinsic protein (MIP) gene AtNIP5;1 and the efflux-type transporter gene AtBOR1, both known for B transport, were identified and nearby molecular markers screened across F2 lines to verify linkage with the B-tolerant phenotype. Most (95%) of the phenotypic variation could be explained by the SSR markers h2_6e22a and h2_21b19a, which flank a cluster of five predicted MIP genes on chromosome 4. Three CAPS markers (MtBtol-1,-2,-3) were developed to dissect the region further. Expression analysis of the five predicted MIPs indicated that only MtNIP3 was expressed when leaf tissue and roots were assessed. MtNIP3 showed low and equal expression in the roots of tolerant and intolerant lines but a 4-fold higher expression level in the leaves of B-tolerant cultivars. The expression profile correlates closely with the B concentration measured in the leaves and roots of tolerant and intolerant plants. Whereas no significant difference in B concentration exists between roots of tolerant and intolerant plants, the B

  4. Assessing children's perceptions of academic interventions: The Kids Intervention Profile.

    PubMed

    Eckert, Tanya L; Hier, Bridget O; Hamsho, Narmene F; Malandrino, Rigby D

    2017-06-01

    The psychometric properties of the Kids Intervention Profile (KIP), a rating scale designed to measure academic intervention acceptability from the perspective of students, were examined as well as the influence of background factors on students' acceptability ratings. Data were extracted from 4 randomized controlled trials investigating the effects of a performance feedback intervention on third-grade students' writing fluency (n = 228). Results indicated that the KIP contains 2 factors (General Intervention Acceptability, Skill Improvement) and has adequate internal consistency and stability across a 3-week period. There were gender differences in students' acceptability ratings, with female students rating the intervention as significantly more acceptable than males. In addition, results suggested a modest, positive relationship between students' intervention acceptability ratings and their intervention outcomes. Considerations regarding the use of the KIP, as well as limitations of the study, are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. INDUCTION OF DONOR-SPECIFIC TRANSPLANTATION TOLERANCE TO SKIN AND CARDIAC ALLOGRAFTS USING MIXED CHIMERISM IN (A + B → A) IN RATS

    PubMed Central

    Markus, Peter M.; Selvaggi, Gennaro; Cai, Xin; Fung, John J.; Starzl, Thomas E.

    2010-01-01

    Mixed allogeneic chimerism (A + B → A) was induced in rats by reconstitution of lethally irradiated LEW recipients with a mixture of T-cell depleted (TCD) syngeneic and TCD allogeneic ACI bone marrow. Thirty-seven percent of animals repopulated as stable mixed lymphopoietic chimeras, while the remainder had no detectable allogeneic chimerism. When evaluated for evidence of donor-specific transplantation tolerance, only those recipients with detectable allogeneic lymphoid chimerism exhibited acceptance of donor-specific skin and cardiac allografts. Despite transplantation over a major histocompatibility complex (MHO)- and minor-disparate barrier, animals accepted donor-specific ACI skin and primarily vascularized cardiac allografts permanently, while rejecting third party Brown Norway (BN) grafts. The tolerance induced was also donor-specific in vitro as evidenced by specific hyporeactivity to the allogeneic donor lymphoid elements, yet normal reactivity to MHC-disparate third party rat lymphoid cells. This model for mixed chimerism in the rat will be advantageous to investigate specific transplantation tolerance to primarily vascularized solid organ grafts that can be performed with relative ease in the rat, but not in the mouse, and may provide a method to study the potential existence of organ- or tissue-specific alloantigens in primarily vascularized solid organ allografts. PMID:8162277

  6. Variation tolerant SoC design

    NASA Astrophysics Data System (ADS)

    Kozhikkottu, Vivek J.

    allocation of shared system resources as a means to combat the adverse impact of within-die variations on multi-core platforms. For multi-threaded programs executing on variation-impacted multi-cores platforms, we make the key observation that thread performance is not only a function of the frequency of the core on which it is executing on, but also depends upon the amount of shared system resources allocated to it. We utilize this insight to design a variation-aware runtime scheme which allocates the ways of a last-level shared L2 cache amongst the different cores/threads of a multi-core platform taking into account both application characteristics as well as chip specific variation profiles. Our experiments on 100 quad-core chips, each with a distinct variation profile, shows on an average 15% performance improvements for a suite of multi-threaded benchmarks. Our final contribution investigates the variation-tolerant design of domain-specific accelerators and demonstrates how the unique architectural properties of these accelerators can be leveraged to create highly effective variation tolerance mechanisms. We explore this concept through the variation-tolerant design of a vector processor that efficiently executes applications from the domains of recognition, mining and synthesis (RMS). We develop a novel design approach for variation tolerance, which leverages the unique nature of the vector reduction operations performed by this processor to effectively predict and preempt the occurrence of timing errors under variations and subsequently restore the correct output at the end of each vector reduction operation. We implement the above predict, preempt and restore operations by suitably enhancing the processor hardware and the application software and demonstrate considerable energy benefits (on an average 32%) across six applications from the domains of RMS. In conclusion, our work provides system designers with powerful tools and mechanisms in their efforts to combat

  7. Environmental peer pressure: CD4+ T cell help in tolerance and transplantation.

    PubMed

    Tedesco, Dana; Grakoui, Arash

    2018-01-01

    The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress, and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, cotransplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance. A variety of players may account for this phenomenon including the interaction of intrahepatic antigen-presenting cells with CD4 + T cells and the preferential induction of forkhead box P3 (Foxp3) expression on CD4 + T cells following injurious stimuli. Ineffective insult management can cause chronic liver disease, which manifests systemically as the following: antibody-mediated disorders, ineffective antiviral and antibacterial immunity, and gastrointestinal disorders. These sequelae sharing the requirement of CD4 + T cell help to coordinate aberrant immune responses. In this review, we will focus on CD4 + T cell help due to the shared requirements in hepatic tolerance and coordination of extrahepatic immune responses. Overall, intrahepatic deviations from steady state can have deleterious systemic immune outcomes and highlight the liver's remarkable capacity to maintain a balance between tolerance and inflammatory response while simultaneously being inundated with a panoply of antigenic stimuli. Liver Transplantation 24 89-97 2018 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  8. Logistic Risk Model for the Unique Effects of Inherent Aerobic Capacity on (+)G(sub z) Tolerance Before and After Simulated Weightlessness

    NASA Technical Reports Server (NTRS)

    Ludwig, David A.; Convertino, Victor A.; Goldwater, Danielle J.; Sandler, Harold

    1987-01-01

    Small sample size (n less than 1O) and inappropriate analysis of multivariate data have hindered previous attempts to describe which physiologic and demographic variables are most important in determining how long humans can tolerate acceleration. Data from previous centrifuge studies conducted at NASA/Ames Research Center, utilizing a 7-14 d bed rest protocol to simulate weightlessness, were included in the current investigation. After review, data on 25 women and 22 men were available for analysis. Study variables included gender, age, weight, height, percent body fat, resting heart rate, mean arterial pressure, Vo(sub 2)max and plasma volume. Since the dependent variable was time to greyout (failure), two contemporary biostatistical modeling procedures (proportional hazard and logistic discriminant function) were used to estimate risk, given a particular subject's profile. After adjusting for pro-bed-rest tolerance time, none of the profile variables remained in the risk equation for post-bed-rest tolerance greyout. However, prior to bed rest, risk of greyout could be predicted with 91% accuracy. All of the profile variables except weight, MAP, and those related to inherent aerobic capacity (Vo(sub 2)max, percent body fat, resting heart rate) entered the risk equation for pro-bed-rest greyout. A cross-validation using 24 new subjects indicated a very stable model for risk prediction, accurate within 5% of the original equation. The result for the inherent fitness variables is significant in that a consensus as to whether an increased aerobic capacity is beneficial or detrimental has not been satisfactorily established. We conclude that tolerance to +Gz acceleration before and after simulated weightlessness is independent of inherent aerobic fitness.

  9. Laboratory evolution of copper tolerant yeast strains

    PubMed Central

    2012-01-01

    Background Yeast strains endowed with robustness towards copper and/or enriched in intracellular Cu might find application in biotechnology processes, among others in the production of functional foods. Moreover, they can contribute to the study of human diseases related to impairments of copper metabolism. In this study, we investigated the molecular and physiological factors that confer copper tolerance to strains of baker's yeasts. Results We characterized the effects elicited in natural strains of Candida humilis and Saccharomyces cerevisiae by the exposure to copper in the culture broth. We observed that, whereas the growth of Saccharomyces cells was inhibited already at low Cu concentration, C. humilis was naturally robust and tolerated up to 1 g · L-1 CuSO4 in the medium. This resistant strain accumulated over 7 mg of Cu per gram of biomass and escaped severe oxidative stress thanks to high constitutive levels of superoxide dismutase and catalase. Both yeasts were then "evolved" to obtain hyper-resistant cells able to proliferate in high copper medium. While in S. cerevisiae the evolution of robustness towards Cu was paralleled by the increase of antioxidative enzymes, these same activities decreased in evolved hyper-resistant Candida cells. We also characterized in some detail changes in the profile of copper binding proteins, that appeared to be modified by evolution but, again, in a different way in the two yeasts. Conclusions Following evolution, both Candida and Saccharomyces cells were able to proliferate up to 2.5 g · L-1 CuSO4 and to accumulate high amounts of intracellular copper. The comparison of yeasts differing in their robustness, allowed highlighting physiological and molecular determinants of natural and acquired copper tolerance. We observed that different mechanisms contribute to confer metal tolerance: the control of copper uptake, changes in the levels of enzymes involved in oxidative stress response and changes in the copper

  10. Noise tolerant illumination optimization applied to display devices

    NASA Astrophysics Data System (ADS)

    Cassarly, William J.; Irving, Bruce

    2005-02-01

    Display devices have historically been designed through an iterative process using numerous hardware prototypes. This process is effective but the number of iterations is limited by the time and cost to make the prototypes. In recent years, virtual prototyping using illumination software modeling tools has replaced many of the hardware prototypes. Typically, the designer specifies the design parameters, builds the software model, predicts the performance using a Monte Carlo simulation, and uses the performance results to repeat this process until an acceptable design is obtained. What is highly desired, and now possible, is to use illumination optimization to automate the design process. Illumination optimization provides the ability to explore a wider range of design options while also providing improved performance. Since Monte Carlo simulations are often used to calculate the system performance but those predictions have statistical uncertainty, the use of noise tolerant optimization algorithms is important. The use of noise tolerant illumination optimization is demonstrated by considering display device designs that extract light using 2D paint patterns as well as 3D textured surfaces. A hybrid optimization approach that combines a mesh feedback optimization with a classical optimizer is demonstrated. Displays with LED sources and cold cathode fluorescent lamps are considered.

  11. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

    NASA Technical Reports Server (NTRS)

    Sun, E.; Gao, Y.; Chen, J.; Roberts, A. I.; Wang, X.; Chen, Z.; Shi, Y.

    2004-01-01

    Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

  12. Incorporation of soybean by-product okara and inulin in a probiotic soy yoghurt: texture profile and sensory acceptance.

    PubMed

    Bedani, Raquel; Campos, Marina M S; Castro, Inar A; Rossi, Elizeu A; Saad, Susana M I

    2014-01-15

    This study evaluated the effect of inulin and okara flour on textural and sensory properties of probiotic soy yoghurt (SY) throughout 28 days of storage at 4 °C. Employing a 2(2) design, four formulations of SY produced from soymilk and fermented with an ABT-4 culture (Lactobacillus acidophilus La-5, Bifidobacterium animalis Bb-12 and Streptococcus thermophilus) were studied: SY-C (control); SY-I (with inulin); SY-O (with okara); SY-IO (with inulin + okara). The addition of okara and the refrigerated storage led to significant differences in the instrumental texture parameters of SY (P < 0.05). Inulin and okara did not affect SY sensory acceptability (P > 0.05), but there was a tendency for higher scores in the presence of inulin. On the other hand, the storage period, particularly at 21 days, was unfavourable regarding the acceptance of the different SY. The results showed that the addition of okara flour and the storage were significant factors to increase firmness of the soy yoghurts. SY acceptability was not affected by the incorporation of inulin or okara. These results suggest that okara, discarded as industrial waste, may be used in probiotic soy yoghurt, helping to increase the nutritional and functional properties without altering its acceptability. © 2013 Society of Chemical Industry.

  13. Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

    PubMed

    Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

    2016-01-01

    Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests. CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.

  14. Transcriptomic Changes of Drought-Tolerant and Sensitive Banana Cultivars Exposed to Drought Stress

    PubMed Central

    Muthusamy, Muthusamy; Uma, Subbaraya; Backiyarani, Suthanthiram; Saraswathi, Marimuthu Somasundaram; Chandrasekar, Arumugam

    2016-01-01

    In banana, drought responsive gene expression profiles of drought-tolerant and sensitive genotypes remain largely unexplored. In this research, the transcriptome of drought-tolerant banana cultivar (Saba, ABB genome) and sensitive cultivar (Grand Naine, AAA genome) was monitored using mRNA-Seq under control and drought stress condition. A total of 162.36 million reads from tolerant and 126.58 million reads from sensitive libraries were produced and mapped onto the Musa acuminata genome sequence and assembled into 23,096 and 23,079 unigenes. Differential gene expression between two conditions (control and drought) showed that at least 2268 and 2963 statistically significant, functionally known, non-redundant differentially expressed genes (DEGs) from tolerant and sensitive libraries. Drought has up-regulated 991 and 1378 DEGs and down-regulated 1104 and 1585 DEGs respectively in tolerant and sensitive libraries. Among DEGs, 15.9% are coding for transcription factors (TFs) comprising 46 families and 9.5% of DEGs are constituted by protein kinases from 82 families. Most enriched DEGs are mainly involved in protein modifications, lipid metabolism, alkaloid biosynthesis, carbohydrate degradation, glycan metabolism, and biosynthesis of amino acid, cofactor, nucleotide-sugar, hormone, terpenoids and other secondary metabolites. Several, specific genotype-dependent gene expression pattern was observed for drought stress in both cultivars. A subset of 9 DEGs was confirmed using quantitative reverse transcription-PCR. These results will provide necessary information for developing drought-resilient banana plants. PMID:27867388

  15. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

    PubMed Central

    Morris, Christopher J.; Yang, Jessica N.; Garcia, Joanna I.; Myers, Samantha; Bozzi, Isadora; Wang, Wei; Buxton, Orfeu M.; Shea, Steven A.; Scheer, Frank A. J. L.

    2015-01-01

    Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show—by using two 8-d laboratory protocols—in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers. PMID:25870289

  16. Designing a two-rank acceptance sampling plan for quality inspection of geospatial data products

    NASA Astrophysics Data System (ADS)

    Tong, Xiaohua; Wang, Zhenhua; Xie, Huan; Liang, Dan; Jiang, Zuoqin; Li, Jinchao; Li, Jun

    2011-10-01

    To address the disadvantages of classical sampling plans designed for traditional industrial products, we originally propose a two-rank acceptance sampling plan (TRASP) for the inspection of geospatial data outputs based on the acceptance quality level (AQL). The first rank sampling plan is to inspect the lot consisting of map sheets, and the second is to inspect the lot consisting of features in an individual map sheet. The TRASP design is formulated as an optimization problem with respect to sample size and acceptance number, which covers two lot size cases. The first case is for a small lot size with nonconformities being modeled by a hypergeometric distribution function, and the second is for a larger lot size with nonconformities being modeled by a Poisson distribution function. The proposed TRASP is illustrated through two empirical case studies. Our analysis demonstrates that: (1) the proposed TRASP provides a general approach for quality inspection of geospatial data outputs consisting of non-uniform items and (2) the proposed acceptance sampling plan based on TRASP performs better than other classical sampling plans. It overcomes the drawbacks of percent sampling, i.e., "strictness for large lot size, toleration for small lot size," and those of a national standard used specifically for industrial outputs, i.e., "lots with different sizes corresponding to the same sampling plan."

  17. Tolerability, pharmacokinetics, and bioequivalence of the tablet and syrup formulations of lacosamide in plasma, saliva, and urine: saliva as a surrogate of pharmacokinetics in the central compartment.

    PubMed

    Cawello, Willi; Bökens, Hilmar; Nickel, Brunhild; Andreas, Jens-Otto; Halabi, Atef

    2013-01-01

    To test for bioequivalence of 200 mg lacosamide oral tablet and syrup formulations. Additional objectives were to compare the pharmacokinetic profile of lacosamide in saliva and plasma, and to evaluate its tolerability. This open-label, randomized, two-way crossover trial was conducted in 16 healthy Caucasian male participants in Germany. The bioequivalence of 200 mg lacosamide tablet and syrup was evaluated using plasma to determine maximum measured concentration (C(max)) and area under the curve from zero to the last time point (AUC)(0-tz). Plasma and saliva samples for evaluation of pharmacokinetic parameters of lacosamide and the major metabolite O-desmethyl lacosamide (SPM 12809) were taken over 15 time points (0.5-72 h) and used to statistically compare bioavailability of the two. Urine samples were collected predose and over five time points (0-48 h) to evaluate the cumulative amount of unchanged drug and metabolite. Lacosamide median time to reach C(max) (t(max)) was 1 h for tablet and 0.5 h for syrup in plasma and saliva. Mean terminal half life (t(½)) for tablet and syrup was 12.5 and 12.4 h in plasma, and 13.1 and 13.3 h in saliva, respectively. Tablet and syrup mean plasma AUC(0-tz) was 84.5 and 83.3 μg/mL*h, respectively. Mean AUC(0-tz) in saliva was 93.2 μg/mL*h for tablet and syrup. Mean C(max) for tablet was 5.26 μg/mL in plasma and 5.63 μg/mL in saliva. Syrup mean C(max) was 5.14 and 8.32 μg/mL in plasma and saliva, respectively. Within 2 h of syrup administration, elevated lacosamide concentration in saliva compared to plasma was observed. The ratio of lacosamide syrup to tablet was 0.98 for C(max) and 0.99 for AUC(0-tz) in plasma, and 1.00 for AUC((0-tz)) in saliva; the 90% confidence intervals (CIs) for these parameters were within the range of 0.80-1.25, which meets accepted bioequivalence criteria. The syrup-to-tablet ratio for C(max) in saliva was 1.48, and the 90% CIs exceeded the accepted upper boundary for bioequivalence (1

  18. Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects.

    PubMed

    Li, Zhaoyang; Hard, Marjie L; Andersen, Grit; Pabst, Günther; Wagener, Gilbert; Singh, Tejdip; Chin, Wai; Culm-Merdek, Kerry; Boltje, Ingrid; von Moltke, Lisa L

    2014-04-01

    To characterize the safety, tolerability, pharmacokinetics (PK) and dose proportionality of mipomersen after single subcutaneous (SC) administration to Japanese healthy subjects; and to compare the PK profiles of Japanese and Western subjects. 20 healthy first-generation Japanese male subjects were enrolled into one of three treatment cohorts (50, 100 and 200 mg SC) in a dose-escalation design. Within each cohort, subjects were randomized in a 4 : 1 ratio to receive mipomersen or placebo. Mipomersen was absorbed rapidly after SC administration; median tmax varied between 2 and 3 hours. After reaching peak levels, plasma concentrations of mipomersen decayed multiphasically with an initial distribution t1/2 in several hours and a terminal t1/2 of 261 - 393 hours. Mean Cmax increased in a dose-linear manner while all mean AUC from time 0 to different cut points increased slightly more than dose proportionally. Although mean terminal t1/2 varied in the dose range tested, it did not show dose-dependence. The PK profiles of mipomersen in Japanese subjects are similar to those observed in Western subjects. A single SC dose of 50 mg, 100 mg and 200 mg mipomersen was well tolerated by male Japanese subjects. Single SC doses of 50 - 200 mg were safe and well tolerated when administered to Japanese subjects. Comparison of PK between Japanese and Western subjects does not support any need for dose adjustment in Japanese population in future clinical development.

  19. Glucose tolerance test - non-pregnant

    MedlinePlus

    Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test; Diabetic - glucose tolerance test ... The most common glucose tolerance test is the oral glucose ... the test begins, a sample of blood will be taken. You will then ...

  20. Vancomycin tolerance in enterococci.

    PubMed

    Saribas, Suat; Bagdatli, Yasar

    2004-11-01

    Tolerance can be defined as the ability of bacteria to grow in the presence of high concentrations of bactericide antimicrobics, so that the killing action of the drug is avoided but the minimal inhibitory concentration (MIC) remains the same. We investigated vancomycin tolerance in the Enterococcus faecium and Enterococcus faecalis strains isolated from different clinical specimens. Vancomycin was obtained from Sigma Chemical Co. We studied 100 enterococci strains. Fifty-six and 44 of Enterococcus strains were idendified as E. feacalis and E. faecium, respectively. To determine MICs and minimal bactericidal concentration (MBC), we inoculated strains from an overnight agar culture to Muller-Hinton broth and incubated them for 4-6 h at 37 degrees C with shaking to obtain a logarithmic phase culture. The inoculum was controlled by performing a colony count for each test. We determined MBC values and MBC/MIC ratios to study tolerance to vancomycin. Vancomycin tolerance was defined as a high MBC value and an MBC/MIC ratio > or =32. Fifty-six and 44 of the Enterococcus strains were identified as E. faecium and E. faecalis, respectively. Thirty-one E. faecium and 48 E. faecalis were found to be susceptible to vancomycin and these susceptible strains were included in this study. The MICs of susceptible strains ranged from < or =1 to 4 mg/l, the MBCs were > or =512 mg/l. Tolerance was detected in all E. faecalis and E. faecium strains. The standard E. faecalis 21913 strain also exhibited tolerance according to the high MBC value and the MBC/MIC ratio. We defined the tolerant strains as having no bactericidal effect and MBC/MIC > or =32. We found that a 100% tolerance was present in susceptible strains. One of the hypotheses for tolerance is that tolerant cells fail to mobilize or create the autolysins needed for enlargement and division. Our data suggests that tolerance may compromise glycopeptide therapy of serious enterococci infections. To add an aminoglycoside to the

  1. Effects of High Toxic Boron Concentration on Protein Profiles in Roots of Two Citrus Species Differing in Boron-Tolerance Revealed by a 2-DE Based MS Approach

    PubMed Central

    Sang, Wen; Huang, Zeng-Rong; Yang, Lin-Tong; Guo, Peng; Ye, Xin; Chen, Li-Song

    2017-01-01

    Citrus are sensitive to boron (B)-toxicity. In China, B-toxicity occurs in some citrus orchards. So far, limited data are available on B-toxicity-responsive proteins in higher plants. Thirteen-week-old seedlings of “Sour pummelo” (Citrus grandis) and “Xuegan” (Citrus sinensis) was fertilized every other day until dripping with nutrient solution containing 10 μM (control) or 400 μM (B-toxicity) H3BO3 for 15 weeks. The typical B-toxic symptom only occurred in 400 μM B-treated C. grandis leaves, and that B-toxicity decreased root dry weight more in C. grandis seedlings than in C. sinensis ones, demonstrating that C. sinensis was more tolerant to B-toxicity than C. grandis. Using a 2-dimensional electrophoresis (2-DE) based MS approach, we identified 27 up- and four down-accumulated, and 28 up- and 13 down-accumulated proteins in B-toxic C. sinensis and C. grandis roots, respectively. Most of these proteins were isolated only from B-toxic C. sinensis or C. grandis roots, only nine B-toxicity-responsive proteins were shared by the two citrus species. Great differences existed in B-toxicity-induced alterations of protein profiles between C. sinensis and C. grandis roots. More proteins related to detoxification were up-accumulated in B-toxic C. grandis roots than in B-toxic C. sinensis roots to meet the increased requirement for the detoxification of the more reactive oxygen species and other toxic compounds such as aldehydes in the former. For the first time, we demonstrated that the active methyl cycle was induced and repressed in B-toxic C. sinensis and C. grandis roots, respectively, and that C. sinensis roots had a better capacity to keep cell wall and cytoskeleton integrity than C. grandis roots in response to B-toxicity, which might be responsible for the higher B-tolerance of C. sinensis. In addition, proteins involved in nucleic acid metabolism, biological regulation and signal transduction might play a role in the higher B-tolerance of C. sinensis

  2. A comparative pharmacokinetic and tolerability analysis of the novel orotic acid salt form of tenofovir disoproxil and the fumaric acid salt form in healthy subjects

    PubMed Central

    Kim, Yu Kyong; Choi, Mun Ju; Oh, Tae Young; Yu, Kyung-Sang; Lee, SeungHwan

    2017-01-01

    A novel orotic acid salt form of tenofovir disoproxil (DA-2802) was developed and is expected to replace the fumaric acid salt form. The pharmacokinetic (PK) characteristics and tolerability profiles of DA-2802 were compared to those of tenofovir disoproxil fumarate (TDF, Viread®) in healthy subjects. A randomized, open-label, single-dose study was conducted in 36 healthy subjects using a two-treatment, two-period, and two-sequence crossover design. Subjects received a single oral dose of 319 mg DA-2802 or 300 mg TDF, during each period, with a 7-day washout. Serial blood samples were collected pre-dosing and up to 72 hours post-dosing in each period, for determination of serum tenofovir concentration, which was measured by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental method was used to obtain PK parameters of tenofovir. For comparison between the two tenofovir disoproxil salts, the 90% confidence intervals (90% CIs) of geometric mean ratios of DA-2802 to TDF for the maximum concentration (Cmax) and the area under the concentration–time curve to the last quantifiable concentration (AUC0–t) were determined. The tolerability profiles of tenofovir were assessed by evaluation of adverse events and vital signs, physical examination, ECG, and clinical laboratory tests. The serum tenofovir concentration–time profiles of DA-2802 or TDF were comparable in 32 subjects who completed the study. In both profiles, a two-compartmental elimination with first-order elimination kinetics in the terminal phase was reported in a few subjects, showing a secondary peak in the initial phase of elimination. The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815–0.990) for Cmax and 0.904 (0.836–0.978) for AUC0–t. There were no clinically significant findings in the tolerability assessments. DA-2802 showed comparable PK characteristics and tolerability profiles to TDF. PMID:29158663

  3. Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance

    PubMed Central

    Li, Huan; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Lu, Yi-Bin; Chen, Li-Song

    2016-01-01

    Seedlings of aluminum-tolerant ‘Xuegan’ (Citrus sinensis) and Al-intolerant ‘sour pummelo’ (Citrus grandis) were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl3·6H2O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ), we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a) better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b) less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c) upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance. PMID:27455238

  4. Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

    PubMed

    Di Bonito, P; Pacifico, L; Chiesa, C; Valerio, G; Miraglia Del Giudice, E; Maffeis, C; Morandi, A; Invitti, C; Licenziati, M R; Loche, S; Tornese, G; Franco, F; Manco, M; Baroni, M G

    2017-04-01

    To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

  5. Accuracy analysis of the space shuttle solid rocket motor profile measuring device

    NASA Technical Reports Server (NTRS)

    Estler, W. Tyler

    1989-01-01

    The Profile Measuring Device (PMD) was developed at the George C. Marshall Space Flight Center following the loss of the Space Shuttle Challenger. It is a rotating gauge used to measure the absolute diameters of mating features of redesigned Solid Rocket Motor field joints. Diameter tolerance of these features are typically + or - 0.005 inches and it is required that the PMD absolute measurement uncertainty be within this tolerance. In this analysis, the absolute accuracy of these measurements were found to be + or - 0.00375 inches, worst case, with a potential accuracy of + or - 0.0021 inches achievable by improved temperature control.

  6. Involvement of miR528 in the Regulation of Arsenite Tolerance in Rice (Oryza sativa L.).

    PubMed

    Liu, Qingpo; Hu, Haichao; Zhu, Leyi; Li, Ruochen; Feng, Ying; Zhang, Liqing; Yang, Yuyan; Liu, Xingquan; Zhang, Hengmu

    2015-10-14

    Tens of miRNAs were previously established as being arsenic (As) stress responsive in rice. However, their functional role in As tolerance remains unclear. This study demonstrates that transgenic plants overexpressing miR528 (Ubi::MIR528) were more sensitive to arsenite [As(III)] compared with wild-type (WT) rice. Under normal and stress conditions, miR528-5p and -3p were highly up-regulated in both the roots and leaves of transgenic plants, which exhibited a negative correlation with the expression of seven target genes. Compared with WT plants, Ubi::MIR528 plants showed excessive oxidative stress generation and remarkable amino acid content changes in the roots and leaves upon As(III) exposure. Notably, the expression profiles of diverse functional genes were clearly different between WT and transgenic plants. Thus, the observed As(III) sensitivity of Ubi::MIR528 plants was likely due to the strong alteration of antioxidant enzyme activity and amino acid profiles and the impairment of the As(III) uptake, translocation, and tolerance systems of rice.

  7. Comparison of the tolerability and efficacy of unit-dose, preservative-free topical ocular anaesthetics.

    PubMed

    Lawrenson, J G; Edgar, D F; Tanna, G K; Gudgeon, A C

    1998-09-01

    Several topical ocular local anaesthetics are available in preservative-free unit-dose applicators. There is little comparative data as to the efficacy and tolerability of these drugs. The purpose of this study was to compare the tolerability, and the depth and duration of corneal anaesthesia following instillation of one drop of 0.4% oxybuprocaine (benoxinate), 0.5% amethocaine, or 0.5% proxymetacaine. The tolerability of each anaesthetic was assessed using a linear ten point arbitrary comfort scale. A group of 14 healthy male subjects, with a wide variation in iris pigment levels, participated in the study (mean age 26.6 years, range 18-40 years). Corneal sensitivity was measured using a slit-lamp mounted Cochet-Bonnet aesthesiometer prior to instillation, and at 1, 2, 5, 10, 15, 20 and 30 min after instillation, and continued if necessary until corneal sensitivity had returned to pre-instillation levels. For each anaesthetic, complete anaesthesia occurred within 1 min of instillation and a return to baseline sensitivity levels occurred by 45 min. No significant difference in anaesthesia was found between the drugs at each time point. Tolerability profiles indicated that proxymetacaine was significantly better tolerated than either amethocaine (p < 0.01) or oxybuprocaine (benoxinate) (p < 0.001). There was considerable inter-subject variability in the duration of anaesthesia, and practitioners should be alert to this when allowing patients to leave the practice following the production of corneal anaesthesia. There seems little to choose clinically between the three active agents as regards clinical effectiveness. Proxymetacaine was significantly better tolerated than either amethocaine or oxybuprocaine.

  8. NMR-metabolomics profiling of mammary gland secretory tissue and milk serum in two goat breeds with different levels of tolerance to seasonal weight loss.

    PubMed

    Palma, Mariana; Hernández-Castellano, Lorenzo E; Castro, Noemí; Arguëllo, Anastasio; Capote, Juan; Matzapetakis, Manolis; de Almeida, André Martinho

    2016-06-21

    Goats are of special importance in the Mediterranean and tropical regions for producing a variety of dairy products. The scarcity of pastures during the dry season leads to seasonal weight loss (SWL), which affects milk production. In this work, we studied the effect of feed-restriction on two dairy goat breeds, with different tolerance levels to SWL: the Majorera breed (tolerant) and the Palmera breed (susceptible). Nuclear magnetic resonance (NMR) was used to compare the metabolome of an aqueous fraction of the mammary gland and milk serum from both breeds. Goats in mid-lactation were divided by breed, and each in two feed-regime groups: the control group and the restricted-fed group (to achieve 15-20% reduction of body weight at the end of the experiment). Milk and mammary gland samples were collected at the end of the experimental period (23rd day). (1)H NMR spectra were collected from the aqueous extract of the mammary gland biopsies and the milk serum. Profiling analysis has led to the identification of 46 metabolites in the aqueous extract of the mammary gland. Lactose, glutamate, glycine and lactate were found to be the most abundant. Analysis of milk serum allowed the identification of 50 metabolites, the most abundant being lactose, citrate and creatine. Significant differences were observed, in mammary gland biopsies and milk serum, between control and restricted-fed groups in both breeds, albeit with no differences between the breeds. Variations seem to be related to metabolism adaptation to the low-energy diet and are indicative of breed-specific microflora. Milk serum showed more metabolites varying between control and restricted groups, than the mammary gland. The Majorera breed also showed more variations than the Palmera breed in milk samples, which could be an indication of a prompt adaptation to SWL by the Majorera breed.

  9. Quantitative fault tolerant control design for a hydraulic actuator with a leaking piston seal

    NASA Astrophysics Data System (ADS)

    Karpenko, Mark

    Hydraulic actuators are complex fluid power devices whose performance can be degraded in the presence of system faults. In this thesis a linear, fixed-gain, fault tolerant controller is designed that can maintain the positioning performance of an electrohydraulic actuator operating under load with a leaking piston seal and in the presence of parametric uncertainties. Developing a control system tolerant to this class of internal leakage fault is important since a leaking piston seal can be difficult to detect, unless the actuator is disassembled. The designed fault tolerant control law is of low-order, uses only the actuator position as feedback, and can: (i) accommodate nonlinearities in the hydraulic functions, (ii) maintain robustness against typical uncertainties in the hydraulic system parameters, and (iii) keep the positioning performance of the actuator within prescribed tolerances despite an internal leakage fault that can bypass up to 40% of the rated servovalve flow across the actuator piston. Experimental tests verify the functionality of the fault tolerant control under normal and faulty operating conditions. The fault tolerant controller is synthesized based on linear time-invariant equivalent (LTIE) models of the hydraulic actuator using the quantitative feedback theory (QFT) design technique. A numerical approach for identifying LTIE frequency response functions of hydraulic actuators from acceptable input-output responses is developed so that linearizing the hydraulic functions can be avoided. The proposed approach can properly identify the features of the hydraulic actuator frequency response that are important for control system design and requires no prior knowledge about the asymptotic behavior or structure of the LTIE transfer functions. A distributed hardware-in-the-loop (HIL) simulation architecture is constructed that enables the performance of the proposed fault tolerant control law to be further substantiated, under realistic operating

  10. Fault-tolerant software - Experiment with the sift operating system. [Software Implemented Fault Tolerance computer

    NASA Technical Reports Server (NTRS)

    Brunelle, J. E.; Eckhardt, D. E., Jr.

    1985-01-01

    Results are presented of an experiment conducted in the NASA Avionics Integrated Research Laboratory (AIRLAB) to investigate the implementation of fault-tolerant software techniques on fault-tolerant computer architectures, in particular the Software Implemented Fault Tolerance (SIFT) computer. The N-version programming and recovery block techniques were implemented on a portion of the SIFT operating system. The results indicate that, to effectively implement fault-tolerant software design techniques, system requirements will be impacted and suggest that retrofitting fault-tolerant software on existing designs will be inefficient and may require system modification.

  11. Fault tolerance issues in nanoelectronics

    NASA Astrophysics Data System (ADS)

    Spagocci, S. M.

    The astonishing success story of microelectronics cannot go on indefinitely. In fact, once devices reach the few-atom scale (nanoelectronics), transient quantum effects are expected to impair their behaviour. Fault tolerant techniques will then be required. The aim of this thesis is to investigate the problem of transient errors in nanoelectronic devices. Transient error rates for a selection of nanoelectronic gates, based upon quantum cellular automata and single electron devices, in which the electrostatic interaction between electrons is used to create Boolean circuits, are estimated. On the bases of such results, various fault tolerant solutions are proposed, for both logic and memory nanochips. As for logic chips, traditional techniques are found to be unsuitable. A new technique, in which the voting approach of triple modular redundancy (TMR) is extended by cascading TMR units composed of nanogate clusters, is proposed and generalised to other voting approaches. For memory chips, an error correcting code approach is found to be suitable. Various codes are considered and a lookup table approach is proposed for encoding and decoding. We are then able to give estimations for the redundancy level to be provided on nanochips, so as to make their mean time between failures acceptable. It is found that, for logic chips, space redundancies up to a few tens are required, if mean times between failures have to be of the order of a few years. Space redundancy can also be traded for time redundancy. As for memory chips, mean times between failures of the order of a few years are found to imply both space and time redundancies of the order of ten.

  12. Pattern of multiresistant to antimicrobials and heavy metal tolerance in bacteria isolated from sewage sludge samples from a composting process at a recycling plant in southern Brazil.

    PubMed

    Heck, Karina; De Marco, Évilin Giordana; Duarte, Mariana Wanderlei; Salamoni, Sabrina Pinto; Van Der Sand, Sueli

    2015-06-01

    The composting process is a viable alternative for the recycling of household organic waste and sewage sludge generated during wastewater treatment. However, this technique can select microorganisms resistant to antimicrobials and heavy metals as a result of excess chemicals present in compost windrow. This study evaluates the antimicrobial multiresistant and tolerance to heavy metals in bacteria isolated from the composting process with sewage sludge. Fourteen antimicrobials were used in 344 strains for the resistance profile and four heavy metals (chromium, copper, zinc, and lead) for the minimum biocide concentration assay. The strains used were from the sewage sludge sample (beginning of the process) and the compost sample (end of the process). Strains with higher antimicrobial and heavy metal profile were identified by 16S rRNA gene sequencing. The results showed a multiresistant profile in 48 % of the strains, with the highest percentage of strains resistant to nitrofurantoin (65 %) and β-lactams (58 %). The strains isolated from the sewage sludge and the end of the composting process were more tolerant to copper, with a lethal dose of approximately 900 mg L(-1) for about 50 % of the strains. The genera that showed the highest multiresistant profile and increased tolerance to the metals tested were Pseudomonas and Ochrobactrum. The results of this study may contribute to future research and the revision and regulation of legislation on sewage sludge reuse in soils.

  13. Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera)

    PubMed Central

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2016-01-01

    γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis, and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine, and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid, and threonic acid), sugars (sucrose, fructose, glucose, galactose, and maltose), and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment, and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis. PMID:27455877

  14. Development of New Lemon-Lime Flavored Beverage for OGTT: Acceptability and Reproducibility.

    PubMed

    Chotwanvirat, Phawinpon; Thewjitcharoen, Yotsapon; Parksook, Wyn; Krittiyawong, Sirinate; Hutaphat, Kritchana; Nakasatien, Soontaree; Kaocharoen, Sming; Himathongkam, Thep

    2016-05-01

    The oral glucose tolerance test (OGTT) is essential procedure in both screening and diagnosis of impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes mellitus (DM), but it is not easy to perform because of intense sweetness of the 75-g glucose test beverage causing abdominal discomfort post-testing. Therefore, the new formula of non-carbonated lemon-lime flavored beverage was developed to increase its palatability and better compliance. To develop a new non-carbonated lemon-lime flavored beverage to replace the standard beverage for OGTT Subsequently, the diagnostic value and acceptability between the new formula and the traditional 75-g OGTT formula were compared in healthy subjects. The new lemon-lime flavored formula was developed to replace the standard beverage for OGTT by adding 1,000 milligram of citric acid and 0.03 gram of lime flavor to 75 gram of anhydrous glucose to a final volume of 300 ml. The study was conducted in 30 healthy subjects who underwent the traditional 75-gram OGTT test and the new formula of OGTT beverage one week later, or vice versa, to access acceptability, indices markers of insulin secretion, and insulin sensitivity. Palatability was determined by rating on a 9-point Hedonic Scale. Thirty healthy subjects (15 females) with the age of 33.2 ± 7.5 years and body mass index of 22.9 ± 3.5 kg/m² were enrolled. No significant difference was found between plasma glucose in 0, 30, 60, 90, and 120 minutes, insulin level (0 and 120 minutes) and four insulin surrogate markers in both traditional 75-gram OGTT and new formula of lemon-lime flavored OGTT beverage. The overall satisfaction score of the new formula OGTT was better when compared with the scores of the traditional OGTT (7.1 ± 1.8 vs. 4.7 ± 2.0). Only one subject complained about abdominal discomfort in both episode of OGTT CONCLUSION: The modified lemon-lime flavored beverage for OGTT demonstrated better acceptance in the subjects without difference in

  15. Plant salt-tolerance mechanisms

    DOE PAGES

    Deinlein, Ulrich; Stephan, Aaron B.; Horie, Tomoaki; ...

    2014-06-01

    Crop performance is severely affected by high salt concentrations in soils. To engineer more salt-tolerant plants it is crucial to unravel the key components of the plant salt-tolerance network. Here we review our understanding of the core salt-tolerance mechanisms in plants. Recent studies have shown that stress sensing and signaling components can play important roles in regulating the plant salinity stress response. We also review key Na+ transport and detoxification pathways and the impact of epigenetic chromatin modifications on salinity tolerance. In addition, we discuss the progress that has been made towards engineering salt tolerance in crops, including marker-assisted selectionmore » and gene stacking techniques. We also identify key open questions that remain to be addressed in the future.« less

  16. Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Multiple-Ascending-Dose Study.

    PubMed

    DeLemos, Byron; Richards, Henry M; Vandenbossche, Joris; Ariyawansa, Jay; Natarajan, Jaya; Alexander, Binu; Ramakrishna, Tage; Murtaugh, Thomas; Stahlberg, Hans-Jürgen

    2017-11-01

    This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUC tau,ss of tramadol increased approximately 2.2- and 3.6-fold for the (+) enantiomer and 2.0- and 3.5-fold for the (-) enantiomer with increasing dose from 200 to 400  and 600 mg/day, whereas the C max,ss increased 2.1- and 3.3-fold for the (+) enantiomer and 2.0- and 3.2-fold for the (-) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment-emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study. © 2017, The American College of Clinical Pharmacology.

  17. Exuberant and inhibited children: Person-centered profiles and links to social adjustment.

    PubMed

    Dollar, Jessica M; Stifter, Cynthia A; Buss, Kristin A

    2017-07-01

    The current study aimed to substantiate and extend our understanding regarding the existence and developmental pathways of 3 distinct temperament profiles-exuberant, inhibited, and average approach-in a sample of 3.5-year-old children (n = 121). The interactions between temperamental styles and specific types of effortful control, inhibitory control and attentional control, were also examined in predicting kindergarten peer acceptance. Latent profile analysis identified 3 temperamental styles: exuberant, inhibited, and average approach. Support was found for the adaptive role of inhibitory control for exuberant children and attentional control for inhibited children in promoting peer acceptance in kindergarten. These findings add to our current understanding of temperamental profiles by using sophisticated methodology in a slightly older, community sample, as well as the importance of examining specific types of self-regulation to identify which skills lower risk for children of different temperamental styles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Lipid profiles of detergent resistant fractions of the plasma membrane in oat and rye in association with cold acclimation and freezing tolerance.

    PubMed

    Takahashi, Daisuke; Imai, Hiroyuki; Kawamura, Yukio; Uemura, Matsuo

    2016-04-01

    Cold acclimation (CA) results in alteration of the plasma membrane (PM) lipid composition in plants, which plays a crucial role in the acquisition of freezing tolerance via membrane stabilization. Recent studies have indicated that PM structure is consistent with the fluid mosaic model but is laterally non-homogenous and contains microdomains enriched in sterols, sphingolipids and specific proteins. In plant cells, the function of these microdomains in relation to CA and freezing tolerance is not yet fully understood. The present study aimed to investigate the lipid compositions of detergent resistant fractions of the PM (DRM) which are considered to represent microdomains. They were prepared from leaves of low-freezing tolerant oat and high-freezing tolerant rye. The DRMs contained higher proportions of sterols, sphingolipids and saturated phospholipids than the PM. In particular, one of the sterol lipid classes, acylated sterylglycoside, was the predominant sterol in oat DRM while rye DRM contained free sterol as the major sterol. Oat and rye showed different patterns (or changes) of sterols and 2-hydroxy fatty acids of sphingolipids of DRM lipids during CA. Taken together, these results suggest that CA-induced changes of lipid classes and molecular species in DRMs are associated with changes in the thermodynamic properties and physiological functions of microdomains during CA and hence, influence plant freezing tolerance. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Revoking Pesticide Tolerances

    EPA Pesticide Factsheets

    EPA revokes pesticide tolerances when all registrations of a pesticide have been canceled in the U.S. and the tolerances are not needed for imported foods or when there are no registered uses for certain crops.

  20. Efficacy and acceptance of professional dental cleaning among nursing home residents.

    PubMed

    Barbe, Anna Greta; Kottmann, Hannah Elisa; Hamacher, Stefanie; Derman, Sonja Henny Maria; Noack, Michael Johannes

    2018-05-13

    To determine the impact of general and oral health status of nursing home residents in Germany on efficacy and acceptance of professional dental cleaning performed by a dental nurse. Participants (N = 41; mean age 83 ± 8 years) living in a nursing home were included. Personal and general health, oral health, oral hygiene habits, and needs were investigated. Individual acceptance regarding professional dental cleaning via different devices (scaler, interdental brushes, ultrasonic cleaning) was assessed, as was the efficacy of this method using after-cleaning indices. Oral health among nursing home residents was impaired and independent from dementia status. Most residents (33/41) performed oral hygiene procedures independently and showed better index values than those in need of external help. Residents requiring help with oral hygiene showed increased risk profiles (higher age, more often immobile, demented, more xerostomia). The dental cleaning procedure required a mean time of 37 ± 11 min, was widely accepted (36/41), and achieved clean results (plaque index 0.1 ± 0.5, oral hygiene index 0.2 ± 1.6, Volpe-Manhold index 0.4 ± 1.6); food residues were reduced to 0 independent from cognitive status. Regarding the cleaning methods, scalers were accepted best without difference between demented and non-demented residents. Professional dental cleaning in nursing homes is an accepted and efficacious oral hygiene procedure among nursing home residents. Professional dental cleaning is an efficacious and accepted method as a first step in line with strategies to improve oral health and should be considered in nursing home residents.

  1. Fault-tolerant processing system

    NASA Technical Reports Server (NTRS)

    Palumbo, Daniel L. (Inventor)

    1996-01-01

    A fault-tolerant, fiber optic interconnect, or backplane, which serves as a via for data transfer between modules. Fault tolerance algorithms are embedded in the backplane by dividing the backplane into a read bus and a write bus and placing a redundancy management unit (RMU) between the read bus and the write bus so that all data transmitted by the write bus is subjected to the fault tolerance algorithms before the data is passed for distribution to the read bus. The RMU provides both backplane control and fault tolerance.

  2. Comparative analysis of root transcriptome profiles between drought-tolerant and susceptible wheat genotypes in response to water stress.

    PubMed

    Hu, Ling; Xie, Yan; Fan, Shoujin; Wang, Zongshuai; Wang, Fahong; Zhang, Bin; Li, Haosheng; Song, Jie; Kong, Lingan

    2018-07-01

    Water deficit is one of the major factors limiting crop productivity worldwide. Plant roots play a key role in uptaking water, perceiving and transducing of water deficit signals to shoot. Although the mechanisms of drought-tolerance have been reported recently, the transcriptional regulatory network of wheat root response to water stress has not been fully understood. In this study, drought-tolerant cultivar JM-262 and susceptible cultivar LM-2 are planted to characterize the root transcriptional changes and physiological responses to water deficit. A total of 8197 drought tolerance-associated differentially expressed genes (DEGs) are identified, these genes are mainly mapped to carbon metabolism, flavonoid biosynthesis, and phytohormone signal transduction. The number and expression level of DEGs involved in antioxidative and antiosmotic stresses are more enhanced in JM-262 under water stress. Furthermore, we find the DEGs related to root development are much more induced in JM-262 in phytohormone signal transduction and carbon metabolism pathway. In conclusion, JM-262 may alleviate the damage of drought by producing more osmoprotectants, ROS scavengers, biomass and energy. Interestingly, hormone signaling and cross-talk probably play an important role in promoting JM-262 greater root systems to take up more water, higher capabilities to induce more drought-related DEGs and higher resisitance to oxidative stresse. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. The Influence of a Personal Values Intervention on Cold Pressor-Induced Distress Tolerance.

    PubMed

    Smith, Brooke M; Villatte, Jennifer L; Ong, Clarissa W; Butcher, Grayson M; Twohig, Michael P; Levin, Michael E; Hayes, Steven C

    2018-06-01

    Research has demonstrated that values and acceptance interventions can increase distress tolerance, but the individual contribution of each remains unclear. The current study examined the isolated effect of a values intervention on immersion time in a cold pressor. Participants randomized to Values ( n = 18) and Control ( n = 14) conditions completed two cold pressor tasks, separated by a 30-min values or control intervention. Immersion time increased 51.06 s for participants in the Values condition and decreased by 10.79 s for those in the Control condition. Increases in self-reported pain and distress predicted decreases in immersion time for Control, but not Values, participants. The best-fitting model accounted for 39% of the variance in immersion time change. Results suggest that a brief isolated values exercise can be used to improve distress tolerance despite increased perceptions of pain and distress, such that values alone may be sufficient to facilitate openness to difficult experiences.

  4. Mechanisms of Oral Tolerance.

    PubMed

    Tordesillas, Leticia; Berin, M Cecilia

    2018-02-27

    Oral tolerance is a state of systemic unresponsiveness that is the default response to food antigens in the gastrointestinal tract, although immune tolerance can also be induced by other routes, such as the skin or inhalation. Antigen can be acquired directly by intestinal phagocytes, or pass through enterocytes or goblet cell-associated passages prior to capture by dendritic cells (DCs) in the lamina propria. Mucin from goblet cells acts on DCs to render them more tolerogenic. A subset of regulatory DCs expressing CD103 is responsible for delivery of antigen to the draining lymph node and induction of Tregs. These DCs also imprint gastrointestinal homing capacity, allowing the recently primed Tregs to home back to the lamina propria where they interact with macrophages that produce IL-10 and expand. Tregs induced by dietary antigen include Foxp3 + Tregs and Foxp3 - Tregs. In addition to Tregs, T cell anergy can also contribute to oral tolerance. The microbiota plays a key role in the development of oral tolerance, through regulation of macrophages and innate lymphoid cells that contribute to the regulatory phenotype of gastrointestinal dendritic cells. Absence of microbiota is associated with a susceptibility to food allergy, while presence of Clostridia strains can suppress development of food allergy through enhancement of Tregs and intestinal barrier function. It is not clear if feeding of antigens can also induce true immune tolerance after a memory immune response has been generated, but mechanistic studies of oral immunotherapy trials demonstrate shared pathways in oral tolerance and oral immunotherapy, with a role for Tregs and anergy. An important role for IgA and IgG antibodies in development of immune tolerance is also supported by studies of oral tolerance in humans. The elucidation of key pathways in oral tolerance could identify new strategies to increase efficacy of immunotherapy treatments for food allergy.

  5. Lea's Shield, a new barrier contraceptive preliminary clinical evaluations three-day tolerance study.

    PubMed

    Hunt, W L; Gabbay, L; Potts, M

    1994-12-01

    In this study the Lea's Shield was evaluated for its tolerance by women who wore the device for three consecutive days. Ten women who wore the Lea's Shield for 72 hours completed the tolerance study without adverse effects. Examination of the cervix and vagina revealed that the device did not provoke any significant cellular or microbial changes among the wearers. No major changes in the appearance or prevalence of vaginal flora occurred in the women after three days of wearing the device. A gradient in the pH could be detected between the contents of the vagina, which was more acidic than the contents of the bowl of the device. The range of cervical shapes and vaginal morphology among the study participants has had no influence upon the ability of the device to remain in its proper position. The device "settles in place" as it is pushed in, thereby obviating any special maneuvers for proper positioning. No vaginal nor cervical trauma occurred. We have concluded from these basic clinical evaluations that Lea's Shield is well tolerated during three days of use. Efficacy trials in women at risk recently completed have confirmed the high degree of acceptability and that the device can function adequately as one size fits all.

  6. Interventions for maintaining nasogastric feeding after stroke: An integrative review of effectiveness and acceptability.

    PubMed

    Mahoney, Catherine; Veitch, Linda

    2018-02-01

    To investigate the effectiveness and acceptability of interventions for maintaining nasogastric tubes in adult stroke patients. Internationally, incidence of cerebral vascular disease continues to increase and stroke is the largest cause of complex disability in adults. Dysphagia is common following a stroke which necessitates feeding via a nasogastric tube. Nasogastric tubes are not well tolerated by stroke patients and may be frequently dislodged. Hence, interventions such as tape, the nasal bridle/loop or hand mittens may be used to maintain nasogastric tube position. However, evidence around the effectiveness and acceptability of these interventions has not been reviewed and synthesised. Integrative literature review. Database searches in MEDLINE, PubMed, CINAHL, Scopus, Cochrane and EMBASE; manual reference list searches. Seven studies met the eligibility criteria and were included in the review. Evidence for the effectiveness of nasal bridle/loop and hand mittens to maintain nasogastric tube position in patients after a stroke is spare and methodologically poor, and especially limited around hand mittens use. There is insufficient evidence about the acceptability of both nasal bridle/loop and hand mittens among stroke patients. Current clinical practice is underpinned by assumptions around the acceptability of nasal bridle/loop and hand mittens to secure nasogastric tubes. This results in reliance on consensual judgement between professional, patients and their families to guide their use among individuals with dysphagia after stroke. Further research is required to assess the effectiveness of hand mittens and acceptability of both nasal bridle/loop and hand mittens among stroke patients to inform guideline development. Given the lack of evidence on the acceptability of hand mittens and nasal bridle/loop among stroke patients to inform evidence-based guidelines and protocols, healthcare professionals should reach consensus on their use by exercising clinical

  7. Validation of Donor-Specific Tolerance of Intestinal Transplant by a Secondary Heart Transplantation Model.

    PubMed

    Pengcheng, Wang; Xiaosong, Li; Xiaofeng, Li; Zhongzhi, Li

    2017-02-01

    It is well accepted that survival after a second organ transplant without immunosuppressive agents indicates tolerance for the first transplant. To validate donor-specific tolerance, we established a rat model with a secondary heart transplant after intestinal transplant, which has so far not been described in the literature. We transplanted intestine from Fischer F344 rats to Lewis rats orthotopically. Lewis rats received tacrolimus pretreatment before transplant and a 14-day course of rapamycin 1 month after transplant. At 120 days after primary intestinal transplant, hearts from 6 F344 rats (group A) or 6 Brown Norway rats (group B) were transplanted to Lewis rats that had survived intestinal transplant and without additional immunosuppressive agents. We analyzed survival data, histologic changes, cells positive for the ED1 macrophage marker in transplanted hearts, and 3 lymphocyte levels in both groups. Thirty days after secondary heart transplant, group A hearts were continuously beating; however, group B hearts stopped beating at around 10 days after transplant (8.5 ± 1.5 d; P < .05). Our histologic study showed that both groups had muscle damage and cellular infiltration in hearts that were distinctly different from normal hearts, with ED1-positive cells counted in both groups (85 ± 16 in group A, 116 ± 28 in group B; P > .05). Fluorescence-activated cell sorting showed that CD4/CD25-positive regulatory T cell, CTLA4/CD4/CD25-positive regulatory T cell, and Natural killer T-cell levels were significantly higher level in group A versus B (P < .05). The donor-specific tolerance that we observed was possibly a state of "clinical tolerance" rather than "immunologic tolerance." Our rat model is a feasible and reliable model to study donor-specific tolerance. The higher levels of lymphocytic T cells shown in intestinal transplant recipients were associated with longer allograft survival, possibly contributing to donor-specific tolerance.

  8. Comparative analysis of the cold acclimation and freezing tolerance capacities of seven diploid Brachypodium distachyon accessions

    PubMed Central

    Colton-Gagnon, Katia; Ali-Benali, Mohamed Ali; Mayer, Boris F.; Dionne, Rachel; Bertrand, Annick; Do Carmo, Sonia; Charron, Jean-Benoit

    2014-01-01

    Background and Aims Cold is a major constraint for cereal cultivation under temperate climates. Winter-hardy plants interpret seasonal changes and can acquire the ability to resist sub-zero temperatures. This cold acclimation process is associated with physiological, biochemical and molecular alterations in cereals. Brachypodium distachyon is considered a powerful model system to study the response of temperate cereals to adverse environmental conditions. To date, little is known about the cold acclimation and freezing tolerance capacities of Brachypodium. The main objective of this study was to evaluate the cold hardiness of seven diploid Brachypodium accessions. Methods An integrated approach, involving monitoring of phenological indicators along with expression profiling of the major vernalization regulator VRN1 orthologue, was followed. In parallel, soluble sugars and proline contents were determined along with expression profiles of two COR genes in plants exposed to low temperatures. Finally, whole-plant freezing tests were performed to evaluate the freezing tolerance capacity of Brachypodium. Key Results Cold treatment accelerated the transition from the vegetative to the reproductive phase in all diploid Brachypodium accessions tested. In addition, low temperature exposure triggered the gradual accumulation of BradiVRN1 transcripts in all accessions tested. These accessions exhibited a clear cold acclimation response by progressively accumulating proline, sugars and COR gene transcripts. However, whole-plant freezing tests revealed that these seven diploid accessions only have a limited capacity to develop freezing tolerance when compared with winter varieties of temperate cereals such as wheat and barley. Furthermore, little difference in terms of survival was observed among the accessions tested despite their previous classification as either spring or winter genotypes. Conclusions This study is the first to characterize the freezing tolerance capacities

  9. Tolerance Signatures in Transplant Recipients

    PubMed Central

    Newell, Kenneth A.; Turka, Laurence A.

    2015-01-01

    Purpose of review The intent of this review is to describe biomarkers that predict or identify individuals who exhibit tolerance to a transplanted organ. The identification of tolerance biomarkers would spare some individuals the toxicity of immunosuppressive agents, enhance the safety of studies to induce tolerance, and provide insights into mechanisms of tolerance that may aid in designing new regimens. Recent findings Studies of tolerant kidney transplant recipients have revealed an association with B cells. More recent studies have suggested that these B cells may be less mature than from those in nontolerant recipients, and specially suited to suppress alloimmune responses. Biomarkers in tolerant liver transplant patients appear to be distinct from those associated renal tolerance. Most reports have identified an association with NK and/or γδ T cells rather than B cells. Recent data indicate biomarkers associated with iron homeostasis within the transplanted liver more accurately predict the tolerant state than do biomarkers expressed in the blood, suggesting that the renal allograft itself, which is infrequently sampled, would be informative. Summary Given the encouraging progress in identifying tolerance biomarkers, it will be important to validate these markers in larger studies of transplant recipients undergoing prospective minimization or withdrawal of immunosuppression. PMID:26107969

  10. Analysis of local acceptance of a radioactive waste disposal facility.

    PubMed

    Chung, Ji Bum; Kim, Hong-Kew; Rho, Sam Kew

    2008-08-01

    Like many other countries in the world, Korea has struggled to site a facility for radioactive waste for almost 30 years because of the strong opposition from local residents. Finally, in 2005, Gyeongju was established as the first Korean site for a radioactive waste facility. The objectives of this research are to verify Gyeongju citizens' average level of risk perception of a radioactive waste disposal facility as compared to other risks, and to explore the best model for predicting respondents' acceptance level using variables related to cost-benefit, risk perception, and political process. For this purpose, a survey is conducted among Gyeongju residents, the results of which are as follows. First, the local residents' risk perception of an accident in a radioactive waste disposal facility is ranked seventh among a total of 13 risks, which implies that nuclear-related risk is not perceived very highly by Gyeongju residents; however, its characteristics are still somewhat negative. Second, the comparative regression analyses show that the cost-benefit and political process models are more suitable for explaining the respondents' level of acceptance than the risk perception model. This may be the result of the current economic depression in Gyeongju, residents' familiarity with the nuclear industry, or cultural characteristics of risk tolerance.

  11. Consumer profile and acceptability of cooked beef steaks with edible and active coating containing oregano and rosemary essential oils.

    PubMed

    Vital, Ana Carolina Pelaes; Guerrero, Ana; Kempinski, Emilia Maria Barbosa Carvalho; Monteschio, Jessica de Oliveira; Sary, Cesar; Ramos, Tatiane Rogelio; Campo, María Del Mar; Prado, Ivanor Nunes do

    2018-09-01

    Fresh animal products are highly perishable and characterized by a short shelf-life. Edible coatings with natural antioxidants (essential oils: EOs) could improve stability, ensure quality, and increase the shelf-life of fresh products. Due to the strong flavor of EOs, their use should consider consumer preferences and sensory acceptability. This study evaluated the effects of edible coating (with oregano and rosemary essential oil) on beef in relation to consumer preferences, besides the determination of habits of consumption and buying intentions of consumers. Acceptability scores from three clusters of consumers was described. Coating with oregano was the preferred. The higher consumer acceptance and willingness to buy this product indicate a great potential and possibility of using coatings with essential oils in fresh animal products. Copyright © 2018. Published by Elsevier Ltd.

  12. The peer effect on pain tolerance.

    PubMed

    Engebretsen, Solveig; Frigessi, Arnoldo; Engø-Monsen, Kenth; Furberg, Anne-Sofie; Stubhaug, Audun; de Blasio, Birgitte Freiesleben; Nielsen, Christopher Sivert

    2018-05-19

    Twin studies have found that approximately half of the variance in pain tolerance can be explained by genetic factors, while shared family environment has a negligible effect. Hence, a large proportion of the variance in pain tolerance is explained by the (non-shared) unique environment. The social environment beyond the family is a potential candidate for explaining some of the variance in pain tolerance. Numerous individual traits have previously shown to be associated with friendship ties. In this study, we investigate whether pain tolerance is associated with friendship ties. We study the friendship effect on pain tolerance by considering data from the Tromsø Study: Fit Futures I, which contains pain tolerance measurements and social network information for adolescents attending first year of upper secondary school in the Tromsø area in Northern Norway. Pain tolerance was measured with the cold-pressor test (primary outcome), contact heat and pressure algometry. We analyse the data by using statistical methods from social network analysis. Specifically, we compute pairwise correlations in pain tolerance among friends. We also fit network autocorrelation models to the data, where the pain tolerance of an individual is explained by (among other factors) the average pain tolerance of the individual's friends. We find a significant and positive relationship between the pain tolerance of an individual and the pain tolerance of their friends. The estimated effect is that for every 1 s increase in friends' average cold-pressor tolerance time, the expected cold-pressor pain tolerance of the individual increases by 0.21 s (p-value: 0.0049, sample size n=997). This estimated effect is controlled for sex. The friendship effect remains significant when controlling for potential confounders such as lifestyle factors and test sequence among the students. Further investigating the role of sex on this friendship effect, we only find a significant peer effect of male friends

  13. Supplementation of OmniGen-AF alters the metabolic response to a glucose tolerance test in beef heifers

    USDA-ARS?s Scientific Manuscript database

    This study was designed to determine whether feeding OmniGen-AF to feedlot heifers would alter metabolic profiles in response to a glucose tolerance test. Heifer calves (n=184; 216±1 kg) were allocated into 2 treatment diets: 1) Control, fed a standard receiving ration, and 2) OmniGen-AF (OG), fed t...

  14. The COMMAND trial of cognitive therapy for harmful compliance with command hallucinations (CTCH): a qualitative study of acceptability and tolerability in the UK.

    PubMed

    Birchwood, Max; Mohan, Laura; Meaden, Alan; Tarrier, Nick; Lewis, Shon; Wykes, Til; Davies, Linda M; Dunn, Graham; Peters, Emmanuelle; Michail, Maria

    2018-06-15

    To explore service user experiences of a 9-month cognitive behavioural therapy for command hallucinations in the context of a randomised controlled trial including their views on acceptability and tolerability of the intervention. Qualitative study using semistructured interviews. The study took place across three sites: Birmingham, Manchester and London. Interviews were carried out at the sites where therapy took place which included service bases and participants' homes. Of 197 patients who consented to the trial, 98 received the Cognitive Behavior Therapy for Command Hallucinations (CTCH) intervention; 25 (15 males) of whom were randomly selected and consented to the qualitative study. The mean age of the sample was 42 years, and 68% were white British. Two superordinate themes were identified: participants' views about the aspects of CTCH they found most helpful; and participants' concerns with therapy. Helpful aspects of the therapy included gaining control over the voices, challenging the power and omniscience of the voices, following a structured approach, normalisation and mainstreaming of the experience of voices, and having peer support alongside the therapy. Concerns with the therapy included anxiety about completing CTCH tasks, fear of talking back to voices, the need for follow-up and ongoing support and concerns with adaptability of the therapy. Interpretation: CTCH was generally well received and the narratives validated the overall approach. Participants did not find it an easy therapy to undertake as they were challenging a persecutor they believed had great power to harm; many were concerned, anxious and occasionally disappointed that the voices did not disappear altogether. The trusting relationship with the therapist was crucial. The need for continued support was expressed. ISRCTN62304114, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is

  15. Improving isopropanol tolerance and production of Clostridium beijerinckii DSM 6423 by random mutagenesis and genome shuffling.

    PubMed

    Gérando, H Máté de; Fayolle-Guichard, F; Rudant, L; Millah, S K; Monot, F; Ferreira, Nicolas Lopes; López-Contreras, A M

    2016-06-01

    Random mutagenesis and genome shuffling was applied to improve solvent tolerance and isopropanol/butanol/ethanol (IBE) production in the strictly anaerobic bacteria Clostridium beijerinckii DSM 6423. Following chemical mutagenesis with N-methyl-N-nitro-N-nitrosoguanidine (NTG), screening of putatively improved strains was done by submitting the mutants to toxic levels of inhibitory chemicals or by screening for their tolerance to isopropanol (>35 g/L). Suicide substrates, such as ethyl or methyl bromobutyrate or alcohol dehydrogenase inhibitors like allyl alcohol, were tested and, finally, 36 mutants were isolated. The fermentation profiles of these NTG mutant strains were characterized, and the best performing mutants were used for consecutive rounds of genome shuffling. Screening of strains with further enhancement in isopropanol tolerance at each recursive shuffling step was then used to spot additionally improved strains. Three highly tolerant strains were finally isolated and able to withstand up to 50 g/L isopropanol on plates. Even if increased tolerance to the desired end product was not always accompanied by higher production capabilities, some shuffled strains showed increased solvent titers compared to the parental strains and the original C. beijerinckii DSM 6423. This study confirms the efficiency of genome shuffling to generate improved strains toward a desired phenotype such as alcohol tolerance. This tool also offers the possibility of obtaining improved strains of Clostridium species for which targeted genetic engineering approaches have not been described yet.

  16. Contrasting cDNA-AFLP profiles between crown and leaf tissues of cold-acclimated wheat plants indicate differing regulatory circuitries for low temperature tolerance.

    PubMed

    Ganeshan, Seedhabadee; Sharma, Pallavi; Young, Lester; Kumar, Ashwani; Fowler, D Brian; Chibbar, Ravindra N

    2011-03-01

    Low-temperature (LT) tolerance in winter wheat (Triticum aestivum L.) is an economically important but complex trait. Four selected wheat genotypes, a winter hardy cultivar, Norstar, a tender spring cultivar, Manitou and two near-isogenic lines with Vrn-A1 (spring Norstar) and vrn-A1 (winter Manitou) alleles of Manitou and Norstar were cold-acclimated at 6°C and crown and leaf tissues were collected at 0, 2, 14, 21, 35, 42, 56 and 70 days of cold acclimation. cDNA-AFLP profiling was used to determine temporal expression profiles of transcripts during cold-acclimation in crown and leaf tissues, separately to determine if LT regulatory circuitries in crown and leaf tissues could be delineated using this approach. Screening 64 primer combinations identified 4,074 and 2,757 differentially expressed transcript-derived fragments (TDFs) out of which 38 and 16% were up-regulated as compared to 3 and 6% that were down-regulated in crown and leaf tissues, respectively. DNA sequencing of TDFs revealed sequences common to both tissues including genes coding for DEAD-box RNA helicase, choline-phosphate cytidylyltransferase and delta-1-pyrroline carboxylate synthetase. TDF specific to crown tissues included genes coding for phospahtidylinositol kinase, auxin response factor protein and brassinosteroid insensitive 1-associated receptor kinase. In leaf, genes such as methylene tetrahydrofolate reductase, NADH-cytochrome b5 reductase and malate dehydrogenase were identified. However, 30 and 14% of the DNA sequences from the crown and leaf tissues, respectively, were hypothetical or unknown proteins. Cluster analysis of up-, down-regulated and unique TDFs, DNA sequence and real-time PCR validation, infer that mechanisms operating in crown and leaf tissue in response to LT are differently regulated and warrant further studies.

  17. Prenatal tolerance induction: relationship between cell dose, marrow T-cells, chimerism, and tolerance.

    PubMed

    Chen, Jeng-Chang; Chang, Ming-Ling; Huang, Shiu-Feng; Chang, Pei-Yeh; Muench, Marcus O; Fu, Ren-Huei; Ou, Liang-Shiou; Kuo, Ming-Ling

    2008-01-01

    It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2K(q)) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2K(b)) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 x 10(6) and host leukocytes could be nearly replaced at a dose of 7.5-10.0 x 10(6). High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft-versus-host disease. Depletion of marrow T cells lessened graft-versus-host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of > or = 2% chimerism at 1 month of age and predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%) only caused hyporesponsiveness to the donor. Tolerance induction did not succeed without peripheral chimerism even if a large amount of injected donor cells persisted in the peritoneum. Neither did an increase in cell doses or donor T-cell contents benefit skin graft survivals unless it had substantially improved peripheral chimerism. Thus, peripheral chimerism level can be a simple and straightforward test to predict the degree of prenatal immune tolerance.

  18. Improvement of flavor profiles in Chinese rice wine by creating fermenting yeast with superior ethanol tolerance and fermentation activity.

    PubMed

    Yang, Yijin; Xia, Yongjun; Lin, Xiangna; Wang, Guangqiang; Zhang, Hui; Xiong, Zhiqiang; Yu, Haiyan; Yu, Jianshen; Ai, Lianzhong

    2018-06-01

    Producing alcoholic beverages with novel flavor are desirable for winemakers. We created fermenting yeast with superior ethanol tolerance and fermentation activity to improve the flavor profiles of Chinese rice wine. Strategies of ethanol domestication, ultraviolet mutagenesis (UV) and protoplast fusion were conducted to create yeast hybrids with excellent oenological characteristic. The obtained diploid hybrid F23 showed a cell viability of 6.2% under 25% ethanol, whereas its diploid parental strains could not survive under 20% ethanol. During Chinese rice wine-making, compared to diploid parents, F23 produced 7.07%-12.44% higher yield of ethanol. Flavor analysis indicated that the total content of flavor compounds in F23 wine was 19.99-26.55% higher than that of parent wines. Specifically, F23 exhibited higher capacity in producing 2-phenylethanol, short-chain and long-chain fatty-acid ethyl-ester than diploid parents. Compared to diploid parents, F23 introduced more flavor contributors with odor activity values (OAVs) above one to Chinese rice wine, and those contributors were found with higher OAVs. Based on principal component analysis (PCA), the flavor characteristic of F23 wine was similar to each of parent wine. Additionally, sensory evaluation showed that F23 wine was highly assessed for its intensive levels in fruit-aroma, alcohol-aroma and mouthfeel. Hybrid F23 not only displayed superior flavor production and oenological performance in making Chinese rice wine, but also could act as potential "mixed-like" starter to enrich wine style and differentiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys

    PubMed Central

    Pathiraja, Vimukthi; Villani, Vincenzo; Tasaki, Masayuki; Matar, Abraham J.; Duran-Struuck, Raimon; Yamada, Rei; Moran, Shannon G.; Clayman, Eric S.; Hanekamp, John; Shimizu, Akira; Sachs, David H.; Huang, Christene A.; Yamada, Kazuhiko

    2016-01-01

    We have previously reported that transplantation (Tx) of prevascularized donor islets as composite Islet-Kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cells (HSC) Tx in an attempt to induce tolerance in non-human primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IKTx. HSCTx was performed following mobilization and leukapheresis of the donors, and conditioning of the recipients with total body irradiation, T-cell depletion and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IKTx was performed either 20–22 (n=3) or 208 (n=1) days after HSCTx. All animals accepted IKs without rejection. All recipients required >20 U/day of insulin before IKTx to maintain less than 200mg/dl, whereas after IKTx 3 animals required minimal doses of insulin (1–3 U/day) and one animal was insulin-free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression. PMID:27376692

  20. Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells

    PubMed Central

    Horst, Andrea Kristina; Neumann, Katrin; Diehl, Linda; Tiegs, Gisa

    2016-01-01

    The liver is a tolerogenic organ with exquisite mechanisms of immune regulation that ensure upkeep of local and systemic immune tolerance to self and foreign antigens, but that is also able to mount effective immune responses against pathogens. The immune privilege of liver allografts was recognized first in pigs in spite of major histo-compatibility complex mismatch, and termed the “liver tolerance effect”. Furthermore, liver transplants are spontaneously accepted with only low-dose immunosuppression, and induce tolerance for non-hepatic co-transplanted allografts of the same donor. Although this immunotolerogenic environment is favorable in the setting of organ transplantation, it is detrimental in chronic infectious liver diseases like hepatitis B or C, malaria, schistosomiasis or tumorigenesis, leading to pathogen persistence and weak anti-tumor effects. The liver is a primary site of T-cell activation, but it elicits poor or incomplete activation of T cells, leading to their abortive activation, exhaustion, suppression of their effector function and early death. This is exploited by pathogens and can impair pathogen control and clearance or allow tumor growth. Hepatic priming of T cells is mediated by a number of local conventional and nonconventional antigen-presenting cells (APCs), which promote tolerance by immune deviation, induction of T-cell anergy or apoptosis, and generating and expanding regulatory T cells. This review will focus on the communication between classical and nonclassical APCs and lymphocytes in the liver in tolerance induction and will discuss recent insights into the role of innate lymphocytes in this process. PMID:27041638

  1. Short-Term Acceptability of the Woman's Condom among Married Couples in Shanghai

    PubMed Central

    Wu, Junqing; Huang, Zirong

    2016-01-01

    Background. The Woman's Condom, a second-generation female condom designed for acceptability, is poised for introduction in China. Method. This single-arm study was conducted among 60 couples in China in 2010 to assess acceptability of the Woman's Condom. Results. Male participants reported that ease of handling, inserting, and removing the device improved significantly from first to fourth use. Female and male participants reported that comfort during insertion, feel of lubricant during insertion, comfort/fit of outer ring during use, and overall comfort improved significantly from first to fourth use. Further, at fourth use, female participants reported significant improvement in the comfort of the feel of the condom material and lubricant. Female and male participants reported that satisfaction with stability and sensation during sex and ability to achieve orgasm improved significantly from first to fourth use. At fourth use, female participants reported statistically significant improvement in sensation compared to using nothing. A majority of participants (78%) stated that they would use the Woman's Condom in the future, primarily due to its dual protection profile. Conclusion. This study has shown that, in China, the Woman's Condom appears to be acceptable to married couples. User experience contributes to improvement in many aspects of device acceptability. PMID:27547481

  2. Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

    PubMed

    Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

    2016-03-01

    Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers

    PubMed Central

    Taïbi, Khaled; del Campo, Antonio D.; Vilagrosa, Alberto; Bellés, José M.; López-Gresa, María Pilar; Pla, Davinia; Calvete, Juan J.; López-Nicolás, José M.; Mulet, José M.

    2017-01-01

    Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis. Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas. PMID:28791030

  4. Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers.

    PubMed

    Taïbi, Khaled; Del Campo, Antonio D; Vilagrosa, Alberto; Bellés, José M; López-Gresa, María Pilar; Pla, Davinia; Calvete, Juan J; López-Nicolás, José M; Mulet, José M

    2017-01-01

    Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis . Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.

  5. Influence of psychological factors on the acceptance of complete dentures.

    PubMed

    al Quran, F; Clifford, T; Cooper, C; Lamey, P J

    2001-07-01

    To assess the influence of psychological factors on the acceptance of complete dentures in a population wearing dentures judged to be clinically satisfactory. Subjects were asked to complete personality profiles and also to rate their dentures using a denture satisfaction questionnaire. The survey was conducted in the prosthetics clinic of a teaching hospital. Patients were selected from those who had new complete dentures constructed in the department within the previous two years. The personality inventory was a self-administered questionnaire comprising 240 items covering the five domains of personality. Denture satisfaction was scored on a nine item scale with four Likert type responses to each. A group of 16% consistently complained about their dentures. Statistical analysis showed that personality factors especially Neuroticism had a significant relationship with denture satisfaction. Psychological factors significantly influence denture satisfaction and profiles may provide useful in predicting potential difficult denture wearers.

  6. Improved performance of analog and digital acousto-optic modulation with feedback under profiled beam propagation for secure communication using chaos

    NASA Astrophysics Data System (ADS)

    Almehmadi, Fares S.; Chatterjee, Monish R.

    2014-12-01

    Using intensity feedback, the closed-loop behavior of an acousto-optic hybrid device under profiled beam propagation has been recently shown to exhibit wider chaotic bands potentially leading to an increase in both the dynamic range and sensitivity to key parameters that characterize the encryption. In this work, a detailed examination is carried out vis-à-vis the robustness of the encryption/decryption process relative to parameter mismatch for both analog and pulse code modulation signals, and bit error rate (BER) curves are used to examine the impact of additive white noise. The simulations with profiled input beams are shown to produce a stronger encryption key (i.e., much lower parametric tolerance thresholds) relative to simulations with uniform plane wave input beams. In each case, it is shown that the tolerance for key parameters drops by factors ranging from 10 to 20 times below those for uniform plane wave propagation. Results are shown to be at consistently lower tolerances for secure transmission of analog and digital signals using parameter tolerance measures, as well as BER performance measures for digital signals. These results hold out the promise for considerably greater information transmission security for such a system.

  7. Video Game Acceptance: A Meta-Analysis of the Extended Technology Acceptance Model.

    PubMed

    Wang, Xiaohui; Goh, Dion Hoe-Lian

    2017-11-01

    The current study systematically reviews and summarizes the existing literature of game acceptance, identifies the core determinants, and evaluates the strength of the relationships in the extended technology acceptance model. Moreover, this study segments video games into two categories: hedonic and utilitarian and examines player acceptance of these two types separately. Through a meta-analysis of 50 articles, we find that perceived ease of use (PEOU), perceived usefulness (PU), and perceived enjoyment (PE) significantly associate with attitude and behavioral intention. PE is the dominant predictor of hedonic game acceptance, while PEOU and PU are the main determinants of utilitarian game acceptance. Furthermore, we find that respondent type and game platform are significant moderators. Findings of this study provide critical insights into the phenomenon of game acceptance and suggest directions for future research.

  8. Comparative transcriptome analysis unveils the tolerance mechanisms of Citrus hystrix in response to 'Candidatus Liberibacter asiaticus' infection.

    PubMed

    Hu, Yan; Zhong, Xi; Liu, Xuelu; Lou, Binghai; Zhou, Changyong; Wang, Xuefeng

    2017-01-01

    Citrus Huanglongbing (HLB), a highly devastating citrus disease, is associated with 'Candidatus Liberibacter asiacitus' (CLas), a member of phloem-inhabiting α-proteobacteria. HLB can affect all cultivated citrus and no cure is currently available. Previous studies showed that Kaffir lime (Citrus hystrix), primarily grown in South Asia and Southeast Asia, was tolerant to HLB but the molecular mechanism remains unknown. In this study, gene expression profiling experiments were performed on HLB-tolerant C. hystrix and HLB-susceptible C. sinensis three months after inoculation with CLas using RNA-seq data. Differentially expressed genes (DEGs) in the two citrus cultivars were mainly involved in diverse cellular functions including carbohydrate metabolism, photosynthesis, cell wall metabolism, secondary metabolism, hormone metabolism and oxidation/reduction processes. Notably, starch synthesis and photosynthesis process were not disturbed in CLas-infected C. hystrix. Most of the DEGs involved in cell wall metabolism and secondary metabolism were up-regulated in C. hystrix. In addition, the activation of peroxidases, Cu/Zn-SOD and POD4, may also enhance the tolerance of C. hystrix to CLas. This study provides an insight into the host response of HLB-tolerant citrus cultivar to CLas. C. hystrix is potentially useful for HLB-tolerant/resistant citrus breeding in the future.

  9. Mixed chimerism and split tolerance

    PubMed Central

    Al-Adra, David P.

    2011-01-01

    Establishing hematopoietic mixed chimerism can lead to donor-specific tolerance to transplanted organs and may eliminate the need for long-term immunosuppressive therapy, while also preventing chronic rejection. In this review, we discuss central and peripheral mechanisms of chimerism induced tolerance. However, even in the long-lasting presence of a donor organ or donor hematopoietic cells, some allogeneic tissues from the same donor can be rejected; a phenomenon known as split tolerance. With the current goal of creating mixed chimeras using clinically feasible amounts of donor bone marrow and with minimal conditioning, split tolerance may become more prevalent and its mechanisms need to be explored. Some predisposing factors that may increase the likelihood of split tolerance are immunogenicity of the graft, certain donor-recipient combinations, prior sensitization, location and type of graft and minimal conditioning chimerism induction protocols. Additionally, split tolerance may occur due to a differential susceptibility of various types of tissues to rejection. The mechanisms involved in a tissue’s differential susceptibility to rejection include the presence of polymorphic tissue-specific antigens and variable sensitivity to indirect pathway effector mechanisms. Finally, we review the clinical attempts at allograft tolerance through the induction of chimerism; studies that are revealing the complex relationship between chimerism and tolerance. This relationship often displays split tolerance, and further research into its mechanisms is warranted. PMID:22509425

  10. Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis.

    PubMed

    Hemmerling, Anke; Harrison, William; Schroeder, Adrienne; Park, Jeanna; Korn, Abner; Shiboski, Stephen; Foster-Rosales, Anne; Cohen, Craig R

    2010-12-01

    Bacterial vaginosis (BV) is a common vaginal infection caused by a lack of endogenous lactobacilli and overgrowth of pathogens that frequently recurs following antibiotic treatment. A phase 2a study assessed colonization efficiency, safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by a vaginal applicator. Twenty-four women with BV were randomized in a 3:1 ratio of active product to placebo. Participants used LACTIN-V at 2 × 10 colony-forming units (cfu)/dose or placebo for 5 initial consecutive days, followed by a weekly application over 2 weeks. They returned for follow-up on Days 10 and 28. Sixty-one percent of the 18 women randomized to the LACTIN-V group were colonized with L. crispatus CTV-05 at Day 10 or Day 28. Among LACTIN-V users with complete adherence to the study regimen, 78% were colonized at Day 10 or Day 28. Of the 120 adverse events (AEs) that occurred, 108 (90%) and 12 (10%) were of mild and moderate severity, respectively. AEs were evenly distributed between the LACTIN-V and placebo group. Of the total AEs, 93 (78%) were genitourinary in origin. The most common genitourinary AEs included vaginal discharge (46%), abdominal pain (46%), dysuria (21%), pollakiuria (21%), vaginal odor (21%), and genital pruritus (17%). No grade 3 or 4 AEs or serious AEs occurred and no deep epithelial disruption was seen during colposcopic evaluation. The product was well tolerated and accepted. LACTIN-V colonized well, and was safe and acceptable in women treated for BV.

  11. Longitudinal stability of social competence indicators in a Portuguese sample: Q-sort profiles of social competence, measures of social engagement, and peer sociometric acceptance.

    PubMed

    Santos, António J; Vaughn, Brian E; Peceguina, Inês; Daniel, João R

    2014-03-01

    This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple indicators. Sociometric status categories (Asher & Dodge, 1986) and reciprocated friendships were derived from sociometric data. Composites for social competence domains were significantly associated across all time points. Within age-periods, social competence domains were associated with both sociometric and friendship status categories; however, neither sociometric status nor reciprocated friendships were stable over time. Nevertheless, analyses examining the social competence antecedents to reciprocated friendship at age-4 and age-5 suggested that more socially competent children in the prior year were more likely to have a reciprocated friendship in the current year. Popular and rejected sociometric status categories were also associated with social competence indicators in prior years, but this was most clearly seen at age-5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  12. Enhancement of oxidative and drought tolerance in Arabidopsis by overaccumulation of antioxidant flavonoids

    PubMed Central

    Nakabayashi, Ryo; Yonekura-Sakakibara, Keiko; Urano, Kaoru; Suzuki, Makoto; Yamada, Yutaka; Nishizawa, Tomoko; Matsuda, Fumio; Kojima, Mikiko; Sakakibara, Hitoshi; Shinozaki, Kazuo; Michael, Anthony J; Tohge, Takayuki; Yamazaki, Mami; Saito, Kazuki

    2014-01-01

    The notion that plants use specialized metabolism to protect against environmental stresses needs to be experimentally proven by addressing the question of whether stress tolerance by specialized metabolism is directly due to metabolites such as flavonoids. We report that flavonoids with radical scavenging activity mitigate against oxidative and drought stress in Arabidopsis thaliana. Metabolome and transcriptome profiling and experiments with oxidative and drought stress in wild-type, single overexpressors of MYB12/PFG1 (PRODUCTION OF FLAVONOL GLYCOSIDES1) or MYB75/PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), double overexpressors of MYB12 and PAP1, transparent testa4 (tt4) as a flavonoid-deficient mutant, and flavonoid-deficient MYB12 or PAP1 overexpressing lines (obtained by crossing tt4 and the individual MYB overexpressor) demonstrated that flavonoid overaccumulation was key to enhanced tolerance to such stresses. Antioxidative activity assays using 2,2-diphenyl-1-picrylhydrazyl, methyl viologen, and 3,3′-diaminobenzidine clearly showed that anthocyanin overaccumulation with strong in vitro antioxidative activity mitigated the accumulation of reactive oxygen species in vivo under oxidative and drought stress. These data confirm the usefulness of flavonoids for enhancing both biotic and abiotic stress tolerance in crops. PMID:24274116

  13. Tolerant (parallel) Programming

    NASA Technical Reports Server (NTRS)

    DiNucci, David C.; Bailey, David H. (Technical Monitor)

    1997-01-01

    In order to be truly portable, a program must be tolerant of a wide range of development and execution environments, and a parallel program is just one which must be tolerant of a very wide range. This paper first defines the term "tolerant programming", then describes many layers of tools to accomplish it. The primary focus is on F-Nets, a formal model for expressing computation as a folded partial-ordering of operations, thereby providing an architecture-independent expression of tolerant parallel algorithms. For implementing F-Nets, Cooperative Data Sharing (CDS) is a subroutine package for implementing communication efficiently in a large number of environments (e.g. shared memory and message passing). Software Cabling (SC), a very-high-level graphical programming language for building large F-Nets, possesses many of the features normally expected from today's computer languages (e.g. data abstraction, array operations). Finally, L2(sup 3) is a CASE tool which facilitates the construction, compilation, execution, and debugging of SC programs.

  14. ANALYSIS OF FOOD TOLERANCE IN PATIENTS SUBMITTED TO BARIATRIC SURGERY USING THE QUESTIONNAIRE QUALITY OF ALIMENTATION.

    PubMed

    Stumpf, Matheo Augusto Morandi; Rodrigues, Marcos Ricardo da Silva; Kluthcovsky, Ana Claudia Garabeli Cavalli; Travalini, Fabiana; Milléo, Fábio Quirillo

    2015-01-01

    Due to the increased prevalence of obesity in many countries, the number of bariatric surgeries is increasing. They are considered the most effective treatment for obesity. In the postoperative there may be difficulties with the quality of alimentation, tolerance to various types of food, as well as vomiting and regurgitation. Few surveys are available to assess these difficulties in the postoperative. To perform a systematic literature review about food tolerance in patients undergoing bariatric surgery using the questionnaire "Quality of Alimentation", and compare the results between different techniques. A descriptive-exploratory study where the portals Medline and Scielo were used. The following headings were used in english, spanish and portuguese: quality of alimentation, bariatric surgery and food tolerance. A total of 88 references were found, 14 used the questionnaire "Quality of Alimentation" and were selected. In total, 2745 patients were interviewed of which 371 underwent to gastric banding, 1006 to sleeve gastrectomy, 1113 to Roux-en-Y gastric bypass, 14 to biliopancreatic diversion associated with duodenal switch, 83 were non-operated obese, and 158 non-obese patients. The questionnaire showed good acceptability. The biliopancreatic diversion with duodenal switch had the best food tolerance in the postoperative when compared to other techniques, but it was evaluated in a single article with a small sample. The longer the time after the operation, the better is the food tolerance. Comparing the sleeve gastrectomy and the Roux-en-Y gastric bypass, there are still controversial results in the literature. The gastric banding had the worst score of food tolerance among all the techniques evaluated. The questionnaire is easy and fast to assess the food tolerance in patients after bariatric surgery. Biliopancreatic diversion with duodenal switch had the best food tolerance in the postoperative when compared to sleeve gastrectomy and the Roux-en-Y gastric

  15. Antimicrobial Tolerance in Biofilms

    PubMed Central

    Stewart, Philip S.

    2015-01-01

    The tolerance of microorganisms in biofilms to antimicrobial agents is examined through a meta-analysis of literature data. A numerical tolerance factor comparing the rates of killing in the planktonic and biofilm states is defined to provide a quantitative basis for the analysis. Tolerance factors for biocides and antibiotics range over three orders of magnitude. This variation is not explained by taking into account the molecular weight of the agent, the chemistry of the agent, the substratum material, or the speciation of the microorganisms. Tolerance factors do depend on the areal cell density of the biofilm at the time of treatment and on the age of the biofilm as grown in a particular experimental system. This suggests that there is something that happens during biofilm maturation, either physical or physiological, that is essential for full biofilm tolerance. Experimental measurements of antimicrobial penetration times in biofilms range over orders of magnitude, with slower penetration (>12 min) observed for reactive oxidants and cationic molecules. These agents are retarded through the interaction of reaction, sorption, and diffusion. The specific physiological status of microbial cells in a biofilm contributes to antimicrobial tolerance. A conceptual framework for categorizing physiological cell states is discussed in the context of antimicrobial susceptibility. It is likely that biofilms harbor cells in multiple states simultaneously (e.g., growing, stress-adapted, dormant, inactive) and that this physiological heterogeneity is an important factor in the tolerance of the biofilm state. PMID:26185072

  16. Wind velocity profile reconstruction from intensity fluctuations of a plane wave propagating in a turbulent atmosphere.

    PubMed

    Banakh, V A; Marakasov, D A

    2007-08-01

    Reconstruction of a wind profile based on the statistics of plane-wave intensity fluctuations in a turbulent atmosphere is considered. The algorithm for wind profile retrieval from the spatiotemporal spectrum of plane-wave weak intensity fluctuations is described, and the results of end-to-end computer experiments on wind profiling based on the developed algorithm are presented. It is shown that the reconstructing algorithm allows retrieval of a wind profile from turbulent plane-wave intensity fluctuations with acceptable accuracy.

  17. Epigenomics and bolting tolerance in sugar beet genotypes.

    PubMed

    Hébrard, Claire; Peterson, Daniel G; Willems, Glenda; Delaunay, Alain; Jesson, Béline; Lefèbvre, Marc; Barnes, Steve; Maury, Stéphane

    2016-01-01

    In sugar beet (Beta vulgaris altissima), bolting tolerance is an essential agronomic trait reflecting the bolting response of genotypes after vernalization. Genes involved in induction of sugar beet bolting have now been identified, and evidence suggests that epigenetic factors are involved in their control. Indeed, the time course and amplitude of DNA methylation variations in the shoot apical meristem have been shown to be critical in inducing sugar beet bolting, and a few functional targets of DNA methylation during vernalization have been identified. However, molecular mechanisms controlling bolting tolerance levels among genotypes are still poorly understood. Here, gene expression and DNA methylation profiles were compared in shoot apical meristems of three bolting-resistant and three bolting-sensitive genotypes after vernalization. Using Cot fractionation followed by 454 sequencing of the isolated low-copy DNA, 6231 contigs were obtained that were used along with public sugar beet DNA sequences to design custom Agilent microarrays for expression (56k) and methylation (244k) analyses. A total of 169 differentially expressed genes and 111 differentially methylated regions were identified between resistant and sensitive vernalized genotypes. Fourteen sequences were both differentially expressed and differentially methylated, with a negative correlation between their methylation and expression levels. Genes involved in cold perception, phytohormone signalling, and flowering induction were over-represented and collectively represent an integrative gene network from environmental perception to bolting induction. Altogether, the data suggest that the genotype-dependent control of DNA methylation and expression of an integrative gene network participate in bolting tolerance in sugar beet, opening up perspectives for crop improvement. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  18. Analysis and Implementation of Accident Tolerant Nuclear Fuels

    NASA Astrophysics Data System (ADS)

    Prewitt, Benjamin Joseph

    To improve the reliability and robustness of LWR, accident tolerant nuclear fuels and cladding materials are being developed to possibly replace the current UO2/zirconium system. This research highlights UN and U3Si 2, two of the most favorable accident tolerant fuels being developed. To evaluate the commercial feasiblilty of these fuels, two areas of research were conducted. Chemical fabrication routes for both fuels were investigated in detail, considering UO2 and UF6 as potential starting materials. Potential pathways for industrial scale fabrication using these methods were discussed. Neutronic performance of 70%UN-30%U3Si2 composite was evaluated in MNCP using PWR assembly and core models. The results showed comparable performance to an identical UO2 fueled simulation with the same configuration. The parameters simulated for composite and oxide fuel include the following: fuel to moderator ratio curves; energy dependent flux spectra; temperature coefficients for fuel and moderator; delayed neutron fractions; power peaking factors; axial and radial flux profiles in 2D and 3D; burnup; critical boron concentration; and shutdown margin. Overall, the neutronic parameters suggest that the transition from UO2 to composite in existing nuclear systems will not require significant changes in operating procedures or modifications to standards and regulations.

  19. Differences in cardiovascular risk profile based on relationship between post-load plasma glucose and fasting plasma levels.

    PubMed

    Succurro, Elena; Marini, Maria Adelaide; Grembiale, Alessandro; Lugarà, Marina; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Lauro, Renato; Perticone, Francesco; Sesti, Giorgio

    2009-05-01

    It has been shown that subjects with normal glucose tolerance (NGT), whose plasma glucose (PG) levels do not return to their fasting PG level within 2 h during an oral glucose tolerance test (OGTT) (Group I), have a significantly higher risk to develop type 2 diabetes than NGT subjects whose 2-h glucose returns to, or drops below, the fasting level (Group I). However, it is still unsettled whether individuals in Group II have a more atherogenic profile than Group I subjects. To address this issue, we examined 266 non-diabetic offspring of type 2 diabetic patients, recruited in the context of EUGENE2 cross-sectional study. All subjects underwent an euglycaemic-hyperinsulinemic clamp to assess glucose tolerance and insulin sensitivity. Furthermore, cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. Individuals in Group II exhibited significantly higher waist circumference, blood pressure, triglycerides, 2-h post-load PG, hsC-reactive protein, interleukin-6, insulin-like growth factor-1 (IGF-1), IMT, and lower insulin sensitivity than subjects in Group I. Subjects with NGT, whose PG concentration does not return to their fasting PG level within 2 h during OGTT, have an atherogenic profile, suggesting that performing OGTT with measurement of PG every 30 min may be useful to assess the risk for cardiovascular disease in glucose-tolerant subjects.

  20. In acceptance we trust? Conceptualising acceptance as a viable approach to NGO security management.

    PubMed

    Fast, Larissa A; Freeman, C Faith; O'Neill, Michael; Rowley, Elizabeth

    2013-04-01

    This paper documents current understanding of acceptance as a security management approach and explores issues and challenges non-governmental organisations (NGOs) confront when implementing an acceptance approach to security management. It argues that the failure of organisations to systematise and clearly articulate acceptance as a distinct security management approach and a lack of organisational policies and procedures concerning acceptance hinder its efficacy as a security management approach. The paper identifies key and cross-cutting components of acceptance that are critical to its effective implementation in order to advance a comprehensive and systematic concept of acceptance. The key components of acceptance illustrate how organisational and staff functions affect positively or negatively an organisation's acceptance, and include: an organisation's principles and mission, communications, negotiation, programming, relationships and networks, stakeholder and context analysis, staffing, and image. The paper contends that acceptance is linked not only to good programming, but also to overall organisational management and structures. © 2013 The Author(s). Journal compilation © Overseas Development Institute, 2013.

  1. Salt-Stress Response Mechanisms Using de Novo Transcriptome Sequencing of Salt-Tolerant and Sensitive Corchorus spp. Genotypes

    PubMed Central

    Yang, Zemao; Lu, Ruike; Dai, Zhigang; Yan, An; Tang, Qing; Cheng, Chaohua; Xu, Ying; Yang, Wenting; Su, Jianguang

    2017-01-01

    High salinity is a major environmental stressor for crops. To understand the regulatory mechanisms underlying salt tolerance, we conducted a comparative transcriptome analysis between salt-tolerant and salt-sensitive jute (Corchorus spp.) genotypes in leaf and root tissues under salt stress and control conditions. In total, 68,961 unigenes were identified. Additionally, 11,100 unigenes (including 385 transcription factors (TFs)) exhibited significant differential expression in salt-tolerant or salt-sensitive genotypes. Numerous common and unique differentially expressed unigenes (DEGs) between the two genotypes were discovered. Fewer DEGs were observed in salt-tolerant jute genotypes whether in root or leaf tissues. These DEGs were involved in various pathways, such as ABA signaling, amino acid metabolism, etc. Among the enriched pathways, plant hormone signal transduction (ko04075) and cysteine/methionine metabolism (ko00270) were the most notable. Eight common DEGs across both tissues and genotypes with similar expression profiles were part of the PYL-ABA-PP2C (pyrabactin resistant-like/regulatory components of ABA receptors-abscisic acid-protein phosphatase 2C). The methionine metabolism pathway was only enriched in salt-tolerant jute root tissue. Twenty-three DEGs were involved in methionine metabolism. Overall, numerous common and unique salt-stress response DEGs and pathways between salt-tolerant and salt-sensitive jute have been discovered, which will provide valuable information regarding salt-stress response mechanisms and help improve salt-resistance molecular breeding in jute. PMID:28927022

  2. Correlation of the plasma sphingoid base profile with results from oral glucose tolerance tests in gestational diabetes mellitus

    PubMed Central

    Khan, Abad; Hornemann, Thorsten

    2017-01-01

    Oral glucose tolerance test (OGTT) is usually insufficient to accurately predict the risk for type 2 diabetes mellitus (T2DM), it is therefore necessary to identify an additional biomarker that would most likely improve the accuracy of OGTT. The current OGTT was performed in 53 volunteers after ingestion of 75 g glucose in 250 ml water to each volunteer. Similarly the sphingoid base profile of these volunteers was explored using liquid-chromatography linked with mass spectrometer (LC-MS) and correlated with the different time-points glucose values of OGTT as well as with total area under the curve (tAUC), incremental area under the curve (iAUC), and positive incremental area under the curve (pAUC). The findings showed that 1-deoxysphinganine (1-deoxySA) was significantly positively correlated with the 1-hour, 2-hour, and 3-hour plasma glucose level as well as with total, incremental, and positive incremental AUC while 1-deoxysphingosine (1-deoxySO) was correlated only with 1-hour, 2-hour glucose levels and tAUC of OGTT. The C18SAdiene was negatively correlated with all-time points glucose values and AUCs followed by negative correlation of C18SO, C16SO and C17SO with 2-hour glucose and tAUC of OGTT. The ratios of 1-deoxySA and 1-deoxySO with respect to C18SAdiene have shown significant correlation with 2-hour and AUCs. These ratios were higher in subjects with gestational diabetes in comparison with normal subjects. These findings underlined that 1-deoxysphingolipids (1-deoxySLs) and their ratios with C18SAdiene could be significantly correlated with the glucose load of OGTT and might be used as predictive biomarkers along with OGTT for the risk assessment of diabetes. PMID:28694753

  3. Blood tolerant laccase by directed evolution.

    PubMed

    Mate, Diana M; Gonzalez-Perez, David; Falk, Magnus; Kittl, Roman; Pita, Marcos; De Lacey, Antonio L; Ludwig, Roland; Shleev, Sergey; Alcalde, Miguel

    2013-02-21

    High-redox potential laccases are powerful biocatalysts with a wide range of applications in biotechnology. We have converted a thermostable laccase from a white-rot fungus into a blood tolerant laccase. Adapting the fitness of this laccase to the specific composition of human blood (above neutral pH, high chloride concentration) required several generations of directed evolution in a surrogate complex blood medium. Our evolved laccase was tested in both human plasma and blood, displaying catalytic activity while retaining a high redox potential at the T1 copper site. Mutations introduced in the second coordination sphere of the T1 site shifted the pH activity profile and drastically reduced the inhibitory effect of chloride. This proof of concept that laccases can be adapted to function in extreme conditions opens an array of opportunities for implantable nanobiodevices, chemical syntheses, and detoxification. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. LEA polypeptide profiling of recalcitrant and orthodox legume seeds reveals ABI3-regulated LEA protein abundance linked to desiccation tolerance.

    PubMed

    Delahaie, Julien; Hundertmark, Michaela; Bove, Jérôme; Leprince, Olivier; Rogniaux, Hélène; Buitink, Julia

    2013-11-01

    In contrast to orthodox seeds that acquire desiccation tolerance during maturation, recalcitrant seeds are unable to survive drying. These desiccation-sensitive seeds constitute an interesting model for comparative analysis with phylogenetically close species that are desiccation tolerant. Considering the importance of LEA (late embryogenesis abundant) proteins as protective molecules both in drought and in desiccation tolerance, the heat-stable proteome was characterized in cotyledons of the legume Castanospermum australe and it was compared with that of the orthodox model legume Medicago truncatula. RNA sequencing identified transcripts of 16 homologues out of 17 LEA genes for which polypeptides are detected in M. truncatula seeds. It is shown that for 12 LEA genes, polypeptides were either absent or strongly reduced in C. australe cotyledons compared with M. truncatula seeds. Instead, osmotically responsive, non-seed-specific dehydrins accumulated to high levels in the recalcitrant cotyledons compared with orthodox seeds. Next, M. truncatula mutants of the abscisic acid insensitive3 (ABI3) gene were characterized. Mature Mtabi3 seeds were found to be desiccation sensitive when dried below a critical water content of 0.4 g H2O g DW(-1). Characterization of the LEA proteome of the Mtabi3 seeds revealed a subset of LEA proteins with severely reduced abundance that were also found to be reduced or absent in C. australe cotyledons. Transcripts of these genes were indeed shown to be ABI3 responsive. The results highlight those LEA proteins that are critical to desiccation tolerance and suggest that comparable regulatory pathways responsible for their accumulation are missing in both desiccation-sensitive genotypes, revealing new insights into the mechanistic basis of the recalcitrant trait in seeds.

  5. LEA polypeptide profiling of recalcitrant and orthodox legume seeds reveals ABI3-regulated LEA protein abundance linked to desiccation tolerance

    PubMed Central

    Hundertmark, Michaela; Buitink, Julia

    2013-01-01

    In contrast to orthodox seeds that acquire desiccation tolerance during maturation, recalcitrant seeds are unable to survive drying. These desiccation-sensitive seeds constitute an interesting model for comparative analysis with phylogenetically close species that are desiccation tolerant. Considering the importance of LEA (late embryogenesis abundant) proteins as protective molecules both in drought and in desiccation tolerance, the heat-stable proteome was characterized in cotyledons of the legume Castanospermum australe and it was compared with that of the orthodox model legume Medicago truncatula. RNA sequencing identified transcripts of 16 homologues out of 17 LEA genes for which polypeptides are detected in M. truncatula seeds. It is shown that for 12 LEA genes, polypeptides were either absent or strongly reduced in C. australe cotyledons compared with M. truncatula seeds. Instead, osmotically responsive, non-seed-specific dehydrins accumulated to high levels in the recalcitrant cotyledons compared with orthodox seeds. Next, M. truncatula mutants of the ABSCISIC ACID INSENSITIVE3 (ABI3) gene were characterized. Mature Mtabi3 seeds were found to be desiccation sensitive when dried below a critical water content of 0.4g H2O g DW–1. Characterization of the LEA proteome of the Mtabi3 seeds revealed a subset of LEA proteins with severely reduced abundance that were also found to be reduced or absent in C. australe cotyledons. Transcripts of these genes were indeed shown to be ABI3 responsive. The results highlight those LEA proteins that are critical to desiccation tolerance and suggest that comparable regulatory pathways responsible for their accumulation are missing in both desiccation-sensitive genotypes, revealing new insights into the mechanistic basis of the recalcitrant trait in seeds. PMID:24043848

  6. Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

    PubMed

    Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

    2015-01-01

    The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

  7. Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to <18-year-old children and adolescents at risk of influenza-related complications.

    PubMed

    Diez-Domingo, Javier; de Martino, Maurizio; Lopez, Jose Garcia-Sicilia; Zuccotti, Gian Vincenzo; Icardi, Giancarlo; Villani, Alberto; Moreno-Perez, David; Hernández, María Méndez; Aldeán, Javier Álvarez; Mateen, Ahmed Abdul; Enweonye, Igwebuike; de Rooij, Richard; Chandra, Richa

    2016-08-01

    This descriptive, non-comparative, phase III study evaluated the safety and tolerability of cell culture-derived (TIVc) and egg-derived (TIV) seasonal influenza vaccines in children at risk of influenza-related complications. Four hundred and thirty subjects were randomized 2:1 to TIVc or TIV. Subjects aged 3 to <9 years received one dose (if previously vaccinated, n=89) or two doses (if not previously vaccinated, n=124) of the study vaccines; the 9 to <18-year-olds (n=213) received one dose. Reactogenicity was assessed for 7 days after vaccination; safety was monitored for 6 months. After any vaccination, the most frequently reported solicited local adverse event (AE) was tenderness/pain (TIVc 44%, 66%, 53% and TIV 56%, 51%, 65% in the age groups 3 to <6 years, 6 to <9 years, and 9 to <18 years, respectively) and the systemic AE was irritability (22% TIVc, 24% TIV) in 3 to <6-year-olds and headache in 6 to <9-year-olds (20% TIVc, 13% TIV) and 9 to <18-year-olds (21% TIVc, 26% TIV). There were no cases of severe fever (≥40°C). No vaccine-related serious AEs were noted. New onset of chronic disease was reported in ≤1% of subjects. TIVc and TIV had acceptable tolerability and similar safety profiles in at-risk children (NCT01998477). Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  8. Comparative transcriptome analysis unveils the tolerance mechanisms of Citrus hystrix in response to ‘Candidatus Liberibacter asiaticus’ infection

    PubMed Central

    Hu, Yan; Zhong, Xi; Liu, Xuelu; Lou, Binghai; Zhou, Changyong

    2017-01-01

    Citrus Huanglongbing (HLB), a highly devastating citrus disease, is associated with ‘Candidatus Liberibacter asiacitus’ (CLas), a member of phloem-inhabiting α-proteobacteria. HLB can affect all cultivated citrus and no cure is currently available. Previous studies showed that Kaffir lime (Citrus hystrix), primarily grown in South Asia and Southeast Asia, was tolerant to HLB but the molecular mechanism remains unknown. In this study, gene expression profiling experiments were performed on HLB-tolerant C. hystrix and HLB-susceptible C. sinensis three months after inoculation with CLas using RNA-seq data. Differentially expressed genes (DEGs) in the two citrus cultivars were mainly involved in diverse cellular functions including carbohydrate metabolism, photosynthesis, cell wall metabolism, secondary metabolism, hormone metabolism and oxidation/reduction processes. Notably, starch synthesis and photosynthesis process were not disturbed in CLas-infected C. hystrix. Most of the DEGs involved in cell wall metabolism and secondary metabolism were up-regulated in C. hystrix. In addition, the activation of peroxidases, Cu/Zn-SOD and POD4, may also enhance the tolerance of C. hystrix to CLas. This study provides an insight into the host response of HLB-tolerant citrus cultivar to CLas. C. hystrix is potentially useful for HLB-tolerant/resistant citrus breeding in the future. PMID:29232716

  9. Metabolite and transcript markers for the prediction of potato drought tolerance.

    PubMed

    Sprenger, Heike; Erban, Alexander; Seddig, Sylvia; Rudack, Katharina; Thalhammer, Anja; Le, Mai Q; Walther, Dirk; Zuther, Ellen; Köhl, Karin I; Kopka, Joachim; Hincha, Dirk K

    2018-04-01

    Potato (Solanum tuberosum L.) is one of the most important food crops worldwide. Current potato varieties are highly susceptible to drought stress. In view of global climate change, selection of cultivars with improved drought tolerance and high yield potential is of paramount importance. Drought tolerance breeding of potato is currently based on direct selection according to yield and phenotypic traits and requires multiple trials under drought conditions. Marker-assisted selection (MAS) is cheaper, faster and reduces classification errors caused by noncontrolled environmental effects. We analysed 31 potato cultivars grown under optimal and reduced water supply in six independent field trials. Drought tolerance was determined as tuber starch yield. Leaf samples from young plants were screened for preselected transcript and nontargeted metabolite abundance using qRT-PCR and GC-MS profiling, respectively. Transcript marker candidates were selected from a published RNA-Seq data set. A Random Forest machine learning approach extracted metabolite and transcript markers for drought tolerance prediction with low error rates of 6% and 9%, respectively. Moreover, by combining transcript and metabolite markers, the prediction error was reduced to 4.3%. Feature selection from Random Forest models allowed model minimization, yielding a minimal combination of only 20 metabolite and transcript markers that were successfully tested for their reproducibility in 16 independent agronomic field trials. We demonstrate that a minimum combination of transcript and metabolite markers sampled at early cultivation stages predicts potato yield stability under drought largely independent of seasonal and regional agronomic conditions. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  10. Multiple-sip temporal dominance of sensations associated with acceptance test: a study on special beers.

    PubMed

    Corrêa Simioni, Síntia Carla; Ribeiro, Michele Nayara; de Souza, Vanessa Rios; Nunes, Cleiton Antônio; Pinheiro, Ana Carla Marques

    2018-03-01

    In this study, we proposed the use of a multiple-sip temporal dominance of sensations (TDS) test alongside with an acceptance test over repeated consumption for the analysis of special beers, with the aim of contributing to a deeper understanding of consumer behavior regarding temporal descriptions and sensory acceptance. Consumers of special beers sequentially evaluated six sips of a particular type of beer by TDS analysis and an acceptance test was performed for each sip. Four different kinds of specialty beers were evaluated [Bohemian Pilsner (BP), Witbier (WB), Belgian Strong Ale Dubbel (BD), and Russian Imperial Stout (RS)]. In general, the descriptive profile of beers varied temporally, i.e., there was an increased dominance of bitterness and a decreased dominance of fruity, floral, toffee, and coffee attributes. Concurrently, a reduction in sensory acceptance with an increased number of sips, especially the last sip, was observed in two kinds of beers that possessed a strong flavor, BD and RS. BP and WB presented smooth attributes and low notable characteristics, which could have contributed to the maintenance of the acceptance grades as the number of sips increased. The combination of TDS and acceptance over repeated sips can be useful for obtaining detailed descriptions of products that are closer to real time consumption by consumers, and thus aids in ensuring good product performance once released. The information obtained can also help product development scientists to fine-tune product formulations and ensure acceptability.

  11. Physical fault tolerance of nanoelectronics.

    PubMed

    Szkopek, Thomas; Roychowdhury, Vwani P; Antoniadis, Dimitri A; Damoulakis, John N

    2011-04-29

    The error rate in complementary transistor circuits is suppressed exponentially in electron number, arising from an intrinsic physical implementation of fault-tolerant error correction. Contrariwise, explicit assembly of gates into the most efficient known fault-tolerant architecture is characterized by a subexponential suppression of error rate with electron number, and incurs significant overhead in wiring and complexity. We conclude that it is more efficient to prevent logical errors with physical fault tolerance than to correct logical errors with fault-tolerant architecture.

  12. Ovarian cancer survivors' acceptance of treatment side effects evolves as goals of care change over the cancer continuum.

    PubMed

    Frey, Melissa K; Ellis, Annie E; Koontz, Laura M; Shyne, Savannah; Klingenberg, Bernhard; Fields, Jessica C; Chern, Jing-Yi; Blank, Stephanie V

    2017-08-01

    Women with ovarian cancer can have long overall survival and goals of treatment change over time from cure to remission to stable disease. We sought to determine whether survivors' acceptance of treatment side effects also changes over the disease continuum. Women with ovarian cancer completed an online survey focusing on survivors' goals and priorities. The survey was distributed through survivor networks and social media. Four hundred and thirty-four women visited the survey website and 328 (76%) completed the survey. Among participants, 141 (43%) identified themselves as having ever recurred, 119 (36%) were undergoing treatment at the time of survey completion and 86 (26%) had received four or more chemotherapy regimens. Respondents' goals of care were cure for 115 women (35%), remission for 156 (48%) and stable disease for 56 (17%). When asked what was most meaningful, 148 women (45%) reported overall survival, 135 (41%) reported quality of life and 40 (12%) reported progression-free survival. >50% of survivors were willing to tolerate the following symptoms for the goal of cure: fatigue (283, 86%), alopecia (281, 86%), diarrhea (232, 71%), constipation (227, 69%), neuropathy (218, 66%), arthralgia (210, 64%), sexual side effects (201, 61%), reflux symptoms (188, 57%), memory loss (180, 55%), nausea/vomiting (180, 55%), hospitalization for treatment side effects (179, 55%) and pain (169, 52%). The rates of tolerance for most symptoms decreased significantly as the goal of treatment changed from cure to remission to stable disease. Women with ovarian cancer willingly accept many treatment side effects when the goal of treatment is cure, however become less accepting when the goal is remission and even less so when the goal is stable disease. Physicians and survivors must carefully consider treatment toxicities and quality of life effects when selecting drugs for patients with incurable disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Mondo/ChREBP-Mlx-Regulated Transcriptional Network Is Essential for Dietary Sugar Tolerance in Drosophila

    PubMed Central

    Havula, Essi; Teesalu, Mari; Hyötyläinen, Tuulia; Seppälä, Heini; Hasygar, Kiran; Auvinen, Petri; Orešič, Matej; Sandmann, Thomas; Hietakangas, Ville

    2013-01-01

    Sugars are important nutrients for many animals, but are also proposed to contribute to overnutrition-derived metabolic diseases in humans. Understanding the genetic factors governing dietary sugar tolerance therefore has profound biological and medical significance. Paralogous Mondo transcription factors ChREBP and MondoA, with their common binding partner Mlx, are key sensors of intracellular glucose flux in mammals. Here we report analysis of the in vivo function of Drosophila melanogaster Mlx and its binding partner Mondo (ChREBP) in respect to tolerance to dietary sugars. Larvae lacking mlx or having reduced mondo expression show strikingly reduced survival on a diet with moderate or high levels of sucrose, glucose, and fructose. mlx null mutants display widespread changes in lipid and phospholipid profiles, signs of amino acid catabolism, as well as strongly elevated circulating glucose levels. Systematic loss-of-function analysis of Mlx target genes reveals that circulating glucose levels and dietary sugar tolerance can be genetically uncoupled: Krüppel-like transcription factor Cabut and carbonyl detoxifying enzyme Aldehyde dehydrogenase type III are essential for dietary sugar tolerance, but display no influence on circulating glucose levels. On the other hand, Phosphofructokinase 2, a regulator of the glycolysis pathway, is needed for both dietary sugar tolerance and maintenance of circulating glucose homeostasis. Furthermore, we show evidence that fatty acid synthesis, which is a highly conserved Mondo-Mlx-regulated process, does not promote dietary sugar tolerance. In contrast, survival of larvae with reduced fatty acid synthase expression is sugar-dependent. Our data demonstrate that the transcriptional network regulated by Mondo-Mlx is a critical determinant of the healthful dietary spectrum allowing Drosophila to exploit sugar-rich nutrient sources. PMID:23593032

  14. Predictors of Abnormal Glucose Tolerance in the Early Postpartum Period in Patients with Gestational Diabetes.

    PubMed

    Inoue, Shigeru; Shinagawa, Takaaki; Horinouchi, Takashi; Kozuma, Yutaka; Yonemoto, Koji; Hori, Daizo; Ushijima, Kimio

    2016-01-01

    This study was designed to investigate the clinical predictors of abnormal glucose tolerance 5-7 weeks after delivery. Subjects were 155 women diagnosed with gestational diabetes mellitus (GDM) between October 2005 and September 2013 whose pregnancy and delivery were managed at our center. Subjects were divided into a normal glucose tolerance group (NGT; n = 113), or abnormal glucose tolerance group (AGT; n = 42) with borderline or overt diabetes mellitus, based on 75-g oral glucose tolerance test (75 gOGTT) results 5-7 weeks after delivery. We extracted profiles by which abnormal glucose tolerance levels 5-7 weeks after delivery were predicted using a classification and regression tree (CART) from parameters measured at the time of GDM diagnosis. Logistic regression analysis was used to determine prediction accuracy. Subjects with fasting plasma glucose (FPG) ≥92 mg/dL and immuno-reactive insulin level <100 μU/mL 60 min after load (IRI60min) at time of diagnosis showed a significantly higher risk of developing abnormal glucose tolerance 5-7 weeks after delivery than subjects with FPG <92 mg/dL (p < 0.0001). Subjects with FPG ≥92 mg/dL and IRI60min ≥ 100 μU/mL had the same risk as those with FPG of <92 mg/dL. Patients with gestational diabetes who met the criteria specified above at diagnosis were at a higher risk of developing diabetes mellitus in the future. By explaining this issue to patients, we expect to improve the rate of postpartum follow-up. This should facilitate early detection of diabetes, and help prevent associated complications.

  15. Tolerance to quaternary ammonium compound disinfectants may enhance growth of Listeria monocytogenes in the food industry.

    PubMed

    Møretrø, Trond; Schirmer, Bjørn C T; Heir, Even; Fagerlund, Annette; Hjemli, Pernille; Langsrud, Solveig

    2017-01-16

    The antibacterial effect of disinfectants is crucial for the control of Listeria monocytogenes in food processing environments. Tolerance of L. monocytogenes to sublethal levels of disinfectants based on quaternary ammonium compounds (QAC) is conferred by the resistance determinants qacH and bcrABC. The presence and distribution of these genes have been anticipated to have a role in the survival and growth of L. monocytogenes in food processing environments where QAC based disinfectants are in common use. In this study, a panel of 680 L. monocytogenes from nine Norwegian meat- and salmon processing plants were grouped into 36 MLVA profiles. The presence of qacH and bcrABC was determined in 101 isolates from the 26 most common MLVA profiles. Five MLVA profiles contained qacH and two contained bcrABC. Isolates with qacH and bcrABC showed increased tolerance to the QAC Benzalkonium chloride (BC), with minimal inhibitory concentrations (MICs) of 5-12, 10-13 and <5ppm for strains with qacH (two allele variants observed), bcrABC, and neither gene, respectively. Isolates with qacH or bcrABC were not more tolerant to BC in bactericidal tests in suspension or in biofilms compared with isolates lacking the genes. Water residue samples collected from surfaces in meat processing plants after QAC disinfection had bactericidal effect against L. monocytogenes when the sample BC levels were high (>100ppm). A sample with lower BC concentrations (14ppm of chain length C-12 and 2.7ppm of chain length C-14) inhibited growth of L. monocytogenes not containing bcrABC or qacH, compared to strains with these genes. The study has shown that L. monocytogenes harbouring the QAC resistance genes qacH and bcrABC are prevalent in the food industry and that residuals of QAC may be present in concentrations after sanitation in the industry that result in a growth advantage for bacteria with such resistance genes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko-Batuangus Nature Reserve, Sulawesi, Indonesia

    PubMed Central

    Duboscq, Julie; Micheletta, Jérôme; Agil, Muhammad; Hodges, Keith; Thierry, Bernard; Engelhardt, Antje

    2013-01-01

    In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared-teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared-teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the

  17. [Usefulness of peristalsis, flatulence and evacuation for predicting oral route tolerance in patients subjected to major abdominal surgery].

    PubMed

    Hernández-Hernández, Betsabé; Figueroa-Gallaga, Luis; Sánchez-Castrillo, Christian; Belmonte-Montes, Carlos

    2007-01-01

    to evaluate the usefulness of bowel sounds, flatus and bowel movement presence to predict tolerance of oral intake in patients following major abdominal surgery. nutrition is one of the most important factors in the management of postoperative care. The early oral intake has shown to contribute to a faster recovery. Traditionally the beginning of postoperative feeding after major abdominal surgery is delayed until bowel sounds, flatus and/or bowel movement are present although there is no enough medical evidence for their usefulness. We studied 88 patients following major abdominal surgery. We registered the presence of bowel sounds, flatus and bowel movement each 24 hours in the postoperative period. We analized the relationship between the presence of these signs and the ability to tolerate oral intake. Predictive values, sensitivity, specificity and ROC curves were calculated. results shown that bowel sounds have an acCeptable sensibility but a very low specificity to predict the ability to tolerate oral intake. Unlike bowel sounds, bowel movements shown a low sensibility and a high specificity. Flatus turned out to have and intermediate sensitivity and specificity in the prediction of tolerance of oral feeding. in this study any of these signs were shown as a reliable indicator for beginning oral feeding because they have a moderate to low usefulness.

  18. A Randomized, Crossover Clinical Trial of Exoskeletal-Assisted Walking to Improve Mobility, Bowel Function, and Cardiometabolic Profiles in Persons with SCI

    DTIC Science & Technology

    2017-10-01

    lipid profile, total testosterone, estradiol levels, and quality of life (QOL). 2. KEYWORDS: Powered exoskeletons, paraplegia, tetraplegia...high density lipoprotein, lipid profile, orthostatic tolerance, total testosterone, estradiol, quality of life , ReWalk, and Ekso 3. ACCOMPLISHMENTS...Nothing to Report What was the impact on society beyond science and technology? Nothing to Report 5. CHANGES/PROBLEMS: Nothing to Report

  19. Interception of the development of self tolerance in fetal lambs.

    PubMed

    McCullagh, P

    1989-08-01

    Investigation of the nature of immunological self tolerance has usually relied upon experimental protocols in which the tolerant state is interrupted in mature animals with the production of autoimmune disease. While such research has improved the understanding of those processes operative in overt autoimmunity, it has not been informative in relation to events associated with the establishment of self tolerance. Any description of this state which is to be based on observation will necessitate the use of experimental systems that permit observation of animals during the development of self tolerance. The present experiment entailed intervention approximately one third of the way through the gestation period of fetal lambs. An earlier experiment had established that 54-day fetal lambs would accept allografts of adult skin. This indicated that the capacity to discriminate between self and non-self had not been acquired at that age. Fetuses at this stage of gestation were submitted to either partial or total removal of the thyroid gland. The excised tissue was then implanted in nude mice for periods of 5 to 9 weeks. It was subsequently replaced subcutaneously, either in the original donor or in another fetus at a comparable stage of gestation. At postmortem examination, several weeks later, self implants in lambs from which the thyroid gland had been completely removed displayed autoimmune thyroiditis of varying degrees of severity. However, self implants in partially thyroidectomized animals were uniformly free from autoimmune manifestations. This implied that these reactions had not been directed against contaminating murine tissues in the implants replaced in completely thyroidectomized lambs. All allogeneic implants were subject to vey heavy lymphocytic infiltration, usually with accompanying necrosis consistent with allograft rejection. This was taken as an indication that hypothyroid fetal lambs had become immunocompetent by the time of thyroid reimplantation

  20. Evaluation of Multiple Immunoassay Technology Platforms to Select the Anti-Drug Antibody Assay Exhibiting the Most Appropriate Drug and Target Tolerance

    PubMed Central

    Collet-Brose, Justine

    2016-01-01

    The aim of this study was, at the assay development stage and thus with an appropriate degree of rigor, to select the most appropriate technology platform and sample pretreatment procedure for a clinical ADA assay. Thus, ELISA, MSD, Gyrolab, and AlphaLISA immunoassay platforms were evaluated in association with target depletion and acid dissociation sample pretreatment steps. An acid dissociation step successfully improved the drug tolerance for all 4 technology platforms and the required drug tolerance was achieved with the Gyrolab and MSD platforms. The target tolerance was shown to be better for the ELISA format, where an acid dissociation treatment step alone was sufficient to achieve the desired target tolerance. However, inclusion of a target depletion step in conjunction with the acid treatment raised the target tolerance to the desired level for all of the technologies. A higher sensitivity was observed for the MSD and Gyrolab assays and the ELISA, MSD, and Gyrolab all displayed acceptable interdonor variability. This study highlights the usefulness of evaluating the performance of different assay platforms at an early stage in the assay development process to aid in the selection of the best fit-for-purpose technology platform and sample pretreatment steps. PMID:27243038

  1. Development of radiation tolerant components for the Quench Protection System at CERN

    NASA Astrophysics Data System (ADS)

    Bitterling, O.; Denz, R.; Steckert, J.; Uznanski, S.

    2016-01-01

    This paper describes the results of irradiation campaigns with the high resolution Analog to Digital Converter (ADC) ADS1281. This ADC will be used as part of a revised quench detection circuit for the 600 A corrector magnets at the CERN Large Hadron Collider (LHC) . To verify the radiation tolerance of the ADC an irradiation campaign using a proton beam, applying doses up to 3,4 kGy was conducted. The resulting data and an analysis of the found failure modes is discussed in this paper. Several mitigation measures are described that allow to reduce the error rate to levels acceptable for operation as part of the LHC QPS.

  2. Which factors influence patients' maximum acceptable waiting time for cataract surgery? - a questionnaire survey.

    PubMed

    Weingessel, Birgit; Richter-Mueksch, Sibylla; Vécsei-Marlovits, Pia V

    2011-05-01

    To evaluate patients’ maximum acceptable waiting time (MAWT) and to assess the determinants of patient perceptions of MAWT. A total of 500 consecutive patients with cataract were asked to fill out a preoperative questionnaire, addressing patients’ MAWT to undergo cataract surgery. Patients’ visual impairment (VF-14 score), education, profession and social status were evaluated, and an ophthalmologic examination was performed. Univariate analysis included Spearman’s correlation test, unpaired Student’s t-test and the Mann–Whitney U test. Univariate and multivariate associations were calculated using unconditional logistic regression. The mean MAWT was 3.17 ± 2.12 months. The mean VF-14 score was 72.10 ± 22.54. Between VF-14 score and MAWT, there was a significant correlation (r = 0.180, p = 0.004). Patients with higher education (high school, university) accepted significantly longer MAWT (3.92 ± 2.38 months versus 3.02 ± 2.00 months, p = 0.009). Patients who had self-noticed visual impairment were nearly four times (OR: 3.88, 95% CI = 2.07–7.28, p < 0.001) more likely to accept only MAWT of <3 months. Patients with low tolerance for waiting had greater self-reported difficulty with vision. Patients’ acceptance of waiting was not associated with clinical visual acuity measures. Education, ability to work, living independently and taking care of dependents were also strong predictors from patients’ perspective. Considering the implementation of standards for waiting lists, these facts should be taken into account. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

  3. Wind profiling based on the optical beam intensity statistics in a turbulent atmosphere.

    PubMed

    Banakh, Victor A; Marakasov, Dimitrii A

    2007-10-01

    Reconstruction of the wind profile from the statistics of intensity fluctuations of an optical beam propagating in a turbulent atmosphere is considered. The equations for the spatiotemporal correlation function and the spectrum of weak intensity fluctuations of a Gaussian beam are obtained. The algorithms of wind profile retrieval from the spatiotemporal intensity spectrum are described and the results of end-to-end computer experiments on wind profiling based on the developed algorithms are presented. It is shown that the developed algorithms allow retrieval of the wind profile from the turbulent optical beam intensity fluctuations with acceptable accuracy in many practically feasible laser measurements set up in the atmosphere.

  4. Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf.

    PubMed

    Prusty, Manas R; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G Q; Jena, Kshirod K

    2018-01-01

    Cultivated rice ( Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na + exclusion mechanism in root which removes Na + from the xylem stream by membrane Na + and K + transporters, and resulted in low Na + accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species ( O . alta, O . latifolia , and O . coarctata ) and four species ( O . rhizomatis, O . eichingeri, O . minuta , and O . grandiglumis ) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na + concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na + in leaf of wild species might be affected by OsHKT1;4 -mediated Na + exclusion in

  5. Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf

    PubMed Central

    Prusty, Manas R.; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G. Q.; Jena, Kshirod K.

    2018-01-01

    Cultivated rice (Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na+ exclusion mechanism in root which removes Na+ from the xylem stream by membrane Na+ and K+ transporters, and resulted in low Na+ accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species (O. alta, O. latifolia, and O. coarctata) and four species (O. rhizomatis, O. eichingeri, O. minuta, and O. grandiglumis) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na+ concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na+ in leaf of wild species might be affected by OsHKT1;4-mediated Na+ exclusion in leaf and the following Na

  6. Measuring Acceptance of Sleep Difficulties: The Development of the Sleep Problem Acceptance Questionnaire.

    PubMed

    Bothelius, Kristoffer; Jernelöv, Susanna; Fredrikson, Mats; McCracken, Lance M; Kaldo, Viktor

    2015-11-01

    Acceptance may be an important therapeutic process in sleep medicine, but valid psychometric instruments measuring acceptance related to sleep difficulties are lacking. The purpose of this study was to develop a measure of acceptance in insomnia, and to examine its factor structure as well as construct validity. In a cross-sectional design, a principal component analysis for item reduction was conducted on a first sample (A) and a confirmatory factor analysis on a second sample (B). Construct validity was tested on a combined sample (C). Questionnaire items were derived from a measure of acceptance in chronic pain, and data were gathered through screening or available from pretreatment assessments in four insomnia treatment trials, administered online, via bibliotherapy and in primary care. Adults with insomnia: 372 in sample A and 215 in sample B. Sample C (n = 820) included sample A and B with another 233 participants added. Construct validity was assessed through relations with established acceptance and sleep scales. The principal component analysis presented a two-factor solution with eight items, explaining 65.9% of the total variance. The confirmatory factor analysis supported the solution. Acceptance of sleep problems was more closely related to subjective symptoms and consequences of insomnia than to diary description of sleep, or to acceptance of general private events. The Sleep Problem Acceptance Questionnaire (SPAQ), containing the subscales "Activity Engagement" and "Willingness", is a valid tool to assess acceptance of insomnia. © 2015 Associated Professional Sleep Societies, LLC.

  7. Large Root Cortical Cell Size Improves Drought Tolerance in Maize1[C][W][OPEN

    PubMed Central

    Chimungu, Joseph G.; Brown, Kathleen M.

    2014-01-01

    The objective of this study was to test the hypothesis that large cortical cell size (CCS) would improve drought tolerance by reducing root metabolic costs. Maize (Zea mays) lines contrasting in root CCS measured as cross-sectional area were grown under well-watered and water-stressed conditions in greenhouse mesocosms and in the field in the United States and Malawi. CCS varied among genotypes, ranging from 101 to 533 µm2. In mesocosms, large CCS reduced respiration per unit of root length by 59%. Under water stress in mesocosms, lines with large CCS had between 21% and 27% deeper rooting (depth above which 95% of total root length is located in the soil profile), 50% greater stomatal conductance, 59% greater leaf CO2 assimilation, and between 34% and 44% greater shoot biomass than lines with small CCS. Under water stress in the field, lines with large CCS had between 32% and 41% deeper rooting (depth above which 95% of total root length is located in the soil profile), 32% lighter stem water isotopic ratio of 18O to 16O signature, signifying deeper water capture, between 22% and 30% greater leaf relative water content, between 51% and 100% greater shoot biomass at flowering, and between 99% and 145% greater yield than lines with small cells. Our results are consistent with the hypothesis that large CCS improves drought tolerance by reducing the metabolic cost of soil exploration, enabling deeper soil exploration, greater water acquisition, and improved growth and yield under water stress. These results, coupled with the substantial genetic variation for CCS in diverse maize germplasm, suggest that CCS merits attention as a potential breeding target to improve the drought tolerance of maize and possibly other cereal crops. PMID:25293960

  8. Comparative Proteomic Analysis of Tolerance and Adaptation of Ethanologenic Saccharomyces cerevisiae to Furfural, a Lignocellulosic Inhibitory Compound▿ †

    PubMed Central

    Lin, Feng-Ming; Qiao, Bin; Yuan, Ying-Jin

    2009-01-01

    The molecular mechanism involved in tolerance and adaptation of ethanologenic Saccharomyces cerevisiae to inhibitors (such as furfural, acetic acid, and phenol) represented in lignocellulosic hydrolysate is still unclear. Here, 18O-labeling-aided shotgun comparative proteome analysis was applied to study the global protein expression profiles of S. cerevisiae under conditions of treatment of furfural compared with furfural-free fermentation profiles. Proteins involved in glucose fermentation and/or the tricarboxylic acid cycle were upregulated in cells treated with furfural compared with the control cells, while proteins involved in glycerol biosynthesis were downregulated. Differential levels of expression of alcohol dehydrogenases were observed. On the other hand, the levels of NADH, NAD+, and NADH/NAD+ were reduced whereas the levels of ATP and ADP were increased. These observations indicate that central carbon metabolism, levels of alcohol dehydrogenases, and the redox balance may be related to tolerance of ethanologenic yeast for and adaptation to furfural. Furthermore, proteins involved in stress response, including the unfolded protein response, oxidative stress, osmotic and salt stress, DNA damage and nutrient starvation, were differentially expressed, a finding that was validated by quantitative real-time reverse transcription-PCR to further confirm that the general stress responses are essential for cellular defense against furfural. These insights into the response of yeast to the presence of furfural will benefit the design and development of inhibitor-tolerant ethanologenic yeast by metabolic engineering or synthetic biology. PMID:19363068

  9. SU-F-T-475: An Evaluation of the Overlap Between the Acceptance Testing and Commissioning Processes for Conventional Medical Linear Accelerators

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

    Morrow, A; Rangaraj, D; Perez-Andujar, A

    2016-06-15

    Purpose: This work’s objective is to determine the overlap of processes, in terms of sub-processes and time, between acceptance testing and commissioning of a conventional medical linear accelerator and to evaluate the time saved by consolidating the two processes. Method: A process map for acceptance testing for medical linear accelerators was created from vendor documentation (Varian and Elekta). Using AAPM TG-106 and inhouse commissioning procedures, a process map was created for commissioning of said accelerators. The time to complete each sub-process in each process map was evaluated. Redundancies in the processes were found and the time spent on each weremore » calculated. Results: Mechanical testing significantly overlaps between the two processes - redundant work here amounts to 9.5 hours. Many beam non-scanning dosimetry tests overlap resulting in another 6 hours of overlap. Beam scanning overlaps somewhat - acceptance tests include evaluating PDDs and multiple profiles but for only one field size while commissioning beam scanning includes multiple field sizes and depths of profiles. This overlap results in another 6 hours of rework. Absolute dosimetry, field outputs, and end to end tests are not done at all in acceptance testing. Finally, all imaging tests done in acceptance are repeated in commissioning, resulting in about 8 hours of rework. The total time overlap between the two processes is about 30 hours. Conclusion: The process mapping done in this study shows that there are no tests done in acceptance testing that are not also recommended to do for commissioning. This results in about 30 hours of redundant work when preparing a conventional linear accelerator for clinical use. Considering these findings in the context of the 5000 linacs in the United states, consolidating acceptance testing and commissioning would have allowed for the treatment of an additional 25000 patients using no additional resources.« less

  10. Tolerance assays: measuring the unknown.

    PubMed

    Newell, Kenneth A; Larsen, Christian P

    2006-06-15

    Distinguishing transplant recipients who will benefit from a reduction in, or even the withdrawal of, immunosuppression from those who require intensive, lifelong immunosuppression will be dependent on developing strategies for immune monitoring. Currently, no assays have been shown to accurately predict the development or presence of donor-specific tolerance in humans after transplantation. In this overview we describe and discuss those assays that we believe may be useful for identifying tolerant transplant recipients. Validation of "tolerance" assays will be critical for the safe development of tolerance regimens in humans.

  11. Comparative Investigation of Copper Tolerance and Identification of Putative Tolerance Related Genes in Tardigrades.

    PubMed

    Hygum, Thomas L; Fobian, Dannie; Kamilari, Maria; Jørgensen, Aslak; Schiøtt, Morten; Grosell, Martin; Møbjerg, Nadja

    2017-01-01

    Tardigrades are microscopic aquatic animals renowned for their tolerance toward extreme environmental conditions. The current study is the first to investigate their tolerance toward heavy metals and we present a novel tardigrade toxicant tolerance assay based on activity assessments as a measure of survival. Specifically, we compare tolerance toward copper in four species representing different evolutionary lineages, habitats and adaptation strategies, i.e., a marine heterotardigrade, Echiniscoides sigismundi , a limno-terrestrial heterotardigrade, Echiniscus testudo , a limno-terrestrial eutardigrade, Ramazzottius oberhaeuseri , and a marine eutardigrade, Halobiotus crispae . The latter was sampled at a time of year, when the population is predominantly represented by aberrant P1 cysts, while the other species were in normal active states prior to exposure. Based on volume measurements and a general relation between body mass and copper tolerance, expected tardigrade EC50 values were estimated at 0.5-2 μg l -1 . Following 24 h of exposure, tolerance was high with no apparent link to lineage or habitat. EC50s (95% CI), 24 h after exposure, were estimated at 178 (168-186) and 310 (295-328) μg l -1 , respectively, for E. sigismundi and R. oberhaeuseri , whereas E. testudo and H. crispae were less affected. Highest tolerance was observed in H. crispae with a mean ± s.e.m . activity of 77 ± 2% ( n = 3) 24 h after removal from ~3 mg l -1 copper, suggesting that tardigrade cysts have increased tolerance toward toxicants. In order to identify putative tolerance related genes, an E. sigismundi transcriptome was searched for key enzymes involved in osmoregulation, antioxidant defense and copper metabolism. We found high expression of Na/K ATPase and carbonic anhydrase, known targets for copper. Our transcriptome, furthermore, revealed high expression of antioxidant enzymes, copper transporters, ATOX1, and a Cu-ATPase. In summary, our results indicate that tardigrades

  12. Low-flow profiles of the Tennessee River tributaries in Georgia

    USGS Publications Warehouse

    Carter, R.F.; Hopkins, E.H.; Perlman, H.A.

    1988-01-01

    Low flow information is provided for use in an evaluation of the capacity of streams to permit withdrawals or to accept waste loads without exceeding the limits of State water quality standards. The purpose of this report is to present the results of a compilation of available low flow data in the form of tables and ' 7Q10 flow profiles ' (minimum average flow for 7 consecutive days with a 10-yr recurrence interval) (7Q10 flow plotted against distance along a stream channel) for all stream reaches of the Tennessee River tributaries where sufficient data of acceptable accuracy are available. Drainage area profiles are included for all stream basins larger than 5 sq mi, except for those in a few remote areas. This report is the fifth in a series of reports that will cover all stream basins north of the Fall Line in Georgia. It includes the parts of the Tennessee River basin in Georgia. Flow records were not adjusted for diversions or other factors that cause measured flows to represent other than natural flow conditions. The 7-day minimum flow profile was omitted for stream reaches where natural flow was known to be altered significantly. (Lantz-PTT)

  13. Molecular Characterization of Acquired Tolerance of Tumor Cells to Picropodophyllin (PPP)

    PubMed Central

    Hashemi, Jamileh; Worrall, Claire; Vasilcanu, Daiana; Fryknäs, Mårten; Sulaiman, Luqman; Karimi, Mohsen; Weng, Wen-Hui; Lui, Weng-Onn; Rudduck, Christina; Axelson, Magnus; Jernberg-Wiklund, Helena; Girnita, Leonard; Larsson, Olle; Larsson, Catharina

    2011-01-01

    Background Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment. Methodology/Principal Findings Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/ amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines. Conclusions Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions. PMID:21423728

  14. Molecular characterization of acquired tolerance of tumor cells to picropodophyllin (PPP).

    PubMed

    Hashemi, Jamileh; Worrall, Claire; Vasilcanu, Daiana; Fryknäs, Mårten; Sulaiman, Luqman; Karimi, Mohsen; Weng, Wen-Hui; Lui, Weng-Onn; Rudduck, Christina; Axelson, Magnus; Jernberg-Wiklund, Helena; Girnita, Leonard; Larsson, Olle; Larsson, Catharina

    2011-03-14

    Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment. Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines. Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions.

  15. Immune Tolerance in Multiple Sclerosis

    PubMed Central

    Goverman, Joan M.

    2011-01-01

    Summary Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been indentified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin-specific T cells. PMID:21488900

  16. Subarachnoid haemorrhage guidelines and clinical practice: a cross-sectional study of emergency department consultants' and neurospecialists' views and risk tolerances.

    PubMed

    Lansley, J; Selai, C; Krishnan, A S; Lobotesis, K; Jäger, H R

    2016-09-15

    To establish if emergency medicine and neuroscience specialist consultants have different risk tolerances for investigation of suspected spontaneous subarachnoid haemorrhage (SAH), and to establish if their risk-benefit appraisals concur with current guidelines. 4 major neuroscience centres in London. 58 consultants in emergency medicine and neuroscience specialities (neurology, neurosurgery and neuroradiology) participated in an anonymous survey. The primary outcome measure was the highest stated acceptable risk of missing SAH in the neurologically intact patient presenting with sudden onset headache. Secondary outcome measures included agreement with guideline recommendations, risk/benefit appraisal and required performance of diagnostic tests, including lumbar puncture. Emergency department clinicians accepted almost 3 times the risk of a missed SAH diagnosis compared with the neuroscience specialists (2.8% vs 1.1%; p=0.02), were more likely to accept a higher risk of missed diagnosis for the benefit of a non-invasive test (p=0.04) and were more likely to disagree with current published guidelines stipulating the need for LP in all CT-negative cases (p=0.001). Divergence from recognised procedures for SAH investigation is often criticised and attributed to a lack of knowledge of guidelines. This study indicates that divergence from guidelines may be explained by alternative risk-benefit appraisals made by doctors with their patients. Guideline recommendations may gain wider acceptance if they accommodate the requirements of the doctors and patients using them. Further study of clinical risk tolerance may help explain patterns of diagnostic test use and other variations in healthcare delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Genome resequencing and transcriptome profiling reveal structural diversity and expression patterns of constitutive disease resistance genes in Huanglongbing-tolerant Poncirus trifoliata and its hybrids

    PubMed Central

    Rawat, Nidhi; Kumar, Brajendra; Albrecht, Ute; Du, Dongliang; Huang, Ming; Yu, Qibin; Zhang, Yi; Duan, Yong-Ping; Bowman, Kim D; Gmitter, Fred G; Deng, Zhanao

    2017-01-01

    Huanglongbing (HLB) is the most destructive bacterial disease of citrus worldwide. While most citrus varieties are susceptible to HLB, Poncirus trifoliata, a close relative of Citrus, and some of its hybrids with Citrus are tolerant to HLB. No specific HLB tolerance genes have been identified in P. trifoliata but recent studies have shown that constitutive disease resistance (CDR) genes were expressed at much higher levels in HLB-tolerant Poncirus hybrids and the expression of CDR genes was modulated by Candidatus Liberibacter asiaticus (CLas), the pathogen of HLB. The current study was undertaken to mine and characterize the CDR gene family in Citrus and Poncirus and to understand its association with HLB tolerance in Poncirus. We identified 17 CDR genes in two citrus genomes, deduced their structures, and investigated their phylogenetic relationships. We revealed that the expansion of the CDR family in Citrus seems to be due to segmental and tandem duplication events. Through genome resequencing and transcriptome sequencing, we identified eight CDR genes in the Poncirus genome (PtCDR1-PtCDR8). The number of SNPs was the highest in PtCDR2 and the lowest in PtCDR7. Most of the deletion and insertion events were observed in the UTR regions of Citrus and Poncirus CDR genes. PtCDR2 and PtCDR8 were in abundance in the leaf transcriptomes of two HLB-tolerant Poncirus genotypes and were also upregulated in HLB-tolerant, Poncirus hybrids as revealed by real-time PCR analysis. These two CDR genes seem to be good candidate genes for future studies of their role in citrus-CLas interactions. PMID:29152310

  18. Drought tolerance in potato (S. tuberosum L.): Can we learn from drought tolerance research in cereals?

    PubMed

    Monneveux, Philippe; Ramírez, David A; Pino, María-Teresa

    2013-05-01

    Drought tolerance is a complex trait of increasing importance in potato. Our knowledge is summarized concerning drought tolerance and water use efficiency in this crop. We describe the effects of water restriction on physiological characteristics, examine the main traits involved, report the attempts to improve drought tolerance through in vitro screening and marker assisted selection, list the main genes involved and analyze the potential interest of native and wild potatoes to improve drought tolerance. Drought tolerance has received more attention in cereals than in potato. The review compares these crops for indirect selection methods available for assessment of drought tolerance related traits, use of genetic resources, progress in genomics, application of water saving techniques and availability of models to anticipate the effects of climate change on yield. It is concluded that drought tolerance improvement in potato could greatly benefit from the transfer of research achievements in cereals. Several promising research directions are presented, such as the use of fluorescence, reflectance, color and thermal imaging and stable isotope techniques to assess drought tolerance related traits, the application of the partial root-zone drying technique to improve efficiency of water supply and the exploitation of stressful memory to enhance hardiness. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. 7 CFR 51.3744 - Tolerances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Standards for Grades of Honey Dew and Honey Ball Type Melons Tolerances § 51.3744 Tolerances. In order to... following tolerances, by count, are provided as specified: (a) U.S. No. 1. 10 percent for melons in any lot... not more than 1 percent for melons affected by decay. (b) U.S. Commercial. 20 percent for melons in...

  20. 7 CFR 51.3744 - Tolerances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Standards for Grades of Honey Dew and Honey Ball Type Melons Tolerances § 51.3744 Tolerances. In order to... following tolerances, by count, are provided as specified: (a) U.S. No. 1. 10 percent for melons in any lot... not more than 1 percent for melons affected by decay. (b) U.S. Commercial. 20 percent for melons in...

  1. Electronic cigarette solutions and resultant aerosol profiles.

    PubMed

    Herrington, Jason S; Myers, Colton

    2015-10-30

    Electronic cigarettes (e-cigarettes) are growing in popularity exponentially. Despite their ever-growing acceptance, their aerosol has not been fully characterized. The current study focused on evaluating e-cigarette solutions and their resultant aerosol for potential differences. A simple sampling device was developed to draw e-cigarette aerosol into a multi-sorbent thermal desorption (TD) tube, which was then thermally extracted and analyzed via a gas chromatography (GC) mass spectrometry (GC-MS) method. This novel application provided detectable levels of over one hundred fifteen volatile organic compounds (VOCs) and semivolatile organic compounds (SVOCs) from a single 40mL puff. The aerosol profiles from four commercially available e-cigarettes were compared to their respective solution profiles with the same GC-MS method. Solution profiles produced upwards of sixty four unidentified and identified (some only tentatively) constituents and aerosol profiles produced upwards of eighty two compounds. Results demonstrated distinct analyte profiles between liquid and aerosol samples. Most notably, formaldehyde, acetaldehyde, acrolein, and siloxanes were found in the aerosol profiles; however, these compounds were never present in the solutions. These results implicate the aerosolization process in the formation of compounds not found in solutions; have potential implications for human health; and stress the need for an emphasis on electronic cigarette aerosol testing. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Nuclear-localized AtHSPR links abscisic acid-dependent salt tolerance and antioxidant defense in Arabidopsis.

    PubMed

    Yang, Tao; Zhang, Liang; Hao, Hongyan; Zhang, Peng; Zhu, Haowei; Cheng, Wei; Wang, Yongli; Wang, Xinyu; Wang, Chongying

    2015-12-01

    Salt stress from soil or irrigation water limits plant growth. A T-DNA insertion mutant in C24, named athspr (Arabidopsis thaliana heat shock protein-related), showed several phenotypes, including reduced organ size and enhanced sensitivity to environmental cues. The athspr mutant is severely impaired under salinity levels at which wild-type (WT) plants grow normally. AtHSPR encodes a nuclear-localized protein with ATPase activity, and its expression was enhanced by high salinity and abscisic acid (ABA). Overexpression (OE) of AtHSPR significantly enhanced tolerance to salt stress by increasing the activities of the antioxidant system and by maintaining K(+) /Na(+) homeostasis. Quantitative RT-PCR analyses showed that OE of AtHSPR increased the expression of ABA/stress-responsive, salt overly sensitive (SOS)-related and antioxidant-related genes. In addition, ABA content was reduced in athspr plants with or without salt stress, and exogenous ABA restored WT-like salt tolerance to athspr plants. athspr exhibited increased leaf stomatal density and stomatal index, slower ABA-induced stomatal closure and reduced drought tolerance relative to the WT. AtHSPR OE enhanced drought tolerance by reducing leaf water loss and stomatal aperture. Transcript profiling in athspr showed a differential salt-stress response for genes involved in accumulation of reactive oxygen species (ROS), ABA signaling, cell death, stress response and photosynthesis. Taken together, our results suggested that AtHSPR is involved in salt tolerance in Arabidopsis through modulation of ROS levels, ABA-dependent stomatal closure, photosynthesis and K(+) /Na(+) homeostasis. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  3. Peer Acceptance of Children with Language and Communication Impairments in a Mainstream Primary School: Associations with Type of Language Difficulty, Problem Behaviours and a Change in Placement Organization

    ERIC Educational Resources Information Center

    Laws, Glynis; Bates, Geraldine; Feuerstein, Maike; Mason-Apps, Emily; White, Catherine

    2012-01-01

    This research investigated peer acceptance of children with language and communication impairments attending a language resource base attached to a mainstream school. Compared to other children in their mainstream peer groups, peer acceptance was poor. Peer rejection was more common for children with profiles consistent with an autistic spectrum…

  4. Drought tolerance conferred to sugarcane by association with Gluconacetobacter diazotrophicus: a transcriptomic view of hormone pathways.

    PubMed

    Vargas, Lívia; Santa Brígida, Ailton B; Mota Filho, José P; de Carvalho, Thais G; Rojas, Cristian A; Vaneechoutte, Dries; Van Bel, Michiel; Farrinelli, Laurent; Ferreira, Paulo C G; Vandepoele, Klaas; Hemerly, Adriana S

    2014-01-01

    Sugarcane interacts with particular types of beneficial nitrogen-fixing bacteria that provide fixed-nitrogen and plant growth hormones to host plants, promoting an increase in plant biomass. Other benefits, as enhanced tolerance to abiotic stresses have been reported to some diazotrophs. Here we aim to study the effects of the association between the diazotroph Gluconacetobacter diazotrophicus PAL5 and sugarcane cv. SP70-1143 during water depletion by characterizing differential transcriptome profiles of sugarcane. RNA-seq libraries were generated from roots and shoots of sugarcane plants free of endophytes that were inoculated with G. diazotrophicus and subjected to water depletion for 3 days. A sugarcane reference transcriptome was constructed and used for the identification of differentially expressed transcripts. The differential profile of non-inoculated SP70-1143 suggests that it responds to water deficit stress by the activation of drought-responsive markers and hormone pathways, as ABA and Ethylene. qRT-PCR revealed that root samples had higher levels of G. diazotrophicus 3 days after water deficit, compared to roots of inoculated plants watered normally. With prolonged drought only inoculated plants survived, indicating that SP70-1143 plants colonized with G. diazotrophicus become more tolerant to drought stress than non-inoculated plants. Strengthening this hypothesis, several gene expression responses to drought were inactivated or regulated in an opposite manner, especially in roots, when plants were colonized by the bacteria. The data suggests that colonized roots would not be suffering from stress in the same way as non-inoculated plants. On the other hand, shoots specifically activate ABA-dependent signaling genes, which could act as key elements in the drought resistance conferred by G. diazotrophicus to SP70-1143. This work reports for the first time the involvement of G. diazotrophicus in the promotion of drought-tolerance to sugarcane cv. SP70

  5. Drought Tolerance Conferred to Sugarcane by Association with Gluconacetobacter diazotrophicus: A Transcriptomic View of Hormone Pathways

    PubMed Central

    Vargas, Lívia; Santa Brígida, Ailton B.; Mota Filho, José P.; de Carvalho, Thais G.; Rojas, Cristian A.; Vaneechoutte, Dries; Van Bel, Michiel; Farrinelli, Laurent; Ferreira, Paulo C. G.; Vandepoele, Klaas; Hemerly, Adriana S.

    2014-01-01

    Sugarcane interacts with particular types of beneficial nitrogen-fixing bacteria that provide fixed-nitrogen and plant growth hormones to host plants, promoting an increase in plant biomass. Other benefits, as enhanced tolerance to abiotic stresses have been reported to some diazotrophs. Here we aim to study the effects of the association between the diazotroph Gluconacetobacter diazotrophicus PAL5 and sugarcane cv. SP70-1143 during water depletion by characterizing differential transcriptome profiles of sugarcane. RNA-seq libraries were generated from roots and shoots of sugarcane plants free of endophytes that were inoculated with G. diazotrophicus and subjected to water depletion for 3 days. A sugarcane reference transcriptome was constructed and used for the identification of differentially expressed transcripts. The differential profile of non-inoculated SP70-1143 suggests that it responds to water deficit stress by the activation of drought-responsive markers and hormone pathways, as ABA and Ethylene. qRT-PCR revealed that root samples had higher levels of G. diazotrophicus 3 days after water deficit, compared to roots of inoculated plants watered normally. With prolonged drought only inoculated plants survived, indicating that SP70-1143 plants colonized with G. diazotrophicus become more tolerant to drought stress than non-inoculated plants. Strengthening this hypothesis, several gene expression responses to drought were inactivated or regulated in an opposite manner, especially in roots, when plants were colonized by the bacteria. The data suggests that colonized roots would not be suffering from stress in the same way as non-inoculated plants. On the other hand, shoots specifically activate ABA-dependent signaling genes, which could act as key elements in the drought resistance conferred by G. diazotrophicus to SP70-1143. This work reports for the first time the involvement of G. diazotrophicus in the promotion of drought-tolerance to sugarcane cv. SP70

  6. Induction of tolerance to poison ivy urushiol in the guinea pig by epicutaneous application of the structural analog 5-methyl-3-n-pentadecylcatechol.

    PubMed

    Stampf, J L; Benezra, C; Byers, V; Castagnoli, N

    1986-05-01

    Previous studies have established that epicutaneous application of 5-methyl-3-n-pentadecylcatechol (5-Me-PDC), a synthetic analog of a poison ivy urushiol component, leads to immune tolerance to 3-n-pentadecylcatechol (PDC) in mice. The induction of tolerance by 5-Me-PDC may be mediated by a protein conjugate formed via selective reaction of thiol nucleophiles present on the carrier macromolecule with the corresponding o-quinone derived from the parent catechol. In order to examine further the tolerogenic properties of 5-Me-PDC, we have extended our studies to the guinea pig, the generally accepted experimental species for the study of contact allergy. The results have established that specific immune tolerance to poison ivy urushiol is induced following 2 epicutaneous applications of the PDC analog. Furthermore, we were able to show that the treated animals remained tolerant for at least 6 weeks, a period of time comparable to that observed following the intravenous administration of the O,O-bis-acetyl derivative of PDC. The data point to the possibility of developing a therapeutically effective topical tolerogen for poison ivy contact dermatitis.

  7. Stable Spheromaks with Profile Control

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

    Fowler, T K; Jayakumar, R

    A spheromak equilibrium with zero edge current is shown to be stable to both ideal MHD and tearing modes that normally produce Taylor relaxation in gun-injected spheromaks. This stable equilibrium differs from the stable Taylor state in that the current density j falls to zero at the wall. Estimates indicate that this current profile could be sustained by non-inductive current drive at acceptable power levels. Stability is determined using the NIMROD code for linear stability analysis. Non-linear NIMROD calculations with non-inductive current drive could point the way to improved fusion reactors.

  8. Hot air vulcanization of rubber profiles

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

    Gerlach, J.

    1995-07-01

    Elastomer profiles are deployed in quantity by the automobile industry as seals and wateproofing in coachwork. The high standards demanded by the industry; improvement in weather prediction, noise reduction, restriction of tolerances, together with powerful demand for EPDM force the rubber processing industry into development, particularly of elastomers. Complex proofing systems must also be achieved with extremely complicated profile forms. All too often such profiles have an extremely large surface together with a low cross-section density. They frequently consist of two or three rubber compounds and are steel reinforced. Sometimes they are flocked and coated with a low friction finish.more » Such high-tech seals require an adjustment of the vulcanization method. The consistent trend in the nineties towards lower quantities of elastomer per sealing unit and the dielectric factor, especially with EPDM, has brought an old fashioned vulcanization method once more to the fore, a method developed over the past years to an extremely high standard, namely the hot-air method. This paper describes various vulcanization and curing methods and their relative merits and disadvantages, the Gerlach hot-air concept, the hot air installation concept, and energy saving and efficiency afforded by this technique. 4 figs.« less

  9. IRON-TOLERANT CYANOBACTERIA: IMPLICATIONS FOR ASTROBIOLOGY

    NASA Technical Reports Server (NTRS)

    Brown, Igor I.; Allen, Carlton C.; Mummey, Daniel L.; Sarkisova, Svetlana A.; McKay, David S.

    2006-01-01

    The review is dedicated to the new group of extremophiles - iron tolerant cyanobacteria. The authors have analyzed earlier published articles about the ecology of iron tolerant cyanobacteria and their diversity. It was concluded that contemporary iron depositing hot springs might be considered as relative analogs of Precambrian environment. The authors have concluded that the diversity of iron-tolerant cyanobacteria is understudied. The authors also analyzed published data about the physiological peculiarities of iron tolerant cyanobacteria. They made the conclusion that iron tolerant cyanobacteria may oxidize reduced iron through the photosystem of cyanobacteria. The involvement of both Reaction Centers 1 and 2 is also discussed. The conclusion that iron tolerant protocyanobacteria could be involved in banded iron formations generation is also proposed. The possible mechanism of the transition from an oxygenic photosynthesis to an oxygenic one is also discussed. In the final part of the review the authors consider the possible implications of iron tolerant cyanobacteria for astrobiology.

  10. Chinese Nurses' Acceptance of PDA: A Cross-Sectional Survey Using a Technology Acceptance Model.

    PubMed

    Wang, Yanling; Xiao, Qian; Sun, Liu; Wu, Ying

    2016-01-01

    This study explores Chinese nurses' acceptance of PDA, using a questionnaire based on the framework of Technology Acceptance Model (TAM). 357 nurses were involved in the study. The results reveal the scores of the nurses' acceptance of PDA were means 3.18~3.36 in four dimensions. The younger of nurses, the higher nurses' title, the longer previous usage time, the more experienced using PDA, and the more acceptance of PDA. Therefore, the hospital administrators may change strategies to enhance nurses' acceptance of PDA, and promote the wide application of PDA.

  11. Transcriptomic analysis of submergence-tolerant and sensitive Brachypodium distachyon ecotypes reveals oxidative stress as a major tolerance factor

    PubMed Central

    Rivera-Contreras, Irma Karla; Zamora-Hernández, Teresa; Huerta-Heredia, Ariana Arlene; Capataz-Tafur, Jacqueline; Barrera-Figueroa, Blanca Estela; Juntawong, Piyada; Peña-Castro, Julián Mario

    2016-01-01

    When excessive amounts of water accumulate around roots and aerial parts of plants, submergence stress occurs. To find the integrated mechanisms of tolerance, we used ecotypes of the monocot model plant Brachypodium distachyon to screen for genetic material with contrasting submergence tolerance. For this purpose, we used a set of previously studied drought sensitive/tolerant ecotypes and the knowledge that drought tolerance is positively associated with submergence stress. We decided to contrast aerial tissue transcriptomes of the ecotype Bd21 14-day-old plants as sensitive and ecotype Bd2-3 as tolerant after 2 days of stress under a long-day photoperiod. Gene ontology and the grouping of transcripts indicated that tolerant Bd2-3 differentially down-regulated NITRATE REDUCTASE and ALTERNATIVE OXIDASE under stress and constitutively up-regulated HAEMOGLOBIN, when compared with the sensitive ecotype, Bd21. These results suggested the removal of nitric oxide, a gaseous phytohormone and concomitant reactive oxygen species as a relevant tolerance determinant. Other mechanisms more active in tolerant Bd2-3 were the pathogen response, glyoxylate and tricarboxylic acid cycle integration, and acetate metabolism. This data set could be employed to design further studies on the basic science of plant tolerance to submergence stress and its biotechnological application in the development of submergence-tolerant crops. PMID:27282694

  12. Accelerating Information Retrieval from Profile Hidden Markov Model Databases.

    PubMed

    Tamimi, Ahmad; Ashhab, Yaqoub; Tamimi, Hashem

    2016-01-01

    Profile Hidden Markov Model (Profile-HMM) is an efficient statistical approach to represent protein families. Currently, several databases maintain valuable protein sequence information as profile-HMMs. There is an increasing interest to improve the efficiency of searching Profile-HMM databases to detect sequence-profile or profile-profile homology. However, most efforts to enhance searching efficiency have been focusing on improving the alignment algorithms. Although the performance of these algorithms is fairly acceptable, the growing size of these databases, as well as the increasing demand for using batch query searching approach, are strong motivations that call for further enhancement of information retrieval from profile-HMM databases. This work presents a heuristic method to accelerate the current profile-HMM homology searching approaches. The method works by cluster-based remodeling of the database to reduce the search space, rather than focusing on the alignment algorithms. Using different clustering techniques, 4284 TIGRFAMs profiles were clustered based on their similarities. A representative for each cluster was assigned. To enhance sensitivity, we proposed an extended step that allows overlapping among clusters. A validation benchmark of 6000 randomly selected protein sequences was used to query the clustered profiles. To evaluate the efficiency of our approach, speed and recall values were measured and compared with the sequential search approach. Using hierarchical, k-means, and connected component clustering techniques followed by the extended overlapping step, we obtained an average reduction in time of 41%, and an average recall of 96%. Our results demonstrate that representation of profile-HMMs using a clustering-based approach can significantly accelerate data retrieval from profile-HMM databases.

  13. Transcriptional Profiling in Cotton Associated with Bacillus Subtilis (UFLA285) Induced Biotic-Stress Tolerance

    USDA-ARS?s Scientific Manuscript database

    Abstract Lint yield and quality in cotton is greatly affected by water-deficit stress. The principal aim of this study was to identify cotton genes associated metabolic pathways involved in the water-deficit stress response. Gene expression profiles were developed for leaf and root tissues subject...

  14. Comparative Investigation of Copper Tolerance and Identification of Putative Tolerance Related Genes in Tardigrades

    PubMed Central

    Hygum, Thomas L.; Fobian, Dannie; Kamilari, Maria; Jørgensen, Aslak; Schiøtt, Morten; Grosell, Martin; Møbjerg, Nadja

    2017-01-01

    Tardigrades are microscopic aquatic animals renowned for their tolerance toward extreme environmental conditions. The current study is the first to investigate their tolerance toward heavy metals and we present a novel tardigrade toxicant tolerance assay based on activity assessments as a measure of survival. Specifically, we compare tolerance toward copper in four species representing different evolutionary lineages, habitats and adaptation strategies, i.e., a marine heterotardigrade, Echiniscoides sigismundi, a limno-terrestrial heterotardigrade, Echiniscus testudo, a limno-terrestrial eutardigrade, Ramazzottius oberhaeuseri, and a marine eutardigrade, Halobiotus crispae. The latter was sampled at a time of year, when the population is predominantly represented by aberrant P1 cysts, while the other species were in normal active states prior to exposure. Based on volume measurements and a general relation between body mass and copper tolerance, expected tardigrade EC50 values were estimated at 0.5–2 μg l−1. Following 24 h of exposure, tolerance was high with no apparent link to lineage or habitat. EC50s (95% CI), 24 h after exposure, were estimated at 178 (168–186) and 310 (295–328) μg l−1, respectively, for E. sigismundi and R. oberhaeuseri, whereas E. testudo and H. crispae were less affected. Highest tolerance was observed in H. crispae with a mean ± s.e.m. activity of 77 ± 2% (n = 3) 24 h after removal from ~3 mg l−1 copper, suggesting that tardigrade cysts have increased tolerance toward toxicants. In order to identify putative tolerance related genes, an E. sigismundi transcriptome was searched for key enzymes involved in osmoregulation, antioxidant defense and copper metabolism. We found high expression of Na/K ATPase and carbonic anhydrase, known targets for copper. Our transcriptome, furthermore, revealed high expression of antioxidant enzymes, copper transporters, ATOX1, and a Cu-ATPase. In summary, our results indicate that tardigrades

  15. Tralokinumab pharmacokinetics and tolerability when administered by different subcutaneous injection methods and rates

    PubMed Central

    Jain, Meena; Doughty, Diane; Clawson, Corbin; Li, Xiaobai; White, Nicholas; Agoram, Balaji; van der Merwe, René

    2017-01-01

    Objective: Tralokinumab, administered as two 1-mL subcutaneous injections every 2 weeks, at the target dose 300 mg, has been shown to improve lung function in patients with asthma. This study evaluated the pharmacokinetic (PK) and tolerability profile of tralokinumab 300 mg when administered by different rates of subcutaneous injection, as part of a pilot investigation of new injection regimens. Methods: This phase I study randomized 60 healthy adults to receive 300 mg tralokinumab, as two 1-mL subcutaneous injections, each delivered over 10 seconds, or one 2-mL injection delivered over 10 seconds (12 mL/min), 1 minute (2 mL/min), or 12 minutes (0.167 mL/min). Results: No differences in the PK profile of tralokinumab were observed between cohorts. Immediately following injection, injection-site pain intensity (mean (SD)) was lowest following 0.167 mL/min injection (5.1 mm (8.0) via visual analog scale (VAS)) and greatest following 12 mL/min injection (41 mm (27.7) via VAS); with mean injection-site pruritus intensity low for all participants. Two types of local injection-site reactions were observed: erythema (58.3%) and hematoma/bleeding (18.3%). All treatment-emergent adverse events were mild. Conclusions: Tralokinumab 300 mg is well tolerated, with comparable PK, when administered by a single 2-mL injection at different rates of subcutaneous injection vs. two 1-mL injections. PMID:28590244

  16. A proposed protocol for acceptance and constancy control of computed tomography systems: a Nordic Association for Clinical Physics (NACP) work group report.

    PubMed

    Kuttner, Samuel; Bujila, Robert; Kortesniemi, Mika; Andersson, Henrik; Kull, Love; Østerås, Bjørn Helge; Thygesen, Jesper; Tarp, Ivanka Sojat

    2013-03-01

    Quality assurance (QA) of computed tomography (CT) systems is one of the routine tasks for medical physicists in the Nordic countries. However, standardized QA protocols do not yet exist and the QA methods, as well as the applied tolerance levels, vary in scope and extent at different hospitals. To propose a standardized protocol for acceptance and constancy testing of CT scanners in the Nordic Region. Following a Nordic Association for Clinical Physics (NACP) initiative, a group of medical physicists, with representatives from four Nordic countries, was formed. Based on international literature and practical experience within the group, a comprehensive standardized test protocol was developed. The proposed protocol includes tests related to the mechanical functionality, X-ray tube, detector, and image quality for CT scanners. For each test, recommendations regarding the purpose, equipment needed, an outline of the test method, the measured parameter, tolerance levels, and the testing frequency are stated. In addition, a number of optional tests are briefly discussed that may provide further information about the CT system. Based on international references and medical physicists' practical experiences, a comprehensive QA protocol for CT systems is proposed, including both acceptance and constancy tests. The protocol may serve as a reference for medical physicists in the Nordic countries.

  17. Breeding of Freeze-tolerant Yeast and the Mechanisms of Stress-tolerance

    NASA Astrophysics Data System (ADS)

    Hino, Akihiro

    Frozen dough method have been adopted in the baking industry to reduce labor and to produce fresh breads in stores. New freeze-tolerant yeasts for frozen dough preparations were isolated from banana peel and identified. To obtain strains that have fermentative ability even after several months of frozen storage in fermented dough, we attempted to breed new freeze-tolerantstrain. The hybrid between S.cerevisiae, which is a isolated freeze-tolerant strain, and a strain isolated from bakers' yeast with sexual conjugation gave a good quality bread made from frozen dough method. Freeze-tolerant strains showed higher surviving and trehalose accumulating abilities than freeze-sensitive strains. The freeze tolerance of the yeasts was associated with the basal amount of intracellular trehalose after rapid degradation at the onset of the prefermentation period. The complicated metabolic pathway and the regulation system of trehalose in yeast cells are introduced. The trehalose synthesis may act as a metabolic buffer system which contribute to maintain the intracellular inorganic phosphate and as a feedback regulation system in the glycolysis. However, it is not known enough how the trehalose protects yeast cells from stress.

  18. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

    PubMed

    Massart, Annick; Pallier, Annaïck; Pascual, Julio; Viklicky, Ondrej; Budde, Klemens; Spasovski, Goce; Klinger, Marian; Sever, Mehmet Sukru; Sørensen, Søren Schwartz; Hadaya, Karine; Oberbauer, Rainer; Dudley, Christopher; De Fijter, Johan W; Yussim, Alexander; Hazzan, Marc; Wekerle, Thomas; Berglund, David; De Biase, Consuelo; Pérez-Sáez, María José; Mühlfeld, Anja; Orlando, Giuseppe; Clemente, Katia; Lai, Quirino; Pisani, Francesco; Kandus, Aljosa; Baas, Marije; Bemelman, Frederike; Ponikvar, Jadranka Buturovic; Mazouz, Hakim; Stratta, Piero; Subra, Jean-François; Villemain, Florence; Hoitsma, Andries; Braun, Laura; Cantarell, Maria Carmen; Colak, Hulya; Courtney, Aisling; Frasca, Giovanni Maria; Howse, Matthew; Naesens, Maarten; Reischig, Tomas; Serón, Daniel; Seyahi, Nurhan; Tugmen, Cem; Alonso Hernandez, Angel; Beňa, Luboslav; Biancone, Luigi; Cuna, Vania; Díaz-Corte, Carmen; Dufay, Alexandre; Gaasbeek, André; Garnier, Arnaud; Gatault, Philippe; Gentil Govantes, Miguel Angel; Glowacki, François; Gross, Oliver; Hurault de Ligny, Bruno; Huynh-Do, Uyen; Janbon, Bénédicte; Jiménez Del Cerro, Luis Antonio; Keller, Frieder; La Manna, Gaetano; Lauzurica, Ricardo; Le Monies De Sagazan, Hervé; Thaiss, Friedrich; Legendre, Christophe; Martin, Séverine; Moal, Marie-Christine; Noël, Christian; Pillebout, Evangeline; Piredda, Gian Benedetto; Puga, Ana Ramírez; Sulowicz, Wladyslaw; Tuglular, Serhan; Prokopova, Michaela; Chesneau, Mélanie; Le Moine, Alain; Guérif, Pierrick; Soulillou, Jean-Paul; Abramowicz, Marc; Giral, Magali; Racapé, Judith; Maggiore, Umberto; Brouard, Sophie; Abramowicz, Daniel

    2016-06-01

    Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  19. MicroRNAs As Potential Targets for Abiotic Stress Tolerance in Plants

    PubMed Central

    Shriram, Varsha; Kumar, Vinay; Devarumath, Rachayya M.; Khare, Tushar S.; Wani, Shabir H.

    2016-01-01

    The microRNAs (miRNAs) are small (20–24 nt) sized, non-coding, single stranded riboregulator RNAs abundant in higher organisms. Recent findings have established that plants assign miRNAs as critical post-transcriptional regulators of gene expression in sequence-specific manner to respond to numerous abiotic stresses they face during their growth cycle. These small RNAs regulate gene expression via translational inhibition. Usually, stress induced miRNAs downregulate their target mRNAs, whereas, their downregulation leads to accumulation and function of positive regulators. In the past decade, investigations were mainly aimed to identify plant miRNAs, responsive to individual or multiple environmental factors, profiling their expression patterns and recognizing their roles in stress responses and tolerance. Altered expressions of miRNAs implicated in plant growth and development have been reported in several plant species subjected to abiotic stress conditions such as drought, salinity, extreme temperatures, nutrient deprivation, and heavy metals. These findings indicate that miRNAs may hold the key as potential targets for genetic manipulations to engineer abiotic stress tolerance in crop plants. This review is aimed to provide recent updates on plant miRNAs, their biogenesis and functions, target prediction and identification, computational tools and databases available for plant miRNAs, and their roles in abiotic stress-responses and adaptive mechanisms in major crop plants. Besides, the recent case studies for overexpressing the selected miRNAs for miRNA-mediated enhanced abiotic stress tolerance of transgenic plants have been discussed. PMID:27379117

  20. What is clearance worth? Patients' stated risk tolerance for psoriasis treatments.

    PubMed

    Fairchild, Angelyn O; Reed, Shelby D; Johnson, F Reed; Anglin, Greg; Wolka, Anne M; Noel, Rebecca A

    2017-12-01

    The purpose of this study was to provide quantitative evidence of patients' tolerance for therapeutic risks associated with psoriasis treatments that could offer psoriasis improvements beyond the PASI 75 benchmark. We used a discrete-choice experiment in which respondents chose between competing psoriasis treatments characterized by benefits (i.e. reduced plaque severity, reduced plaque area), risks (i.e. 10-year risk of tuberculosis, 10-year risk of death from infection), and treatment regimen. We analyzed choice data using random-parameters logit models for psoriasis affecting the body, face, or hands. Of 927 eligible members of the National Psoriasis Foundation who completed the survey, 28% were unwilling to accept any greater risk of treatment-related infection mortality. Among the remaining 72%, respondents were willing to accept higher risks of infection-related mortality associated with treatment to completely remove plaques covering only 1% of the body, compared to reducing lesions from 10 to 1% of the affected area. This finding was more pronounced for lesions on the face. Most patients placed greater value on eliminating even very small plaques compared to avoiding treatment-related risks. The perceived importance of complete versus near-complete clearance was stronger than previously documented.

  1. A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena.

    PubMed

    Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

    2009-09-01

    The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes.

  2. Texture and acceptability of goat meat frankfurters processed with 3 different sources of fat.

    PubMed

    Bratcher, C L; Dawkins, N L; Solaiman, S; Kerth, C R; Bartlett, J R

    2011-05-01

    The objective of this research was to evaluate the texture and consumer acceptability of goat meat frankfurter formulations with no added fat (NAF), beef fat (BF), or canola oil (CO). Consumer sensory evaluation, fat, and moisture and texture profile analyses were performed on goat meat frankfurters produced with the fat sources BF, CO, and NAF. For sensory evaluations, NAF was less tender (P = 0.007; 4.90 vs. 4.11 and 4.35 for BF and CO, respectively) and the flavor was liked less (P = 0.004; 4.59 vs. 3.83 and 4.30 for BF and CO, respectively); BF was scored as the juiciest (P = 0.003; 3.86 vs. 4.49 and 4.58 for CO and NAF, respectively); and CO had the least amount of flavor (P = 0.029; 3.65 vs. 3.12 and 3.10 for BF and NAF, respectively). Moisture was least (P < 0.001) in CO (46.59%), followed by BF (48.57%) and NAF (55.80%). The amount of fat was not different (P = 0.761) in BF (24.36%) or CO (24.43%) but was less (P < 0.001) in NAF (9.06%), as expected. The NAF had the most protein (P < 0.001; 34.14%), followed by CO (27.98%) and BF (26.07%). For texture profile analyses, NAF had the least hardness value (P = 0.008; 3.92 vs. 4.48 and 4.40 for BF and CO, respectively) and least chewiness value (P = 0.026; 2.89 vs. 3.39 and 3.29 for BF and CO, respectively). Beef fat and CO were not different for hardness (P = 0.596) or chewiness (P = 0.530). No differences were observed in springiness (P = 0.954) or resilience (P = 0.561). The sensory panelists tended to prefer BF for overall acceptability. Results from these data revealed that value-added goat meat products received acceptable sensory scores; therefore, continued research and development will greatly expand the knowledge of goat meat and increase the acceptance of value-added products.

  3. Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice.

    PubMed

    Smith, Douglas A; Bailey, Jessica M; Williams, Diarria; Fantegrossi, William E

    2014-12-01

    The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N,N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

    PubMed Central

    Smith, Douglas A.; Bailey, Jessica M.; Williams, Diarria

    2014-01-01

    The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N,N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context. PMID:25271256

  5. High doses of lercanidipine are better tolerated than other dihydropyridines in hypertensive patients with metabolic syndrome: results from the TOLERANCE study

    PubMed Central

    Barrios, V; Escobar, C; de la Figuera, M; Honorato, J; Llisterri, J L; Segura, J; Calderón, A

    2008-01-01

    Aims/Introduction The TOlerabilidad de LERcanidipino 20 mg frente a Amlodipino y Nifedipino en CondicionEs normales de uso study was aimed to compare the tolerability of high doses of lercanidipine with amlodipine and nifedipine gastro-intestinal therapeutic system (GITS) in the treatment of hypertension in daily clinical practice. Patients/methods Essential hypertensives ≥ 18 years, treated during at least 1 month with lercanidipine 20 mg, amlodipine 10 mg or nifedipine GITS 60 mg, after a previous treatment course of at least 1 month with half the dose of the corresponding drugs were included. We present the data of the subgroup of patients with metabolic syndrome (MetS). Results Three hundred and thirty-seven of the 650 study population fulfilled criteria of MetS, 233 (69.1%) on lercanidipine and 104 (30.9%) on amlodipine/nifedipine GITS. Overall, a significantly lower proportion of lercanidipine-treated patients showed adverse reactions (ARs) when compared with patients receiving other-dihydropyridines (DHPs) (60.1% vs. 73.1%, p = 0.003). Similarly, the most common vasodilation-related ARs (oedema, swelling, flushing and headache) were significantly less frequent in lercanidipine group (all p < 0.01). Conclusion In conclusion, lercanidipine appears to exhibit a better tolerability profile and less vasodilation-related ARs compared with other DHPs in hypertensive patients with MetS. PMID:18355238

  6. Age and Acceptance of Euthanasia.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1980-01-01

    Study explores relationship between age (and sex and race) and acceptance of euthanasia. Women and non-Whites were less accepting because of religiosity. Among older people less acceptance was attributable to their lesser education and greater religiosity. Results suggest that quality of life in old age affects acceptability of euthanasia. (Author)

  7. Explaining tolerance for bitterness in chocolate ice cream using solid chocolate preferences

    PubMed Central

    Harwood, Meriel L.; Loquasto, Joseph R.; Roberts, Robert F.; Ziegler, Gregory R.; Hayes, John E.

    2016-01-01

    Chocolate ice cream is commonly formulated with higher sugar levels than nonchocolate flavors to compensate for the inherent bitterness of cocoa. Bitterness, however, is an integral part of the complex flavor of chocolate. In light of the global obesity epidemic, many consumers and health professionals are concerned about the levels of added sugars in foods. Once a strategy for balancing undesirable bitterness and health concerns regarding added sugars has been developed, the task becomes determining whether that product will be acceptable to the consumer. Thus, the purpose of this research was to manipulate the bitterness of chocolate ice cream to examine how this influences consumer preferences. The main goal of this study was to estimate group rejection thresholds for bitterness in chocolate ice cream, and to see if solid chocolate preferences (dark vs. milk) generalized to ice cream. A food-safe bitter ingredient, sucrose octaacetate, was added to chocolate ice cream to alter bitterness without disturbing other the sensory qualities of the ice cream samples, including texture. Untrained chocolate ice cream consumers participated in a large-scale sensory test by indicating their preferences for blinded pairs of unspiked and spiked samples, where the spiked sample had increasing levels of the added bitterant. As anticipated, the group containing individuals who prefer milk chocolate had a much lower tolerance for bitterness in their chocolate ice cream compared with the group of individuals who prefer dark chocolate; indeed, the dark chocolate group tolerated almost twice as much added bitterant in the ice cream before indicating a significant preference for the unspiked (control) ice cream. This work demonstrates the successful application of the rejection threshold method to a complex dairy food. Estimating rejection thresholds could prove to be an effective tool for determining acceptable formulations or quality limits when considering attributes that become

  8. An investigation of experiential avoidance, emotion dysregulation, and distress tolerance in young adult outpatients with borderline personality disorder symptoms.

    PubMed

    Iverson, Katherine M; Follette, Victoria M; Pistorello, Jacqueline; Fruzzetti, Alan E

    2012-10-01

    In this study we investigated 3 domains of emotional functioning--emotion dysregulation, distress tolerance, and experiential avoidance--in young adult outpatients with borderline personality disorder (BPD) symptoms. Participants were 40 young adult outpatients at a university counseling center who reported current suicidal ideation and met diagnostic criteria for BPD or experienced subthreshold BPD symptoms (i.e., met diagnostic criteria for 3 or 4 symptoms). Participants completed 3 self-report measures of emotional functioning-experiential avoidance (Acceptance and Action Questionnaire-2; Bond et al., 2011; Hayes et al., 2004), emotion dysregulation (Difficulties in Emotion Regulation Scale; Gratz & Roemer, 2004), and distress tolerance (Distress Tolerance Scale; Simons & Gaher, 2005)-and a behavioral measure of distress tolerance (Paced Auditory Serial Addition Task-Computerized; Lejuez, Kahler, & Brown, 2003), in addition to self-report measures of depression and BPD symptom severity. Partial correlations demonstrated that both emotion dysregulation and experiential avoidance were significantly associated with BPD symptom severity after accounting for depression. However, neither the self-report nor behavioral measure of distress tolerance were related to BPD symptom severity. A regression analysis with emotion dysregulation and experiential avoidance as independent variables revealed that only experiential avoidance was significantly associated with BPD symptom severity after controlling for depression symptoms. The current findings suggest that experiential avoidance may be a central process in BPD symptom severity. Future research directions are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  9. Efficacy and Tolerability of Antihypertensive Drugs in Diabetic and Nondiabetic Patients.

    PubMed

    Aslam, Maria; Ahmad, Mobasher; Mobasher, Fizza

    2017-01-01

    The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs) with essential hypertension. The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals) diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP) above 130 mmHg and diastolic blood pressure (DBP) above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI), beta-blocker (βB), calcium-channel blocker (CCB), diuretics (D), angiotensin receptor blocker (ARB) as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July-October). After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP) and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. Significant control in mean BP by all drug groups was observed in "both groups that is patients with diabetes and without diabetes." The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well as DBP. Adverse effects observed were dry cough, pedal edema

  10. Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India.

    PubMed

    Weber, Jacklyn M; Ryan, Kelsey N; Tandon, Rajiv; Mathur, Meeta; Girma, Tsinuel; Steiner-Asiedu, Matilda; Saalia, Firibu; Zaidi, Shujaat; Soofi, Sajid; Okos, Martin; Vosti, Stephen A; Manary, Mark J

    2017-04-01

    Successful treatment of severe acute malnutrition has been achieved with ready-to-use therapeutic food (RUTF), but only 15% of children with severe acute malnutrition receive RUTF. The objective of this study was to determine whether new formulations of RUTF produced using locally available ingredients were acceptable to young children in Ethiopia, Ghana, Pakistan and India. The local RUTFs were formulated using a linear programming tool that allows for inclusion of only local ingredients and minimizes cost. The study consisted of 4 two-arm, crossover, site-randomized food acceptability trials to test the acceptability of an alternative RUTF formula compared with the standard peanut-based RUTF containing powdered milk. Fifty children with moderate wasting in each country were enrolled in the 2-week study. Acceptability was measured by overall consumption, likeability and adverse effects reported by caregivers. Two of the four RUTFs did not include peanut, and all four used alternative dairy proteins rather than milk. The ingredient cost of all of the RUTFs was about 60% of standard RUTF. In Ethiopia, Ghana and India, the local RUTF was tolerated well without increased reports of rash, diarrhoea or vomiting. Children consumed similar amounts of local RUTF and standard RUTF and preferred them similarly as well. In Pakistan, local RUTF was consumed in similar quantities, but mothers perceived that children did not enjoy it as much as standard RUTF. Our results support the further investigation of these local RUTFs in Ethiopia, Ghana and India in equivalency trials and suggest that local RUTFs may be of lower cost. © 2016 John Wiley & Sons Ltd.

  11. SU-F-T-313: Clinical Results of a New Customer Acceptance Test for Elekta VMAT

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

    Rusk, B; Fontenot, J

    Purpose: To report the results of a customer acceptance test (CAT) for VMAT treatments for two matched Elekta linear accelerators. Methods: The CAT tests were performed on two clinically matched Elekta linear accelerators equipped with a 160-leaf MLC. Functional tests included performance checks of the control system during dynamic movements of the diaphragms, MLC, and gantry. Dosimetric tests included MLC picket fence tests at static and variable dose rates and a diaphragm alignment test, all performed using the on-board EPID. Additionally, beam symmetry during arc delivery was measured at the four cardinal angles for high and low dose rate modesmore » using a 2D detector array. Results of the dosimetric tests were analyzed using the VMAT CAT analysis tool. Results: Linear accelerator 1 (LN1) met all stated CAT tolerances. Linear accelerator 2 (LN2) passed the geometric, beam symmetry, and MLC position error tests but failed the relative dose average test for the diaphragm abutment and all three picket fence fields. Though peak doses in the abutment regions were consistent, the average dose was below the stated tolerance corresponding to a leaf junction that was too narrow. Despite this, no significant differences in patient specific VMAT quality assurance measured were observed between the accelerators and both passed monthly MLC quality assurance performed with the Hancock test. Conclusion: Results from the CAT showed LN2 with relative dose averages in the abutment regions of the diaphragm and MLC tests outside the tolerances resulting from differences in leaf gap distances. Tolerances of the dose average tests from the CAT may be small enough to detect MLC errors which do not significantly affect patient QA or the routine MLC tests.« less

  12. Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability

    PubMed Central

    Abrouk, Michael; Levin, Ethan; Brodsky, Merrick; Gandy, Jessica R; Nakamura, Mio; Zhu, Tian Hao; Farahnik, Benjamin; Koo, John; Bhutani, Tina

    2016-01-01

    Introduction The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. PMID:29387603

  13. Identifying a maximum tolerated contour in two-dimensional dose-finding

    PubMed Central

    Wages, Nolan A.

    2016-01-01

    The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

  14. New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance.

    PubMed

    Daiber, A; Wenzel, P; Oelze, M; Münzel, T

    2008-01-01

    Organic nitrates still represent a group of very effective anti-ischemic drugs used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. Long-term therapy with organic nitrates, however, results in a rapid development of nitrate tolerance blunting their hemodynamic and antiischemic efficacy. Recent studies revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role for the development of nitrate and crosstolerance. The present review focuses firstly on the role of ALDH-2 for organic nitrate bioactivation and secondly on the role of oxidative stress in the development of tolerance and cross-tolerance (endothelial dysfunction) in response to various organic nitrates. Finally, we would like to draw the reader's attention to the protective properties of the organic nitrate pentaerithrityl tetranitrate (PETN), which, in contrast to all other organic nitrates, is able to upregulate enzymes with a strong antioxidative capacity thereby preventing tolerance and the development of endothelial dysfunction.

  15. Transcriptome Analysis of the Response to NaCl in Suaeda maritima Provides an Insight into Salt Tolerance Mechanisms in Halophytes

    PubMed Central

    Tambat, Subodh; Vasudevan, Madavan

    2016-01-01

    Although salt tolerance is a feature representative of halophytes, most studies on this topic in plants have been conducted on glycophytes. Transcriptome profiles are also available for only a limited number of halophytes. Hence, the present study was conducted to understand the molecular basis of salt tolerance through the transcriptome profiling of the halophyte Suaeda maritima, which is an emerging plant model for research on salt tolerance. Illumina sequencing revealed 72,588 clustered transcripts, including 27,434 that were annotated using BLASTX. Salt application resulted in the 2-fold or greater upregulation of 647 genes and downregulation of 735 genes. Of these, 391 proteins were homologous to proteins in the COGs (cluster of orthologous groups) database, and the majorities were grouped into the poorly characterized category. Approximately 50% of the genes assigned to MapMan pathways showed homology to S. maritima. The majority of such genes represented transcription factors. Several genes also contributed to cell wall and carbohydrate metabolism, ion relation, redox responses and G protein, phosphoinositide and hormone signaling. Real-time PCR was used to validate the results of the deep sequencing for the most of the genes. This study demonstrates the expression of protein kinase C, the target of diacylglycerol in phosphoinositide signaling, for the first time in plants. This study further reveals that the biochemical and molecular responses occurring at several levels are associated with salt tolerance in S. maritima. At the structural level, adaptations to high salinity levels include the remodeling of cell walls and the modification of membrane lipids. At the cellular level, the accumulation of glycinebetaine and the sequestration and exclusion of Na+ appear to be important. Moreover, this study also shows that the processes related to salt tolerance might be highly complex, as reflected by the salt-induced enhancement of transcription factor

  16. Validation of the "Security Needs Assessment Profile" for measuring the profiles of security needs of Chinese forensic psychiatric inpatients.

    PubMed

    Siu, B W M; Au-Yeung, C C Y; Chan, A W L; Chan, L S Y; Yuen, K K; Leung, H W; Yan, C K; Ng, K K; Lai, A C H; Davies, S; Collins, M

    Mapping forensic psychiatric services with the security needs of patients is a salient step in service planning, audit and review. A valid and reliable instrument for measuring the security needs of Chinese forensic psychiatric inpatients was not yet available. This study aimed to develop and validate the Chinese version of the Security Needs Assessment Profile for measuring the profiles of security needs of Chinese forensic psychiatric inpatients. The Security Needs Assessment Profile by Davis was translated into Chinese. Its face validity, content validity, construct validity and internal consistency reliability were assessed by measuring the security needs of 98 Chinese forensic psychiatric inpatients. Principal factor analysis for construct validity provided a six-factor security needs model explaining 68.7% of the variance. Based on the Cronbach's alpha coefficient, the internal consistency reliability was rated as acceptable for procedural security (0.73), and fair for both physical security (0.62) and relational security (0.58). A significant sex difference (p=0.002) in total security score was found. The Chinese version of the Security Needs Assessment Profile is a valid and reliable instrument for assessing the security needs of Chinese forensic psychiatric inpatients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Tolerating Uncertainty: Perceptions of the Future for Ageing Parent Carers and Their Adult Children with Intellectual Disabilities.

    PubMed

    Pryce, Laura; Tweed, Alison; Hilton, Amanda; Priest, Helena M

    2017-01-01

    Improved life expectancy means that more adults with intellectual disabilities are now living with ageing parents. This study explored older families' perceptions of the future. Semi-structured interviews were conducted with nine older parents and three adults with intellectual disabilities and analysed to produce an explanatory thematic framework. 'Tolerating uncertainty' was the major theme in participants' attempts to manage anxieties about the future, encompassing sub-themes of 'accepting the parenting role', 'facing challenges', 'being supported/isolated', 'positive meaning making', 're-evaluating as time moves on' and 'managing future thinking'. Some participants expressed preferences for their future which were in contrast to their parents' views, and provide a unique perspective that has often been neglected in prior research. This research has found commonalities in how families tolerate the uncertainty of the future, but also unique differences that require tailored interventions and prospective action by services. © 2015 John Wiley & Sons Ltd.

  18. Statistical Tolerance and Clearance Analysis for Assembly

    NASA Technical Reports Server (NTRS)

    Lee, S.; Yi, C.

    1996-01-01

    Tolerance is inevitable because manufacturing exactly equal parts is known to be impossible. Furthermore, the specification of tolerances is an integral part of product design since tolerances directly affect the assemblability, functionality, manufacturability, and cost effectiveness of a product. In this paper, we present statistical tolerance and clearance analysis for the assembly. Our proposed work is expected to make the following contributions: (i) to help the designers to evaluate products for assemblability, (ii) to provide a new perspective to tolerance problems, and (iii) to provide a tolerance analysis tool which can be incorporated into a CAD or solid modeling system.

  19. Adjunctive use of a facial moisturizer SPF 30 containing ceramide precursor improves tolerability of topical tretinoin 0.05%: a randomized, investigator-blinded, split-face study.

    PubMed

    Schorr, Ethlynn S; Sidou, Farzi; Kerrouche, Nabil

    2012-09-01

    To assess the benefit of adjunctive use of a SPF 30 moisturizing lotion in reducing local side effects associated with atopical tretinoin cream. This was a randomized, investigator/evaluator-blinded, split-face comparison in subjects with healthy skin. Subjects applied tretinoin cream 0.05% once daily to the whole face and Cetaphil 174; Dermacontrol Moisturizer (CDM) once daily to one side of the face based on randomization. Tolerability, perference and skin hydration were evaluated at each week, and a cosmetic acceptability questionnaire regarding CDM was completed at the end of the study. The majority (about 83% to 86%) of subjects experienced skin irritations on both sides of their face, though predominantly mild for the CDM + tretinoin treated side. Tolerability preferences favored the CDM+tretinoin sides. Adjunctive use of CDM with a topical tretinoin cream improves tolerance of the treatment.

  20. A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena

    PubMed Central

    Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

    2009-01-01

    Background and purpose: The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Experimental approach: Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Key results: Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. Conclusions and implications: The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes. PMID:19563531

  1. Molecular profile of tumor-specific CD8+ T cell hypofunction in a transplantable murine cancer model1

    PubMed Central

    Waugh, Katherine A.; Leach, Sonia M.; Moore, Brandon L.; Bruno, Tullia C.; Buhrman, Jonathan D.; Slansky, Jill E.

    2016-01-01

    Mechanisms of self-tolerance often result in CD8+ tumor-infiltrating lymphocytes (TIL) with a hypofunctional phenotype incapable of tumor clearance. Using a transplantable colon carcinoma model, we found that CD8+ T cells became tolerized in less than 24 hours in an established tumor environment. To define the collective impact of pathways suppressing TIL function, we compared genome-wide mRNA expression of tumor-specific CD8+ T cells from the tumor and periphery. Notably, gene expression induced during TIL hypofunction more closely resembled self-tolerance than viral-exhaustion. Differential gene expression was refined to identify a core set of genes that defined hypofunctional TIL; these data comprise the first “molecular profile” of tumor-specific TIL that are naturally responding and represent a polyclonal repertoire. The molecular profile of TIL was further dissected to determine the extent of overlap and distinction between pathways that collectively restrict T cell functions. As suggested by the molecular profile of TIL, protein expression of inhibitory receptor LAG-3 was differentially regulated throughout prolonged late-G1/early-S phase of the cell cycle. Our data may accelerate efficient identification of combination therapies to boost anti-tumor function of TIL specifically against tumor cells. PMID:27371726

  2. Proteomic analysis of a high aluminum tolerant yeast Rhodotorula taiwanensis RS1 in response to aluminum stress.

    PubMed

    Wang, Chao; Wang, Chang Yi; Zhao, Xue Qiang; Chen, Rong Fu; Lan, Ping; Shen, Ren Fang

    2013-10-01

    Rhodotorula taiwanensis RS1 is a high-aluminum (Al)-tolerant yeast that can survive in Al concentrations up to 200mM. The mechanisms for the high Al tolerance of R. taiwanensis RS1 are not well understood. To investigate the molecular mechanisms underlying Al tolerance and toxicity in R. taiwanensis RS1, Al toxicity-induced changes in the total soluble protein profile were analyzed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry. A total of 33 differentially expressed proteins responding to Al stress were identified from approximately 850 reproducibly detected proteins. Among them, the abundance of 29 proteins decreased and 4 increased. In the presence of 100mM Al, the abundance of proteins involved in DNA transcription, protein translation, DNA defense, Golgi functions and glucose metabolism was decreased. By contrast, Al treatment led to increased abundance of malate dehydrogenase, which correlated with increased malate dehydrogenase activity and the accumulation of intracellular citrate, suggesting that Al-induced intracellular citrate could play an important role in detoxification of Al in R. taiwanensis RS1. © 2013.

  3. Genomic regions associated with freezing tolerance and snow mold tolerance in winter wheat

    USDA-ARS?s Scientific Manuscript database

    Crops grown through the winter are subject to selective pressures that vary with each year’s unique conditions, necessitating tolerance of numerous stress factors. The objective of this study was to identify molecular markers in winter wheat (Triticum aestivum L. em Thell) associated with tolerance...

  4. Analysis of Hand and Wrist Postural Synergies in Tolerance Grasping of Various Objects

    PubMed Central

    Liu, Yuan; Jiang, Li; Yang, Dapeng; Liu, Hong

    2016-01-01

    Human can successfully grasp various objects in different acceptable relative positions between human hand and objects. This grasp functionality can be described as the grasp tolerance of human hand, which is a significant functionality of human grasp. To understand the motor control of human hand completely, an analysis of hand and wrist postural synergies in tolerance grasping of various objects is needed. Ten healthy right-handed subjects were asked to perform the tolerance grasping with right hand using 6 objects of different shapes, sizes and relative positions between human hand and objects. Subjects were wearing CyberGlove attaching motion tracker on right hand, allowing a measurement of the hand and wrist postures. Correlation analysis of joints and inter-joint/inter-finger modules were carried on to explore the coordination between joints or modules. As the correlation between hand and wrist module is not obvious in tolerance grasping, individual analysis of wrist synergies would be more practical. In this case, postural synergies of hand and wrist were then presented separately through principal component analysis (PCA), expressed through the principal component (PC) information transmitted ratio, PC elements distribution and reconstructed angle error of joints. Results on correlation comparison of different module movements can be well explained by the influence factors of the joint movement correlation. Moreover, correlation analysis of joints and modules showed the wrist module had the lowest correlation among all inter-finger and inter-joint modules. Hand and wrist postures were both sufficient to be described by a few principal components. In terms of the PC elements distribution of hand postures, compared with previous investigations, there was a greater proportion of movement in the thumb joints especially the interphalangeal (IP) and opposition rotation (ROT) joint. The research could serve to a complete understanding of hand grasp, and the design

  5. Changes in the retreatment radiation tolerance of the spinal cord with time after the initial treatment.

    PubMed

    Woolley, Thomas E; Belmonte-Beitia, Juan; Calvo, Gabriel F; Hopewell, John W; Gaffney, Eamonn A; Jones, Bleddyn

    2018-06-01

    To estimate, from experimental data, the retreatment radiation 'tolerances' of the spinal cord at different times after initial treatment. A model was developed to show the relationship between the biological effective doses (BEDs) for two separate courses of treatment with the BED of each course being expressed as a percentage of the designated 'retreatment tolerance' BED value, denoted [Formula: see text] and [Formula: see text]. The primate data of Ang et al. ( 2001 ) were used to determine the fitted parameters. However, based on rodent data, recovery was assumed to commence 70 days after the first course was complete, and with a non-linear relationship to the magnitude of the initial BED (BED init ). The model, taking into account the above processes, provides estimates of the retreatment tolerance dose after different times. Extrapolations from the experimental data can provide conservative estimates for the clinic, with a lower acceptable myelopathy incidence. Care must be taken to convert the predicted [Formula: see text] value into a formal BED value and then a practical dose fractionation schedule. Used with caution, the proposed model allows estimations of retreatment doses with elapsed times ranging from 70 days up to three years after the initial course of treatment.

  6. Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children's Oncology Group study.

    PubMed

    DuBois, Steven G; Shusterman, Suzanne; Reid, Joel M; Ingle, Ashish M; Ahern, Charlotte H; Baruchel, Sylvain; Glade-Bender, Julia; Ivy, Percy; Adamson, Peter C; Blaney, Susan M

    2012-04-01

    Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m(2)/day. This study was conducted to evaluate sunitinib given as a powder formulation. Sunitinib 15 mg/m(2) was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated. 12 patients, median age 13 (range 4-21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand-foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 6-36) ng/ml was reached at a median of 4 (range 4-8) h after the first dose. The median exposure (AUC(0-48)) was 585 (range 196-1,059) h ng/l. The median half-life was 23 (range 13-36) h. The median trough concentration measured before day 14 dosing was 32 (range 12-58) ng/ml. The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib.

  7. TOLERANCE TO AMINO ACID MIXTURES AND CASEIN DIGESTS GIVEN INTRAVENOUSLY

    PubMed Central

    Madden, S. C.; Woods, R. R.; Shull, F. W.; Remington, J. H.; Whipple, G. H.

    1945-01-01

    Several synthetic mixtures of natural and racemic crystalline amino acids suitable for the daily nitrogen requirement are tested in dogs for their tolerance upon intravenous injection. Certain mixtures of the ten essential amino acids plus non-essential amino acids exclusive of glutamic acid are accepted without any obvious sign of disturbance even at rates above 10 mg. nitrogen per kilo per minute for quantities greater than 300 mg. per kilo. One such mixture consists in parts per 100 of dl-threonine 7, dl-valine 15, l(-)-leucine 10.9, dl-isoleucine 9.9, l(+)-lysine· HCl·H2O 10.9, dl-tryptophane 3, dl-phenylalanine 9.9, dl-methionine 6, l(+)-histidine·HCl·H2O 5, l(+)-arginine-HCl 5, glycine 9.9, dl-α-alanine 4, dl-serine 2, l(-)-cystine 0.5, and l(-)-tyrosine 1. In addition other well tolerated mixtures included the prolines. When glutamic acid, natural or racemic, is included in similar mixtures vomiting reactions frequently occur at nitrogen rates above 4 mg. per kilo per minute. Vomiting almost always occurs on the first daily injection containing glutamic acid and usually on any subsequent injection containing more than 100 mg. glutamic acid per kilo unless given very slowly. Upon the addition of glycine certain mixtures of the ten essential amino acids show an improved tolerance. Two casein digests tested usually produced vomiting at injection rates above 2 mg. nitrogen per kilo per minute, probably because of their glutamic acid content. No serious reaction has ever occurrred to any mixture of amino acids or casein digest tested. Elimination of minor reactions such as vomiting appears possible and desirable for greater usefulness of these solutions in parenteral feeding. PMID:19871468

  8. Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.

    PubMed

    Nirogi, Ramakrishna; Mudigonda, Koteshwara; Bhyrapuneni, Gopinadh; Muddana, Nageswara Rao; Goyal, Vinod Kumar; Pandey, Santosh Kumar; Palacharla, Raghava Choudary

    2018-05-01

    SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease. The objective of this study was to characterize the safety, tolerability and pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects following single and multiple oral doses. Single doses (5, 15, 50, 100 and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100 mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose) was evaluated using an open-label, two-period, randomized, fed and fasted in a crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored using validated analytical methods. SUVN-502 is safe and well tolerated up to the highest tested single dose of 200 mg in healthy young adults and multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more than dose-proportional over the evaluated dose range. Food and gender did not have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total (AUC 0-∞ , and AUC 0-last ) and peak exposures (C max ) were 2.9- and 2.2-fold higher, respectively, in elderly subjects compared to young subjects. Steady-state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of SUVN-502. SUVN-502 exhibited an acceptable safety, tolerability and pharmacokinetic profile in healthy young adults and elderly subjects. Based on the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to Phase 2 evaluation in patients with moderate AD.

  9. Salt tolerant green crop species for sodium management in space agriculture

    NASA Astrophysics Data System (ADS)

    Yamashita, Masamichi; Hashimoto, Hirofumi; Tomita-Yokotani, Kaori; Shimoda, Toshifumi; Nose, Akihiro; Space Agriculture Task Force, J.

    Ecological system and materials recycling loop of space agriculture are quite tight compared to natural ecological system on Earth. Sodium management will be a keen issue for space agricul-ture. Human nutritional requirements include sodium salt. Since sodium at high concentration is toxic for most of plant growth, excreted sodium of human waste should be removed from compost fertilizer. Use of marine algae is promising for harvesting potassium and other min-erals required for plant growth and returning remained sodium to satisfy human need of its intake. Farming salt tolerant green crop species is another approach to manage sodium problem in both space and terrestrial agriculture. We chose ice plant and New Zealand spinach. These two plant species are widely accepted green vegetable with many recipe. Ice plant can grow at the salinity level of sea water, and contain sodium salt up to 30% of its dry mass. Sodium distributes mainly in its bladder cells. New Zealand spinach is a plant species found in the front zone of sea shore, and tolerant against high salinity as well. Plant body size of both species at harvest is quite large, and easy to farm. Capability of bio-remediation of high saline soil is examined with ice plant and New Zealand spinach. Incubation medium was chosen to contain high concentration of sodium and potassium at the Na/K ratio of human excreta. In case Na/K ratio of plant body grown by this medium is greatly higher than that of incubation medium or soil, these halophytes are effective to remediate soil for farming less tolerant plant crop. Experimental results was less positive in this context.

  10. 40 CFR 180.245 - Streptomycin; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Streptomycin; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.245 Streptomycin; tolerances for residues. (a) General. (1) Tolerances are established for...

  11. 40 CFR 180.637 - Mandipropamid; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Mandipropamid; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.637 Mandipropamid; tolerances for residues. (a) General. Tolerances are established for residues...

  12. 40 CFR 180.245 - Streptomycin; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Streptomycin; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.245 Streptomycin; tolerances for residues. (a) General. (1) Tolerances are established for...

  13. 47 CFR 74.661 - Frequency tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... pursuant to an application filed before March 17, 2005, for tolerance values exceeding those specified... 16, 2003, authorized via certification or verification before March 17, 2005, for tolerance values... 47 Telecommunication 4 2010-10-01 2010-10-01 false Frequency tolerance. 74.661 Section 74.661...

  14. Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

    PubMed

    Appleton, D J; Rand, J S; Sunvold, G D; Priest, J

    2002-03-01

    The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation. Copyright 2002 ESFM and AAFP.

  15. Adaptive laboratory evolution of ethanologenic Zymomonas mobilis strain tolerant to furfural and acetic acid inhibitors.

    PubMed

    Shui, Zong-Xia; Qin, Han; Wu, Bo; Ruan, Zhi-yong; Wang, Lu-shang; Tan, Fu-Rong; Wang, Jing-Li; Tang, Xiao-Yu; Dai, Li-Chun; Hu, Guo-Quan; He, Ming-Xiong

    2015-07-01

    Furfural and acetic acid from lignocellulosic hydrolysates are the prevalent inhibitors to Zymomonas mobilis during cellulosic ethanol production. Developing a strain tolerant to furfural or acetic acid inhibitors is difficul by using rational engineering strategies due to poor understanding of their underlying molecular mechanisms. In this study, strategy of adaptive laboratory evolution (ALE) was used for development of a furfural and acetic acid-tolerant strain. After three round evolution, four evolved mutants (ZMA7-2, ZMA7-3, ZMF3-2, and ZMF3-3) that showed higher growth capacity were successfully obtained via ALE method. Based on the results of profiling of cell growth, glucose utilization, ethanol yield, and activity of key enzymes, two desired strains, ZMA7-2 and ZMF3-3, were achieved, which showed higher tolerance under 7 g/l acetic acid and 3 g/l furfural stress condition. Especially, it is the first report of Z. mobilis strain that could tolerate higher furfural. The best strain, Z. mobilis ZMF3-3, has showed 94.84% theoretical ethanol yield under 3-g/l furfural stress condition, and the theoretical ethanol yield of ZM4 is only 9.89%. Our study also demonstrated that ALE method might also be used as a powerful metabolic engineering tool for metabolic engineering in Z. mobilis. Furthermore, the two best strains could be used as novel host for further metabolic engineering in cellulosic ethanol or future biorefinery. Importantly, the two strains may also be used as novel-tolerant model organisms for the genetic mechanism on the "omics" level, which will provide some useful information for inverse metabolic engineering.

  16. 40 CFR 180.315 - Methamidophos; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Methamidophos; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.315 Methamidophos; tolerances for residues. (a) Tolerances are established for residues of the...

  17. 40 CFR 180.425 - Clomazone; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Clomazone; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.425 Clomazone; tolerances for residues. (a) General. Tolerances are established for residues of...

  18. 40 CFR 180.601 - Cyazofamid; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Cyazofamid; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.601 Cyazofamid; tolerances for residues. (a) General. Tolerances are established for residues of...

  19. 40 CFR 180.478 - Rimsulfuron; tolerances for residues

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Rimsulfuron; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.478 Rimsulfuron; tolerances for residues (a) General. Tolerances are established for residues of...

  20. 40 CFR 180.433 - Fomesafen; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Fomesafen; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.433 Fomesafen; tolerances for residues. (a) General. Tolerances are established for residues of...

  1. 40 CFR 180.627 - Fluopicolide; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Fluopicolide; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.627 Fluopicolide; tolerances for residues. (a) General. Tolerances are established for residues of...

  2. 40 CFR 180.603 - Dinotefuran; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Dinotefuran; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.603 Dinotefuran; tolerances for residues. (a) General. (1) Tolerances are established for residues...

  3. 40 CFR 180.517 - Fipronil; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Fipronil; tolerances for residues. 180... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.517 Fipronil; tolerances for residues. (a) General. Therefore, tolerances are established for combined residues...

  4. Factor Structure and Reliability of the Dutch Version of Seven Scales of the Communication Profile for the Hearing Impaired (CPHI)

    ERIC Educational Resources Information Center

    Mokkink, Lidwine B.; Knol, Dirk L.; Zekveld, Adriana A.; Goverts, S. Theo; Kramer, Sophia E.

    2009-01-01

    Purpose: Seven scales of the Communication Profile for the Hearing Impaired (CPHI; M. E. Demorest & S. A. Erdman, 1987) were translated into Dutch: Maladaptive Behavior, Verbal Strategies, and Nonverbal Strategies (within the area of Communication Strategies) and Self-Acceptance, Acceptance of Loss, Stress, and Withdrawal (within the area of…

  5. Global Transcriptome Analysis Reveals Acclimation-Primed Processes Involved in the Acquisition of Desiccation Tolerance in Boea hygrometrica.

    PubMed

    Zhu, Yan; Wang, Bo; Phillips, Jonathan; Zhang, Zhen-Nan; Du, Hong; Xu, Tao; Huang, Lian-Cheng; Zhang, Xiao-Fei; Xu, Guang-Hui; Li, Wen-Long; Wang, Zhi; Wang, Ling; Liu, Yong-Xiu; Deng, Xin

    2015-07-01

    Boea hygrometrica resurrection plants require a period of acclimation by slow soil-drying in order to survive a subsequent period of rapid desiccation. The molecular basis of this observation was investigated by comparing gene expression profiles under different degrees of water deprivation. Transcripts were clustered according to the expression profiles in plants that were air-dried (rapid desiccation), soil-dried (gradual desiccation), rehydrated (acclimated) and air-dried after acclimation. Although phenotypically indistinguishable, it was shown by principal component analysis that the gene expression profiles in rehydrated, acclimated plants resemble those of desiccated plants more closely than those of hydrated acclimated plants. Enrichment analysis based on gene ontology was performed to deconvolute the processes that accompanied desiccation tolerance. Transcripts associated with autophagy and α-tocopherol accumulation were found to be activated in both air-dried, acclimated plants and soil-dried non-acclimated plants. Furthermore, transcripts associated with biosynthesis of ascorbic acid, cell wall catabolism, chaperone-assisted protein folding, respiration and macromolecule catabolism were activated and maintained during soil-drying and rehydration. Based on these findings, we hypothesize that activation of these processes leads to the establishment of an optimal physiological and cellular state that enables tolerance during rapid air-drying. Our study provides a novel insight into the transcriptional regulation of critical priming responses to enable survival following rapid dehydration in B. hygrometrica. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Metabolomic profiling in Selaginella lepidophylla at various hydration states provides new insights into the mechanistic basis of desiccation tolerance

    USDA-ARS?s Scientific Manuscript database

    Selaginella lepidophylla is one of only a few species of spike mosses (Selaginellaceae) that have evolved desiccation tolerance (DT) or the ability to ‘resurrect’ from an air-dried state. In order to understand the metabolic basis of DT, S. lepidophylla was subjected to a five-stage, rehydration/de...

  7. 40 CFR 180.261 - Phosmet; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Phosmet; tolerances for residues. 180... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.261 Phosmet; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide...

  8. 40 CFR 180.503 - Cymoxanil, tolerance for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Cymoxanil, tolerance for residues. 180... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.503 Cymoxanil, tolerance for residues. (a) General. Tolerances are established for residues of the fungicide...

  9. 40 CFR 180.567 - Zoxamide; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Zoxamide; tolerances for residues. 180... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.567 Zoxamide; tolerances for residues. (a) General. (1) Tolerances are established for residues of zoxamide (3...

  10. 40 CFR 180.567 - Zoxamide; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Zoxamide; tolerances for residues. 180... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.567 Zoxamide; tolerances for residues. (a) General. (1) Tolerances are established for residues of zoxamide (3...

  11. The Paradoxes of Tolerance

    ERIC Educational Resources Information Center

    Pasamonik, Barbara

    2004-01-01

    Teachers who endeavor to build tolerant attitudes in their students often fall into the trap of political correctness. Political correctness can suspend free reflection on the differences inherent in otherness, which is the subject of tolerance, and creates an ideology of the generalized, abstract Other. As a result, teachers prefer to talk about…

  12. Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis

    PubMed Central

    Cortese, Samuele; Adamo, Nicoletta; Mohr-Jensen, Christina; Hayes, Adrian J; Bhatti, Sahar; Carucci, Sara; Del Giovane, Cinzia; Atkinson, Lauren Z; Banaschewski, Tobias; Simonoff, Emily; Zuddas, Alessandro; Barbui, Corrado; Purgato, Marianna; Steinhausen, Hans-Christoph; Shokraneh, Farhad; Xia, Jun; Coghill, David

    2017-01-01

    Introduction Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. Methods and analysis We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and

  13. Wheat TaSP gene improves salt tolerance in transgenic Arabidopsis thaliana.

    PubMed

    Ma, Xiaoli; Cui, Weina; Liang, Wenji; Huang, Zhanjing

    2015-12-01

    A novel salt-induced gene with unknown functions was cloned through analysis of gene expression profile of a salt-tolerant wheat mutant RH8706-49 under salt stress. The gene was named Triticum aestivum salt-related protein (TaSP) and deposited in GenBank (Accession No. KF307326). Quantitative polymerase chain reaction (qPCR) results showed that TaSP expression was induced under salt, abscisic acid (ABA), and polyethylene glycol (PEG) stresses. Subcellular localization revealed that TaSP was mainly localized in cell membrane. Overexpression of TaSP in Arabidopsis could improve salt tolerance of 35S::TaSP transgenic Arabidopsis. 35S::TaSP transgenic Arabidopsis lines after salt stress presented better physiological indexes than the control group. In the non-invasive micro-test (NMT), an evident Na(+) excretion was observed at the root tip of salt-stressed 35S::TaSP transgenic Arabidopsis. TaSP promoter was cloned, and its beta-glucuronidase (GUS) activities before and after ABA, salt, cold, heat, and salicylic acid (SA) stresses were determined. Full-length TaSP promoter contained ABA and salt response elements. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Evaluation of positive G sub Z tolerance following simulated weightlessness (bedrest)

    NASA Technical Reports Server (NTRS)

    Jacobson, L. B.; Hyatt, K. H.; Sullivan, R. W.; Cantor, S. A.; Sandler, H.; Rositano, S. A.; Mancini, R. E.

    1973-01-01

    The magnitude of physiologic changes which are known to occur in human subjects exposed to varying levels of + G sub Z acceleration following bed rest simulation of weightlessness was studied. Bed rest effects were documented by fluid and electrolyte balance studies, maximal exercise capability, 70 deg passive tilt and lower body negative pressure tests and the ability to endure randomly prescribed acceleration profiles of +2G sub Z, +3G sub Z, and +4G sub Z. Six healthy male volunteers were studied during two weeks of bed rest after adequate control observations, followed by two weeks of recovery, followed by a second two-week period of bed rest at which time an Air Force cutaway anti-G suit was used to determine its effectiveness as a countermeasure for observed cardiovascular changes during acceleration. Results showed uniform and significant changes in all measured parameters as a consequence of bed rest including a reduced ability to tolerate +G sub Z acceleration. The use of anti-G suits significantly improved subject tolerance to all G exposures and returned measured parameters such as heart rate and blood pressure towards or to pre-bed-rest (control) values in four of the six cases.

  15. Identification of proteins involved in desiccation tolerance in the red seaweed Pyropia orbicularis (Rhodophyta, Bangiales).

    PubMed

    López-Cristoffanini, Camilo; Zapata, Javier; Gaillard, Fanny; Potin, Philippe; Correa, Juan A; Contreras-Porcia, Loretto

    2015-12-01

    Extreme reduction in cellular water content leads to desiccation, which, if persistent, affects the physiology of organisms, mainly through oxidative stress. Some organisms are highly tolerant to desiccation, including resurrection plants and certain intertidal seaweeds. One such species is Pyropia orbicularis, a rhodophycean that colonizes upper intertidal zones along the Chilean coast. Despite long, daily periods of air exposure due to tides, this alga is highly tolerant to desiccation. The present study examined the proteome of P. orbicularis by 2DE and LC-MS/MS analyses to determine the proteins associated with desiccation tolerance (DT). The results showed that, under natural conditions, there were significant changes in the protein profile during low tide as compared to naturally hydrated plants at high tide. These changes were mainly in newly appeared proteins spots such as chaperones, monodehydroascorbate reductase, and manganese superoxide dismutase, among others. Previously undescribed proteins under desiccation conditions included phycobiliproteins, glyoxalase I, and phosphomannomutase. These changes evidenced that several physiological responses involved in DT are activated during low tide, including decreased photosynthetic activity, increased antioxidant capacity, and the preservation of cell physiology by regulating water content, cell wall structure, and cell volume. Similar responses have been observed in resurrection plants and bryophytes exposed to desiccation. Therefore, the coordinated activation of different desiccation tolerance pathways in P. orbicularis could explain the successful biological performance of this seaweed in the upper intertidal rocky zones. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. FBX aqueous chemical dosimeter for measurement of virtual wedge profiles.

    PubMed

    Semwal, Manoj K; Bansal, Anil K; Thakur, Pradeep K; Vidyasagar, Pandit B

    2008-10-24

    We investigated the ferrous sulfate-benzoic acid-xylenol orange (FBX) aqueous chemical dosimeter for measurement of virtual (dynamic) wedge profiles on a linear accelerator. The layout for irradiation of the FBX-filled tubes mimicked a conventional linear detector array geometry. A comparison of the resulting measurements with film-measured profiles showed that, in the main beam region, the difference between the FBX system and the film system was within +/-2% and that, in the penumbra region, the difference varied from +/-1 mm to +/-2.5 mm in terms of positional equivalence, depending on the size of the dosimeter tubes. We thus believe that the energy-independent FBX dosimetry system can measure virtual wedge profiles with reasonable accuracy at reasonable cost. However, efficiency improvement is required before this dosimetry system can be accepted into routine practice.

  17. Cold tolerance of Littorinidae from southern Africa: intertidal snails are not constrained to freeze tolerance.

    PubMed

    Sinclair, Brent J; Marshall, David J; Singh, Sarika; Chown, Steven L

    2004-11-01

    All intertidal gastropods for which cold tolerance strategies have been assessed have been shown to be freeze tolerant. Thus, freeze tolerance is considered an adaptation to the intertidal environment. We investigated the cold tolerance strategies of three species of subtropical and temperate snails (Gastropoda: Littorinidae) to determine whether this group is phylogenetically constrained to freeze tolerance. We exposed 'dry' acclimated and 'wet' rehydrated snails to low temperatures to determine temperature of crystallisation (Tc), lower lethal temperature and LT(50) and to examine the relationship between ice formation and mortality. Tc was lowest in dry Afrolittorina knysnaensis (-13.6+/-0.4 degrees C), followed by dry Echinolittorina natalensis (-10.9+/-0.2 degrees C) and wet A. knysnaensis (-10.2+/-0.2 degrees C) . The Tc of both A. knysnaensis and E. natalensis increased with rehydration, whereas Tc of dry and wet Afrolittorina africana did not differ (-9.6+/-0.2 and -9.0+/-0.2 degrees C respectively). Wet snails of all species exhibited no or low survival of inoculative freezing, whereas dry individuals of A. knysnaensis could survive subzero temperatures above -8 degrees C when freezing was inoculated with ice . In the absence of external ice, Afrolittorina knysnaensis employs a freeze-avoidance strategy of cold tolerance, the first time this has been reported for an intertidal snail, indicating that there is no family-level phylogenetic constraint to freeze tolerance. Echinolittorina natalensis and A. africana both showed pre-freeze mortality and survival of some internal ice formation, but were not cold hardy in any strict sense.

  18. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.

    PubMed

    Glue, Paul; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, Cheung-Tak; Friedhoff, Lawrence

    2015-02-01

    Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers. © 2014, The American College of Clinical Pharmacology.

  19. 40 CFR 180.413 - Imazalil; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.413 Imazalil; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of..., hay 0.5 Wheat, straw 0.5 (2) Tolerances are established for the combined residues of the fungicide...

  20. LIMS user acceptance testing.

    PubMed

    Klein, Corbett S

    2003-01-01

    Laboratory Information Management Systems (LIMS) play a key role in the pharmaceutical industry. Thorough and accurate validation of such systems is critical and is a regulatory requirement. LIMS user acceptance testing is one aspect of this testing and enables the user to make a decision to accept or reject implementation of the system. This paper discusses key elements in facilitating the development and execution of a LIMS User Acceptance Test Plan (UATP).