Sample records for induction previous studies

  1. Elective repeat caesarean section versus induction of labour for women with a previous caesarean birth.

    PubMed

    Dodd, Jodie M; Crowther, Caroline A; Grivell, Rosalie M; Deussen, Andrea R

    2014-12-19

    When a woman has had a previous caesarean birth and requires induction of labour in a subsequent pregnancy there are two options for her care, an elective repeat caesarean or planned induction of labour. While there are risks and benefits for both elective repeat caesarean birth and planned induction of labour, current sources of information are limited to non-randomised cohort studies. Studies designed in this way have significant potential for bias and consequently any conclusions based on these results are limited in their reliability and should be interpreted with caution. To assess, using the best available evidence, the benefits and harms of elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth, who require induction of labour in a subsequent pregnancy. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 October 2014). Randomised controlled trials with reported data that compared outcomes in mothers and babies for women who planned an elective repeat caesarean section with outcomes in women who planned induction of labour, where a previous birth had been by caesarean. There was no data extraction performed. There were no randomised controlled trials identified. Both planned elective repeat caesarean section and planned induction of labour for women with a prior caesarean birth are associated with benefits and harms. Evidence for these care practices is drawn from non-randomised studies that are associated with potential bias. Any results and conclusions must therefore be interpreted with caution. Randomised controlled trials are required to provide the most reliable evidence regarding the benefits and harms of both planned elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth.

  2. The Hog1 Mitogen-Activated Protein Kinase Mediates a Hypoxic Response in Saccharomyces cerevisiae

    PubMed Central

    Hickman, Mark J.; Spatt, Dan; Winston, Fred

    2011-01-01

    We have studied hypoxic induction of transcription by studying the seripauperin (PAU) genes of Saccharomyces cerevisiae. Previous studies showed that PAU induction requires the depletion of heme and is dependent upon the transcription factor Upc2. We have now identified additional factors required for PAU induction during hypoxia, including Hog1, a mitogen-activated protein kinase (MAPK) whose signaling pathway originates at the membrane. Our results have led to a model in which heme and ergosterol depletion alters membrane fluidity, thereby activating Hog1 for hypoxic induction. Hypoxic activation of Hog1 is distinct from its previously characterized response to osmotic stress, as the two conditions cause different transcriptional consequences. Furthermore, Hog1-dependent hypoxic activation is independent of the S. cerevisiae general stress response. In addition to Hog1, specific components of the SAGA coactivator complex, including Spt20 and Sgf73, are also required for PAU induction. Interestingly, the mammalian ortholog of Spt20, p38IP, has been previously shown to interact with the mammalian ortholog of Hog1, p38. Taken together, our results have uncovered a previously unknown hypoxic-response pathway that may be conserved throughout eukaryotes. PMID:21467572

  3. Induction of labor in grand multiparous women with previous cesarean delivery: how safe is this?

    PubMed

    Chibber, Rachana; Al-Harmi, Jehad; Foda, Mohamed; Mohammed K, Zeinab; Al-Saleh, Eyad; Mohammed, Asiya Tasneem

    2015-02-01

    To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section (CS), so that the safety of labor induction could be assessed. In 102 women (study group), labor was induced and the outcome was compared with 280 women (control group) who went into spontaneous labor. All 382 women were grand multiparous and had one previous CS. There were no significant difference in oxytocin augmentation, CS, scar dehiscence, fetal birth weight or apgar scores between groups. There was one neonatal death, two still births, one early neonatal death and one congenital malformation in the study group and this was not significant. There was no significant difference in vaginal birth in the study (80.9%) and the control group (83.8%). In this moderate-sized study, induction of labor may be a safe option in grand multiparous women, if there is no absolute induction for repeating CS.

  4. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

    PubMed Central

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara EF; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia CM; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M

    2016-01-01

    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

  5. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats.

    PubMed

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara E F; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia C M; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M; Soares, Telma de J

    2016-02-01

    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. © 2016 by the Society for Experimental Biology and Medicine.

  6. Double balloon catheter for induction of labour in Chinese women with previous caesarean section: one-year experience and literature review.

    PubMed

    Cheuk, Queenie K Y; Lo, T K; Lee, C P; Yeung, Anita P C

    2015-06-01

    To evaluate the efficacy and safety of double balloon catheter for induction of labour in Chinese women with one previous caesarean section and unfavourable cervix at term. Retrospective cohort study. A regional hospital in Hong Kong. Women with previous caesarean delivery requiring induction of labour at term and with an unfavourable cervix from May 2013 to April 2014. Primary outcome was to assess rate of successful vaginal delivery (spontaneous or instrument-assisted) using double balloon catheter. Secondary outcomes were double balloon catheter induction-to-delivery and removal-to-delivery interval; cervical score improvement; oxytocin augmentation; maternal or fetal complications during cervical ripening, intrapartum and postpartum period; and risk factors associated with unsuccessful induction. All 24 Chinese women tolerated double balloon catheter well. After double balloon catheter expulsion or removal, the cervix successfully ripened in 18 (75%) cases. The improvement in Bishop score 3 (interquartile range, 2-4) was statistically significant (P<0.001). Overall, 18 (75%) cases were delivered vaginally. The median insertion-to-delivery and removal-to-delivery intervals were 19 (interquartile range, 13.4-23.0) hours and 6.9 (interquartile range, 4.1-10.8) hours, respectively. Compared with cases without, the interval to delivery was statistically significantly shorter in those with spontaneous balloon expulsion or spontaneous membrane rupture during ripening (7.8 vs 3.0 hours; P=0.025). There were no major maternal or neonatal complications. The only factor significantly associated with failed vaginal birth after caesarean was previous caesarean section for failure to progress (P<0.001). This is the first study using double balloon catheter for induction of labour in Asian Chinese women with previous caesarean section. Using double balloon catheter, we achieved a vaginal birth after caesarean rate of 75% without major complications.

  7. The discovery of the causes of leprosy: A computational analysis

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

    Corruble, V.; Ganascia, J.G.

    1996-12-31

    The role played by the inductive inference has been studied extensively in the field of Scientific Discovery. The work presented here tackles the problem of induction in medical research. The discovery of the causes of leprosy is analyzed and simulated using computational means. An inductive algorithm is proposed, which is successful in simulating some essential steps in the progress of the understanding of the disease. It also allows us to simulate the false reasoning of previous centuries through the introduction of some medical a priori inherited form archaic medicine. Corroborating previous research, this problem illustrates the importance of the socialmore » and cultural environment on the way the inductive inference is performed in medicine.« less

  8. Differences in sensitivity of murine spermatogonia and somatic cells in vivo to sister-chromatid exchange induction by nitrosoureas.

    PubMed

    Morales-Ramírez, P; Cruz-Vallejo, V; Rodríguez-Reyes, R

    2001-07-01

    Previously published data indicate that spermatogonia (SPG) are less sensitive to a sister-chromatid exchange (SCE) induction for different mutagens. In an earlier study, we have observed that bromodeoxyuridine (BrdU) substituted murine SPG are less sensitive to SCE induction by gamma ray in cells, than bone marrow (BM) and salivary gland (SG) cells in vivo. This was interpreted to mean that SPG are more efficient in DNA repair or are less prone to SCE induction. That the lower induction of SCE could be due to a reduced accessibility of mutagens to the SPG by virtue of a physiological barrier, was discarded by using gamma radiation. The aim of the present study was to establish whether or not there are differences in SCE induction by nitrosoureas among SPG, SG and BM cells with BrdU substituted or unsubstituted DNA. It was observed that SCE induction by methylnitrosourea (MNU) or by ethylnitrosourea (ENU) in SPG was, respectively, five and two times lower than in SG, and ten and three times lower than in BM. In SPG after BrdU incorporation, there was no increase in efficiency of SCE induction; in fact, there was even a slight decrease by exposure to MNU or ENU. BM and SG cells showed an increased efficiency in SCE induction after BrdU incorporation. This implies that SPG are also less sensitive to SCE induction by nitrosoureas, which cause a different kind of damage from previously assayed mutagens.

  9. A dynamic model of reasoning and memory.

    PubMed

    Hawkins, Guy E; Hayes, Brett K; Heit, Evan

    2016-02-01

    Previous models of category-based induction have neglected how the process of induction unfolds over time. We conceive of induction as a dynamic process and provide the first fine-grained examination of the distribution of response times observed in inductive reasoning. We used these data to develop and empirically test the first major quantitative modeling scheme that simultaneously accounts for inductive decisions and their time course. The model assumes that knowledge of similarity relations among novel test probes and items stored in memory drive an accumulation-to-bound sequential sampling process: Test probes with high similarity to studied exemplars are more likely to trigger a generalization response, and more rapidly, than items with low exemplar similarity. We contrast data and model predictions for inductive decisions with a recognition memory task using a common stimulus set. Hierarchical Bayesian analyses across 2 experiments demonstrated that inductive reasoning and recognition memory primarily differ in the threshold to trigger a decision: Observers required less evidence to make a property generalization judgment (induction) than an identity statement about a previously studied item (recognition). Experiment 1 and a condition emphasizing decision speed in Experiment 2 also found evidence that inductive decisions use lower quality similarity-based information than recognition. The findings suggest that induction might represent a less cautious form of recognition. We conclude that sequential sampling models grounded in exemplar-based similarity, combined with hierarchical Bayesian analysis, provide a more fine-grained and informative analysis of the processes involved in inductive reasoning than is possible solely through examination of choice data. PsycINFO Database Record (c) 2016 APA, all rights reserved.

  10. Finite element residual stress analysis of induction heating bended ferritic steel piping

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

    Kima, Jong Sung; Kim, Kyoung-Soo; Oh, Young-Jin

    2014-10-06

    Recently, there is a trend to apply the piping bended by induction heating process to nuclear power plants. Residual stress can be generated due to thermo-mechanical mechanism during the induction heating bending process. It is well-known that the residual stress has important effect on crack initiation and growth. The previous studies have focused on the thickness variation. In part, some studies were performed for residual stress evaluation of the austenitic stainless steel piping bended by induction heating. It is difficult to find the residual stresses of the ferritic steel piping bended by the induction heating. The study assessed the residualmore » stresses of induction heating bended ferriticsteel piping via finite element analysis. As a result, it was identified that high residual stresses are generated on local outersurface region of the induction heating bended ferritic piping.« less

  11. Periodic acid‑Schiff staining method for function detection of liver cells is affected by 2% horse serum in induction medium.

    PubMed

    Hui, Hui; Ma, Wenjun; Cui, Jiejie; Gong, Mengjia; Wang, Yi; Zhang, Yuanyuan; He, Tongchuan; Bi, Yang; He, Yun

    2017-12-01

    Developing a thorough understanding of experimental methods of hepatic differentiation in hepatic progenitor cells (HPCs) should expand the knowledge of hepatocyte induction in vitro and may help to develop cell transplantation therapies for the clinical usage of HPCs in liver diseases. A previous induction method effectively induced differentiation and metabolic abilities in HPCs. Periodic acid‑Schiff (PAS) staining is used to identify glycogen synthesis and hepatocyte function; however, this method failed to detect induced hepatocytes. The present study aimed to investigate the possible factors affecting the previous confusing results of PAS staining. Removal of single induction factors, including dexamethasone, hepatic growth factor and fibroblast growth factor 4 from the induction media did not restore PAS staining, whereas replacement of 2% horse serum (HS) with 10% fetal bovine serum (FBS) significantly increased the number of PAS positive cells. Following 12 days of basal induction, replacing the induction medium with media containing 10% FBS for 12‑72 h significantly improved PAS staining, but did not influence indocyanine green uptake. Furthermore, incubation in induction medium with 10% FBS following 12 days of normal induction did not affect the expression of hepatic markers and mature function of HPCs. Therefore, the present study suggested that 2% HS in the induction medium did not affect the hepatic function of induced cells, but did affect glycogen storage, whereas replacement of medium with 10% FBS in advance of PAS staining may restore the failure of PAS staining in low serum concentrations of induced hepatocytes.

  12. Confirming the Multidimensionality of Psychologically Controlling Parenting among Chinese-American Mothers: Love Withdrawal, Guilt Induction, and Shaming

    ERIC Educational Resources Information Center

    Yu, Jing; Cheah, Charissa S. L.; Hart, Craig H.; Sun, Shuyan; Olsen, Joseph A.

    2015-01-01

    Despite the theoretical conceptualization of parental psychological control as a multidimensional construct, the majority of previous studies have examined psychological control as a unidimensional scale. Moreover, the conceptualization of shaming and its associations with love withdrawal and guilt induction are unclear. The current study aimed to…

  13. Reinduction therapy for adult acute leukemia with adriamycin, vincristine, and prednisone: a Southwest Oncology Group study.

    PubMed

    Elias, L; Shaw, M T; Raab, S O

    1979-08-01

    In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.

  14. Effects of previous ovarian surgery on the follicular response to ovulation induction in an in vitro fertilization program.

    PubMed

    Hornstein, M D; Barbieri, R L; McShane, P M

    1989-04-01

    This study examined the effects of previous ovarian surgery on the clinical response to ovulation induction with clomiphene citrate-human menopausal gonadotropin in an in vitro fertilization program. Patients were divided into five clinical groups: group A (n = 63), no previous ovarian surgery; B (n = 9), unilateral cystectomy; C (n = 6), unilateral oophorectomy with no contralateral ovarian surgery; D (n = 7), bilateral ovarian surgery with both ovaries present; and E (n = 4), unilateral oophorectomy and contralateral cystectomy. Patients in group E demonstrated significantly lower serum estradiol on cycle days 9-11 (P less than or equal to .05) and fewer follicles on cycle days 11-12 (P less than or equal to .05) than did patients in groups A-D. The percentage of cancelled cycles increased with increasing amounts of ovarian surgery (P less than or equal to .03). The study suggests that one cause of a poor response to ovulation induction for in vitro fertilization may be prior extensive ovarian surgery.

  15. Enhancing Induction Coil Reliability

    NASA Astrophysics Data System (ADS)

    Kreter, K.; Goldstein, R.; Yakey, C.; Nemkov, V.

    2014-12-01

    In induction hardening, thermal fatigue is one of the main copper failure modes of induction heat treating coils. There have been papers published that describe this failure mode and others that describe some good design practices. The variables previously identified as the sources of thermal fatigue include radiation from the part surface, frequency, current, concentrator losses, water pressure and coil wall thickness. However, there is very little quantitative data on the factors that influence thermal fatigue in induction coils is available in the public domain. By using finite element analysis software this study analyzes the effect of common design variables of inductor cooling, and quantifies the relative importance of these variables. A comprehensive case study for a single shot induction coil with Fluxtrol A concentrator applied is used for the analysis.

  16. Introducing AC inductive reactance with a power tool

    NASA Astrophysics Data System (ADS)

    Bryant, Wesley; Baker, Blane

    2016-09-01

    The concept of reactance in AC electrical circuits is often non-intuitive and difficult for students to grasp. In order to address this lack of conceptual understanding, classroom exercises compare the predicted resistance of a power tool, based on electrical specifications, to measured resistance. Once students discover that measured resistance is smaller than expected, they are asked to explain these observations using previously studied principles of magnetic induction. Exercises also introduce the notion of inductive reactance and impedance in AC circuits and, ultimately, determine self-inductance of the motor windings within the power tool.

  17. Maize Haploid Induction and Doubling II – Experience with Exotic and Elite Maize Populations

    USDA-ARS?s Scientific Manuscript database

    As a follow-up to our previous study, second year information will be presented addressing questions on haploid induction and doubling, utilizing exotic and elite maize. These projects result from collaborations between Iowa State Doubled Haploid Facility (http://www.plantbreeding.iastate.edu/DHF/D...

  18. Induction of Innate Host Responses in the Lungs of Chickens Following Infection With A Very Virulent Strain of Marek's Disease Virus

    USDA-ARS?s Scientific Manuscript database

    The natural route of entry of Marek’s disease virus (MDV) is via the respiratory system. However, induction of host responses in the respiratory system of chickens following inhalation of the virus has not been studied previously. The objective of the study was to examine MDV replication and inducti...

  19. Investigating the procedural variables that determine whether rats will display negative anticipatory contrast or positive induction.

    PubMed

    Weatherly, Jeffrey N; Nurnberger, Jeri T; Hanson, Brent C

    2005-08-31

    Previous studies have demonstrated that consumption of a low-valued food substance may decrease if access to a high-valued substance will soon be available (negative anticipatory contrast). Research has also demonstrated that responding for a low-valued reinforcer may increase if responding for a high-valued reinforcer will soon be possible (positive induction). The present experiment employed rats to respond in a procedure similar to that typically used to produce negative anticipatory contrast. The goal was to determine what factors contribute to when a contrast or an induction effect will occur. Based on previous research, the influence of auditory cues, temporal delays, food deprivation, and location of substance delivery were investigated. Auditory cues and temporal delays did little to influence whether subjects increased or decreased their consumption of 1% sucrose when access to 32% sucrose was upcoming. The appearance of contrast or induction was related to level of deprivation, with deprivation promoting induction. Which effect occurred also depended on whether subjects consumed the two substances from one spout in one location (induction) or from two different spouts in two different locations (contrast). The present results help identify the procedural link(s) between these two effects. They also provide insight to why positive induction may occur (i.e., higher-order place conditioning).

  20. Expression profiling reveals distinct sets of genes altered during induction and regression of cardiac hypertrophy

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

    Friddle, Carl J; Koga, Teiichiro; Rubin, Edward M.

    2000-03-15

    While cardiac hypertrophy has been the subject of intensive investigation, regression of hypertrophy has been significantly less studied, precluding large-scale analysis of the relationship between these processes. In the present study, using pharmacological models of hypertrophy in mice, expression profiling was performed with fragments of more than 3,000 genes to characterize and contrast expression changes during induction and regression of hypertrophy. Administration of angiotensin II and isoproterenol by osmotic minipump produced increases in heart weight (15% and 40% respectively) that returned to pre-induction size following drug withdrawal. From multiple expression analyses of left ventricular RNA isolated at daily time-points duringmore » cardiac hypertrophy and regression, we identified sets of genes whose expression was altered at specific stages of this process. While confirming the participation of 25 genes or pathways previously known to be altered by hypertrophy, a larger set of 30 genes was identified whose expression had not previously been associated with cardiac hypertrophy or regression. Of the 55 genes that showed reproducible changes during the time course of induction and regression, 32 genes were altered only during induction and 8 were altered only during regression. This study identified both known and novel genes whose expression is affected at different stages of cardiac hypertrophy and regression and demonstrates that cardiac remodeling during regression utilizes a set of genes that are distinct from those used during induction of hypertrophy.« less

  1. Validation of a low-cost EEG device for mood induction studies.

    PubMed

    Rodríguez, Alejandro; Rey, Beatriz; Alcañiz, Mariano

    2013-01-01

    New electroencephalography (EEG) devices, more portable and cheaper, are appearing on the market. Studying the reliability of these EEG devices for emotional studies would be interesting, as these devices could be more economical and compatible with Virtual Reality (VR) settings. Therefore, the aim in this work was to validate a low-cost EEG device (Emotiv Epoc) to monitor brain activity during a positive emotional induction procedure. Emotional pictures (IAPS) were used to induce a positive mood in sixteen participants. Changes in the brain activity of subjects were compared between positive induction and neutral conditions. Obtained results were in accordance with previous scientific literature regarding frontal EEG asymmetry, which supports the possibility of using this low-cost EEG device in future mood induction studies combined with VR.

  2. Characteristics of Teacher Induction Programs and Turnover Rates of Beginning Teachers

    ERIC Educational Resources Information Center

    Kang, Seok; Berliner, David C.

    2012-01-01

    The federal School and Staffing Survey (SASS) and Teacher Follow-up Survey (TFS) were used to examine the impacts of induction activities on beginning teacher turnover. This study excluded those teachers who moved or left schools for unavoidable and involuntary reasons, a confounding factor in previous research. This analysis revealed that three…

  3. Bcr-Abl-independent mechanism of resistance to imatinib in K562 cells: Induction of cyclooxygenase-2 (COX-2) by histone deacetylases (HDACs).

    PubMed

    Kalle, Arunasree M; Sachchidanand, Sachchidanand; Pallu, Reddanna

    2010-09-01

    Our previous studies have shown that overexpression of MDR1 and cyclooygenase-2 (COX-2) resulted in resistance development to imatinib in chronic myelogenous leukemia (CML) K562 (IR-K562) cells. In the present study, the regulatory mechanism of MDR1 induction by COX-2 was investigated. A gradual overexpression of MDR1 and COX-2 during the process of development was observed. Furthermore, down regulation of MDR1 upon COX-2 knockdown by siRNA showed a decrease in the PKC levels and activation of PKC by addition of PGE(2) to K562 cells, suggesting a role for PKC in the COX-2 mediated induction of MDR1. The present study demonstrates COX-2 induction by HDACs and MDR1 induction by COX-2 via PGE(2)-cAMP-PKC-mediated pathway. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Induction of labor in women with a history of fast labor.

    PubMed

    Kenny, Tiffany H; Fenton, Bradford W; Melrose, Erica L; McCarroll, Michele L; von Gruenigen, Vivian E

    2016-01-01

    History of fast labor is currently subjectively defined and inductions for non-medical indications are becoming restricted. We hypothesized that women induced for a history of fast labor do not have faster previous labors and do not deliver more quickly. A retrospective case-control cohort design studied multiparas undergoing elective induction at one high risk center. Outcomes of dyads electively induced for a history of previous fast labor indication (PFast) were compared to controls with a psychosocial indication. A total of 612 elective inductions with 1074 previous deliveries were evaluated: 81 (13%) PFast and 531 (87%) control. PFast had faster previous labors (median 5.5 h, IQR: 4.5-6) versus. control (10 h, IQR: 9-10.5; p < 0.001). Subsequent delivery time from start to expulsion was shorter for PFast (median 7 h, IQR: 5-9, p < 0.001) than controls with and without a previous labor <5.5 h (8.6 h, IQR: 6-14 and 9.5 h, IQR: 7-15, respectively). PFast were less likely to have a serious maternal complication. Neonatal complications were similar. Patients induced for a history of fast labor do have faster previous labors, suggesting a significant history of fast labor can be defined as <5.5 h. These women deliver more quickly and with lower morbidity than controls when subsequently induced, therefore the benefit may warrant the risk for a select number of women with a history of a prior labor length <5.5 h.

  5. Further Improvement in Outcomes of Nasopharyngeal Carcinoma With Optimized Radiotherapy and Induction Plus Concomitant Chemotherapy: An Update of the Milan Experience

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

    Palazzi, Mauro; Orlandi, Ester; Bossi, Paolo

    2009-07-01

    Purpose: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Methods and Materials: Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. Results:more » With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Conclusions: Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.« less

  6. Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats.

    PubMed

    Amaral, Liliany Souza de Brito; Souza, Cláudia Silva; Volpini, Rildo Aparecido; Shimizu, Maria Heloisa Massola; de Bragança, Ana Carolina; Canale, Daniele; Seguro, Antonio Carlos; Coimbra, Terezila Machado; de Magalhães, Amélia Cristina Mendes; Soares, Telma de Jesus

    2018-01-01

    The aim of this study is to evaluate the effects of regular moderate exercise training initiated previously or after induction of diabetes mellitus on renal oxidative stress and inflammation in STZ-induced diabetic female rats. For this purpose, Wistar rats were divided into five groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD), and previously trained diabetic (PTD). Only the PTD group was submitted to treadmill running for 4 weeks previously to DM induction with streptozotocin (40 mg/kg, i.v). After confirming diabetes, the PTD, TD, and TC groups were submitted to eight weeks of exercise training. At the end of the training protocol, we evaluated the following: glycosuria, body weight gain, plasma, renal and urinary levels of nitric oxide and thiobarbituric acid reactive substances, renal glutathione, and immunolocalization of lymphocytes, macrophages, and nuclear factor-kappa B (NF- κ B/p65) in the renal cortex. The results showed that exercise training reduced glycosuria, renal TBARS levels, and the number of immune cells in the renal tissue of the TD and PTD groups. Of note, only previous exercise increased weight gain and urinary/renal NO levels and reduced NF- κ B (p65) immunostaining in the renal cortex of the PTD group. In conclusion, our study shows that exercise training, especially when initiated previously to diabetes induction, promotes protective effects in diabetic kidney by reduction of renal oxidative stress and inflammation markers in female Wistar rats.

  7. Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats

    PubMed Central

    Souza, Cláudia Silva; Volpini, Rildo Aparecido; Shimizu, Maria Heloisa Massola; de Bragança, Ana Carolina; Canale, Daniele; Seguro, Antonio Carlos; Coimbra, Terezila Machado; de Magalhães, Amélia Cristina Mendes

    2018-01-01

    The aim of this study is to evaluate the effects of regular moderate exercise training initiated previously or after induction of diabetes mellitus on renal oxidative stress and inflammation in STZ-induced diabetic female rats. For this purpose, Wistar rats were divided into five groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD), and previously trained diabetic (PTD). Only the PTD group was submitted to treadmill running for 4 weeks previously to DM induction with streptozotocin (40 mg/kg, i.v). After confirming diabetes, the PTD, TD, and TC groups were submitted to eight weeks of exercise training. At the end of the training protocol, we evaluated the following: glycosuria, body weight gain, plasma, renal and urinary levels of nitric oxide and thiobarbituric acid reactive substances, renal glutathione, and immunolocalization of lymphocytes, macrophages, and nuclear factor-kappa B (NF-κB/p65) in the renal cortex. The results showed that exercise training reduced glycosuria, renal TBARS levels, and the number of immune cells in the renal tissue of the TD and PTD groups. Of note, only previous exercise increased weight gain and urinary/renal NO levels and reduced NF-κB (p65) immunostaining in the renal cortex of the PTD group. In conclusion, our study shows that exercise training, especially when initiated previously to diabetes induction, promotes protective effects in diabetic kidney by reduction of renal oxidative stress and inflammation markers in female Wistar rats. PMID:29785400

  8. Influences of Agrobacterium rhizogenes strains, plant genotypes, and tissue types on the induction of transgenic hairy roots in Vitis species

    USDA-ARS?s Scientific Manuscript database

    Agrobacterium rhizogenes-mediated induction of transgenic hairy roots was previously demonstrated in Vitis vinifera L. and a few other Vitis species. In this study, 13 Vitis species, including V. aestivalis, V. afghanistan, V. champinii, V. doaniana, V. flexuosa, V. labrusca, V. nesbittiana, V. pal...

  9. INDUCTION OF DNA ADDUCTS, TUMORS, AND KI-RAS ONCOGENE MUTATIONS IN STRAIN A/J MOUSE LUNG BY IP. ADMINISTRATION OF DIBENZ[A,H]ANTHRACENE

    EPA Science Inventory

    Induction of DNA adducts, tumors, and Ki-ras oncogene mutations in strain AlJ mouse lung by ip. administration of dibenz[a,h]anthracene

    Previous studies of polycyclic aromatic hydrocarbon (P AH) induced lung tumors in the strain NJ mouse model system have demonstrated qua...

  10. Feature-based versus category-based induction with uncertain categories.

    PubMed

    Griffiths, Oren; Hayes, Brett K; Newell, Ben R

    2012-05-01

    Previous research has suggested that when feature inferences have to be made about an instance whose category membership is uncertain, feature-based inductive reasoning is used to the exclusion of category-based induction. These results contrast with the observation that people can and do use category-based induction when category membership is known. The present experiments examined the conditions that drive feature-based and category-based strategies in induction under category uncertainty. Specifically, 2 experiments investigated whether reliance on feature-based inductive strategies is a product of the lack of coherence in the categories used in previous research or is due to the use of a decision-only induction procedure. Experiment 1 found that feature-based reasoning remained the preferred strategy even when categories with relatively high internal coherence were used. Experiment 2 found a shift toward category-based reasoning when participants were trained to classify category members prior to feature induction. Together, these results suggest that an appropriate conceptual representation must be formed through experience with a category before it is likely to be used as a basis for feature induction. (c) 2012 APA, all rights reserved.

  11. Broadening the study of inductive reasoning: confirmation judgments with uncertain evidence.

    PubMed

    Mastropasqua, Tommaso; Crupi, Vincenzo; Tentori, Katya

    2010-10-01

    Although evidence in real life is often uncertain, the psychology of inductive reasoning has, so far, been confined to certain evidence. The present study extends previous research by investigating whether people properly estimate the impact of uncertain evidence on a given hypothesis. Two experiments are reported, in which the uncertainty of evidence is explicitly (by means of numerical values) versus implicitly (by means of ambiguous pictures) manipulated. The results show that people's judgments are highly correlated with those predicted by normatively sound Bayesian measures of impact. This sensitivity to the degree of evidential uncertainty supports the centrality of inductive reasoning in cognition and opens the path to the study of this issue in more naturalistic settings.

  12. Effects of ubiquilin 1 on the unfolded protein response.

    PubMed

    Lu, Alice; Hiltunen, Mikko; Romano, Donna M; Soininen, Hilkka; Hyman, Bradley T; Bertram, Lars; Tanzi, Rudolph E

    2009-05-01

    Previous studies have implicated the unfolded protein response (UPR) in the pathogenesis of Alzheimer's disease (AD). We previously reported that DNA variants in the ubiquilin 1 (UBQLN1) gene increase the risk for AD. Since UBQLN1 has been shown to play a role in the UPR, we assessed the effects of overexpression and downregulation of UBQLN1 splice variants during tunicamycin-induced ER stress. In addition to previously described transcript variants, TV1 and TV2, we identified two novel transcript variants of UBQLN1 in brain: TV3 (lacking exons 2-4) and TV4 (lacking exon 4). Overexpression of TV1-3, but not TV4 significantly decreased the mRNA induction of UPR-inducible genes, C/EBP homologous protein (CHOP), BiP/GRP78, and protein disulfide isomerase (PDI) during the UPR. Stable overexpression of TV1-3, but not TV4, also significantly decreased the induction of CHOP protein and increased cell viability during the UPR. In contrast, downregulation of UBQLN1 did not affect CHOP mRNA induction, but instead increased PDI mRNA levels. These findings suggest that overexpression UBQLN1 transcript variants TV1-3, but not TV4, exert a protective effect during the UPR by attenuating CHOP induction and potentially increasing cell viability.

  13. [Risk factors of pregnancy termination at second and third trimester in women with scarred uterus and placenta previa].

    PubMed

    Tian, Ji-shun; Pan, Fei-xia; He, Sai-nan; Hu, Wen-sheng

    2015-05-01

    To investigate the risk factors of pregnancy termination at second and third trimester in women with scarred uterus and placenta previa. Clinical data of 24 pregnant women of second and third trimester with a scarred uterus and placenta previa,who requested termination in Women's Hospital Zhejiang University School of Medicine from July 2009 to June 2014, were retrospectively analyzed. The method of mifepristone combined with ethacridine lactate was adopted for all cases. Mifepristone combined with ethacridine lactate and uterine artery embolization were routinely given for patients with complete placenta previa. Cesarean section was performed for patients who failed to delivery or underwent massive vaginal bleeding before delivery. Age, gestational weeks, gravidity and parity, times of previous cesarean section, the interval from previous operation, the position and the type of placenta previa, placenta accretet, the indication and method of termination, postpartum hemorrhage, successful rate of labor induction, placental retention ratio and uterus rupture were documented. The successful rate of labor induction was 83.3%. The analysis showed that age, gestational weeks, gravidity and parity and times of previous cesarean section were not risk factors for failed labor induction, however the interval time from previous operation was related to induction failure (P<0.05). Patients with previous cesarean section ≥ 13 years were more likely to require cesarean section than those <13 years (P<0.05). The placenta adhered to the antetheca of the uterus or placenta accrete increased risk to have cesarean section. There were no significant differences in postpartum hemorrhage, the successful rate of labor induction, placental retention ratio and the rate of uterine rupture between patients with uterine artery embolization and those without. The labor induction would be feasible for women with a scarred uterus and placenta previa in second and third-trimester pregnancy. The previous operation ≥ 13 years, the antetheca placenta or placenta accrete might increase the incidence of labor induction, while the uterine artery embolization would rise the successful rate of labor induction.

  14. Back to "once a caesarean: always a caesarean"? A trend analysis in Switzerland.

    PubMed

    Christmann-Schmid, Corina; Raio, Luigi; Scheibner, Katrin; Müller, Martin; Surbek, Daniel

    2016-11-01

    Caesarean sections (CS) have significantly increased worldwide and a previous CS is nowadays an important and increasingly reported indication to perform a repeat CS. There is a paucity of information in Switzerland on the incidence of repeat CS after previous CS and relationship between the rates of vaginal birth after CS (VBAC). The aim of this study was to analyse the actual trend in VBAC in Switzerland. We performed a retrospective cohort study to analyse the proportion of VBAC among all pregnant women with previous sections which give birth during two time periods (group 1:1998/1999 vs. group 2:2004/2005) in our tertiary care referral hospital and in the annual statistics of Swiss Women's Hospitals (ASF-Statistics). In addition, the proportion of induction of labour after a previous caesarean and its success was analysed. In both cohorts studied, we found a significant decrease of vaginal births (p < 0.05) and a significant increase of primary elective repeat caesarean section (p < 0.05) from the first to the second time period, while there was a decrease of secondary repeat caesarean sections. The prevalence of labour induction did not decrease. Our study shows that vaginal birth after a prior caesarean section has decreased over time in Switzerland. There was no significant change in labour induction during the study period. While this trend might reflect an increasing demand for safety in pregnancy and childbirth, it concomitantly increases maternal risks of further pregnancies, and women need to be appropriately informed about long-term risks.

  15. Heat and cold acclimation in helium-cold hypothermia in the hamster.

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.

    1972-01-01

    A study was made of the effects of acclimation of hamsters to high (34-35 C) and low (4-5 C) temperatures for periods up to 6 weeks on the induction of hypothermia in hamsters. Hypothermia was achieved by exposing hamsters to a helox mixture of 80% helium and 20% oxygen at 0 C. Hypothermic induction was most rapid (2-3 hr) in heat-acclimated hamsters and slowest (6-12 hr) in cold-acclimated hamsters. The induction period was intermediate (5-8 hr) in room temperature nonacclimated animals (controls). Survival time in hypothermia was relatable to previous temperature acclimations. The hypothesis that thermogenesis in cold-acclimated hamsters would accentuate resistance to induction of hypothermia was substantiated.

  16. Plasminogen activator: analysis of enzyme induction by ultraviolet irradiation mapping

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

    Miskin, R.; Reich, E.; Dixon, K.

    1981-10-01

    Ultraviolet irradiation mapping techniques have previously been used to study the organization of eucaryotic gene classes and transcription units. We used the same method to probe some regulatory phenomena observed in the induction of plasminogen activator (PA) biosynthesis: PA synthesis in chicken embryo fibroblasts is induced by tumor-promoting phorbol esters and by retinoic acid; furthermore, PA induction by phorbol esters is synergistic with transformation, being 10- to 20-fold greater in virus-transformed cells than in normal cells. We found that the ultraviolet irradiation inactivation cross sections for PA induction by phorbol esters and by retinoate differed significantly, suggesting that these agentsmore » induce PA biosynthesis by different mechanisms. On the other hand, the ultraviolet irradiation sensitivity of phorbol ester induction in normal chicken embryo fibroblasts was the same as in transformed cells, indicating that the synergism of transformation and phorbol esters is probably not due to different pathways of PA induction.« less

  17. Predictors of self-reported negative mood following a depressive mood induction procedure across previously depressed, currently anxious, and control individuals.

    PubMed

    Scherrer, Martin C; Dobson, Keith S; Quigley, Leanne

    2014-09-01

    This study identified and examined a set of potential predictors of self-reported negative mood following a depressive mood induction procedure (MIP) in a sample of previously depressed, clinically anxious, and control participants. The examined predictor variables were selected on the basis of previous research and theories of depression, and included symptoms of depression and anxiety, negative and positive affect, negative and positive automatic thoughts, dysfunctional beliefs, rumination, self-concept, and occurrence and perceived unpleasantness of recent negative events. The sample consisted of 33 previously depressed, 22 currently anxious, and 26 non-clinical control participants, recruited from community sources. Participant group status was confirmed through structured diagnostic interviews. Participants completed the Velten negative self-statement MIP as well as self-report questionnaires of affective, cognitive, and psychosocial variables selected as potential predictors of mood change. Symptoms of anxiety were associated with increased self-reported negative mood shift following the MIP in previously depressed participants, but not clinically anxious or control participants. Increased occurrence of recent negative events was a marginally significant predictor of negative mood shift for the previously depressed participants only. None of the other examined variables was significant predictors of MIP response for any of the participant groups. These results identify factors that may increase susceptibility to negative mood states in previously depressed individuals, with implications for theory and prevention of relapse to depression. The findings also identify a number of affective, cognitive, and psychosocial variables that do not appear to influence mood change following a depressive MIP in previously depressed, currently anxious, and control individuals. Limitations of the study and directions for future research are discussed. Current anxiety symptomatology was a significant predictor and occurrence of recent negative events was a marginally significant predictor of greater negative mood shift following the depressive mood induction for previously depressed individuals. None of the examined variables predicted change in mood following the depressive mood induction for currently anxious or control individuals. These results suggest that anxiety symptoms and experience with negative events may increase risk for experiencing depressive mood states among individuals with a vulnerability to depression. The generalizability of the present results to individuals with comorbid depression and anxiety is limited. Future research employing appropriate statistical approaches for confirmatory research is needed to test and confirm the present results. © 2014 The British Psychological Society.

  18. Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue

    NASA Astrophysics Data System (ADS)

    González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.

    2013-04-01

    Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

  19. Inductive electronegativity scale. Iterative calculation of inductive partial charges.

    PubMed

    Cherkasov, Artem

    2003-01-01

    A number of novel QSAR descriptors have been introduced on the basis of the previously elaborated models for steric and inductive effects. The developed "inductive" parameters include absolute and effective electronegativity, atomic partial charges, and local and global chemical hardness and softness. Being based on traditional inductive and steric substituent constants these 3D descriptors provide a valuable insight into intramolecular steric and electronic interactions and can find broad application in structure-activity studies. Possible interpretation of physical meaning of the inductive descriptors has been suggested by considering a neutral molecule as an electrical capacitor formed by charged atomic spheres. This approximation relates inductive chemical softness and hardness of bound atom(s) with the total area of the facings of electrical capacitor formed by the atom(s) and the rest of the molecule. The derived full electronegativity equalization scheme allows iterative calculation of inductive partial charges on the basis of atomic electronegativities, covalent radii, and intramolecular distances. A range of inductive descriptors has been computed for a variety of organic compounds. The calculated inductive charges in the studied molecules have been validated by experimental C-1s Electron Core Binding Energies and molecular dipole moments. Several semiempirical chemical rules, such as equalized electronegativity's arithmetic mean, principle of maximum hardness, and principle of hardness borrowing could be explicitly illustrated in the framework of the developed approach.

  20. The gram-negative sensing receptor PGRP-LC contributes to grooming induction in Drosophila

    PubMed Central

    Neyen, Claudine; Lemaitre, Bruno; Marion-Poll, Frédéric

    2017-01-01

    Behavioral resistance protects insects from microbial infection. However, signals inducing insect hygiene behavior are still relatively unexplored. Our previous study demonstrated that olfactory signals from microbes enhance insect hygiene behavior, and gustatory signals even induce the behavior. In this paper, we postulated a cross-talk between behavioral resistance and innate immunity. To examine this hypothesis, we employed a previously validated behavioral test to examine the function of taste signals in inducing a grooming reflex in decapitated flies. Microbes, which activate different pattern recognition systems upstream of immune pathways, were applied to see if there was any correlation between microbial perception and grooming reflex. To narrow down candidate elicitors, the grooming induction tests were conducted with highly purified bacterial components. Lastly, the role of DAP-type peptidoglycan in grooming induction was confirmed. Our results demonstrate that cleaning behavior can be triggered through recognition of DAP-type PGN by its receptor PGRP-LC. PMID:29121087

  1. Feature-Based versus Category-Based Induction with Uncertain Categories

    ERIC Educational Resources Information Center

    Griffiths, Oren; Hayes, Brett K.; Newell, Ben R.

    2012-01-01

    Previous research has suggested that when feature inferences have to be made about an instance whose category membership is uncertain, feature-based inductive reasoning is used to the exclusion of category-based induction. These results contrast with the observation that people can and do use category-based induction when category membership is…

  2. Mood state dependency of dysfunctional attitudes in bipolar affective disorder.

    PubMed

    Babakhani, Anet; Startup, Mike

    2012-01-01

    Studies of cognitive styles among euthymic people with bipolar affective disorder (BAD) without use of mood induction techniques to access those cognitive styles give misleading impressions of normality of those cognitions. The aim of this study was to assess dysfunctional attitudes of participants with BAD, and control participants with no previous psychiatric histories, after mood inductions. Sad and happy moods were induced within 49 BAD and 37 controls. Dysfunctional attitudes were measured following mood inductions using the Dysfunctional Attitude Scale-short form (DAS-24), which has three subscales of achievement, interpersonal, and goal attainment. It was hypothesised that within BAD the sad mood induction would help in accessing dysfunctional attitudes in all three domains relative to the happy mood induction. This was supported. It was also hypothesised that the mood inductions would not affect dysfunctional attitudes within controls. This was supported. When diagnosis was entered as a between group variable, achievement dysfunctional attitudes were significantly higher in BAD compared to controls after a happy induction. Both sad and happy moods provoked higher levels of dysfunctional attitudes within BAD. Euphoria may be related to elevated achievement dysfunctional attitudes, raising risk for mania.

  3. Asymptotic Representations of Quantum Affine Superalgebras

    NASA Astrophysics Data System (ADS)

    Zhang, Huafeng

    2017-08-01

    We study representations of the quantum affine superalgebra associated with a general linear Lie superalgebra. In the spirit of Hernandez-Jimbo, we construct inductive systems of Kirillov-Reshetikhin modules based on a cyclicity result that we established previously on tensor products of these modules, and realize their inductive limits as modules over its Borel subalgebra, the so-called q-Yangian. A new generic asymptotic limit of the same inductive systems is proposed, resulting in modules over the full quantum affine superalgebra. We derive generalized Baxter's relations in the sense of Frenkel-Hernandez for representations of the full quantum group.

  4. Effect of Prior Immunization on Induction of Cervical Cancer in Mice by Herpes Simplex Virus Type 2

    NASA Astrophysics Data System (ADS)

    Budd Wentz, W.; Heggie, Alfred D.; Anthony, Donald D.; Reagan, James W.

    1983-12-01

    Previous studies at this laboratory showed that repeated application of inactivated herpes simplex virus type 2 to the mouse cervix produces premalignant and malignant lesions. In the present study mice were inoculated with inactivated herpes simplex virus type 2 or control solution and Freund's adjuvant by intraperitoneal and subcutaneous routes before exposure of the cervix to inactivated virus. It appears that immunization with inactivated virus conferred a protection against the induction of cervical carcinoma.

  5. Depletion of CD8 Memory T Cells for Induction of Tolerance of a Previously Transplanted Kidney Allograft

    PubMed Central

    Koyama, I.; Nadazdin, O.; Boskovic, S.; Ochiai, T.; Smith, R. N.; Sykes, M.; Sogawa, H.; Murakami, T.; Strom, T. B.; Colvin, R. B.; Sachs, D. H.; Benichou, G.; Cosimi, A. B.; Kawai, T.

    2013-01-01

    Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti- CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naïve T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide ‘proof of principle’ that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled. PMID:17286617

  6. Differential suppression of glial nitric oxide synthase induction by structurally related tyrosine kinase inhibitors.

    PubMed

    Galea, E; Reddi, J; Feinstein, D L

    1995-11-24

    Incubation of C6 astrocytoma cells with bacterial endotoxin (lipopolysaccharide; LPS) plus interferon-gamma (IFN-gamma), or with a combination of cytokines (TNF-alpha, IL1-beta, and IFN-gamma) leads to high levels of inducible nitric oxide synthase (iNOS) expression. Previous results demonstrated a requirement for tyrosine kinase (TK) activities for iNOS induction. In the present study, a set of structurally related TK inhibitors, the tyrphostins (TYRs), were used to characterize possible differences between LPS and cytokine iNOS induction. All TYRs tested suppressed both types of induction. However, dose-response curves revealed significant differences in the IC50 values obtained for some TYRs (T25 and T56), and significant differences in the IC50 potency rank order when comparing inhibition of LPS versus cytokine-dependent iNOS induction. These results are consistent with differential TK utilization by the LPS versus cytokine pathways of iNOS induction, and establish a basis for developing further selective inhibitors of iNOS expression.

  7. Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

    PubMed

    Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

    2016-01-01

    We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance.

  8. From Inductive Reasoning to Proof

    ERIC Educational Resources Information Center

    Yopp, David A.

    2009-01-01

    Mathematical proof is an expression of deductive reasoning (drawing conclusions from previous assertions). However, it is often inductive reasoning (conclusions drawn on the basis of examples) that helps learners form their deductive arguments, or proof. In addition, not all inductive arguments generate more formal arguments. This article draws a…

  9. Cyberbullying Among Adolescent Bystanders: Role of Affective Versus Cognitive Empathy in Increasing Prosocial Cyberbystander Behavior

    PubMed Central

    Barlińska, Julia; Szuster, Anna; Winiewski, Mikołaj

    2018-01-01

    The purpose of this study was to investigate if affective (vicarious sharing of emotions) and cognitive empathy (mental perspective taking) induction may stimulate adolescent online bystanders’ intervention in cyberbullying cases. The role of reporting the abuse is crucial because it is a form of active support to the victim, initiated by children, to stop the bullying. The effectiveness of empathy activation in decreasing negative cyberbystander reinforcing behavior has been proved in previous studies. The effects of affective and cognitive empathy activation on positive cyberbystander behavior, defined as reporting the bullying online, were explored in two follow-up studies N = 271 and N = 265. The influence of experiencing cyberbullying as perpetrator, victim, and as determined by gender on prosocial cyberbystander behavior was also controlled. The results indicate that only cognitive empathy activation increases the likelihood of intervening bystander behavior. Neither affective empathy induction, previous experience of cyberperpetration, cybervictimization, nor gender affected the engagement in prosocial bystander behavior. The conclusion of the research is that a program consequently activating more reflective cognitive empathy induction can contribute toward the establishment of healthier behavioral patterns among bystanders to cyberbullying, increasing the probability of their reporting the cyberbullying acts. PMID:29899715

  10. Cyberbullying Among Adolescent Bystanders: Role of Affective Versus Cognitive Empathy in Increasing Prosocial Cyberbystander Behavior.

    PubMed

    Barlińska, Julia; Szuster, Anna; Winiewski, Mikołaj

    2018-01-01

    The purpose of this study was to investigate if affective (vicarious sharing of emotions) and cognitive empathy (mental perspective taking) induction may stimulate adolescent online bystanders' intervention in cyberbullying cases. The role of reporting the abuse is crucial because it is a form of active support to the victim, initiated by children, to stop the bullying. The effectiveness of empathy activation in decreasing negative cyberbystander reinforcing behavior has been proved in previous studies. The effects of affective and cognitive empathy activation on positive cyberbystander behavior, defined as reporting the bullying online, were explored in two follow-up studies N = 271 and N = 265. The influence of experiencing cyberbullying as perpetrator, victim, and as determined by gender on prosocial cyberbystander behavior was also controlled. The results indicate that only cognitive empathy activation increases the likelihood of intervening bystander behavior. Neither affective empathy induction, previous experience of cyberperpetration, cybervictimization, nor gender affected the engagement in prosocial bystander behavior. The conclusion of the research is that a program consequently activating more reflective cognitive empathy induction can contribute toward the establishment of healthier behavioral patterns among bystanders to cyberbullying, increasing the probability of their reporting the cyberbullying acts.

  11. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut James A. Lovell (standing left) applauds former astronaut Sally K. Ride at her induction ceremony into the U.S. Astronaut Hall of Fame. Seated on the dais, from left, are former astronauts Gordon Cooper, Scott Carpenter, and Buzz Aldrin, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut James A. Lovell (standing left) applauds former astronaut Sally K. Ride at her induction ceremony into the U.S. Astronaut Hall of Fame. Seated on the dais, from left, are former astronauts Gordon Cooper, Scott Carpenter, and Buzz Aldrin, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  12. The role of the DLPFC in inductive reasoning of MCI patients and normal agings: an fMRI study.

    PubMed

    Yang, YanHui; Liang, PeiPeng; Lu, ShengFu; Li, KunCheng; Zhong, Ning

    2009-08-01

    Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal aging, and whether the activation pattern of this region was different between MCI patients and normal aging. The fMRI results indicated that MCI patients had no difference from normal aging in behavior performance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD response of the DLPFC region for MCI patients was weaker than that for normal aging, and the functional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal aging. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of aging, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.

  13. p21 induction plays a dual role in anti-cancer activity of ursolic acid

    PubMed Central

    Zhang, Xudong; Song, Xinhua; Yin, Shutao; Zhao, Chong; Fan, Lihong

    2015-01-01

    Previous studies have shown that induction of G1 arrest and apoptosis by ursolic acid is associated with up-regulation of cyclin-dependent kinase inhibitor (CDKI) protein p21 in multiple types of cancer cells. However, the functional role of p21 induction in G1 cell cycle arrest and apoptosis, and the mechanisms of p21 induction by ursolic acid have not been critically addressed. In the current study, we demonstrated that p21 played a mediator role in G1 cell cycle arrest by ursolic acid, whereas p21-mediated up-regulation of Mcl-1 compromised apoptotic effect of ursolic acid. These results suggest that p21 induction plays a dual role in the anti-cancer activity of ursolic acid in terms of cell cycle and apoptosis regulation. p21 induction by ursolic acid was attributed to p53 transcriptional activation. Moreover, we found that ursolic acid was able to inhibit murine double minute-2 protein (MDM2) and T-LAK cell-originated protein kinase (TOPK), the two negative regulator of p53, which in turn contributed to ursolic acid-induced p53 activation. Our findings provided novel insights into understanding of the mechanisms involved in cell cycle arrest and apoptosis induction in response to ursolic acid exposure. PMID:26582056

  14. Activity in the fronto-parietal network indicates numerical inductive reasoning beyond calculation: An fMRI study combined with a cognitive model

    PubMed Central

    Liang, Peipeng; Jia, Xiuqin; Taatgen, Niels A.; Borst, Jelmer P.; Li, Kuncheng

    2016-01-01

    Numerical inductive reasoning refers to the process of identifying and extrapolating the rule involved in numeric materials. It is associated with calculation, and shares the common activation of the fronto-parietal regions with calculation, which suggests that numerical inductive reasoning may correspond to a general calculation process. However, compared with calculation, rule identification is critical and unique to reasoning. Previous studies have established the central role of the fronto-parietal network for relational integration during rule identification in numerical inductive reasoning. The current question of interest is whether numerical inductive reasoning exclusively corresponds to calculation or operates beyond calculation, and whether it is possible to distinguish between them based on the activity pattern in the fronto-parietal network. To directly address this issue, three types of problems were created: numerical inductive reasoning, calculation, and perceptual judgment. Our results showed that the fronto-parietal network was more active in numerical inductive reasoning which requires more exchanges between intermediate representations and long-term declarative knowledge during rule identification. These results survived even after controlling for the covariates of response time and error rate. A computational cognitive model was developed using the cognitive architecture ACT-R to account for the behavioral results and brain activity in the fronto-parietal network. PMID:27193284

  15. Activity in the fronto-parietal network indicates numerical inductive reasoning beyond calculation: An fMRI study combined with a cognitive model.

    PubMed

    Liang, Peipeng; Jia, Xiuqin; Taatgen, Niels A; Borst, Jelmer P; Li, Kuncheng

    2016-05-19

    Numerical inductive reasoning refers to the process of identifying and extrapolating the rule involved in numeric materials. It is associated with calculation, and shares the common activation of the fronto-parietal regions with calculation, which suggests that numerical inductive reasoning may correspond to a general calculation process. However, compared with calculation, rule identification is critical and unique to reasoning. Previous studies have established the central role of the fronto-parietal network for relational integration during rule identification in numerical inductive reasoning. The current question of interest is whether numerical inductive reasoning exclusively corresponds to calculation or operates beyond calculation, and whether it is possible to distinguish between them based on the activity pattern in the fronto-parietal network. To directly address this issue, three types of problems were created: numerical inductive reasoning, calculation, and perceptual judgment. Our results showed that the fronto-parietal network was more active in numerical inductive reasoning which requires more exchanges between intermediate representations and long-term declarative knowledge during rule identification. These results survived even after controlling for the covariates of response time and error rate. A computational cognitive model was developed using the cognitive architecture ACT-R to account for the behavioral results and brain activity in the fronto-parietal network.

  16. [Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial].

    PubMed

    Simoni, Ricardo Francisco; Miziara, Luiz Eduardo de Paula Gomes; Esteves, Luis Otávio; Silva, Diógenes de Oliveira; Ribeiro, Cristina Alves; Smith, Mariana Oki; Paula, Leonardo Ferreira de; Cangiani, Luis Henrique

    2015-01-01

    studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-μg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1μg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0μg.ml(-1)) at Es, and waited until loss of consciousness. in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56μg.mL(-1), respectively, p=0.004). the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  17. Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa.

    PubMed

    Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

    2016-01-01

    Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants' attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients' body image disturbance.

  18. Knowledge, Expectations, and Inductive Reasoning within Conceptual Hierarchies

    ERIC Educational Resources Information Center

    Coley, John D.; Hayes, Brett; Lawson, Christopher; Moloney, Michelle

    2004-01-01

    Previous research (e.g. "Cognition" 64 (1997) 73) suggests that the privileged level for inductive inference in a folk biological conceptual hierarchy does not correspond to the ''basic'' level (i.e. the level at which concepts are both informative and distinct). To further explore inductive inference within conceptual hierarchies, we examine…

  19. Time-Resolved O3 Chemical Chain Reaction Kinetics Via High-Resolution IR Laser Absorption Methods

    NASA Technical Reports Server (NTRS)

    Kulcke, Axel; Blackmon, Brad; Chapman, William B.; Kim, In Koo; Nesbitt, David J.

    1998-01-01

    Excimer laser photolysis in combination with time-resolved IR laser absorption detection of OH radicals has been used to study O3/OH(v = 0)/HO2 chain reaction kinetics at 298 K, (i.e.,(k(sub 1) is OH + 03 yields H02 + 02 and (k(sub 2) is H02 + 03 yields OH + 202). From time-resolved detection of OH radicals with high-resolution near IR laser absorption methods, the chain induction kinetics have been measured at up to an order of magnitude higher ozone concentrations ([03] less than or equal to 10(exp 17) molecules/cu cm) than accessible in previous studies. This greater dynamic range permits the full evolution of the chain induction, propagation, and termination process to be temporally isolated and measured in real time. An exact solution for time-dependent OH evolution under pseudo- first-order chain reaction conditions is presented, which correctly predicts new kinetic signatures not included in previous OH + 03 kinetic analyses. Specifically, the solutions predict an initial exponential loss (chain "induction") of the OH radical to a steady-state level ([OH](sub ss)), with this fast initial decay determined by the sum of both chain rate constants, k(sub ind) = k(sub 1) + k(sub 2). By monitoring the chain induction feature, this sum of the rate constants is determined to be k(sub ind) = 8.4(8) x 10(exp -14) cu cm/molecule/s for room temperature reagents. This is significantly higher than the values currently recommended for use in atmospheric models, but in excellent agreement with previous results from Ravishankara et al.

  20. Confirming the Multidimensionality of Psychologically Controlling Parenting among Chinese-American Mothers: Love Withdrawal, Guilt Induction, and Shaming.

    PubMed

    Cheah, Charissa; Yu, Jing; Hart, Craig; Sun, Shuyan; Olsen, Joseph

    2015-05-01

    Despite the theoretical conceptualization of parental psychological control as a multidimensional construct, the majority of previous studies have examined psychological control as a unidimensional scale. Moreover, the conceptualization of shaming and its associations with love withdrawal and guilt induction are unclear. The current study aimed to fill these gaps by evaluating the latent factor structure underlying 18 items from Olsen et al. (2002) that were conceptually relevant to love withdrawal, guilt induction, and shaming practices in a sample of 169 mothers of Chinese-American preschoolers. A multidimensional three-factor model and bi-factor model were specified based on our formulated operational definitions for the three dimensions of psychological control. Both models were found to be superior to the unidimensional model. In addition, results from the bi-factor model and an additional second-order factor model indicated that psychological control is essentially empirically isomorphic with guilt induction. Although love withdrawal and shaming factors were also fairly strong indicators of psychological control, each exhibited important additional unique variability and mutual distinctiveness. Implications for the conceptualization of love withdrawal, guilt induction, and shaming as well as directions for future studies are discussed.

  1. Confirming the Multidimensionality of Psychologically Controlling Parenting among Chinese-American Mothers: Love Withdrawal, Guilt Induction, and Shaming

    PubMed Central

    Cheah, Charissa; Yu, Jing; Hart, Craig; Sun, Shuyan; Olsen, Joseph

    2014-01-01

    Despite the theoretical conceptualization of parental psychological control as a multidimensional construct, the majority of previous studies have examined psychological control as a unidimensional scale. Moreover, the conceptualization of shaming and its associations with love withdrawal and guilt induction are unclear. The current study aimed to fill these gaps by evaluating the latent factor structure underlying 18 items from Olsen et al. (2002) that were conceptually relevant to love withdrawal, guilt induction, and shaming practices in a sample of 169 mothers of Chinese-American preschoolers. A multidimensional three-factor model and bi-factor model were specified based on our formulated operational definitions for the three dimensions of psychological control. Both models were found to be superior to the unidimensional model. In addition, results from the bi-factor model and an additional second-order factor model indicated that psychological control is essentially empirically isomorphic with guilt induction. Although love withdrawal and shaming factors were also fairly strong indicators of psychological control, each exhibited important additional unique variability and mutual distinctiveness. Implications for the conceptualization of love withdrawal, guilt induction, and shaming as well as directions for future studies are discussed. PMID:26052168

  2. Characterizing RecA-Independent Induction of Shiga toxin2-Encoding Phages by EDTA Treatment

    PubMed Central

    Imamovic, Lejla; Muniesa, Maite

    2012-01-01

    Background The bacteriophage life cycle has an important role in Shiga toxin (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages) increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA. Methodology/Principal Findings The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by Real-Time PCR. RecA-independent mechanisms described for phage λ induction (RcsA and DsrA) were not involved in Stx2 phage induction. In addition, mutations in the pathway for the stress response of the bacterial envelope to EDTA did not contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is due to its chelating properties, which was also confirmed by the use of citrate, another chelating agent. Our results indicate that EDTA affects Stx2 phage induction by disruption of the bacterial outer membrane due to chelation of Mg2+. In all the conditions evaluated, the pH value had a decisive role in Stx2 phage induction. Conclusions/Significance Chelating agents, such as EDTA and citrate, induce Stx phages, which raises concerns due to their frequent use in food and pharmaceutical products. This study contributes to our understanding of the phenomenon of induction and release of Stx phages as an important factor in the pathogenicity of Shiga toxin-producing Escherichia coli (STEC) and in the emergence of new pathogenic strains. PMID:22393404

  3. An Integrated Account of Generalization across Objects and Features

    ERIC Educational Resources Information Center

    Kemp, Charles; Shafto, Patrick; Tenenbaum, Joshua B.

    2012-01-01

    Humans routinely make inductive generalizations about unobserved features of objects. Previous accounts of inductive reasoning often focus on inferences about a single object or feature: accounts of causal reasoning often focus on a single object with one or more unobserved features, and accounts of property induction often focus on a single…

  4. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Daniel Brandenstein (standing right) is presented to the audience at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are former astronauts John H. Glenn and Gordon Cooper, both previously inducted into the Hall of Fame. Being inducted with Brandenstein are Space Shuttle astronauts Robert "Hoot" Gibson, Story Musgrave, and Sally K. Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Daniel Brandenstein (standing right) is presented to the audience at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are former astronauts John H. Glenn and Gordon Cooper, both previously inducted into the Hall of Fame. Being inducted with Brandenstein are Space Shuttle astronauts Robert "Hoot" Gibson, Story Musgrave, and Sally K. Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  5. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut James A. Lovell (standing left) greets former astronaut Story Musgrave (standing right) at his induction ceremony into the U.S. Astronaut Hall of Fame. Also seated on the dais are, from left, former astronaut and Senator John H. Glenn, astronaut and Associate Director (Technical) of the Johnson Space Center John W. Young, and former astronaut Buzz Aldrin, all previously inducted into the Hall of Fame. Being inducted with Musgrave are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Sally Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut James A. Lovell (standing left) greets former astronaut Story Musgrave (standing right) at his induction ceremony into the U.S. Astronaut Hall of Fame. Also seated on the dais are, from left, former astronaut and Senator John H. Glenn, astronaut and Associate Director (Technical) of the Johnson Space Center John W. Young, and former astronaut Buzz Aldrin, all previously inducted into the Hall of Fame. Being inducted with Musgrave are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Sally Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  6. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Frederick H. (Rick) Hauck (standing right) congratulates former astronaut Daniel Brandenstein (standing center) at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are former astronauts John H. Glenn and Gordon Cooper, both previously inducted into the Hall of Fame. Being inducted with Brandenstein are Space Shuttle astronauts Robert "Hoot" Gibson, Story Musgrave, and Sally K. Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Frederick H. (Rick) Hauck (standing right) congratulates former astronaut Daniel Brandenstein (standing center) at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are former astronauts John H. Glenn and Gordon Cooper, both previously inducted into the Hall of Fame. Being inducted with Brandenstein are Space Shuttle astronauts Robert "Hoot" Gibson, Story Musgrave, and Sally K. Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  7. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Robert L. Crippen (right) presents former astronaut Sally K. Ride (standing center) at her induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais are, from left, former astronauts John H. Glenn, Gordon Cooper, Buzz Aldrin, and Walter Cunningham, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Robert L. Crippen (right) presents former astronaut Sally K. Ride (standing center) at her induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais are, from left, former astronauts John H. Glenn, Gordon Cooper, Buzz Aldrin, and Walter Cunningham, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  8. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Robert L. Crippen (standing right) congratulates former astronaut Sally K. Ride at her induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are former astronauts Gordon Cooper, Scott Carpenter, Buzz Aldrin, Walter Cunningham, Edgar B. Mitchell, and Fred W. Haise, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Robert L. Crippen (standing right) congratulates former astronaut Sally K. Ride at her induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are former astronauts Gordon Cooper, Scott Carpenter, Buzz Aldrin, Walter Cunningham, Edgar B. Mitchell, and Fred W. Haise, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert "Hoot" Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  9. Indications of caesarean section in overweight and obese versus normal-weight pregnant women: a retrospective cohort study.

    PubMed

    Fernández Alba, Juan Jesús; Paublete Herrera, Carmen; Vilar Sanchez, Angel; Gonzalez-Macias, Carmen; Castillo Lara, Maria; Torrejón, Rafael; Moreno Corral, Luis Javier

    2018-02-01

    The aim of this study was to test the hypothesis that indications of c-section in overweight or obese pregnant women are different from those with normal-weight. Retrospective cohort study at University Hospital of Puerto Real (Cádiz-Spain). We compared frequency distribution of c-section indications in overweight and obese versus normal-weight. The risk of c-section by different indications was calculated as relative risk. A total of 4685 births were included in the study. There are significant differences in the frequency distribution of caesarean indications among normal weight and overweight or obese women. In overweight, we found an increased risk of c-section due to previous c-section (RR: 1.73; confidence interval [CI] 95% 1.24-2.42), obstructed/non-progressive labour (RR: 1.34; CI 95% 1.03-1.75), failed induction of labour (RR: 2.38; CI 95% 1.30-4.34) and foetal distress (RR: 1.73; CI 95% 1.21-2.49). This risk was even higher in obese women: previous c-section (RR: 3.25; CI 95% 2.24-4.71), obstructed/non-progressive labour (RR: 2; CI 95% 1.45-2.77), failed induction (RR: 2.52; CI 95% 1.15-5.51) and foetal distress (RR: 2.35; CI 95% 1.51-3.65). The risk of caesarean section due to previous caesarean section, obstructed/non-progressive labour, failed induction of labour or foetal distress is greater in overweight and obese than in normal-weight. This increase in risk also increases progressively as maternal BMI increases.

  10. Pregnancy outcome after induction of labor in women with previous cesarean section.

    PubMed

    Ashwal, Eran; Hiersch, Liran; Melamed, Nir; Ben-Zion, Maya; Brezovsky, Alex; Wiznitzer, Arnon; Yogev, Yariv

    2015-03-01

    As conflicting data exist concerning the safety of induction of labor (IoL) in women with previous single lower segment cesarean section (CS), we aimed to assess pregnancy outcome following IoL in such patient population. All singleton pregnancies with previous single CS which underwent IoL during 2008-2012 were included (study group). Their pregnancy outcome was compared to those pregnancies with previous single CS that admitted with spontaneous onset of labor (control group). Overall, 1898 pregnancies were eligible, of them, 259 underwent IoL, and 1639 were admitted with spontaneous onset of labor. Parity, gestational age at delivery and birthweight were similar. Women in the study group were more likely to undergo CS mainly due to labor dystocia (8.1 versus 3.7%, p < 0.01). The rate of CS due to non-reassuring fetal heart rate was similar. No difference was found in the rate of uterine rupture/dehiscence. Short-term neonatal outcome was similar between the groups. On multivariable logistic regression analysis, IoL was not independently associated with uterine rupture (OR 1.33, 95% C.I 0.46-3.84, p = 0.59). Our data suggest that IoL in women with one previous low segment CS neither increases the risk of uterine rupture nor adversely affects immediate neonatal outcome.

  11. Audiovisual aid viewing immediately before pediatric induction moderates the accompanying parents' anxiety.

    PubMed

    Berghmans, Johan; Weber, Frank; van Akoleyen, Candyce; Utens, Elisabeth; Adriaenssens, Peter; Klein, Jan; Himpe, Dirk

    2012-04-01

    Parents accompanying their child during induction of anesthesia experience stress. The impact of audiovisual aid (AVA) on parental state anxiety and assessment of the child's anxiety at induction have been studied previously but need closer scrutiny. One hundred and twenty parents whose children were scheduled for day-care surgery entered this randomized, controlled study. The intervention group (n = 60) was exposed to an AVA in the holding area. Parental anxiety was measured with the Spielberger State-Trait Anxiety Inventory and the Amsterdam Preoperative Anxiety and Information Scale (APAIS) at three time points: (i) on admission [T1]; (ii) in the holding area just before entering the operating theater [T2]; and (iii) after leaving [T3]. Additionally, at [T3], both parent and attending anesthetist evaluated the child's anxiety using a visual analogue scale. The anesthetist also filled out the Induction Compliance Checklist. On the state anxiety subscale, APAIS parental anxiety at T2 (P = 0.015) and T3 (P = 0.009) was lower in the AVA intervention group than in the control group. After induction, the child's anxiety rating by the anesthetist was significantly lower than by the parent, in both intervention and control groups. Preoperative AVA shown to parents immediately before induction moderates the increase in anxiety associated with the anesthetic induction of their child. Present results suggest that behavioral characteristics seem better predictors of child's anxiety during induction than anxiety ratings per se and that anesthetists are better than parents in predicting child's anxiety during induction. © 2011 Blackwell Publishing Ltd.

  12. Cognitive Training for Children: Effects on Inductive Reasoning, Deductive Reasoning, and Mathematics Achievement in an Australian School Setting

    ERIC Educational Resources Information Center

    Barkl, Sophie; Porter, Amy; Ginns, Paul

    2012-01-01

    Inductive reasoning is a core cognitive process of fluid intelligence, predicting a variety of educational outcomes. The Cognitive Training for Children (CTC) program is an educational intervention designed to develop children's inductive reasoning skills, with previous investigations finding substantial effects of the program on both inductive…

  13. A Theoretical Model to Predict Both Horizontal Displacement and Vertical Displacement for Electromagnetic Induction-Based Deep Displacement Sensors

    PubMed Central

    Shentu, Nanying; Zhang, Hongjian; Li, Qing; Zhou, Hongliang; Tong, Renyuan; Li, Xiong

    2012-01-01

    Deep displacement observation is one basic means of landslide dynamic study and early warning monitoring and a key part of engineering geological investigation. In our previous work, we proposed a novel electromagnetic induction-based deep displacement sensor (I-type) to predict deep horizontal displacement and a theoretical model called equation-based equivalent loop approach (EELA) to describe its sensing characters. However in many landslide and related geological engineering cases, both horizontal displacement and vertical displacement vary apparently and dynamically so both may require monitoring. In this study, a II-type deep displacement sensor is designed by revising our I-type sensor to simultaneously monitor the deep horizontal displacement and vertical displacement variations at different depths within a sliding mass. Meanwhile, a new theoretical modeling called the numerical integration-based equivalent loop approach (NIELA) has been proposed to quantitatively depict II-type sensors’ mutual inductance properties with respect to predicted horizontal displacements and vertical displacements. After detailed examinations and comparative studies between measured mutual inductance voltage, NIELA-based mutual inductance and EELA-based mutual inductance, NIELA has verified to be an effective and quite accurate analytic model for characterization of II-type sensors. The NIELA model is widely applicable for II-type sensors’ monitoring on all kinds of landslides and other related geohazards with satisfactory estimation accuracy and calculation efficiency. PMID:22368467

  14. A theoretical model to predict both horizontal displacement and vertical displacement for electromagnetic induction-based deep displacement sensors.

    PubMed

    Shentu, Nanying; Zhang, Hongjian; Li, Qing; Zhou, Hongliang; Tong, Renyuan; Li, Xiong

    2012-01-01

    Deep displacement observation is one basic means of landslide dynamic study and early warning monitoring and a key part of engineering geological investigation. In our previous work, we proposed a novel electromagnetic induction-based deep displacement sensor (I-type) to predict deep horizontal displacement and a theoretical model called equation-based equivalent loop approach (EELA) to describe its sensing characters. However in many landslide and related geological engineering cases, both horizontal displacement and vertical displacement vary apparently and dynamically so both may require monitoring. In this study, a II-type deep displacement sensor is designed by revising our I-type sensor to simultaneously monitor the deep horizontal displacement and vertical displacement variations at different depths within a sliding mass. Meanwhile, a new theoretical modeling called the numerical integration-based equivalent loop approach (NIELA) has been proposed to quantitatively depict II-type sensors' mutual inductance properties with respect to predicted horizontal displacements and vertical displacements. After detailed examinations and comparative studies between measured mutual inductance voltage, NIELA-based mutual inductance and EELA-based mutual inductance, NIELA has verified to be an effective and quite accurate analytic model for characterization of II-type sensors. The NIELA model is widely applicable for II-type sensors' monitoring on all kinds of landslides and other related geohazards with satisfactory estimation accuracy and calculation efficiency.

  15. Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines : a mechanism for induction of apoptosis via the 18 kDa mitochondrial translocator protein.

    PubMed

    Veenman, Leo; Alten, Julia; Linnemannstöns, Karen; Shandalov, Yulia; Zeno, Sivan; Lakomek, Max; Gavish, Moshe; Kugler, Wilfried

    2010-07-01

    Erucylphosphohomocholine (ErPC3, Erufosine) was reported previously to induce apoptosis in otherwise highly apoptosis-resistant malignant glioma cell lines while sparing their non-tumorigenic counterparts. We also previously found that the mitochondrial 18 kDa Translocator Protein (TSPO) is required for apoptosis induction by ErPC3. These previous studies also suggested involvement of reactive oxygen species (ROS). In the present study we further investigated the potential involvement of ROS generation, the participation of the mitochondrial respiration chain, and the role of the mitochondrial F(O)F(1)-ATP(synth)ase in the pro-apoptotic effects of ErPC3 on U87MG and U118MG human glioblastoma cell lines. For this purpose, cells were treated with the ROS chelator butylated hydroxyanisole (BHA), the mitochondrial respiration chain inhibitors rotenone, antimycin A, myxothiazol, and the uncoupler CCCP. Also oligomycin and piceatannol were studied as inhibitors of the F(O) and F(1) subunits of the mitochondrial F(O)F(1)-ATP(synth)ase, respectively. BHA was able to attenuate apoptosis induction by ErPC3, including mitochondrial ROS generation as determined with cardiolipin oxidation, as well as collapse of the mitochondrial membrane potential (Deltapsi(m)). Similarly, we found that oligomycin attenuated apoptosis and collapse of the Deltapsi(m), normally induced by ErPC3, including the accompanying reductions in cellular ATP levels. Other inhibitors of the mitochondrial respiration chain, as well as piceatannol, did not show such effects. Consequently, our findings strongly point to a role for the F(O) subunit of the mitochondrial F(O)F(1)-ATP(synth)ase in ErPC3-induced apoptosis and dissipation of Deltapsi(m) as well as ROS generation by ErPC3 and TSPO.

  16. Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study.

    PubMed

    A Santos, Jose C; Nassif, Houssam; Page, David; Muggleton, Stephen H; E Sternberg, Michael J

    2012-07-11

    There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP), which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. In addition to confirming literature results, ProGolem's model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners.

  17. Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa

    PubMed Central

    Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

    2016-01-01

    Objective Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. Method In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. Results After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants’ attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. Discussion The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients’ body image disturbance. PMID:27123587

  18. Magnetoacoustic imaging of human liver tumor with magnetic induction

    NASA Astrophysics Data System (ADS)

    Hu, Gang; Cressman, Erik; He, Bin

    2011-01-01

    Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

  19. Determination of optimum time for intravenous cannulation after induction with sevoflurane and nitrous oxide in children premedicated with midazolam.

    PubMed

    Kilicaslan, Alper; Gök, Funda; Erol, Atilla; Okesli, Selmin; Sarkilar, Gamze; Otelcioglu, Seref

    2014-06-01

    It has been shown that early placement of an intravenous line in children administered sevoflurane anesthesia increased the incidence of laryngospasm and movement. However, the optimal time for safe cannulation after the loss of the eyelash reflex during the administration of sevoflurane and nitrous oxide is not known. The aim of the study was to determine the optimum time for intravenous cannulation after the induction of anesthesia with sevoflurane and nitrous oxide in children premedicated with oral midazolam. We performed a prospective, observer-blinded, up-down sequential, allocation study, and children, aged 2-6 years, ASA physical status I, scheduled for an elective procedure undergoing inhalational induction were included in the study. Anesthesia was induced with sevoflurane and nitrous oxide after premedication with oral midazolam. For the first child, 4 min after the loss of the eyelash reflex, the intravenous cannulation was attempted by an experienced anesthesiologist. The time for intravenous cannulation was considered adequate if movement, coughing, or laryngospasm did not occur. The time for cannulation was increased by 15 s if the time was inadequate in the previous patient, and conversely, the time for cannulation was decreased by 15 s if the time was adequate in the previous patient. The probit test was used in the analysis of up-down sequences. A total of 32 children were enrolled sequentially during the study period. The adequate time for effective intravenous cannulation after induction with sevoflurane and nitrous oxide in 50% and 95% of patients were 1.29 min (95% confidence interval, 0.96-1.54 min) and 1.86 min (95% confidence interval 1.58-4.35 min), respectively. We recommend waiting 2 min for attempting intravenous placement following the loss of the eyelash reflex in children sedated with midazolam and receiving an inhalation induction with sevoflurane and nitrous oxide. © 2014 John Wiley & Sons Ltd.

  20. INDUCTION OF ALBENDAZOLE RESISTANCE IN GIARDIA LAMBLIA

    EPA Science Inventory

    Previous studies have shown that Giardia lamblia resistance to metronidazole can be induced in the laboratory, and treatment failures with this drug have also been documented. As replacement theraples, anthelmintic benzimidazoles have antigiardial activity with few clinical side ...

  1. Systematic review: elective induction of labor versus expectant management of pregnancy.

    PubMed

    Caughey, Aaron B; Sundaram, Vandana; Kaimal, Anjali J; Gienger, Allison; Cheng, Yvonne W; McDonald, Kathryn M; Shaffer, Brian L; Owens, Douglas K; Bravata, Dena M

    2009-08-18

    The rates of induction of labor and elective induction of labor are increasing. Whether elective induction of labor improves outcomes or simply leads to greater complications and health care costs is commonly debated in the literature. To compare the benefits and harms of elective induction of labor and expectant management of pregnancy. MEDLINE (through February 2009), Web of Science, CINAHL, Cochrane Central Register of Controlled Trials (through March 2009), bibliographies of included studies, and previous systematic reviews. Experimental and observational studies of elective induction of labor reported in English. Two authors abstracted study design; patient characteristics; quality criteria; and outcomes, including cesarean delivery and maternal and neonatal morbidity. Of 6117 potentially relevant articles, 36 met inclusion criteria: 11 randomized, controlled trials (RCTs) and 25 observational studies. Overall, expectant management of pregnancy was associated with a higher odds ratio (OR) of cesarean delivery than was elective induction of labor (OR, 1.22 [95% CI, 1.07 to 1.39]; absolute risk difference, 1.9 percentage points [CI, 0.2 to 3.7 percentage points]) in 9 RCTs. Women at or beyond 41 completed weeks of gestation who were managed expectantly had a higher risk for cesarean delivery (OR, 1.21 [CI, 1.01 to 1.46]), but this difference was not statistically significant in women at less than 41 completed weeks of gestation (OR, 1.73 [CI, 0.67 to 4.5]). Women who were expectantly managed were more likely to have meconium-stained amniotic fluid than those who were electively induced (OR, 2.04 [CI, 1.34 to 3.09]). There were no recent RCTs of elective induction of labor at less than 41 weeks of gestation. The 2 studies conducted at less than 41 weeks of gestation were of poor quality and were not generalizable to current practice. RCTs suggest that elective induction of labor at 41 weeks of gestation and beyond is associated with a decreased risk for cesarean delivery and meconium-stained amniotic fluid. There are concerns about the translation of these findings into actual practice; thus, future studies should examine elective induction of labor in settings where most obstetric care is provided.

  2. Kidney versus Islet Allograft Survival after Induction of Mixed Chimerism with Combined Donor Bone Marrow Transplantation

    PubMed Central

    Oura, Tetsu; Ko, Dicken S.C.; Boskovic, Svjetlan; O'Neil, John J.; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R. Neal; Cosimi, A. B.; Kawai, Tatsuo

    2016-01-01

    Background We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC-mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. Methods A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that includes low dose total body and thymic irradiation, horse ATG (Atgam), six doses of anti-CD154 monoclonal antibody (mAb) and a one month course of cyclosporine (CyA) (Islet-A). In Islet-B, anti-CD8 mAb was administered in place of CyA. In Islet-C, two recipients were treated with Islet-B but without Atgam. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and bone marrow transplantation (Kidney-A) following the same conditioning regimen used in Islet-A. Results The majority of Kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned Islet/BM recipients (Islet-A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to calcineurin inhibitor (CNI) toxicity, three recipients were treated with anti-CD8 mAb in place of CNI. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet-C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Conclusion Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CNI-free regimen that includes anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance. PMID:26337731

  3. Induction Based on Circumscription

    NASA Astrophysics Data System (ADS)

    Saito, Haruka; Inoue, Katsumi

    We investigate induction from the viewpoint of nonmonotonic reasoning. Induction we consider in this paper is descriptive induction. Hypotheses from descriptive induction have the weak property that they only describe rules with respect to the observations and do not realize an inductive leap. In this paper, we define a new form of descriptive induction with circumscription and the idea of explanation and show two procedures for computing it. The new descriptive induction is called circumscriptive induction. By deciding the roles of predicates in circumscription, we can intentionally minimize models of a given inductive problem. By adopting the idea of explanation, we can distinguish between background knowledge and observations. Additionally, we consider the relationship between the way of choosing the roles of predicates in computing circumscription and the property of hypotheses obtained by circumscriptive induction. It is shown that hypotheses from circumscriptive induction reflect a difference between background knowledge and observations and do not realize an inductive leap. We also investigate revision of hypotheses which is as important as generation of hypotheses. In a process of hypothesis revision, a difference between previous induction and circumscriptive induction is clearly characterised.

  4. Training the elderly on the ability factors of spatial orientation and inductive reasoning.

    PubMed

    Willis, S L; Schaie, K W

    1986-09-01

    We examined the effects of cognitive training with elderly participants from the Seattle Longitudinal Study. Subjects were classified as having remained stable or having declined over the previous 14-year interval on each of two primary abilities, spatial orientation and inductive reasoning. Subjects who had declined on one of these abilities received training on that ability; subjects who had declined on both abilities or who had remained stable on both were randomly assigned to the spatial orientation or inductive reasoning training programs. Training outcomes were examined within an ability-measurement framework with empirically determined factorial structure. Significant training effects, at the level of the latent ability constructs, occurred for both spatial orientation and inductive reasoning. These effects were general, in that no significant interactions with decline status or gender were found. Thus, training interventions were effective both in remediating cognitive decline on the target abilities and in improving the performance of stable subjects.

  5. Hyperosmolarity leads to an increase in derepressed system A activity in the renal epithelial cell line NBL-1.

    PubMed Central

    Soler, C; Felipe, A; Casado, F J; McGivan, J D; Pastor-Anglada, M

    1993-01-01

    Hyperosmolarity induced an increase in Na(+)-dependent L-alanine uptake in confluent monolayers of the established renal epithelial cell line NBL-1. This induction was attributable to system A and was only seen when the cells had been previously deprived of amino acids in the culture medium to derepress system A activity. It was additive to the adaptive regulation induction, and both were inhibited by cycloheximide. However, the hyperosmolarity effect was inhibited by colcemid (an inhibitor of microtubular function), but adaptive regulation was not. Otherwise, when cell monolayers were incubated in a control medium, basal Na(+)-dependent L-alanine uptake mediated by system B0 decreased. The results of this study show that: (i) system A activity was not induced by cell shrinkage and subsequent swelling due to extracellular hyperosmolarity when cells were incubated in control medium; (ii) previous expression of system A activity induced by amino acid starvation seems to be a prerequisite for further induction due to hyperosmolarity; and (iii) the effects of adaptive regulation and hyperosmotic stress are mediated by different mechanisms. PMID:8435065

  6. Induction when Rats Respond for Liquid-Sucrose Reinforcement as a Function of Amount of Upcoming "Work"

    ERIC Educational Resources Information Center

    Weatherly, Jeffrey N.; Bauste, Grant A.; McDougall, Casey L.; Nurnberger, Jeri T.

    2006-01-01

    Previous research has shown that rats increase their rate of responding for 1% sucrose reinforcement in the first half of the session if food-pellet, rather than 1% sucrose, reinforcement will be available in the second half (i.e., positive induction). Four experiments investigated whether this induction effect would be changed by altering the…

  7. Word, Thought, and Deed: The Role of Object Categories in Children's Inductive Inferences and Exploratory Play

    ERIC Educational Resources Information Center

    Schulz, Laura E.; Standing, Holly R.; Bonawitz, Elizabeth B.

    2008-01-01

    Previous research (e.g., S. A. Gelman & E. M. Markman, 1986; A. Gopnik & D. M. Sobel, 2000) suggests that children can use category labels to make inductive inferences about nonobvious causal properties of objects. However, such inductive generalizations can fail to predict objects' causal properties when (a) the property being projected varies…

  8. Different strategies in solving series completion inductive reasoning problems: an fMRI and computational study.

    PubMed

    Liang, Peipeng; Jia, Xiuqin; Taatgen, Niels A; Zhong, Ning; Li, Kuncheng

    2014-08-01

    Neural correlate of human inductive reasoning process is still unclear. Number series and letter series completion are two typical inductive reasoning tasks, and with a common core component of rule induction. Previous studies have demonstrated that different strategies are adopted in number series and letter series completion tasks; even the underlying rules are identical. In the present study, we examined cortical activation as a function of two different reasoning strategies for solving series completion tasks. The retrieval strategy, used in number series completion tasks, involves direct retrieving of arithmetic knowledge to get the relations between items. The procedural strategy, used in letter series completion tasks, requires counting a certain number of times to detect the relations linking two items. The two strategies require essentially the equivalent cognitive processes, but have different working memory demands (the procedural strategy incurs greater demands). The procedural strategy produced significant greater activity in areas involved in memory retrieval (dorsolateral prefrontal cortex, DLPFC) and mental representation/maintenance (posterior parietal cortex, PPC). An ACT-R model of the tasks successfully predicted behavioral performance and BOLD responses. The present findings support a general-purpose dual-process theory of inductive reasoning regarding the cognitive architecture. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Effects of Induction-System Icing on Aircraft-Engine Operating Characteristics

    NASA Technical Reports Server (NTRS)

    Stevens, Howard C., Jr.

    1947-01-01

    An investigation was conducted on a multicylinder aircraft engine on a dynamometer stand to determine the effect of induction-system icing on engine operating characteristics and to compare the results with those of a previous laboratory investigation in which only the carburetor and the engine-stage supercharger assembly from the engine were used. The experiments were conducted at simulated glide power, low cruise power, and normal rated power through a range of humidity ratios and air temperatures at approximately sea-level pressure. Induction-system icing was found to occur within approximately the same limits as those established by the previous laboratory investigation after making suitable allowances for the difference in fuel volatility and throttle angles. Rough operation of the engine was experienced when ice caused a marked reduction in the air flow. Photographs of typical ice formations from this investigation indicate close similarity to icing previously observed in the laboratory.

  10. Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

    PubMed

    Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

    2015-11-01

    In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Inter- and Intra-Dimensional Dependencies in Implicit Phonotactic Learning

    ERIC Educational Resources Information Center

    Moreton, Elliott

    2012-01-01

    Is phonological learning subject to the same inductive biases as learning in other domains? Previous studies of non-linguistic learning found that intra-dimensional dependencies (between two instances of the same feature) were learned more easily than inter-dimensional ones. This study compares implicit learning of intra- and inter-dimensional…

  12. Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck.

    PubMed

    Bae, Woo Kyun; Hwang, Jun Eul; Shim, Hyun Jeong; Cho, Sang Hee; Lee, Ki Hyeong; Han, Hye Suk; Song, Eun-Kee; Yun, Hwan Jung; Cho, In Sung; Lee, Joon Kyoo; Lim, Sang-Chul; Chung, Woong-Ki; Chung, Ik-Joo

    2013-03-06

    The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m(2) docetaxel on day 1 and 8, 60 mg/m(2) cisplatin on day 1, and 70 mg/m(2) S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3-4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC. ClinicalTrials.gov: NCT01645748.

  13. Aroused with heart: Modulation of heartbeat evoked potential by arousal induction and its oscillatory correlates

    PubMed Central

    Luft, Caroline Di Bernardi; Bhattacharya, Joydeep

    2015-01-01

    Recent studies showed that the visceral information is constantly processed by the brain, thereby potentially influencing cognition. One index of such process is the heartbeat evoked potential (HEP), an ERP component related to the cortical processing of the heartbeat. The HEP is sensitive to a number of factors such as motivation, attention, pain, which are associated with higher levels of arousal. However, the role of arousal and its associated brain oscillations on the HEP has not been characterized, yet it could underlie the previous findings. Here we analysed the effects of high- (HA) and low-arousal (LA) induction on the HEP. Further, we investigated the brain oscillations and their role in the HEP in response to HA and LA inductions. As compared to LA, HA was associated with a higher HEP and lower alpha oscillations. Interestingly, individual differences in the HEP modulation by arousal induction were correlated with alpha oscillations. In particular, participants with higher alpha power during the arousal inductions showed a larger HEP in response to HA compared to LA. In summary, we demonstrated that arousal induction affects the cortical processing of heartbeats; and that the alpha oscillations may modulate this effect. PMID:26503014

  14. An essential role of a FoxD gene in notochord induction in Ciona embryos.

    PubMed

    Imai, Kaoru S; Satoh, Nori; Satou, Yutaka

    2002-07-01

    A key issue for understanding the early development of the chordate body plan is how the endoderm induces notochord formation. In the ascidian Ciona, nuclear accumulation of beta-catenin is the first step in the process of endoderm specification. We show that nuclear accumulation of beta-catenin directly activates the gene (Cs-FoxD) for a winged helix/forkhead transcription factor and that this gene is expressed transiently at the 16- and 32-cell stages in endodermal cells. The function of Cs-FoxD, however, is not associated with differentiation of the endoderm itself but is essential for notochord differentiation or induction. In addition, it is likely that the inductive signal that appears to act downstream of Cs-FoxD does not act over a long range. It has been suggested that FGF or Notch signal transduction pathway mediates ascidian notochord induction. Our previous study suggests that Cs-FGF4/6/9 is partially involved in the notochord induction. The present experimental results suggest that the expression and function of Cs-FGF4/6/9 and Cs-FoxD are not interdependent, and that the Notch pathway is involved in B-line notochord induction downstream of Cs-FoxD.

  15. Development, awareness and inductive selectivity.

    PubMed

    Hayes, Brett K; Lim, Melissa

    2013-05-01

    Two studies examined whether adults and children could learn to make context-dependent inferences about novel stimuli and the role of awareness of context cues in such learning. Participants were trained to match probes to targets on the basis of shape or color with the relevant dimension shifting according to item context. A selective induction test then examined context-dependent responding in a more complex matching task. Awareness of the role of context was assessed using a behavioral task and explicit questions. Experiment 1 showed that after training with the procedure described by Sloutsky and Fisher (2008), only a minority of adults showed evidence of context-dependent responding in the selective induction test. Experiment 2 used a modified training protocol that promoted attention to context cues. This led to reliable selective induction in a majority of adults and a sizeable proportion of 4- to 6-year-olds. Crucially, in both age groups, selective induction was dependent on awareness of context. Hence, children as young as 4 can learn to make selective inferences about novel stimuli, but only when they are aware of the relevant context cues. These results challenge previous claims that selective induction in children is the product of implicit learning.

  16. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group.

    PubMed

    Geyer, J Russell; Sposto, Richard; Jennings, Mark; Boyett, James M; Axtell, Richard A; Breiger, David; Broxson, Emmett; Donahue, Bernadine; Finlay, Jonathan L; Goldwein, Joel W; Heier, Linda A; Johnson, Dennis; Mazewski, Claire; Miller, Douglas C; Packer, Roger; Puccetti, Diane; Radcliffe, Jerilynn; Tao, May Lin; Shiminski-Maher, Tania

    2005-10-20

    To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

  17. The Fusion Gain Analysis of the Inductively Driven Liner Compression Based Fusion

    NASA Astrophysics Data System (ADS)

    Shimazu, Akihisa; Slough, John

    2016-10-01

    An analytical analysis of the fusion gain expected in the inductively driven liner compression (IDLC) based fusion is conducted to identify the fusion gain scaling at various operating conditions. The fusion based on the IDLC is a magneto-inertial fusion concept, where a Field-Reversed Configuration (FRC) plasmoid is compressed via the inductively-driven metal liner to drive the FRC to fusion conditions. In the past, an approximate scaling law for the expected fusion gain for the IDLC based fusion was obtained under the key assumptions of (1) D-T fuel at 5-40 keV, (2) adiabatic scaling laws for the FRC dynamics, (3) FRC energy dominated by the pressure balance with the edge magnetic field at the peak compression, and (4) the liner dwell time being liner final diameter divided by the peak liner velocity. In this study, various assumptions made in the previous derivation is relaxed to study the change in the fusion gain scaling from the previous result of G ml1 / 2 El11 / 8 , where ml is the liner mass and El is the peak liner kinetic energy. The implication from the modified fusion gain scaling on the performance of the IDLC fusion reactor system is also explored.

  18. Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis1

    PubMed Central

    Traw, M. Brian; Bergelson, Joy

    2003-01-01

    Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332

  19. Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

    PubMed

    Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

    2015-07-10

    Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Weight change during childhood acute lymphoblastic leukemia induction therapy predicts obesity: a report from the Children's Oncology Group.

    PubMed

    Withycombe, Janice S; Smith, Lynette M; Meza, Jane L; Merkle, Carrie; Faulkner, Melissa Spezia; Ritter, Leslie; Seibel, Nita L; Moore, Ki

    2015-03-01

    Obesity is a well documented problem associated with childhood acute lymphoblastic leukemia (ALL) with increasing body mass index often observed during therapy. This study aims to evaluate if weight gain, early in therapy, is predictive of obesity at the end of treatment. In this secondary analysis, data from 1,017 high-risk ALL patients previously treated on a Children's Oncology Group protocol (CCG study 1961) were reviewed. Logistic regression was used to examine whether change in BMI z-score at Induction or Delayed Intensification (DI) 1 were predictive of obesity at the end of therapy. The BMI z-score at the beginning of Induction and the change in BMI z-score during Induction were both significant predictors of obesity at the end of therapy. The change in BMI z-score during cycle 1 of DI was not found to be associated with obesity. It is well know that obesity at the beginning of therapy is predictive of obesity at the end of ALL therapy. The new, and more important, finding from this study is that even after adjusting for baseline weight, the increase in BMI z-scores during induction was an independent predictor of obesity at the end of therapy. Most researchers agree that prevention is the best form of treatment for obesity as it is difficult to reverse once it is present. This study suggests that monitoring weight trends during Induction may be useful in guiding healthcare practitioners in identifying which patients are at highest risk for obesity development so that early intervention may occur. © 2014 Wiley Periodicals, Inc.

  1. Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study

    PubMed Central

    2012-01-01

    Background There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP), which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. Results The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. Conclusions In addition to confirming literature results, ProGolem’s model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners. PMID:22783946

  2. The Role of a Novel Long Noncoding RNA TUC40- in Cardiomyocyte Induction and Maturation in P19 Cells.

    PubMed

    Li, Huijuan; Jiang, Li; Yu, Zhangbin; Han, Shuping; Liu, Xuehua; Li, Mengmeng; Zhu, Chun; Qiao, Lixing; Huang, Li

    2017-12-01

    In previous studies, TUC40-, a new long noncoding RNA, was found to be overexpressed in human ventricular septal defect (VSD) embryonic heart samples. In this article, we carried out experiments on the P19 cell line to elucidate the effects of TUC40- overexpression on cardiomyocyte development relevant to VSD pathogenesis. We established the overexpression cell model by plasmid transfection, and explored the expression profile of Pbx1, the sense gene of TUC40-, and the marker genes of cardiomyocyte linage commitment (Nkx2.5 and GATA4) and maturation (cardiac troponin T). In addition, we combined cell cycle and Cell Counting Kit-8 analysis to detect cell proliferation and used flow cytometry and caspase-3 assays to test apoptosis. At last, bioinformatics analysis was performed to show the possible role of TUC40-. In the control group, Pbx1 elevated steadily during cardiomyocyte induction; whereas in the overexpression group, it showed significantly lower expression at day 6, 8 and 10 of induction. Cells in the overexpression group failed to induce cardiomyocytes indicated by GATA4 and cardiac troponin T. Proliferation was inhibited possibly owing to G2/M cell cycle arrest and the induced apoptosis rate was higher in the overexpression group. TUC40- overexpression reduced Pbx1 expression, cardiomyocyte induction and differentiation, inhibited proliferation and promoted apoptosis. Combining the results and previous studies, we propose TUC40- as a potential pathologic factor for VSD. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  3. The Opinions of Mentors and Beginning Teachers. What Do They Say about Induction? Research Report 91-1.

    ERIC Educational Resources Information Center

    Reiman, Alan J.; Edelfelt, Roy A.

    This paper summarizes and analyzes the results of a questionnaire study of mentors and beginning teachers. The objective of the questionnaire study was to corroborate and extend the information gathered in a previous interview study. Mentors and beginning teachers were presented with statements describing the support given to beginning teachers…

  4. Analysis of SOS-Induced Spontaneous Prophage Induction in Corynebacterium glutamicum at the Single-Cell Level

    PubMed Central

    Nanda, Arun M.; Heyer, Antonia; Krämer, Christina; Grünberger, Alexander; Kohlheyer, Dietrich

    2014-01-01

    The genome of the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 contains three integrated prophage elements (CGP1 to -3). Recently, it was shown that the large lysogenic prophage CGP3 (∼187 kbp) is excised spontaneously in a small number of cells. In this study, we provide evidence that a spontaneously induced SOS response is partly responsible for the observed spontaneous CGP3 induction. Whereas previous studies focused mainly on the induction of prophages at the population level, we analyzed the spontaneous CGP3 induction at the single-cell level using promoters of phage genes (Pint2 and Plysin) fused to reporter genes encoding fluorescent proteins. Flow-cytometric analysis revealed a spontaneous CGP3 activity in about 0.01 to 0.08% of the cells grown in standard minimal medium, which displayed a significantly reduced viability. A PrecA-eyfp promoter fusion revealed that a small fraction of C. glutamicum cells (∼0.2%) exhibited a spontaneous induction of the SOS response. Correlation of PrecA to the activity of downstream SOS genes (PdivS and PrecN) confirmed a bona fide induction of this stress response rather than stochastic gene expression. Interestingly, the reporter output of PrecA and CGP3 promoter fusions displayed a positive correlation at the single-cell level (ρ = 0.44 to 0.77). Furthermore, analysis of the PrecA-eyfp/Pint2-e2-crimson strain during growth revealed the highest percentage of spontaneous PrecA and Pint2 activity in the early exponential phase, when fast replication occurs. Based on these studies, we postulate that spontaneously occurring DNA damage induces the SOS response, which in turn triggers the induction of lysogenic prophages. PMID:24163339

  5. INDUCTION OF DNA STRAND BREAKS BY TRIHALOMETHANES IN PRIMARY HUMAN LUNG EPITHELIAL CELLS

    EPA Science Inventory


    Abstract

    Trihalomethanes (TEMs) are disinfection by-products and suspected human carcinogens present in chlorinated drinking water. Previous studies have shown that many THMs induce sister chromatid exchanges and DNA strand breaks in human peripheral blood lymphocyte...

  6. EFFECTS OF BDE-47 ON NUCLEAR RECEPTOR REGULATED GENES AND IMPLICATIONS FOR THYROID HORMONE DISRUPTION.

    EPA Science Inventory

    Previous studies have shown that exposure to polybrominated diphenyl ethers (PBDEs) can decrease thyroid hormone levels via the induction of hepatic uridinediphosphate-glucoronosyltransferase, (UGTs) which catalyze glucuronidation of T4 resulting in T4-glucuronide excretion. Bas...

  7. Using Implicit Instructional Cues to Influence False Memory Induction.

    PubMed

    Cirelli, Laura K; Dickinson, Joël; Poirier, Marie

    2015-10-01

    Previous research has shown that explicit cues specific to the encoding process (endogenous) or characteristic of the stimuli themselves (exogenous) can be used to direct a reader's attentional resources towards either relational or item-specific information. By directing attention to relational information (and therefore away from item-specific information) the rate of false memory induction can be increased. The purpose of the current study was to investigate if a similar effect would be found by manipulating implicitly endogenous cues. An instructional manipulation was used to influence the perceptual action participants performed on word stimuli during the encoding of DRM list words. Results demonstrated that the instructional conditions that encouraged faster processing also led to an increased rate of false memory induction for semantically related words, supporting the hypothesis that attention was directed towards relational information. This finding supports the impoverished relational processing account of false memory induction. This supports the idea that implicitly endogenous cues, exogenous cues (like font) or explicitly endogenous cues (like training) can direct attentional resources during encoding.

  8. Doubt and fear of self in bulimia nervosa.

    PubMed

    Wilson, Samantha; Aardema, Frederick; O'Connor, Kieron

    2017-12-01

    Several overlapping cognitive processes have been identified in eating disorders (EDs) and obsessive compulsive disorder (OCD). Drawing from the OCD literature, the present study examined whether bulimia nervosa (BN) is associated with a maladaptive inductive reasoning style characterized by the over-investment in possibility-based (as opposed to reality-based) information. Women with BN (n = 25) and healthy controls (HC; n = 24) completed the Inference Processes Task (IPT), an ecological inductive reasoning task previously validated in OCD samples. Participants also completed the Fear of Self Questionnaire (FSQ) that evaluates investment in a feared possible identity. Significant differences on the IPT indicate that the BN group was more influenced by possibility-based information throughout the task than the HC group (F[5.44, 255.78] = 6.94, p > .001). It was also found that the BN group scored significantly higher on the FSQ than the HC group (t[29.98] = 8.4, p > .001), replicating previous findings. Finally, scores on the IPT were significantly correlated with measures of symptom severity. These findings suggest that BN may be associated with maladaptive inductive reasoning processes characterized by over-investment in possibility-based feared outcomes and identities. © 2017 Wiley Periodicals, Inc.

  9. Regulating Anger under Stress via Cognitive Reappraisal and Sadness.

    PubMed

    Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

    2017-01-01

    Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., "sadness counteracts anger" (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants' subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one's ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was found to reduce the level of subjective anger more, but this difference only existed in non-stressful conditions. By contrast, irrespective of stress, the levels of aggressive behavior and related skin conductance after sadness induction were both significantly lower than those after CER induction or neutral emotion induction, thus suggesting the immunity of the regulatory effect of SCA strategy to the stress factor.

  10. Regulating Anger under Stress via Cognitive Reappraisal and Sadness

    PubMed Central

    Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

    2017-01-01

    Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., “sadness counteracts anger” (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants’ subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one’s ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was found to reduce the level of subjective anger more, but this difference only existed in non-stressful conditions. By contrast, irrespective of stress, the levels of aggressive behavior and related skin conductance after sadness induction were both significantly lower than those after CER induction or neutral emotion induction, thus suggesting the immunity of the regulatory effect of SCA strategy to the stress factor. PMID:28855881

  11. Outpatient versus inpatient induction of labour for improving birth outcomes.

    PubMed

    Kelly, Anthony J; Alfirevic, Zarko; Ghosh, Arpita

    2013-11-12

    More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013). Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. We included four trials, with a combined total of 1439 women in the review; each trial examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (two studies including 1028 women). There were no differences between women managed as outpatients versus inpatients for most review outcomes. There was no evidence of a difference between the likelihood of women requiring instrumental delivery in either setting (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.79 to 2.13). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10 mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale, RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.

  12. Outpatient versus inpatient induction of labour for improving birth outcomes.

    PubMed

    Kelly, Anthony J; Alfirevic, Zarko; Dowswell, Therese

    2009-04-15

    More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2008). Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. We included three trials, with a combined total of 612 women in the review; each examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (One study including 201 women). There were no differences between women managed as out- versus inpatients for most review outcomes. Women in the outpatient group were more likely to have instrumental deliveries (risk ratio (RR) 1.74; 95% confidence interval (CI) 1.03 to 2.93). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.

  13. Effects of mood induction on consumers with vs. without compulsive buying propensity: an experimental study.

    PubMed

    Vogt, Sinje; Hunger, Antje; Türpe, Tina; Pietrowsky, Reinhard; Gerlach, Alexander L

    2014-12-15

    Compulsive buying (CB) is excessive and leads to impairment and distress. Several studies aimed to explore the phenomenology and antecedents of CB, especially affective states. However, these studies mostly used retrospective self-report and mostly focused on compulsive buyers only. Therefore, this study aims to directly compare consumers with CB propensity and controls on experimental proxies of buying behavior and to investigate 1) effects of neutral vs. negative mood inductions and 2) whether mood effects on buying behavior are specific to CB. Forty female consumers with CB propensity and 40 female controls were randomly assigned to a neutral or negative mood induction. Buying related behavior (likelihood to expose oneself to a shopping situation, urge and probability to buy, willingness to pay) was assessed. Consumers with CB propensity differed from controls in all buying behavior aspects except for willingness to pay. Neither main effects of mood nor group×mood interaction effects on buying behavior were found. However, consumers with CB propensity were emotionally more strongly affected by a negative mood induction. Although negative affect has previously been reported to precede buying episodes in CB, our findings do not indicate specific negative mood effects on buying, neither in CB nor in controls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. KSC-03PD-2020

    NASA Technical Reports Server (NTRS)

    2003-01-01

    KENNEDY SPACE CENTER, FLA. At the KSC Visitor Complex, former astronaut James A. Lovell (standing left) applauds former astronaut Sally K. Ride at her induction ceremony into the U.S. Astronaut Hall of Fame. Seated on the dais, from left, are former astronauts Gordon Cooper, Scott Carpenter, and Buzz Aldrin, all previously inducted into the Hall of Fame. Being inducted with Ride are Space Shuttle astronauts Daniel Brandenstein, Robert 'Hoot' Gibson, and Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  15. Deductive and inductive reasoning in obsessive-compulsive disorder.

    PubMed

    Pélissier, Marie-Claude; O'Connor, Kieron P

    2002-03-01

    This study tested the hypothesis that people with obsessive-compulsive disorder (OCD) show an inductive reasoning style distinct from people with generalized anxiety disorder (GAD) and from participants in a non-anxious (NA) control group. The experimental procedure consisted of administering a range of six deductive and inductive tasks and a probabilistic task in order to compare reasoning processes between groups. Recruitment was in the Montreal area within a French-speaking population. The participants were 12 people with OCD, 12 NA controls and 10 people with GAD. Participants completed a series of written and oral reasoning tasks including the Wason Selection Task, a Bayesian probability task and other inductive tasks, designed by the authors. There were no differences between groups in deductive reasoning. On an inductive "bridging task", the participants with OCD always took longer than the NA control and GAD groups to infer a link between two statements and to elaborate on this possible link. The OCD group alone showed a significant decrease in their degree of conviction about an arbitrary statement after inductively generating reasons to support this statement. Differences in probabilistic reasoning replicated those of previous authors. The results pinpoint the importance of examining inference processes in people with OCD in order to further refine the clinical applications of behavioural-cognitive therapy for this disorder.

  16. Controllability of Free-piston Stirling Engine/linear Alternator Driving a Dynamic Load

    NASA Technical Reports Server (NTRS)

    Kankam, M. David; Rauch, Jeffrey S.

    1994-01-01

    This paper presents the dynamic behavior of a Free-Piston Stirling Engine/linear alternator (FPSE/LA) driving a single-phase fractional horse-power induction motor. The controllability and dynamic stability of the system are discussed by means of sensitivity effects of variations in system parameters, engine controller, operating conditions, and mechanical loading on the induction motor. The approach used expands on a combined mechanical and thermodynamic formulation employed in a previous paper. The application of state-space technique and frequency domain analysis enhances understanding of the dynamic interactions. Engine-alternator parametric sensitivity studies, similar to those of the previous paper, are summarized. Detailed discussions are provided for parametric variations which relate to the engine controller and system operating conditions. The results suggest that the controllability of a FPSE-based power system is enhanced by proper operating conditions and built-in controls.

  17. Evaluation of rolling contact fatigue of induction heated 13Cr-2Ni-2Mo Stainless steel bar with Si3N4-ball

    NASA Astrophysics Data System (ADS)

    Yadoiwa, Ariyasu; Mizobe, Koshiro; Kida, Katsuyuki

    2018-03-01

    13Cr % martensitic stainless steels were used in various industry, because they have excellent corrosion resistance and high hardness among other stainless steels. They are also expected as a bearing material, however, the research on rolling contact fatigue (RCF) is not enough. In this study, 13Cr-2Ni-2Mo stainless steels were quenched by induction heating and their RCF lives were evaluated. A Si3N4-ball was used in order to apply higher stress (Pmax = 5.6 GPa) than our previous tests (Pmax=5.3 GPa), in a single-ball RCF testing machine. It was found that the basic life (L10) was 2.20×106 cycles and Median life (L50) was 6.04×106 cycles. In addition, Weibull modulus became higher than the previous tests.

  18. Induction Heating Systems

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Induction heating technology, a magnetic non-deforming process, was developed by Langley researchers to join plastic and composite components in space. Under NASA license, Inductron Corporation uses the process to produce induction heating systems and equipment for numerous applications. The Torobonder, a portable system, comes with a number of interchangeable heads for aircraft repair. Other developments are the E Heating Head, the Toroid Joining Gun, and the Torobrazer. These products perform bonding applications more quickly, safely and efficiently than previous methods.

  19. A Comparison of the Intellectual Abilities of Good and Poor Problem Solvers: An Exploratory Study.

    ERIC Educational Resources Information Center

    Meyer, Ruth Ann

    This study examined a selected sample of fourth-grade students who had been previously identified as good or poor problem solvers. The pupils were compared on variables considered as "reference tests" for Verbal, Induction, Numerical, Word Fluency, Memory, Spatial Visualization, and Perceptual Speed abilities. The data were compiled to…

  20. The Sequence of Study Changes What Information Is Attended to, Encoded, and Remembered during Category Learning

    ERIC Educational Resources Information Center

    Carvalho, Paulo F.; Goldstone, Robert L.

    2017-01-01

    The sequence of study influences how we learn. Previous research has identified different sequences as potentially beneficial for learning in different contexts and with different materials. Here we investigate the mechanisms involved in inductive category learning that give rise to these sequencing effects. Across 3 experiments we show evidence…

  1. Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

    NASA Technical Reports Server (NTRS)

    Chappell, Lori J.; Cucinotta, Francis A.

    2010-01-01

    There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies.

  2. Redox-Regulated Pathway of Tyrosine Phosphorylation Underlies NF-κB Induction by an Atypical Pathway Independent of the 26S Proteasome

    PubMed Central

    Cullen, Sarah; Ponnappan, Subramaniam; Ponnappan, Usha

    2015-01-01

    Alternative redox stimuli such as pervanadate or hypoxia/reoxygenation, induce transcription factor NF-κB by phospho-tyrosine-dependent and proteasome-independent mechanisms. While considerable attention has been paid to the absence of proteasomal regulation of tyrosine phosphorylated IκBα, there is a paucity of information regarding proteasomal regulation of signaling events distinct from tyrosine phosphorylation of IκBα. To delineate roles for the ubiquitin-proteasome pathway in the phospho-tyrosine dependent mechanism of NF-κB induction, we employed the proteasome inhibitor, Aclacinomycin, and the phosphotyrosine phosphatase inhibitor, pervanadate (PV). Results from these studies demonstrate that phospho-IκBα (Tyr-42) is not subject to proteasomal degradation in a murine stromal epithelial cell line, confirming results previously reported. Correspondingly, proteasome inhibition had no discernable effect on the key signaling intermediaries, Src and ERK1/2, involved in the phospho-tyrosine mechanisms regulating PV-mediated activation of NF-κB. Consistent with previous reports, a significant redox imbalance leading to the activation of tyrosine kinases, as occurs with pervanadate, is required for the induction of NF-κB. Strikingly, our studies demonstrate that proteasome inhibition can potentiate oxidative stress associated with PV-stimulation without impacting kinase activation, however, other cellular implications for this increase in intracellular oxidation remain to be fully delineated. PMID:25671697

  3. Ionotropic NMDA receptor signaling is required for the induction of long-term depression in the mouse hippocampal CA1 region.

    PubMed

    Babiec, Walter E; Guglietta, Ryan; Jami, Shekib A; Morishita, Wade; Malenka, Robert C; O'Dell, Thomas J

    2014-04-09

    Previous studies have provided strong support for the notion that NMDAR-mediated increases in postsynaptic Ca(2+) have a crucial role in the induction of long-term depression (LTD). This view has recently been challenged, however, by findings suggesting that LTD induction is instead attributable to an ion channel-independent, metabotropic form of NMDAR signaling. Thus, to explore the role of ionotropic versus metabotropic NMDAR signaling in LTD, we examined the effects of varying extracellular Ca(2+) levels or blocking NMDAR channel ion fluxes with MK-801 on LTD and NMDAR signaling in the mouse hippocampal CA1 region. We find that the induction of LTD in the adult hippocampus is highly sensitive to extracellular Ca(2+) levels and that MK-801 blocks NMDAR-dependent LTD in the hippocampus of both adult and immature mice. Moreover, MK-801 inhibits NMDAR-mediated activation of p38-MAPK and dephosphorylation of AMPAR GluA1 subunits at sites implicated in LTD. Thus, our results indicate that the induction of LTD in the hippocampal CA1 region is dependent on ionotropic, rather than metabotropic, NMDAR signaling.

  4. Vertical spatial sensitivity and exploration depth of low-induction-number electromagnetic-induction instruments

    USGS Publications Warehouse

    Callegary, J.B.; Ferré, T.P.A.; Groom, R.W.

    2007-01-01

    Vertical spatial sensitivity and effective depth of exploration (d e) of low-induction-number (LIN) instruments over a layered soil were evaluated using a complete numerical solution to Maxwell's equations. Previous studies using approximate mathematical solutions predicted a vertical spatial sensitivity for instruments operating under LIN conditions that, for a given transmitter-receiver coil separation (s), coil orientation, and transmitter frequency, should depend solely on depth below the land surface. When not operating under LIN conditions, vertical spatial sensitivity and de also depend on apparent soil electrical conductivity (??a) and therefore the induction number (??). In this new evaluation, we determined the range of ??a and ?? values for which the LIN conditions hold and how de changes when they do not. Two-layer soil models were simulated with both horizontal (HCP) and vertical (VCP) coplanar coil orientations. Soil layers were given electrical conductivity values ranging from 0.1 to 200 mS m-1. As expected, de decreased as ??a increased. Only the least electrically conductive soil produced the de expected when operating under LIN conditions. For the VCP orientation, this was 1.6s, decreasing to 0.8s in the most electrically conductive soil. For the HCP orientation, de decreased from 0.76s to 0.51s. Differences between this and previous studies are attributed to inadequate representation of skin-depth effect and scattering at interfaces between layers. When using LIN instruments to identify depth to water tables, interfaces between soil layers, and variations in salt or moisture content, it is important to consider the dependence of de on ??a. ?? Soil Science Society of America.

  5. Kinetics of the melting front movement in process of centrifugal induction surfacing of powder material with nanoscale modificaters

    NASA Astrophysics Data System (ADS)

    Sasnouski, I.; Kurylionak, A.

    2018-03-01

    For solving the problem of improving the powder coatings modified by nanostructure components obtained by induction surfacing method tribological characteristics it is necessary to study the kinetics of the powdered layer melting and define the minimum time of melting. For powdered layer predetermined temperature maintenance at sintering mode stage it is required to determine the temperature difference through blank thickness of the for one hundred-day of the define the warm-up swing on of the stocking up by solving the thermal conductivity stationary problem for quill (hollow) cylinder with internal heat source. Herewith, since in practice thickness of the cylinder wall is much less then its diameter and the temperature difference is comparatively small, the thermal conductivity dependence upon the temperature can be treated as negligible. As it was shown by our previous studies, in the induction heating process under powdered material centrifugal surfacing (i.e. before achieving the melting temperature) the temperature distribution in powdered layer thickness may be considered even. Hereinafter, considering the blank part induction heating process quasi-stationarity under Fo big values, it is possible to consider its internal surface heating as developing with constant velocity. As a result of development the melting front movement mathematical model in a powdered material with nanostructure modifiers the minimum surfacing time is defined. It allows to minimize negative impact of thermal influence on formation of applied coating structure, to raise productivity of the process, to lower power inputs and to ensure saving of nonferrous and high alloys by reducing the allowance for machining. The difference of developed mathematical model of melting front movement from previously known is that the surface temperature from which the heat transfer occures is a variable and varies with a time after the linear law.

  6. Special Education Teacher Education Research: Current Status and Future Directions

    ERIC Educational Resources Information Center

    Sindelar, Paul T.; Brownell, Mary T.; Billingsley, Bonnie

    2010-01-01

    In this article, the authors propose an agenda for special education teacher education researchers, with particular attention to policy work and studies of innovations in pre-service preparation, induction and mentoring, and professional development. Because previous research is limited and unfocused, the foundation for future research is weak,…

  7. THE USE OF GENE ARRAYS TO DETERMINE TEMPORAL GENE INDUCTION IN SHEEPSHEAD MINNOWS EXPOSED TO E2

    EPA Science Inventory

    Gene arrays provide a means to study differential gene expression in fish exposed to environmental estrogens by providing a "snapshot" of the genes expressed at a given time. Such array data may also uncover previously unknown biochemical pathways affected by estrogenic compounds...

  8. Semantic Similarity of Labels and Inductive Generalization: Taking a Second Look

    ERIC Educational Resources Information Center

    Fisher, Anna V.; Matlen, Bryan J.; Godwin, Karrie E.

    2011-01-01

    Prior research suggests that preschoolers can generalize object properties based on category information conveyed by semantically-similar labels. However, previous research did not control for co-occurrence probability of labels in natural speech. The current studies re-assessed children's generalization with semantically-similar labels.…

  9. Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool.

    PubMed

    Paskulin, Roman; Jamnik, Polona; Obermajer, Natasa; Slavić, Marija; Strukelj, Borut

    2010-02-10

    Ibogaine has been extensively studied in the last decades in relation to its anti-addictive properties that have been repeatedly reported as being addiction interruptive and craving eliminative. In our previous study we have already demonstrated induction of energy related enzymes in rat brains treated with ibogaine at a dose of 20mg/kg i.p. 24 and 72 h prior to proteomic analysis. In this study a model organism yeast Saccharomyces cerevisiae was cultivated with ibogaine in a concentration of 1mg/l. Energy metabolism cluster enzymes glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase and alcohol dehydrogenase were induced after 5h of exposure. This is a compensation of demonstrated ATP pool decrease after ibogaine. Yeast in a stationary growth phase is an accepted model for studies of housekeeping metabolism of eukaryotes, including humans. Study showed that ibogaine's influence on metabolism is neither species nor tissue specific. Effect is not mediated by binding of ibogaine to receptors, as previously described in literature since they are lacking in this model. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  10. Exposure-efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn's Disease.

    PubMed

    Rosario, Maria; French, Jonathan L; Dirks, Nathanael L; Sankoh, Serap; Parikh, Asit; Yang, Huyuan; Danese, Silvio; Colombel, Jean-Frédéric; Smyth, Michael; Sandborn, William J; Feagan, Brian G; Reinisch, Walter; Sands, Bruce E; Sans, Miguel; Fox, Irving

    2017-08-01

    A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [UC] or Crohn's disease [CD] has been reported. Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data. Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated. Exposure-efficacy relationships at Week 6 and potential baseline covariate effects were explored using logistic regression and individual predicted cumulative average concentration through Week 6 [Caverage] as exposure measure. Higher vedolizumab concentrations were associated with higher clinical remission rates; the exposure-efficacy relationship was steeper for UC than CD. Unadjusted analyses overestimated the relationship, more so for CD. From covariate-adjusted models, average probability of remission at Week 6 increased by approximately 15% for UC and 10% for CD between Caverage values of 35 and 84 µg/ml [5th and 95th percentiles, respectively]. On average, patients with higher albumin, lower faecal calprotectin [UC only], lower C-reactive protein [CD only], and no previous tumour necrosis factor-α [TNFα] antagonist use had a higher remission probability. Previous TNFα antagonist use had the greatest impact; remission probability was approximately 10% higher in treatment-naïve patients. Higher vedolizumab serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD. This relationship is affected by several factors, including previous TNFα antagonist use. Prospective studies are needed to assess vedolizumab dose individualisation and optimisation. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  11. Wnt signaling induces vulva development in the nematode Pristionchus pacificus.

    PubMed

    Tian, Huiyu; Schlager, Benjamin; Xiao, Hua; Sommer, Ralf J

    2008-01-22

    The Caenorhabditis elegans vulva is induced by a member of the epidermal growth factor (EGF) family that is expressed in the gonadal anchor cell, representing a prime example of signaling processes in animal development. Comparative studies indicated that vulva induction has changed rapidly during evolution. However, nothing was known about the molecular mechanisms underlying these differences. By analyzing deletion mutants in five Wnt pathway genes, we show that Wnt signaling induces vulva formation in Pristionchus pacificus. A Ppa-bar-1/beta-catenin deletion is completely vulvaless. Several Wnt ligands and receptors act redundantly in vulva induction, and Ppa-egl-20/Wnt; Ppa-mom-2/Wnt; Ppa-lin-18/Ryk triple mutants are strongly vulvaless. Wnt ligands are differentially expressed in the somatic gonad, the anchor cell, and the posterior body region, respectively. In contrast, previous studies indicated that Ppa-lin-17, one of the Frizzled-type receptors, has a negative role in vulva formation. We found that mutations in Ppa-bar-1 and Ppa-egl-20 suppress the phenotype of Ppa-lin-17. Thus, an unexpected complexity of Wnt signaling is involved in vulva induction and vulva repression in P. pacificus. This study provides the first molecular identification of the inductive vulva signal in a nematode other than Caenorhabditis.

  12. Cognitive vulnerability to depression in young people in secure accommodation: the influence of ethnicity and current suicidal ideation.

    PubMed

    Woolgar, Matthew; Tranah, Troy

    2010-10-01

    Young people in secure accommodation are at high risk of depression and self-harm. This study investigates the relationship between depressive symptoms, negative self-schemas and the cognitive vulnerability to depression in 38 young people in secure accommodation. The impact of a) current suicidal ideation and b) a previous history of self-harm behaviour on latent negative self-schemas was examined using a mood induction task. The low mood condition indicated these young people had a latent cognitive vulnerability to depression. However, this vulnerability was exacerbated in the context of current suicidal ideation but not by a history of self-harm behaviours. An unexpected finding was the negative self-schemas of young people from ethnic minority backgrounds were particularly susceptible to the mood induction. The findings are discussed both in terms of the cognitive vulnerabilities of adolescents detained in secure accommodation and the role of participant characteristics on the validity of mood induction studies in adolescence.

  13. Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

    PubMed

    Vickers, Adrian D; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S; Medjedovic, Jasmina; Smyth, Michael

    2016-01-01

    Biological therapies are increasingly used to treat ulcerative colitis (UC). To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

  14. Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment.

    PubMed

    Geber, Selmo; Ferreira, Daniela Parreiras; Spyer Prates, Luis Felipe Víctor; Sales, Liana; Sampaio, Marcos

    2002-01-01

    Endometriosis affects 2-50% of women at reproductive age. Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility. Also, the removal of ovarian endometrioma might lead to a reduction in the follicular reserve and response to stimulation. Therefore, the aim of this study was to evaluate the effect of previous ovarian surgery for endometriosis on the ovarian response in assisted reproduction treatment cycles and its pregnancy outcome. A total of 61 women, with primary infertility and previously having undergone ovarian surgery for endometriosis, who had received 74 IVF/intracytoplasmic sperm injection (ICSI) cycles, were studied (study group). A further 74 patients with primary infertility who underwent 77 IVF/ICSI cycles within#10; the same period of time, at the same clinic and without previous ovarian surgery or endometriosis were studied as a control group. Patients were matched for age and treatment performed. Patients 35 years with previous ovarian surgery needed more ampoules for ovulation induction (P = 0.017) and had fewer follicles and oocytes than women in the control group (P = 0.001). Duration of folliculogenesis was similar in both groups, as was fertilization rate. A total of 10 patients achieved pregnancy in the study group (34.5%) and 14 (48.3%) in the control group. Although a lower pregnancy rate was observed in patients who had undergone previous ovarian surgery, this difference was not statistically significant (P = 0.424). In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. Therefore, for infertile patients, non-surgical treatment might be a better option to avoid reduction of the ovarian response.

  15. Students' Perceptions about Online Teaching Effectiveness: A Bottom-Up Approach for Identifying Online Instructors' Roles

    ERIC Educational Resources Information Center

    Gómez-Rey, Pilar; Barbera, Elena; Fernández-Navarro, Francisco

    2018-01-01

    The topic of online instructors' roles has been of interest to the educational community since the late twentieth century. In previous studies, the identification of online instructors' roles was done using a top-down (deductive) approach. This study applied a bottom-up (inductive) procedure to examine not only the roles of online instructors from…

  16. Testing the attentional boundary conditions of subliminal semantic priming: the influence of semantic and phonological task sets

    PubMed Central

    Adams, Sarah C.; Kiefer, Markus

    2012-01-01

    Recent studies challenged the classical notion of automaticity and indicated that even unconscious automatic semantic processing is under attentional control to some extent. In line with our attentional sensitization model, these data suggest that a sensitization of semantic pathways by a semantic task set is necessary for subliminal semantic priming to occur while non-semantic task sets attenuate priming. In the present study, we tested whether masked semantic priming is also reduced by phonological task sets using the previously developed induction task paradigm. This would substantiate the notion that attention to semantics is necessary for eliciting unconscious semantic priming. Participants first performed semantic and phonological induction tasks that should either activate a semantic or a phonological task set. Subsequent to the induction task, a masked prime word, either associated or non-associated with the following lexical decision target word, was presented. Across two experiments, we varied the nature of the phonological induction task (word phonology vs. letter phonology) to assess whether the attentional focus on the entire word vs. single letters modulates subsequent masked semantic priming. In both experiments, subliminal semantic priming was only found subsequent to the semantic induction task, but was attenuated following either phonological induction task. These results indicate that attention to phonology attenuates subsequent semantic processing of unconsciously presented primes whether or not attention is directed to the entire word or to single letters. The present findings therefore substantiate earlier evidence that an attentional orientation toward semantics is necessary for subliminal semantic priming to be elicited. PMID:22952461

  17. Neural network based control of Doubly Fed Induction Generator in wind power generation

    NASA Astrophysics Data System (ADS)

    Barbade, Swati A.; Kasliwal, Prabha

    2012-07-01

    To complement the other types of pollution-free generation wind energy is a viable option. Previously wind turbines were operated at constant speed. The evolution of technology related to wind systems industry leaded to the development of a generation of variable speed wind turbines that present many advantages compared to the fixed speed wind turbines. In this paper the phasor model of DFIG is used. This paper presents a study of a doubly fed induction generator driven by a wind turbine connected to the grid, and controlled by artificial neural network ANN controller. The behaviour of the system is shown with PI control, and then as controlled by ANN. The effectiveness of the artificial neural network controller is compared to that of a PI controller. The SIMULINK/MATLAB simulation for Doubly Fed Induction Generator and corresponding results and waveforms are displayed.

  18. Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells.

    PubMed

    Geng, Shuang; Yu, Yang; Kang, Youmin; Pavlakis, George; Jin, Huali; Li, Jinyao; Hu, Yanxin; Hu, Weibin; Wang, Shuang; Wang, Bin

    2011-05-05

    We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40 low IL-10 high tolerogenic DCs, which in turn stimulates the expansion of antigen-specific CD4+CD25-Foxp3+ regulatory T cells (CD25- iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25- iTreg induction. In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25- iTreg induction. Firstly, we showed that the induction of CD25- iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25- iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25- iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. Our data thus indicate that efficient induction of CD25- iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25- iTreg for clinical applications such as flea allergic dermatitis.

  19. Induced electric fields in workers near low-frequency induction heating machines.

    PubMed

    Kos, Bor; Valič, Blaž; Kotnik, Tadej; Gajšek, Peter

    2014-04-01

    Published data on occupational exposure to induction heating equipment are scarce, particularly in terms of induced quantities in the human body. This article provides some additional information by investigating exposure to two such machines-an induction furnace and an induction hardening machine. Additionally, a spatial averaging algorithm for measured fields we developed in a previous publication is tested on new data. The human model was positioned at distances where measured values of magnetic flux density were above the reference levels. All human exposure was below the basic restriction-the lower bound of the 0.1 top percentile induced electric field in the body of a worker was 0.193 V/m at 30 cm from the induction furnace. © 2013 Wiley Periodicals, Inc.

  20. Does Mood Influence Text Processing and Comprehension? Evidence from an Eye-Movement Study

    ERIC Educational Resources Information Center

    Scrimin, Sara; Mason, Lucia

    2015-01-01

    Background: Previous research has indicated that mood influences cognitive processes. However, there is scarce data regarding the link between everyday emotional states and readers' text processing and comprehension. Aim: We aim to extend current research on the effects of mood induction on science text processing and comprehension, using…

  1. Adolescents' Response to Parental Efforts to Influence Eating Habits: When Parental Warmth Matters

    ERIC Educational Resources Information Center

    Lessard, Jared; Greenberger, Ellen; Chen, Chuansheng

    2010-01-01

    Previous findings have shown both beneficial and adverse effects of parents' attempts to influence adolescents' eating habits. The current study examined the differential effect of parents' persuasion (e.g., encouragement, giving information) and pressure tactics (e.g., guilt induction, ridicule) and the moderating influence of parental warmth on…

  2. PCB-153 AND BDE-47 INCREASE THYROXINE T4) CATABOLISM IN RAT AND HUMAN HEPATOCYTES

    EPA Science Inventory

    Previous studies demonstrate that in vivo exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) decrease serum thyroxine (T4) levels in rats. This decrease is thought to occur through the induction of hepatic metabolizing enzymes ...

  3. An Online Learning Community for Beginning In-Service Teachers

    ERIC Educational Resources Information Center

    Taranto, Gregory A.

    2011-01-01

    The purpose of this study was to design, implement, and evaluate the effectiveness of incorporating an online learning community as part of a comprehensive new teacher induction program. First, the researcher created an online learning community model based on the results of a comprehensive review of literature and from the previous year's…

  4. Effect of oxidation and extent of oxidation on biologically active PACs in asphalt products.

    PubMed

    Trumbore, David; Osborn, Linda; Blackburn, Gary; Niebo, Ron; Kriech, Anthony; Maxim, L Daniel

    2011-10-01

    Recent studies have reported divergent results in rodent cancer assays using fume condensates from a variety of asphalt products. This paper presents results of a study investigating the role of oxidation, or extent of oxidation, on these findings. Five straight run asphalts, made from widely used crude oils, were used as inputs to both production scale and laboratory oxidation units and processed to a range of softening points used in common roofing products. For each of the five asphalts studied, the oxidation reaction significantly decreased measures of polycyclic aromatic compounds (PACs) that have been linked, previously and in analyses included in this study, to tumor induction in rodent bioassays. Mutagenicity index determined by the modified Ames assay was reduced between 41% and 50% from the input asphalt to the final oxidized product. A fluorescence method tuned to a subset of PAC compounds that have been associated with carcinogenic behavior in mouse bioassays was reduced between 39% and 71%. The decrease was largest in the first quarter of the oxidation reaction. These findings indicate that oxidation, by itself, was not a likely factor in the tumor induction seen in the previous studies. Rather, other factors such as the conditions of fume generation and crude source (coupled with possible differences in distillation endpoints) were more likely to have determined the outcomes. Analyses of previously published data, presented in this paper, suggest that the modified Ames and fluorescence assays are valuable screening tools for use in future health-related asphalt research.

  5. Induction of labor versus expectant management for women with a prior cesarean delivery.

    PubMed

    Palatnik, Anna; Grobman, William A

    2015-03-01

    Previous studies of induction of labor in the setting of trial of labor after cesarean have compared women undergoing trial of labor after cesarean to those undergoing spontaneous labor. However, the clinically relevant comparison is to those undergoing expectant management. The objective of this study was to compare obstetric outcomes between women undergoing induction of labor and those undergoing expectant management ≥39 weeks of gestation. This was a secondary analysis of data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Cesarean Registry that included women with singleton gestations at a gestational age of ≥39 weeks and a history of 1 low transverse cesarean delivery. Outcomes of induction at 39, 40, and 41 weeks were compared to expectant management beyond each gestational age period using univariable and multivariable analyses. Women with scheduled repeat cesarean deliveries done for the indication of prior cesarean delivery were excluded from the analysis. In all, 12,676 women were eligible for analysis. The rate of vaginal birth after cesarean (VBAC) was higher among women undergoing induction of labor at 39 weeks compared to expectant management (73.8% vs 61.3%, P < .001). The risk of uterine rupture also was higher among women undergoing induction of labor at 39 weeks compared to expectant management (1.4% vs 0.5%, P = .006, respectively). In multivariable analysis, induction of labor at 39 weeks remained associated with a significantly higher chance of VBAC and uterine rupture (odds ratio, 1.31; 95% confidence interval, 1.03-1.67; and odds ratio, 2.73; 95% confidence interval, 1.22-6.12, respectively). Induction of labor at 39 weeks, when compared to expectant management, was associated with a higher chance of VBAC but also of uterine rupture. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Induction of antiviral genes, Mx and vig-1, by dsRNA and Chum salmon reovirus in rainbow trout monocyte/macrophage and fibroblast cell lines.

    PubMed

    DeWitte-Orr, Stephanie J; Leong, Jo-Ann C; Bols, Niels C

    2007-09-01

    The expression of potential antiviral genes, Mx1, Mx2, Mx3 and vig-1, was studied in two rainbow trout cell lines: monocyte/macrophage RTS11 and fibroblast-like RTG-2. Transcripts were monitored by RT-PCR; Mx protein by Western blotting. In unstimulated cultures Mx1 and vig-1 transcripts were seen occasionally in RTS11 but rarely in RTG-2. A low level of Mx protein was seen in unstimulated RTS11 but not in RTG-2. In both cell lines, Mx and vig-1 transcripts were induced by a dsRNA, poly inosinic: poly cytidylic acid (poly IC), and by Chum salmon reovirus (CSV). Medium conditioned by cells previously exposed to poly IC or CSV and assumed to contain interferon (IFN) induced the antiviral genes in RTS11. However, RTG-2 responded only to medium conditioned by RTG-2 exposed previously to CSV. In both cell lines, poly IC and CSV induced Mx transcripts in the presence of cycloheximide, suggesting a direct induction mechanism, independent of IFN, was also possible. For CSV, ribavirin blocked induction in RTS11 but not in RTG-2, suggesting viral RNA synthesis was required for induction only in RTS11. In both RTS11 and RTG-2 cultures, Mx protein showed enhanced accumulation by 24h after exposure to poly IC and CSV, but subsequently Mx protein levels declined back to control levels in RTS11 but not in RTG-2. These results suggest that Mx can be regulated differently in macrophages and fibroblasts.

  7. STRAIN-SPECIFIC SENSITIVITY TO INDUCTION OF MURINE LUNG TUMORS FOLLOWING IN UTERO EXPOSURE TO 3-METHYLCHOLANTHRENE

    EPA Science Inventory

    We previously demonstrated that different strains of fetal mice were more sensitive to lung tumor induction by 3-methylcholanthrene (MC) than were adults. Offspring from either a D2 x B6D2F1 backcross or from parental Balb/c mice exhibited a similar high incidence of lung tumors ...

  8. Hitting Is Contagious: Experience and Action Induction

    ERIC Educational Resources Information Center

    Gray, Rob; Beilock, Sian L.

    2011-01-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing…

  9. Does Research Degree Supervisor Training Work? The Impact of a Professional Development Induction Workshop on Supervision Practice

    ERIC Educational Resources Information Center

    McCulloch, Alistair; Loeser, Cassandra

    2016-01-01

    Supervisor induction and continued professional development programmes constitute good practice and are enshrined in institutional policies and national codes of practice. However, there is little evidence about whether they have an impact on either supervisors' learning or day-to-day practice. Set in a discussion of previous literature, this…

  10. Induction of soybean resistance to the Mexican bean beetle (Coleoptera: Coccinellidae)

    Treesearch

    A.L. Iverson; R.B. Hammond; L.R. Iverson

    2001-01-01

    We tested chemical and insect feeding-induced insect resistance on soybean plants.The chemical induction effects of jasmonic acid (JA) and salicylic acid (SA) were investigated. We also evaluated the effects of plants stressed with previous insect herbivory. A larval antibiosis screening technique (LAST) and a preference test were performed in petri dishes using...

  11. Particle-in-cell simulations of electron beam control using an inductive current divider

    DOE PAGES

    Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.; ...

    2015-11-18

    Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam’s return current. The current divider concept was proposed and studied theoretically in a previous publication [Phys. Plasmas 22, 023107 (2015)] A central post carries a portion of the return current (I 1) while the outer conductor carries the remainder (I 2) with the injected beam current given by I b=I 1+I 2. The simulations are in agreement with the theory whichmore » predicts that the total force on the beam trajectory is proportional to (I 2-I 1) and the force on the beam envelope is proportional to I b. For a fixed central post, the beam trajectory is controlled by varying the outer conductor radius which changes the inductance in the return-current path. The simulations show that the beam emittance is approximately constant as the beam propagates through the current divider to the target. As a result, independent control over both the current density and the beam angle at the target is possible by choosing the appropriate return-current geometry.« less

  12. Physiological Effects of Enriched Environment Exposure and LTP Induction in the Hippocampus In Vivo Do Not Transfer Faithfully to In Vitro Slices

    ERIC Educational Resources Information Center

    Eckert, Michael J.; Abraham, Wickliffe C.

    2010-01-01

    A number of experimental paradigms use in vitro brain slices to test for changes in synaptic transmission and plasticity following a behavioral manipulation. For example, a number of previous studies have reported a variety of effects of environmental enrichment (EE) exposure on field potential responses in hippocampal slices, but in no study was…

  13. Interspecific variation within the genus Asclepias in response to herbivory by a phloem-feeding insect herbivore.

    PubMed

    Zehnder, Caralyn B; Hunter, Mark D

    2007-11-01

    Induced plant responses to leaf-chewing insects have been well studied, but considerably less is known about the effects of phloem-feedings insects on induction. In a set of laboratory experiments, we examined density-dependent induction by the milkweed-oleander aphid, Aphis nerii, of putative defenses in four milkweed species (Asclepias incarnata, Asclepias syriaca, Asclepias tuberosa, and Asclepias viridis). We hypothesized that high aphid density would lead to increased cardenolide expression in species with low constitutive levels of cardenolides (e.g., A. tuberosa), but that there would be no induction in high constitutive cardenolide species (e.g., A. viridis). Based on previous studies, we did not expect cardenolide induction in A. incarnata. Contrary to our predictions, we observed feeding-induced declines of cardenolide concentrations in A. viridis. Cardenolide concentrations did not respond to aphid feeding in the other three milkweed species. Aphids also caused reductions in biomass accumulation by two of four Asclepias species, A. viridis and A. incarnata. High aphid density led to a decrease in A. viridis foliar nitrogen concentration. However, aphids had no effect on the defensive chemistry, growth, or nutritional quality of either A. syriaca or A. tuberosa. Our results highlight that congeneric plant species may respond differently to the same levels of herbivore damage.

  14. Fully non-inductive second harmonic electron cyclotron plasma ramp-up in the QUEST spherical tokamak

    NASA Astrophysics Data System (ADS)

    Idei, H.; Kariya, T.; Imai, T.; Mishra, K.; Onchi, T.; Watanabe, O.; Zushi, H.; Hanada, K.; Qian, J.; Ejiri, A.; Alam, M. M.; Nakamura, K.; Fujisawa, A.; Nagashima, Y.; Hasegawa, M.; Matsuoka, K.; Fukuyama, A.; Kubo, S.; Shimozuma, T.; Yoshikawa, M.; Sakamoto, M.; Kawasaki, S.; Nakashima, H.; Higashijima, A.; Ide, S.; Maekawa, T.; Takase, Y.; Toi, K.

    2017-12-01

    Fully non-inductive second (2nd) harmonic electron cyclotron (EC) plasma current ramp-up was demonstrated with a newlly developed 28 GHz system in the QUEST spherical tokamak. A high plasma current of 54 kA was non-inductively ramped up and sustained stably for 0.9 s with a 270 kW 28 GHz wave. A higher plasma current of 66 kA was also non-inductively achieved with a slow ramp-up of the vertical field. We have achieved a significantly higher plasma current than those achieved previously with the 2nd harmonic EC waves. This fully non-inductive 2nd harmonic EC plasma ramp-up method might be useful for future burning plasma devices and fusion reactors, in particular for operations at half magnetic field with the same EC heating equipment.

  15. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β

    PubMed Central

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-01-01

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ. PMID:28404976

  16. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

    PubMed

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-06-13

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

  17. Limonin Methoxylation Influences Induction of Glutathione S-Transferase and Quinone Reductase

    PubMed Central

    PEREZ, JOSE LUIS; JAYAPRAKASHA, G. K.; VALDIVIA, VIOLETA; MUNOZ, DIANA; DANDEKAR, DEEPAK V.; AHMAD, HASSAN; PATIL, BHIMANAGOUDA S.

    2009-01-01

    Previous studies have indicated the chemoprevention potential of citrus limonoids due to the induction of phase II detoxifying enzymes. In the present study, three citrus limonoids were purified and identified from sour orange seeds as limonin, limonin glucoside (LG), deacetylnomilinic acid glucoside (DNAG). In addition, limonin was modified to defuran limonin and limonin 7-methoxime. The structures of these compounds were confirmed by NMR studies. These five compounds were used to investigate the influence of Phase II enzymes in female A/J mice. Our results indicated that the highest induction of Glutathione S-Transferase (GST) activity against 1-chloro-2, 4-dinitrobenzene (CDNB) by DNAG (67%) in lung homogenates followed by limonin-7-methoxime (32%) in treated liver homogenates. Interestingly, the limonin-7-methoxime showed the highest GST activity (270%) in liver against 4-nitroquinoline 1-oxide (4NQO), while the same compound in stomach induced GST by 51% compared to the control. DNAG treated group induced 55% in stomach homogenates. Another Phase II enzyme, quinone reductase (QR), was significantly induced by limonin-7-methoxime by 65 and 32% in liver and lung homogenates, respectively. Defuran limonin, induced QR in lung homogenates by 45%. Our results indicated that modification of the limonin have differential induction of phase II enzymes. These findings are indicative of a possible mechanism for the prevention of cancer by aiding in detoxification of xenobiotics. PMID:19480426

  18. In vitro T lymphocyte adherence capabilities under the influence of lower induction values (0.1 - 0.01 mT) of 50 Hz external magnetic fields

    NASA Astrophysics Data System (ADS)

    Čoček, A.; Jandová, A.; Hahn, A.; Mártonová, J.; Ambruš, M.; Dohnalová, A.; Nedbalová, M.; Pokorný, J.

    2011-12-01

    Our research thus far has concerned the impact of external magnetic fields (50 Hz) and low (0.01-10 mT) induction on adherence capabilities of T lymphocytes obtained from the blood of patients with head and neck tumors. We know that the in vitro adherence capability of T lymphocytes towards surfaces in cancer patients is less than that of control. Previously, we have found that exposure to magnetic fields (50 Hz / 0.01-10 mT) increases the capability of T lymphocytes, in larynx/pharynx cancer patients, to adhere in vitro to surfaces, achieving almost physiological values, in not only pre-treatment patients but also those receiving treatment in the course of follow-up. The capability of T lymphocytes in controls (voluntary blood donors) to adhere to surfaces was also increased (50 Hz / 0.01-0.5 mT). The present study concentrates on the significance of the level of magnetic field induction in order to determine whether low induction values can restore T lymphocytes adherence capabilities. Testing a set of 20 patients showed a statistically significant difference (p < 0.05) in the in vitro adherence capacity of T lymphocytes between both 0.01 and 0.05, and 0.1 mT induction levels. In the control group (patients diagnosed with chronic sensorineural hearing loss) there was even a statistically significant difference between induction values of 0.05 and 0.01 mT. Therefore, we concluded that lower induction values resulted in a more biologically significant response.

  19. Diagnostic studies of ion beam formation in inductively coupled plasma

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

    Jacobs, Jenee L.

    2015-01-01

    This dissertation describes a variety of studies focused on the plasma and the ion beam in inductively coupled plasma mass spectrometry (ICP-MS). The ability to use ICP-MS for measurements of trace elements in samples requires the analytes to be efficiently ionized. Updated ionization efficiency tables are discussed for ionization temperatures of 6500 K and 7000 K with an electron density of 1 x 10 15 cm -3. These values are reflective of the current operating parameters of ICP-MS instruments. Calculations are also discussed for doubly charged (M 2+) ion formation, neutral metal oxide (MO) ionization, and metal oxide (MO +)more » ion dissociation for similar plasma temperature values. Ionization efficiency results for neutral MO molecules in the ICP have not been reported previously.« less

  20. Comparing the Relative Importance of Water-Borne Cues and Direct Grazing for the Induction of Defenses in the Brown Seaweed Fucus vesiculosus

    PubMed Central

    Flöthe, Carla R.; John, Uwe; Molis, Markus

    2014-01-01

    Some seaweed species have been shown to release water-borne cues after herbivore attack, for example, to attract natural enemies of the herbivore. These cues may also be sensed by neighboring seaweeds and used to adjust their defenses in anticipation of a possible herbivore attack. Several studies indicated information transfer between seaweed individuals in the past, including the brown seaweed Fucus vesiculosus. Previous work showed induction of defenses in F. vesiculosus in response to water-borne cues released by isopod-grazed conspecifics. In contrast, another study on induced responses after exposure to cues from isopod-grazed neighbors using the same seaweed species yielded contradictory results. This study reassessed the ability of F. vesiculosus individuals to sense water-borne cues released by isopod-grazed neighbors in a series of experiments that monitored F. vesiculosus palatability in response to direct grazing by Idotea baltica and water-borne cues from isopod-grazed neighbors relative to unmanipulated seaweed pieces. Two-choice feeding assays were conducted with both fresh and reconstituted seaweed pieces. Direct grazing by I. baltica induced a chemical defense in F. vesiculosus, confirming results of previous studies. In contrast, evidence for increased herbivore resistance in seaweed pieces that were located downstream of isopod-grazed F. vesiculosus could not be provided. The lack of defense induction in response to grazing of conspecific neighbors may be explained by the environmental conditions and the scattered distribution of F. vesiculosus individuals in the intertidal zone of Helgoland, which may render resource investment in the emission and/or response to water-borne cues at this site unprofitable. PMID:25279662

  1. Reinforcement of Rat Hippocampal LTP by Holeboard Training

    ERIC Educational Resources Information Center

    Frey, Julietta U.; Korz, Volker; Uzakov, Shukhrat

    2005-01-01

    Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4-5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be…

  2. GH and IGF-I induction by passive immunization of rainbow trout Oncorhynchus mykiss Walbaum using a somatostatin 14 antibody

    USDA-ARS?s Scientific Manuscript database

    Inhibition of the growth axis by somatostatin was studied in juvenile rainbow trout using passive immunization with a previously isolated somatostatin antibody (antiSS-14). Upon subcutaneously injection of laying hens (Gallus domesticus) with conjugated somatostatin-14 (SS-14), the antiSS-14 was iso...

  3. Gender Differences in Figural Matrices: The Moderating Role of Item Design Features

    ERIC Educational Resources Information Center

    Arendasy, Martin E.; Sommer, Markus

    2012-01-01

    There is a heated debate on whether observed gender differences in some figural matrices in adults can be attributed to gender differences in inductive reasoning/G[subscript f] or differential item functioning and/or test bias. Based on previous studies we hypothesized that three specific item design features moderate the effect size of the gender…

  4. Induction signals from Callisto's ionosphere and their implications on a possible subsurface ocean

    NASA Astrophysics Data System (ADS)

    Hartkorn, Oliver; Saur, Joachim

    2017-11-01

    We investigate whether induction within Callisto's electrically conductive ionosphere can explain observed magnetic fields which have previously been interpreted as evidence of induction in a saline, electrically conductive subsurface ocean. Callisto's ionosphere is subject to the flow of time-periodic magnetized plasma of Jupiter's magnetosphere, which induces electric fields and electric currents in Callisto's electrically conductive ionosphere. We develop a simple analytic model for a first quantitative understanding of the effects of induction in Callisto's ionosphere caused by the interaction with a time-variable magnetic field environment. With this model, we also investigate how the associated ionospheric currents close in the ambient magnetospheric plasma. Based on our model, we find that the anisotropic nature of Callisto's ionospheric conductivity generates an enhancement effect on ionospheric loop currents which are driven by the time-variable magnetic field. This effect is similar to the Cowling channel effect known from Earth's ionosphere. Subsequently, we numerically calculate the expected induced magnetic fields due to Jupiter's time-variable magnetic field in an anisotropic conductive ionosphere and compare our results with the Galileo C-3 and C-9 flybys. We find that induction within Callisto's ionosphere is responsible for a significant part of the observed magnetic fields. Ionospheric induction creates induced magnetic fields to some extent similar as expected from a subsurface water ocean. Depending on currently unknown properties such as Callisto's nightside ionosphere, the existence of layers of "dirty ice" and the details of the plasma interaction, a water ocean might be located much deeper than previously thought or might not exist at all.

  5. Phytoalexin Induction in French Bean 1

    PubMed Central

    Dixon, Richard A.; Dey, Prakash M.; Lawton, Michael A.; Lamb, Christopher J.

    1983-01-01

    Treatment of hypocotyl sections or cell suspension cultures of dwarf French bean (Phaseolus vulgaris L.) with an abiotic elicitor (denatured ribonuclease A) resulted in increased extractable activity of the enzyme l-phenylalanine ammonia-lyase. This induction could be transmitted from treated cells through a dialysis membrane to cells which were not in direct contact with the elicitor. In hypocotyl sections, induction of isoflavonoid phytoalexin accumulation was also transmitted across a dialysis membrane, although levels of insoluble, lignin-like phenolic material remained unchanged in elicitor-treated and control sections. In bean cell suspension cultures, the induction of phenylalanine ammonia-lyase in cells separated from ribonuclease-treated cells by a dialysis membrane was also accompanied by increases in the activities of chalcone synthase and chalcone isomerase, two enzymes previously implicated in the phytoalexin defense response. Such intercellular transmission of elicitation did not occur in experiments with cells treated with a biotic elicitor preparation heat-released from the cell walls of the bean pathogen Colletotrichum lindemuthianum. The results confirm and extend previous suggestions that a low molecular weight, diffusible factor of host plant origin is involved (in French bean) in the intercellular transmission of the elicitation response to abiotic elicitors. PMID:16662813

  6. Geophysical Interpretation of Induction Arrows Observed at Jeju Island, Korea

    NASA Astrophysics Data System (ADS)

    Yang, J.; Choi, H.

    2015-12-01

    Jeju Island, a volcanic island located on the continental margin in the southern end of the Korean Peninsula, has been paid a special attention to geological and geophysical society for a long time due to its tectonic importance associated with the volcanism of the island. In this study, we try to interpret induction arrows observed at the island that have been estimated from broad-band magnetotelluric (MT) data and existing magnetovariational data, which are sensitive to lateral conductivity distribution of the Earth. Overall pattern of observed induction arrows is clearly frequency-dependent: perpendicular to nearby coastline of the observation site for higher frequencies than 0.1 Hz but rotating toward south or southeastern direction for lower frequency than 0.01 Hz. Furthermore, induction arrows at frequencies lower than 0.001 Hz, which derived from the existing magnetovariational data, point to the south or the southeast as well. In order to examine whether observed induction arrows can be explained by only surrounding seas, 3-D MT modeling considering seas surrounding the island is carried out. The results demonstrate that induction arrows at higher frequencies than 0.01 Hz can be explained well by the surrounding seas but for lower frequencies than 0.01 Hz there are significant discrepancies between observed and calculated arrows. This strongly implies the existence of deep-seated conductor located beneath the farther south of the island, namely, the East China Sea. The existence of this deep-seated conductor can be supported by other previous geophysical studies, which is likely to be caused by mantle upwelling derived from shear traction of horizontal mantle flow in tensional back arc of Kyushu Island, Japan.

  7. Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis

    PubMed Central

    Vickers, Adrian D.; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S.; Medjedovic, Jasmina; Smyth, Michael

    2016-01-01

    Background Biological therapies are increasingly used to treat ulcerative colitis (UC). Aim To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. Methods A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Results Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35–3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49–5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21–4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients ‘straight through’. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14–9.20], golimumab 2.33 [1.04–5.41], and adalimumab 3.96 [1.67–9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36–41.0]). Conclusions This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design. PMID:27776175

  8. Mesodermal Fgf10b cooperates with other Fgfs during induction of otic and epibranchial placodes in zebrafish.

    PubMed Central

    Maulding, Kirstin; Padanad, Mahesh S.; Dong, Jennifer; Riley, Bruce B.

    2015-01-01

    Background Vertebrate otic and epibranchial placodes develop in close proximity in response to localized Fgf signaling. Although less is known about epibranchial induction, the process of otic induction in highly conserved, with important roles for Fgf3 and Fgf8 reported in all species examined. Fgf10 is also critical for otic induction in mouse, but the only zebrafish ortholog examined to date, fgf10a, is not expressed early enough to play such a role. A second zebrafish ortholog, fgf10b, has not been previously examined. Results We find that zebrafish fgf10b is expressed at tailbud stage in paraxial cephalic mesoderm beneath prospective epibranchial tissue, lateral to the developing otic placode. Knockdown of fgf10b does not affect initial otic induction but impairs subsequent accumulation of otic cells. Formation of epibranchial placodes and ganglia are also moderately impaired. Combinatorial disruption of fgf10b and fgf3 exacerbates the deficiency of otic cells and eliminates epibranchial induction entirely. Disruption of fgf10b and fgf24 also strongly reduces, but does not eliminate, epibranchial induction. Conclusions fgf10b participates in a late phase of otic induction and, in combination with fgf3, is especially critical for epibranchial induction. PMID:24677486

  9. Mesodermal Fgf10b cooperates with other fibroblast growth factors during induction of otic and epibranchial placodes in zebrafish.

    PubMed

    Maulding, Kirstin; Padanad, Mahesh S; Dong, Jennifer; Riley, Bruce B

    2014-10-01

    Vertebrate otic and epibranchial placodes develop in close proximity in response to localized fibroblast growth factor (Fgf) signaling. Although less is known about epibranchial induction, the process of otic induction in highly conserved, with important roles for Fgf3 and Fgf8 reported in all species examined. Fgf10 is also critical for otic induction in mouse, but the only zebrafish ortholog examined to date, fgf10a, is not expressed early enough to play such a role. A second zebrafish ortholog, fgf10b, has not been previously examined. We find that zebrafish fgf10b is expressed at tailbud stage in paraxial cephalic mesoderm beneath prospective epibranchial tissue, lateral to the developing otic placode. Knockdown of fgf10b does not affect initial otic induction but impairs subsequent accumulation of otic cells. Formation of epibranchial placodes and ganglia are also moderately impaired. Combinatorial disruption of fgf10b and fgf3 exacerbates the deficiency of otic cells and eliminates epibranchial induction entirely. Disruption of fgf10b and fgf24 also strongly reduces, but does not eliminate, epibranchial induction. fgf10b participates in a late phase of otic induction and, in combination with fgf3, is especially critical for epibranchial induction. Copyright © 2014 Wiley Periodicals, Inc.

  10. Cognitive dissonance induction in everyday life: An fMRI study.

    PubMed

    de Vries, Jan; Byrne, Mark; Kehoe, Elizabeth

    2015-01-01

    This functional magnetic resonance imaging (fMRI) study explored the neural substrates of cognitive dissonance during dissonance "induction." A novel task was developed based on the results of a separate item selection study (n = 125). Items were designed to generate dissonance by prompting participants to reflect on everyday personal experiences that were inconsistent with values they had expressed support for. One experimental condition (dissonance) and three control conditions (justification, consonance, and non-self-related inconsistency) were used for comparison. Items of all four types were presented to each participant (n = 14) in a randomized design. The fMRI analysis used a whole-brain approach focusing on the moments dissonance was induced. Results showed that in comparison with the control conditions the dissonance experience led to higher levels of activation in several brain regions. Specifically dissonance was associated with increased neural activation in key brain regions including the anterior cingulate cortex (ACC), anterior insula, inferior frontal gyrus, and precuneus. This supports current perspectives that emphasize the role of anterior cingulate and insula in dissonance processing. Less extensive activation in the prefrontal cortex than in some previous studies is consistent with this study's emphasis on dissonance induction, rather than reduction. This article also contains a short review and comparison with other fMRI studies of cognitive dissonance.

  11. Possible role of jasmonic acid in the regulation of floral induction, evocation and floral differentiation in Lemna minor L.

    PubMed

    Krajncic, B; Kristl, J; Janzekovic, I

    2006-01-01

    Jasmonic acid (JA) is implicated in a wide variety of developmental and physiological processes in plants. Here, we studied the effects of JA and the combination of JA and ethylenediamine-dio-hydroxyphenyl-acetic acid (EDDHA) on flowering in Lemna minor in axenical cultures. JA (0.475-47.5 nmol l(-1)) enhanced floral induction in L. minor under long-day (LD) conditions. Under the same conditions, at a concentration of 237.5 nmol l(-1), JA inhibited floral induction, and at a concentration of 475 nmol l(-1) it prevented floral induction. Under LD conditions with LD preculture, a combination of EDDHA (20,500 nmol l(-1)) and JA (47.5 nmol l(-1)) had a synergistic effect on the promotion of floral induction. Floral induction was enhanced to the greatest extent in experiments with LD precultures. Microscopic examination of microphotographs of histological sections showed that JA and, to an even greater extent, JA+EDDHA at optimal concentrations promote apical floral induction (evocation). Furthermore, JA, and to an even greater extent JA in combination with EDDHA in an optimal concentration, also promote flower differentiation, especially the development of stamens, as is evident from the microphotographs. The experimental results show that JA promotes floral induction in other species of Lemnaceae from various groups according to their photoperiodic response. The results support our hypothesis that, in addition to previously ascribed functions, JA may regulate floral induction, evocation and floral differentiation. Our hypothesis is supported also by the results obtained by quantitative determination of endogenous JA levels in L. minor at three growth stages. The levels of endogenous JA decreased from 389 ng JA g(-1) (fresh weight) of L. minor during the vegetative stage to 217 ng JA g(-1) during the evocation stage, and to 37.5 ng JA g(-1) during the flowering stage, which proves that JA is used for flowering.

  12. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    PubMed Central

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  13. Morphology and contractile gene expression of adipose-derived mesenchymal stem cells in response to short-term cyclic uniaxial strain and TGF-β1.

    PubMed

    Rashidi, Neda; Tafazzoli-Shadpour, Mohammad; Haghighipour, Nooshin; Khani, Mohammad-Mehdi

    2018-06-27

    Previous studies have shown smooth muscle induction in adipose-derived mesenchymal stem cells (ASCs) caused by long-term cyclic stretch. Here we examined the capability of the short-term straining with time steps of 4, 8, 16 and 24 h alone or combined with TGF-β1 on smooth muscle induction of rabbit ASCs. Alterations in cell morphology were quantified through the cell shape index and orientation angle, and expression levels of α-SMA, SM22-α, h-caldesmon and calponin3 markers were examined using the real-time polymerase chain reaction (PCR) method. Moreover, F-actin cytoskeleton organization was observed by fluorescence staining. Mechanical strain either alone or combined with growth factor treatment caused significant up-regulation of both early and intermediate smooth muscle cells (SMCs) specific markers during the initial hours of stimulation peaking in 8 to 16 h. Furthermore, gradual alignment of cells perpendicular to the strain direction during loading time, and cell elongation resembling contractile SMC phenotype, together with alignment and reorganization of F-actin fibers were observed. Considering previously reported protein up-regulation in following days of straining, the effects of short-term cyclic stretch on smooth muscle induction of ASCs were revealed which can be helpful in achieving functional contractile SMCs through synergistic mechano-chemical regulation of ASCs as an appealing cell source for vascular tissue engineering.

  14. HIT and brain reward function: A case of mistaken identity (theory).

    PubMed

    Wright, Cory; Colombo, Matteo; Beard, Alexander

    2017-08-01

    This paper employs a case study from the history of neuroscience-brain reward function-to scrutinize the inductive argument for the so-called 'Heuristic Identity Theory' (HIT). The case fails to support HIT, illustrating why other case studies previously thought to provide empirical support for HIT also fold under scrutiny. After distinguishing two different ways of understanding the types of identity claims presupposed by HIT and considering other conceptual problems, we conclude that HIT is not an alternative to the traditional identity theory so much as a relabeling of previously discussed strategies for mechanistic discovery. Copyright © 2017. Published by Elsevier Ltd.

  15. Magnetic targeting of mechanosensors in bone cells for tissue engineering applications.

    PubMed

    Hughes, Steven; Dobson, Jon; El Haj, Alicia J

    2007-01-01

    Mechanical signalling plays a pivotal role in maintaining bone cell function and remodelling of the skeleton. Our previous work has highlighted the potential role of mechano-induction in tissue engineering applications. In particular, we have highlighted the potential for using magnetic particle techniques for tissue engineering applications. Previous studies have shown that manipulation of integrin attached magnetic particles leads to changes in intracellular calcium signalling within osteoblasts. However, due to the phenomenon of particle internalisation, previous studies have typically focused on short-term stimulation experiments performed within 1-2 h of particle attachment. For tissue engineering applications, bone tissue growth occurs over a period of 3-5 weeks. To date, no study has investigated the cellular responses elicited from osteoblasts over time following stimulation with internalised magnetic particles. Here, we demonstrate the long-term biocompatibility of 4.5 microm RGD-coated particles with osteoblasts up to 21 days in culture, and detail a time course of responses elicited from osteoblasts following mechanical stimulation with integrin attached magnetic particles (<2h post attachment) and internalised particles (>48h post attachment). Mechanical manipulation of both integrin attached and internalised particles were found to induce intracellular calcium signalling. It is concluded that magnetic particles offer a tool for applying controlled mechanical forces to osteoblasts, and can be used to stimulate intracellular calcium signalling over prolonged periods of time. Magnetic particle technology presents a potentially valuable tool for tissue engineering which permits the delivery of highly localised mechano-inductive forces directly to cells.

  16. Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.

    PubMed

    Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen

    2016-02-01

    Fear memory-encoding thalamic input synapses to the lateral amygdala (T-LA) exhibit dynamic efficacy changes that are tightly correlated with fear memory strength. Previous studies have shown that auditory fear conditioning involves strengthening of synaptic strength, and conversely, fear extinction training leads to T-LA synaptic weakening and occlusion of long-term depression (LTD) induction. These findings suggest that the mechanisms governing LTD at T-LA synapses may determine the behavioral outcomes of extinction training. Here, we explored this hypothesis by implementing food deprivation (FD) stress in mice to determine its effects on fear extinction and LTD induction at T-LA synapses. We found that FD increased plasma acylated ghrelin levels and enhanced fear extinction and its retention. Augmentation of fear extinction by FD was blocked by pretreatment with growth hormone secretagogue receptor type-1a antagonist D-Lys(3)-GHRP-6, suggesting an involvement of ghrelin signaling. Confirming previous findings, two distinct forms of LTD coexist at thalamic inputs to LA pyramidal neurons that can be induced by low-frequency stimulation (LFS) or paired-pulse LFS (PP-LFS) paired with postsynaptic depolarization, respectively. Unexpectedly, we found that FD impaired the induction of PP-LFS- and group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD, but not LFS-induced LTD. Ghrelin mimicked the effects of FD to impair the induction of PP-LFS- and DHPG-induced LTD at T-LA synapses, which were blocked by co-application of D-Lys(3)-GHRP-6. The sensitivity of synaptic transmission to 1-naphthyl acetyl spermine was not altered by either FD or ghrelin treatment. These results highlight distinct features of fear extinction and LTD at T-LA synapses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Early induction of c-Myc is associated with neuronal cell death.

    PubMed

    Lee, Hyun-Pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

    2011-11-14

    Neuronal cell cycle activation has been implicated in neurodegenerative diseases such as Alzheimer's disease, while the initiating mechanism of cell cycle activation remains to be determined. Interestingly, our previous studies have shown that cell cycle activation by c-Myc (Myc) leads to neuronal cell death which suggests Myc might be a key regulator of cell cycle re-entry mediated neuronal cell death. However, the pattern of Myc expression in the process of neuronal cell death has not been addressed. To this end, we examined Myc induction by the neurotoxic agents camptothecin and amyloid-β peptide in a differentiated SH-SY5Y neuronal cell culture model. Myc expression was found to be significantly increased following either treatment and importantly, the induction of Myc preceded neuronal cell death suggesting it is an early event of neuronal cell death. Since ectopic expression of Myc in neurons causes the cell cycle activation and neurodegeneration in vivo, the current data suggest that induction of Myc by neurotoxic agents or other disease factors might be a key mediator in cell cycle activation and consequent cell death that is a feature of neurodegenerative diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Public sector low threshold office-based buprenorphine treatment: outcomes at year 7.

    PubMed

    Bhatraju, Elenore Patterson; Grossman, Ellie; Tofighi, Babak; McNeely, Jennifer; DiRocco, Danae; Flannery, Mara; Garment, Ann; Goldfeld, Keith; Gourevitch, Marc N; Lee, Joshua D

    2017-02-28

    Buprenorphine maintenance for opioid dependence remains of limited availability among underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care treatment models including the use of unobserved, "home," buprenorphine induction may simplify initiation of care and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently among large, naturalistic cohorts treated in low threshold safety net primary care settings. This prospective clinical registry cohort design estimated rates of induction-related adverse events, treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic retention, buprenorphine dosages, and urine sample results. Of the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%; serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a median 38 weeks (range 0-320) for inductions, compared to 110 (0-354) weeks for transfers and 57 for the entire clinic population. Older age, later years of first clinic visit (vs. 2006-2007), and baseline heroin abstinence were associated with increased treatment retention overall. Unobserved "home" buprenorphine induction in a public sector primary care setting appeared a feasible and safe clinical practice. Post-induction treatment retention of a median 38 weeks was in line with previous naturalistic studies of real-world office-based opioid treatment. Low threshold treatment protocols, as compared to national guidelines, may compliment recently increased prescriber patient limits and expand access to buprenorphine among public sector opioid use disorder patients.

  19. Obstetricians' rising liability insurance premiums and inductions at late preterm gestations.

    PubMed

    Murthy, Karna; Grobman, William A; Lee, Todd A; Holl, Jane L

    2009-04-01

    To estimate the association between professional liability insurance premiums for obstetricians and late preterm induction (LPI) rates. Data from the National Center for Health Statistics were used to identify all Illinois women pregnant with singletons at 34 weeks' gestation from 1991 to 2003. The independent association between LPI (induction between 34 and 37 weeks' gestation) rates and the previous year's obstetric malpractice insurance premiums was evaluated using linear regression. The mean annual LPI rate (5.4/1000 in 1991 to 15.2/1000 in 2003, P < 0.001) nearly tripled, and obstetricians' professional liability insurance premiums ($55,480 to $110,613, P < 0.001) approximately doubled. After adjusting for race, previous cesarean delivery, marital status, and the presence of antepartum risk factors for indicated preterm delivery, LPI rates increased by 1/1000 births (P = 0.004) for each annual $10,000 increase in the county's obstetric malpractice insurance premium. Rising premiums are associated with increased frequency of LPI among women with singleton gestations.

  20. Scaling and Systems Considerations in Pulsed Inductive Thrusters

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.

    2007-01-01

    Performance scaling in pulsed inductive thrusters is discussed in the context of previous experimental studies and modeling results. Two processes, propellant ionization and acceleration, are interconnected where overall thruster performance and operation are concerned, but they are separated here to gain physical insight into each process and arrive at quantitative criteria that should be met to address or mitigate inherent inductive thruster difficulties. The effects of preionization in lowering the discharge energy requirements relative to a case where no preionization is employed, and in influencing the location of the initial current sheet, are described. The relevant performance scaling parameters for the acceleration stage are reviewed, emphasizing their physical importance and the numerical values required for efficient acceleration. The scaling parameters are then related to the design of the pulsed power train providing current to the acceleration stage. The impact of various choices in pulsed power train and circuit topology selection are reviewed, paying special attention to how these choices mitigate or exacerbate switching, lifetime, and power consumption issues.

  1. Medical therapeutics: from induction to scientific evolution.

    PubMed

    Nunes, José Pedro Lopes

    2013-01-01

    The field of medical therapeutics may be characterized as having suffered major scientific evolution in the last decades. The publication of landmark studies has been important enough to produce shifts in patient care. However, the scientific evolution in this field does not necessarily imply a progressively greater degree of certitude. In fact, it is not uncommon for new knowledge, when reflected in clinical practice, to weaken previous knowledge. In medical therapeutics, strict inductive reasoning implies the existence of empirical intervention data, typically clinical trial data. In many instances, however, such data does not exist-leaving room for a mixture of inductive and "pseudo-deductive" reasoning. It is often necessary to establish treatment on the basis of incomplete and inconclusive information, more so when the clinical situation is grave, but when no valid information exists, no treatment may be an option. In many instances, the rule "I wish not to impose on others" has superseded the concept "Do not impose on others what you yourself do not desire."

  2. Induction of food craving experience: the role of mental imagery, dietary restraint, mood and coping strategies.

    PubMed

    Jáuregui-Lobera, I; Bolaños-Ríos, P; Valero, E; Ruiz Prieto, I

    2012-01-01

    Food craving consists of a strong motivational state whereby a person is driven to seek and ingest a specifically desired food. To explore the influence of mental imagery on the food craving experience as well as to analyse the role of different psychological variables. Participants consisted of 65 normal weight undergraduate students. An experimental induction of food craving was analysed considering the actual previous craving and the induced one as a state food craving. Measures of trait food craving, imaging ability, dietary restraint, anxiety, depression, and coping strategies were considered. Sweet foods in general and chocolate in particular were the most craved foods. During the induction thoughts and images were the most highly rated triggers, and all the different sensory modalities were involved. Anxiety, depression, and negative coping strategies influenced the results with regards to the food craving. This study confirms the role of mental imagery, the correlation between state and trait food craving, and the influence of different psychological variables on the food craving.

  3. Proteomic Analysis of the Secretory Response of Aspergillus niger to D-Maltose and D-Xylose

    PubMed Central

    Ferreira de Oliveira, José Miguel P.; van Passel, Mark W. J.; Schaap, Peter J.; de Graaff, Leo H.

    2011-01-01

    Fungi utilize polysaccharide substrates through extracellular digestion catalyzed by secreted enzymes. Thus far, protein secretion by the filamentous fungus Aspergillus niger has mainly been studied at the level of individual proteins and by genome and transcriptome analyses. To extend these studies, a complementary proteomics approach was applied with the aim to investigate the changes in secretome and microsomal protein composition resulting from a shift to a high level secretion condition. During growth of A. niger on d-sorbitol, small amounts of d-maltose or d-xylose were used as inducers of the extracellular amylolytic and xylanolytic enzymes. Upon induction, protein compositions in the extracellular broth as well as in enriched secretory organelle (microsomal) fractions were analyzed using a shotgun proteomics approach. In total 102 secreted proteins and 1,126 microsomal proteins were identified in this study. Induction by d-maltose or d-xylose resulted in the increase in specific extracellular enzymes, such as glucoamylase A on d-maltose and β-xylosidase D on d-xylose, as well as of microsomal proteins. This reflects the differential expression of selected genes coding for dedicated extracellular enzymes. As expected, the addition of extra d-sorbitol had no effect on the expression of carbohydrate-active enzymes, compared to addition of d-xylose or d-maltose. Furthermore, d-maltose induction caused an increase in microsomal proteins related to translation (e.g., Rpl15) and vesicular transport (e.g., the endosomal-cargo receptor Erv14). Millimolar amounts of the inducers d-maltose and d-xylose are sufficient to cause a direct response in specific protein expression levels. Also, after induction by d-maltose or d-xylose, the induced enzymes were found in microsomes and extracellular. In agreement with our previous findings for d-xylose induction, d-maltose induction leads to recruitment of proteins involved in proteasome-mediated degradation. PMID:21698107

  4. Proteomic analysis of the secretory response of Aspergillus niger to D-maltose and D-xylose.

    PubMed

    de Oliveira, José Miguel P Ferreira; van Passel, Mark W J; Schaap, Peter J; de Graaff, Leo H

    2011-01-01

    Fungi utilize polysaccharide substrates through extracellular digestion catalyzed by secreted enzymes. Thus far, protein secretion by the filamentous fungus Aspergillus niger has mainly been studied at the level of individual proteins and by genome and transcriptome analyses. To extend these studies, a complementary proteomics approach was applied with the aim to investigate the changes in secretome and microsomal protein composition resulting from a shift to a high level secretion condition. During growth of A. niger on D-sorbitol, small amounts of D-maltose or D-xylose were used as inducers of the extracellular amylolytic and xylanolytic enzymes. Upon induction, protein compositions in the extracellular broth as well as in enriched secretory organelle (microsomal) fractions were analyzed using a shotgun proteomics approach. In total 102 secreted proteins and 1,126 microsomal proteins were identified in this study. Induction by D-maltose or D-xylose resulted in the increase in specific extracellular enzymes, such as glucoamylase A on D-maltose and β-xylosidase D on D-xylose, as well as of microsomal proteins. This reflects the differential expression of selected genes coding for dedicated extracellular enzymes. As expected, the addition of extra D-sorbitol had no effect on the expression of carbohydrate-active enzymes, compared to addition of D-xylose or D-maltose. Furthermore, D-maltose induction caused an increase in microsomal proteins related to translation (e.g., Rpl15) and vesicular transport (e.g., the endosomal-cargo receptor Erv14). Millimolar amounts of the inducers D-maltose and D-xylose are sufficient to cause a direct response in specific protein expression levels. Also, after induction by D-maltose or D-xylose, the induced enzymes were found in microsomes and extracellular. In agreement with our previous findings for D-xylose induction, D-maltose induction leads to recruitment of proteins involved in proteasome-mediated degradation.

  5. The nucleus raphe magnus suppresses vomiting, and the solitary nucleus and 5-HT are not involved in this suppression.

    PubMed

    Hattori, Yuka; Hamaguchi, Chie; Yamada, Yuko; Urayama, Yukiko; Nakamura, Emi; Koga, Tomoshige; Fukuda, Hiroyuki

    2010-01-15

    In previous paper, we reported that stimulation of the nucleus raphe magnus (stim-NRM) inhibits the induction of retching by afferent vagal fibers (VAs). We performed the present study to identity the transmitter of inhibition and then the site. The following results were obtained in decerebrated and paralyzed dogs. 1) The induction of fictive retching was suppressed by i.v. injection of 5-HT, and by 4th ventricular administration of 5-HT or a 5-HT3-receptor (R) agonist, 1-(m-chlorophenyl)-biguanade hydrochloride (m-CPBG). 2) Both forms of suppression were antagonized by i.v. injection of ondansetron, a 5-HT3-R antagonist. 3) Administration of the antagonist into the 4th ventricle did not affect the induction or its suppression by stim-NRM. These results suggest that the transmission from VAs to neurons in the nucleus solitarius (NTS) is suppressed by 5-HT via 5-HT3-R. However, these results also suggest that both the transmitter and receptor are not involved in the induction of retching by VAs or in its suppression by the NRM. Next, we examined the site of suppression. Unitary firings of NTS neurons in response to pulse-train stimulation of VAs were not inhibited by NRM stimulation. Moreover, the firing of NTS neurons during the induction of retching by vagal stimulation did not significantly decrease with the superimposition of stim-NRM, although the induction of retching was completely suppressed. These results suggest that suppression of the induction of retching by the descending inhibitory system of pain did not occur in the synapse between afferent vagal fibers and NTS neurons. The site of suppression is discussed.

  6. Similarities of the neuronal circuit for the induction of fictive vomiting between ferrets and dogs.

    PubMed

    Onishi, Takako; Mori, Takashi; Yanagihara, Mamoru; Furukawa, Naohiro; Fukuda, Hiroyuki

    2007-10-30

    Previous studies suggested that the following neuronal circuit participates in the induction of vomiting by afferent vagal stimulation in decerebrated paralyzed dogs: (1) afferent fibers of the vagus nerve, (2) neurons of the solitary nucleus (NTS), (3) neurons of the prodromal sign center near the semicompact part of the nucleus ambiguus (scAMB), (4) neurons of the central pattern generator in the reticular area adjacent to the compact part of nucleus ambiguus (cAMB), (5) respiratory premotor neurons in the caudal medulla, (6) motor neurons of the diaphragm and abdominal muscles. However, the commonality of this neuronal circuit in different species has not yet been clarified. Thus, this study was conducted to clarify this point. This study clarified for the first time that fictive vomiting in decerebrated paralyzed ferrets could be induced by vagal stimulation, and could be identified by centrifugal activity patterns of the phrenic and abdominal muscle nerves. The distributions of c-Fos immunoreactive neurons in the NTS, scAMB and cAMB areas in ferrets that exhibited fictive vomiting were denser than those in ferrets that did not. Application of the nonNMDA receptor antagonist into the 4th ventricle produced the reversible suppression of fictive vomiting. The NK1 receptor immunoreactive puncta were found in the reticular area adjacent to the scAMB. Microinjections of NK1 receptor antagonist into the reticular areas on both sides abolished fictive vomiting. All these results in the ferrets are identical with results previously obtained in dogs and cats. Therefore, this suggests that the above neuronal circuit commonly participates in the induction of emesis in these animal species.

  7. Usefulness of an injectable anaesthetic protocol for semen collection through urethral catheterisation in domestic cats.

    PubMed

    Pisu, Maria Carmela; Ponzio, Patrizia; Rovella, Chiara; Baravalle, Michela; Veronesi, Maria Cristina

    2017-10-01

    Objectives Although less often requested in comparison with dogs, the collection of semen in cats can be necessary for artificial insemination, for semen evaluation in tom cats used for breeding and for semen storage. Urethral catheterisation after pharmacological induction with medetomidine has proved to be useful for the collection of semen in domestic cats. However, most of the previously used protocols require the administration of high doses of medetomidine that can increase the risk of side effects, especially on the cardiovascular system. In routine clinical practice, one safe and useful injectable anaesthetic protocol for short-term clinical investigations or surgery in cats involves premedication with low intramuscular doses of dexmedetomidine with methadone, followed by intravenous propofol bolus injection. We aimed to assess the usefulness of this injectable anaesthetic protocol for semen collection, via urethral catheterisation, in domestic cats. Methods The study was performed on 38 purebred, adult cats, during the breeding season, and semen was collected via urethral catheterisation using an injectable anaesthesia protocol with methadone (0.2 mg/kg) and dexmedetomidine (5 µg/kg) premedication, followed by induction with propofol. Results The anaesthetic protocol used in the present study allowed the collection of large-volume semen samples, characterised by good parameters and without side effects. Conclusions and relevance The results from the present study suggest that the injectable anaesthetic protocol using methadone and dexmedetomidine premedication, followed by induction with propofol, could be suitable and safe for the collection of a good-quality semen sample, via urethral catheterisation, in domestic cats. It can therefore be used as an alternative to previous medetomidine-based sedation protocols.

  8. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

    PubMed

    Petrich, Adam M; Gandhi, Mitul; Jovanovic, Borko; Castillo, Jorge J; Rajguru, Saurabh; Yang, David T; Shah, Khushboo A; Whyman, Jeremy D; Lansigan, Frederick; Hernandez-Ilizaliturri, Francisco J; Lee, Lisa X; Barta, Stefan K; Melinamani, Shruthi; Karmali, Reem; Adeimy, Camille; Smith, Scott; Dalal, Neil; Nabhan, Chadi; Peace, David; Vose, Julie; Evens, Andrew M; Shah, Namrata; Fenske, Timothy S; Zelenetz, Andrew D; Landsburg, Daniel J; Howlett, Christina; Mato, Anthony; Jaglal, Michael; Chavez, Julio C; Tsai, Judy P; Reddy, Nishitha; Li, Shaoying; Handler, Caitlin; Flowers, Christopher R; Cohen, Jonathon B; Blum, Kristie A; Song, Kevin; Sun, Haowei Linda; Press, Oliver; Cassaday, Ryan; Jaso, Jesse; Medeiros, L Jeffrey; Sohani, Aliyah R; Abramson, Jeremy S

    2014-10-09

    Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed. © 2014 by The American Society of Hematology.

  9. New Method for Solving Inductive Electric Fields in the Ionosphere

    NASA Astrophysics Data System (ADS)

    Vanhamäki, H.

    2005-12-01

    We present a new method for calculating inductive electric fields in the ionosphere. It is well established that on large scales the ionospheric electric field is a potential field. This is understandable, since the temporal variations of large scale current systems are generally quite slow, in the timescales of several minutes, so inductive effects should be small. However, studies of Alfven wave reflection have indicated that in some situations inductive phenomena could well play a significant role in the reflection process, and thus modify the nature of ionosphere-magnetosphere coupling. The input to our calculation method are the time series of the potential part of the ionospheric electric field together with the Hall and Pedersen conductances. The output is the time series of the induced rotational part of the ionospheric electric field. The calculation method works in the time-domain and can be used with non-uniform, time-dependent conductances. In addition no particular symmetry requirements are imposed on the input potential electric field. The presented method makes use of special non-local vector basis functions called Cartesian Elementary Current Systems (CECS). This vector basis offers a convenient way of representing curl-free and divergence-free parts of 2-dimensional vector fields and makes it possible to solve the induction problem using simple linear algebra. The new calculation method is validated by comparing it with previously published results for Alfven wave reflection from uniformly conducting ionosphere.

  10. The HOG pathway controls osmotic regulation of transcription via the stress response element (STRE) of the Saccharomyces cerevisiae CTT1 gene.

    PubMed Central

    Schüller, C; Brewster, J L; Alexander, M R; Gustin, M C; Ruis, H

    1994-01-01

    The HOG signal pathway of the yeast Saccharomyces cerevisiae is defined by the PBS2 and HOG1 genes encoding members of the MAP kinase kinase and of the MAP kinase family, respectively. Mutations in this pathway (deletions of PBS2 or HOG1, or point mutations in HOG1) almost completely abolish the induction of transcription by osmotic stress that is mediated by stress response elements (STREs). We have demonstrated previously that STREs also mediate induction of transcription by heat shock, nitrogen starvation and oxidative stress. This study shows that they are also activated by low external pH, sorbate, benzoate or ethanol stress. Induction by these other stress signals appears to be HOG pathway independent. HOG1-dependent osmotic induction of transcription of the CTT1 gene encoding the cytosolic catalase T occurs in the presence of a protein synthesis inhibitor and can be detected rapidly after an increase of tyrosine phosphorylation of Hog1p triggered by high osmolarity. Consistent with a role of STREs in the induction of stress resistance, a number of other stress protein genes (e.g. HSP104) are regulated like CTT1. Furthermore, catalase T was shown to be important for viability under severe osmotic stress, and heat shock was demonstrated to provide cross-protection against osmotic stress. Images PMID:7523111

  11. The HOG pathway controls osmotic regulation of transcription via the stress response element (STRE) of the Saccharomyces cerevisiae CTT1 gene.

    PubMed

    Schüller, C; Brewster, J L; Alexander, M R; Gustin, M C; Ruis, H

    1994-09-15

    The HOG signal pathway of the yeast Saccharomyces cerevisiae is defined by the PBS2 and HOG1 genes encoding members of the MAP kinase kinase and of the MAP kinase family, respectively. Mutations in this pathway (deletions of PBS2 or HOG1, or point mutations in HOG1) almost completely abolish the induction of transcription by osmotic stress that is mediated by stress response elements (STREs). We have demonstrated previously that STREs also mediate induction of transcription by heat shock, nitrogen starvation and oxidative stress. This study shows that they are also activated by low external pH, sorbate, benzoate or ethanol stress. Induction by these other stress signals appears to be HOG pathway independent. HOG1-dependent osmotic induction of transcription of the CTT1 gene encoding the cytosolic catalase T occurs in the presence of a protein synthesis inhibitor and can be detected rapidly after an increase of tyrosine phosphorylation of Hog1p triggered by high osmolarity. Consistent with a role of STREs in the induction of stress resistance, a number of other stress protein genes (e.g. HSP104) are regulated like CTT1. Furthermore, catalase T was shown to be important for viability under severe osmotic stress, and heat shock was demonstrated to provide cross-protection against osmotic stress.

  12. 5-HT1a Receptor Antagonists Block Perforant Path-Dentate LTP Induced in Novel, but Not Familiar, Environments

    ERIC Educational Resources Information Center

    Sanberg, Cyndy Davis; Jones, Floretta L.; Do, Viet H.; Dieguez, Dario, Jr.; Derrick, Brian E.

    2006-01-01

    Numerous studies suggest roles for monoamines in modulating long-term potentiation (LTP). Previously, we reported that both induction and maintenance of perforant path-dentate gyrus LTP is enhanced when induced while animals explore novel environments. Here we investigate the contribution of serotonin and 5-HT1a receptors to the novelty-mediated…

  13. Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

    PubMed

    Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

    2018-06-01

    Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

  14. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut John H. Glenn (at podium) presents former astronaut Robert "Hoot" Gibson (standing right) at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are actor and Master of Ceremonies Lance Henriksen (left), and former astronauts Sally K. Ride and Daniel Brandenstein (right), both inducted into the Hall of Fame today. Also being inducted is Space Shuttle astronaut Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut John H. Glenn (at podium) presents former astronaut Robert "Hoot" Gibson (standing right) at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are actor and Master of Ceremonies Lance Henriksen (left), and former astronauts Sally K. Ride and Daniel Brandenstein (right), both inducted into the Hall of Fame today. Also being inducted is Space Shuttle astronaut Story Musgrave. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  15. Pulmonary Hypertensive Crisis on Induction of Anesthesia.

    PubMed

    Schisler, Travis; Marquez, Jose M; Hilmi, Ibtesam; Subramaniam, Kathirvel

    2017-03-01

    Anesthesia for lung transplantation remains one of the highest risk surgeries in the domain of the cardiothoracic anesthesiologist. End-stage lung disease, pulmonary hypertension, and right heart dysfunction as well as other comorbid disease factors predispose the patient to cardiovascular, respiratory and metabolic dysfunction during general anesthesia. Perhaps the highest risk phase of surgery in the patient with severe pulmonary hypertension is during the induction of anesthesia when the removal of intrinsic sympathetic tone and onset of positive pressure ventilation can decompensate a severely compromised cardiovascular system. Severe hypotension, cardiac arrest, and death have been reported previously. Here we present 2 high-risk patients for lung transplantation, their anesthetic induction course, and outcomes. We offer suggestions for the safe management of anesthetic induction to mitigate against hemodynamic and respiratory complications.

  16. Dynamics of Carbon-Concentrating Mechanism Induction and Protein Relocalization during the Dark-to-Light Transition in Synchronized Chlamydomonas reinhardtii1[W][OPEN

    PubMed Central

    Mitchell, Madeline C.; Meyer, Moritz T.; Griffiths, Howard

    2014-01-01

    In the model green alga Chlamydomonas reinhardtii, a carbon-concentrating mechanism (CCM) is induced under low CO2 in the light and comprises active inorganic carbon transport components, carbonic anhydrases, and aggregation of Rubisco in the chloroplast pyrenoid. Previous studies have focused predominantly on asynchronous cultures of cells grown under low versus high CO2. Here, we have investigated the dynamics of CCM activation in synchronized cells grown in dark/light cycles compared with induction under low CO2. The specific focus was to undertake detailed time course experiments comparing physiology and gene expression during the dark-to-light transition. First, the CCM could be fully induced 1 h before dawn, as measured by the photosynthetic affinity for inorganic carbon. This occurred in advance of maximum gene transcription and protein accumulation and contrasted with the coordinated induction observed under low CO2. Between 2 and 1 h before dawn, the proportion of Rubisco and the thylakoid lumen carbonic anhydrase in the pyrenoid rose substantially, coincident with increased CCM activity. Thus, other mechanisms are likely to activate the CCM before dawn, independent of gene transcription of known CCM components. Furthermore, this study highlights the value of using synchronized cells during the dark-to-light transition as an alternative means of investigating CCM induction. PMID:25106822

  17. Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

    PubMed Central

    Daiber, Andreas; Oelze, Matthias; Wenzel, Philip; Bollmann, Franziska; Pautz, Andrea; Kleinert, Hartmut

    2012-01-01

    Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy. PMID:22506100

  18. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut James Lovell makes the opening remarks at the induction ceremony of four Space Shuttle astronauts into the U.S. Astronaut Hall of Fame. Being inducted are Daniel Brandenstein, Robert "Hoot" Gibson, Story Musgrave, and Sally Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut James Lovell makes the opening remarks at the induction ceremony of four Space Shuttle astronauts into the U.S. Astronaut Hall of Fame. Being inducted are Daniel Brandenstein, Robert "Hoot" Gibson, Story Musgrave, and Sally Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  19. Formation and sustainment of field reversed configuration (FRC) plasmas by spheromak merging and neutral beam injection

    DOE PAGES

    Yamada, Masaaki

    2016-01-01

    This study briefly reviews a compact toroid reactor concept that addresses critical issues for forming, stabilizing and sustaining a field reversed configuration (FRC) with the use of plasma merging, plasma shaping, conducting shells, neutral beam injection (NBI). In this concept, an FRC plasma is generated by the merging of counter-helicity spheromaks produced by inductive discharges and sustained by the use of neutral beam injection (NBI). Plasma shaping, conducting shells, and the NBI would provide stabilization to global MHD modes. Although a specific FRC reactor design is outside the scope of the present paper, an example of a promising FRC reactormore » program is summarized based on the previously developed SPIRIT (Self-organized Plasmas by Induction, Reconnection and Injection Techniques) concept in order to connect this concept to the recently achieved the High Performance FRC plasmas obtained by Tri Alpha Energy [Binderbauer et al, Phys. Plasmas 22,056110, (2015)]. This paper includes a brief summary of the previous concept paper by M. Yamada et al, Plasma Fusion Res. 2, 004 (2007) and the recent experimental results from MRX.« less

  20. Evaluation of Hha and Hha SepB Mutant Strains of Escherichia coli O157:H7 as Bacterins for Reducing E. coli O157:H7 Shedding in Cattle

    USDA-ARS?s Scientific Manuscript database

    Escherichia coli O157:H7 colonizes cattle intestines by using locus of enterocyte effacement (LEE)-encoded proteins. Induction of systemic immune response against LEE-encoded proteins, therefore, will prove effective in reducing E. coli O157:H7 colonization in cattle. Previous studies have demonstra...

  1. Synaptic Activation of Ribosomal Protein S6 Phosphorylation Occurs Locally in Activated Dendritic Domains

    ERIC Educational Resources Information Center

    Pirbhoy, Patricia Salgado; Farris, Shannon; Steward, Oswald

    2016-01-01

    Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6)…

  2. Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

    PubMed

    Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

    2017-02-15

    The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  3. Excitation of lateral habenula neurons as a neural mechanism underlying ethanol‐induced conditioned taste aversion

    PubMed Central

    Keefe, Kristen A.; Taha, Sharif A.

    2016-01-01

    Key points The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Abstract Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press‐evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham‐ and LHb‐lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol‐induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. PMID:27682823

  4. Cellular mechanism of resistance of human colorectal adenocarcinoma cells against apoptosis-induction by Russell's Viper venom L-amino acid oxidase (Rusvinoxidase).

    PubMed

    Mukherjee, Ashis K; Saviola, Anthony J; Mackessy, Stephen P

    2018-04-24

    The present study highlights the cellular mechanism of resistance in human adenocarcinoma (Colo-205) cells against apoptosis induction by Rusvinoxidase, an L-amino acid oxidase purified from Russell's Viper venom (RVV). The significantly lower cytotoxicity as well as apoptotic activity of Rusvinoxidase towards Colo-205 cells (compared to MCF-7 breast cancer cells) is correlated with lower depletion of cellular glutathione content and increased down-regulation of catalase activity of Colo-205 cells following Rusvinoxidase treatment. Exposure to Rusvinoxidase subsequently diminished reactive oxygen species (ROS) production and failed to impair mitochondrial membrane potential, resulting in apoptosis induction resistance in Colo-205 cells. Further, higher expression levels of caspase 8, compared to caspase 9, indicate that Rusvinoxidase preferentially triggers the extrinsic pathway of apoptosis in Colo-205 cells. A time-dependent lower ratio of the relative expression of Bax and Bcl-xL (pro- and anti-apoptotic proteins) in Colo-205 cells, compared to our previous study on MCF-7 cells, unambiguously supports a higher cellular resistance mechanism in Colo-205 cells against Rusvinoxidase-induced apoptosis. Copyright © 2018. Published by Elsevier B.V.

  5. Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus.

    PubMed

    Li, Shuang; Choi, Veronica; Tzounopoulos, Thanos

    2013-06-11

    Tinnitus, the perception of phantom sound, is often a debilitating condition that affects many millions of people. Little is known, however, about the molecules that participate in the induction of tinnitus. In brain slices containing the dorsal cochlear nucleus, we reveal a tinnitus-specific increase in the spontaneous firing rate of principal neurons (hyperactivity). This hyperactivity is observed only in noise-exposed mice that develop tinnitus and only in the dorsal cochlear nucleus regions that are sensitive to high frequency sounds. We show that a reduction in Kv7.2/3 channel activity is essential for tinnitus induction and for the tinnitus-specific hyperactivity. This reduction is due to a shift in the voltage dependence of Kv7 channel activation to more positive voltages. Our in vivo studies demonstrate that a pharmacological manipulation that shifts the voltage dependence of Kv7 to more negative voltages prevents the development of tinnitus. Together, our studies provide an important link between the biophysical properties of the Kv7 channel and the generation of tinnitus. Moreover, our findings point to previously unknown biological targets for designing therapeutic drugs that may prevent the development of tinnitus in humans.

  6. 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.

  7. Dendritic spine dynamics leading to spine elimination after repeated inductions of LTD

    PubMed Central

    Hasegawa, Sho; Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2015-01-01

    Memory is fixed solidly by repetition. However, the cellular mechanism underlying this repetition-dependent memory consolidation/reconsolidation remains unclear. In our previous study using stable slice cultures of the rodent hippocampus, we found long-lasting synaptic enhancement/suppression coupled with synapse formation/elimination after repeated inductions of chemical LTP/LTD, respectively. We proposed these phenomena as useful model systems for analyzing repetition-dependent memory consolidation. Recently, we analyzed the dynamics of dendritic spines during development of the enhancement, and found that the spines increased in number following characteristic stochastic processes. The current study investigates spine dynamics during the development of the suppression. We found that the rate of spine retraction increased immediately leaving that of spine generation unaltered. Spine elimination occurred independent of the pre-existing spine density on the dendritic segment. In terms of elimination, mushroom-type spines were not necessarily more stable than stubby-type and thin-type spines. PMID:25573377

  8. Imaging biological tissues with electrical conductivity contrast below 1 S m−1 by means of magnetoacoustic tomography with magnetic induction

    PubMed Central

    Hu, Gang; Li, Xu; He, Bin

    2010-01-01

    Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently introduced imaging modality for noninvasive electrical impedance imaging, with ultrasound imaging resolution and a contrast reflecting the electrical conductivity properties of tissues. However, previous MAT-MI systems can only image samples that are much more conductive than real human or animal tissues. To image real biological tissue samples, a large-current-carrying coil that can give stronger magnetic stimulations and stronger MAT-MI acoustic signals is employed in this study. The conductivity values of all the tissue samples employed in this study are also directly measured using a well calibrated four-electrode system. The experimental results demonstrated the feasibility to image biological tissues with electrical conductivity contrast below 1.0 S∕m using the MAT-MI technique with safe level of electromagnetic energy applied to tissue samples. PMID:20938494

  9. How far can attraction-caused misalignment account for the Morinaga misalignment effect?

    PubMed

    Hotopf, W H; Brown, S

    1990-01-01

    When a line (the pointer) is collinear with a dot, the addition of a second line (the induction line) contiguous with the dot or near it may cause the pointer to appear to be collinear with a point further along or nearer to the induction line. The geometrical relations upon which this effect (which we call attraction-caused misalignment) depends, have been studied with the Obonai and Wundt-Loeb (Hotopf, 1981; Hotopf & Brown, 1988) figures. Drawing upon the studies of misalignment in the Morinaga figure carried out by Restle (1976), Day, Bellamy, and Norman (1983), and Day and Kasperczyk (1985), as well as upon two new experiments, we show that misalignment in the Morinaga figure is also attraction-caused misalignment, as previously defined. We conclude with a discussion of a number of theories that aim at accounting for attraction misalignment.

  10. Imaging biological tissues with electrical conductivity contrast below 1 S m-1 by means of magnetoacoustic tomography with magnetic induction

    NASA Astrophysics Data System (ADS)

    Hu, Gang; Li, Xu; He, Bin

    2010-09-01

    Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently introduced imaging modality for noninvasive electrical impedance imaging, with ultrasound imaging resolution and a contrast reflecting the electrical conductivity properties of tissues. However, previous MAT-MI systems can only image samples that are much more conductive than real human or animal tissues. To image real biological tissue samples, a large-current-carrying coil that can give stronger magnetic stimulations and stronger MAT-MI acoustic signals is employed in this study. The conductivity values of all the tissue samples employed in this study are also directly measured using a well calibrated four-electrode system. The experimental results demonstrated the feasibility to image biological tissues with electrical conductivity contrast below 1.0 S/m using the MAT-MI technique with safe level of electromagnetic energy applied to tissue samples.

  11. The measurement of cognitive reactivity to sad mood in patients remitted from major depressive disorder.

    PubMed

    Figueroa, Caroline A; Mocking, Roel J T; Mahmoud, Gelera A; Koeter, Maarten W; Bockting, Claudi L; van der Does, Willem; Ruhe, Henricus G; Schene, Aart H

    2018-02-27

    Cognitive reactivity (CR) to sad mood is a risk factor for major depressive disorder (MDD). CR is usually measured by assessing change on the Dysfunctional Attitudes Scale (DAS-change) after sad mood-induction. It has, however, been suggested that the versions of the DAS (A/B) are not interchangeable, impacting the reliability and validity of the change score. The Leiden Index of Depression Sensitivity-Revised (LEIDS-R) is an alternative self-report measure of CR. Studies examining the relationship between LEIDS-R and DAS-change have shown mixed results. We examined whether scores of these CR measures differed between remitted MDD and controls, the relationship between these CR measures, and the effect of order of DAS administration on DAS-change. Cross-sectional design with two groups (remitted MDD and controls). Sixty-eight MDD patients remitted from ≥2 previous episodes, not taking antidepressants, and 43 never-depressed controls participated in a mood-induction and filled in the DAS-A/B in randomized order before and after mood-induction, and LEIDS-R separately. LEIDS-R scores and pre-mood-induction DAS scores were significantly higher in remitted MDD than controls (p < .001, Cohen's d = 1.48; p = .001, Cohen's d = 0.66, respectively). DAS-change did not differ between these groups (p = .67, Cohen's d = 0.08). LEIDS-R correlated with DAS-change (r = .30, p = .042), but only in the group that filled in DAS-B before DAS-A. In remitted MDD, DAS-change was dependent on the order of DAS versions before and after mood-induction (10.6 ± 19.0 vs. -1.2 ± 10.5, for order B-A and A-B, respectively), with a significant group × order interaction (p = .012). Existing DAS versions are not interchangeable, which compromises the usefulness of mood-inductions in clinical practice. The LEIDS-R seems a valid measure of cognitive vulnerability to depression. Clinical implications: Cognitive reactivity (CR) is a risk factor of depressive recurrence. The current measurement of CR, by assessing change on the Dysfunctional Attitudes Scale (DAS) after mood-induction, is not reliable. The Leiden Index Depression Sensitivity-Revised (LEIDS-R) is an alternative CR measure. In contrast to mood-induction, it reliably assesses depression vulnerability. The use of mood-inductions for clinical/research purposes is unnecessary. We were not able to examine the effect of previous treatment, which could have affected results as psychological treatments probably have differential effects on CR. Examining un-medicated patients may have led to selection of a sample not completely representative for the general MDD population. We did not administer both parallel versions of the DAS (A/B) before and after mood-induction. This might have provided better understanding of their differential sensitivity to change. © 2018 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

  12. Resting connectivity between salience nodes predicts recognition memory.

    PubMed

    Andreano, Joseph M; Touroutoglou, Alexandra; Dickerson, Bradford C; Barrett, Lisa F

    2017-06-01

    The resting connectivity of the brain's salience network, particularly the ventral subsystem of the salience network, has been previously associated with various measures of affective reactivity. Numerous studies have demonstrated that increased affective arousal leads to enhanced consolidation of memory. This suggests that individuals with greater ventral salience network connectivity will exhibit greater responses to affective experience, leading to a greater enhancement of memory by affect. To test this hypothesis, resting ventral salience connectivity was measured in 41 young adults, who were then exposed to neutral and negative affect inductions during a paired associate memory test. Memory performance for material learned under both negative and neutral induction was tested for correlation with resting connectivity between major ventral salience nodes. The results showed a significant interaction between mood induction (negative vs neutral) and connectivity between ventral anterior insula and pregenual anterior cingulate cortex, indicating that salience node connectivity predicted memory for material encoded under negative, but not neutral induction. These findings suggest that the network state of the perceiver, measured prior to affective experience, meaningfully influences the extent to which affect modulates memory. Implications of these findings for individuals with affective disorder, who show alterations in both connectivity and memory, are considered. © The Author (2017). Published by Oxford University Press.

  13. Reasoning in people with obsessive-compulsive disorder.

    PubMed

    Simpson, Jane; Cove, Jennifer; Fineberg, Naomi; Msetfi, Rachel M; J Ball, Linden

    2007-11-01

    The aim of this study was to investigate the inductive and deductive reasoning abilities of people with obsessive-compulsive disorder (OCD). Following previous research, it was predicted that people with OCD would show different abilities on inductive reasoning tasks but similar abilities to controls on deductive reasoning tasks. A two-group comparison was used with both groups matched on a range of demographic variables. Where appropriate, unmatched variables were entered into the analyses as covariates. Twenty-three people with OCD and 25 control participants were assessed on two tasks: an inductive reasoning task (the 20-questions task) and a deductive reasoning task (a syllogistic reasoning task with a content-neutral and content-emotional manipulation). While no group differences emerged on several of the parameters of the inductive reasoning task, the OCD group did differ on one, and arguably the most important, parameter by asking fewer correct direct-hypothesis questions. The syllogistic reasoning task results were analysed using both correct response and conclusion acceptance data. While no main effects of group were evident, significant interactions indicated important differences in the way the OCD group reasoned with content neutral and emotional syllogisms. It was argued that the OCD group's patterns of response on both tasks were characterized by the need for more information, states of uncertainty, and doubt and postponement of a final decision.

  14. Oral administration of soluble β-glucan preparation from the cauliflower mushroom, Sparassis crispa (Higher Basidiomycetes) modulated cytokine production in mice.

    PubMed

    Hida, Toshie H; Kawaminami, Hiromi; Ishibashi, Ken-Ichi; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2013-01-01

    Soluble β-glucan preparation from the cold NaOH extract of Sparassis crispa (SCG) is a six-branched 1,3-β-D-glucan that is a major cell-wall structural component in fungi. Leukocytes from DBA/2 mice are highly sensitive to SCG, producing cytokines in vitro. We previously reported that the intraperitoneal (i.p.) administration of β-glucan decreased cytokine induction by SCG in vitro in DBA/2 mice. In this study, we examined the effects of the oral (p.o.) administration of polysaccharide fractions extracted from S. crispa, using hot water (SCHWE), a β-glucan from S. crispa, to DBA/2 mice on cytokine induction by SCG in the spleen in vitro. The level of induction of IFN-γ and GM-CSF by SCG was significantly increased in SCHWE-treated mice. This activity was more clearly observed when chlorpromazine was administered as a pretreatment in SCHWE-treated mice. The production of GM-CSF, IFN-γ, and IL-6 by immune cells in Peyer's patches was higher in SCHWE-treated mice than in control mice. These results suggest that orally administered β-glucan may modulate cytokine induction by SCG in the spleen through the activation of Peyer's patches.

  15. [Investigating phonological planning processes in speech production through a speech-error induction technique].

    PubMed

    Nakayama, Masataka; Saito, Satoru

    2015-08-01

    The present study investigated principles of phonological planning, a common serial ordering mechanism for speech production and phonological short-term memory. Nakayama and Saito (2014) have investigated the principles by using a speech-error induction technique, in which participants were exposed to an auditory distracIor word immediately before an utterance of a target word. They demonstrated within-word adjacent mora exchanges and serial position effects on error rates. These findings support, respectively, the temporal distance and the edge principles at a within-word level. As this previous study induced errors using word distractors created by exchanging adjacent morae in the target words, it is possible that the speech errors are expressions of lexical intrusions reflecting interactive activation of phonological and lexical/semantic representations. To eliminate this possibility, the present study used nonword distractors that had no lexical or semantic representations. This approach successfully replicated the error patterns identified in the abovementioned study, further confirming that the temporal distance and edge principles are organizing precepts in phonological planning.

  16. Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling.

    PubMed

    Wachter, Franziska; Grunert, Michaela; Blaj, Cristina; Weinstock, David M; Jeremias, Irmela; Ehrhardt, Harald

    2013-04-17

    The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling. We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity. In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.

  17. A theoretical study of the acoustic impedance of orifices in the presence of a steady grazing flow

    NASA Technical Reports Server (NTRS)

    Rice, E. J.

    1976-01-01

    An analysis of the oscillatory fluid flow in the vicinity of a circular orifice with a steady grazing flow is presented. The study is similar to that of Hersh and Rogers but with the addition of the grazing flow. Starting from the momentum and continuity equations, a considerably simplified system of partial differential equations is developed with the assumption that the flow can be described by an oscillatory motion superimposed upon the known steady flow. The equations are seen to be linear in the region where the grazing flow effects are dominant, and a solution and the resulting orifice impedance are presented for this region. The nonlinearity appears to be unimportant for the usual conditions found in aircraft noise suppressors. Some preliminary conclusions of the study are that orifice resistance is directly proportional to grazing flow velocity (known previously from experimental data) and that the orifice inductive (mass reactance) end correction is not a function of grazing flow. This latter conclusion is contrary to the widely held notion that grazing flow removes the effect of the orifice inductive end correction. This conclusion also implies that the experimentally observed total inductance reduction with grazing flow might be in the flow within the orifice rather than in the end correction.

  18. Ectopical expression of FABP4 gene can induce bovine muscle-derived stem cells adipogenesis.

    PubMed

    Zhang, Le; Zhao, Yanfang; Ning, Yue; Wang, Hongbao; Zan, Linsen

    2017-01-08

    Fatty acid binding protein 4 (FABP4) plays a key role in Fatty acid catabolism in mammals. Findings from our previous studies have indicated that FABP4 neither affect the differentiation of bovine preadipocytes nor does it change the expression of upstream genes. To investigate whether ectopically expressed FABP4 can induces Muscle-Derived Stem Cells (MDSCs) lipid synthesis and understand the regulatory mechanism behind it. In this study, adenoviruses infection is achieved to ectopically expressed FABP4 in bovine MDSCs, RNA-seq analyses at the very early stages of induction were performed to reveal gene expression level changes during MDSCs transdifferentiation. Results showed FABP4 can induce bovine Muscle-Derived Stem Cells transdifferentiation into adipocyte-like cells, 23 genes' expression levels changed after 24 h inducing although there is no significant change in cell phenotypes. Along with induction time, more differently expressed genes (256 genes changes after 48 h induction) were screened out. These genes should be at the downstream of signal pathways and be regulated by the 23 genes identified before. Our findings may provide a unique new model for studying the molecular control of cattle cross-talk between adipose and skeletal muscle. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The Magnetic INduction Ocean Sounder (MINOS) Concept Mission: Exploring Small Ocean Worlds With Nanosatellites

    NASA Astrophysics Data System (ADS)

    Steuer, C. J.

    2016-12-01

    Nanosatellite capabilities continue to steadily increase, showcasing ongoing advancement in key systems including GNC, communications, and power utilization. With focused high impact payloads, these small spacecraft can produce extraordinarily valuable planetary science datasets previously only retrievable by large, expensive, flagship science missions. The new capabilities provided by these nano-class spacecraft, in conjunction with, or even in lieu of, more traditional large monolithic spacecraft, can clear the way for a paradigm shift in the logistics and architecture of planetary science missions. Key near term targets for this technology are the icy moons of the outer solar system where advances in propulsion technology coupled with the low mass of nanosatellites and the shallow gravity wells of the moons allow for orbital capture. As part of a JPL funded study, the authors investigated the feasibility of placing a nanosatellite with magnetometer payload in Europa orbit to enhance and compliment the upcoming flagship mission to Europa through multi-frequency magnetic induction sounding. The study concluded that the enhanced dataset provided by coordinated observation between flagship, in Jovian orbit, and nanosatellite, in Europa orbit, using a fluxgate magnetometer of Rosetta heritage, would enable a more complete understanding of Europa's induction response by providing synchronous datasets between the Jovian plasma torus and the induced magnetosphere of Europa. We propose that these Magnetic INduction Ocean Sounders or MINOS spacecraft can play a similar role for all of the icy moons of the Jovian and Saturnian systems, providing close proximity multi-period magnetic induction sounding to compliment plasma suites and ice penetrating radar while setting the stage for alternative payloads and enhanced exploration of these potentially habitable worlds.

  20. Statistical optimization of medium composition and culture condition for the production of recombinant anti-lipopolysaccharide factor of Eriocheir sinensis in Escherichia coli

    NASA Astrophysics Data System (ADS)

    Jiang, Shan; Liu, Mei; Wang, Baojie; Jiang, Keyong; Wang, Lei

    2011-11-01

    Anti-lipopolysaccharide factors (ALFs) are important antimicrobial peptides that are isolated from some aquatic species. In a previous study, we isolated ALF genes from Chinese mitten crab, Eriocheir sinensis. In this study, we optimized the production of a recombinant ALF by expressing E. sinensis ALF genes in Escherichia coli maintained in shake-flasks. In particular, we focused on optimization of both the medium composition and the culture condition. Various medium components were analyzed by the Plackett-Burman design, and two significant screened factors, (NH4)2SO4 and KH2PO4, were further optimized via the central composite design (CCD). Based on the CCD analysis, we investigated the induction start-up time, the isopropylthio-D-galactoside (IPTG) concentration, the post-induction time, and the temperature by response surface methodology. We found that the highest level of ALF fusion protein was achieved in the medium containing 1.89 g/L (NH4)2SO4 and 3.18 g/L KH2PO4, with a cell optical density of 0.8 at 600 nm before induction, an IPTG concentration of 0.5 mmol/L, a post-induction temperature of 32.7°C, and a post-induction time of 4 h. Applying the whole optimization strategy using all optimal factors improved the target protein content from 6.1% (without optimization) to 13.2%. We further applied the optimized medium and conditions in high cell density cultivation, and determined that the soluble target protein constituted 10.5% of the total protein. Our identification of the economic medium composition, optimal culture conditions, and details of the fermentation process should facilitate the potential application of ALF for further research.

  1. Unexpectedly high incidence of hypothermia before induction of anesthesia in elective surgical patients.

    PubMed

    Wetz, Anna J; Perl, Thorsten; Brandes, Ivo F; Harden, Markus; Bauer, Martin; Bräuer, Anselm

    2016-11-01

    Perioperative hypothermia is a frequently observed phenomenon of general anesthesia and is associated with adverse patient outcome. Recently, a significant influence of core temperature before induction of anesthesia has been reported. However, there are still little existing data on core temperature before induction of anesthesia and no data regarding potential risk factors for developing preoperative hypothermia. The purpose of this investigation was to estimate the incidence of hypothermia before anesthesia and to determine if certain factors predict its incidence. Data from 7 prospective studies investigating core temperature previously initiated at our department were analyzed. Patients undergoing a variety of elective surgical procedures were included. Core temperature was measured before induction of anesthesia with an oral (314 patients), infrared tympanic (143 patients), or tympanic contact thermometer (36 patients). Available potential predictors included American Society of Anesthesiologists status, sex, age, weight, height, body mass index, adipose ratio, and lean body weight. Association with preoperative hypothermia was assessed separately for each predictor using logistic regression. Independent predictors were identified using multivariable logistic regression. A total of 493 patients were included in the study. Hypothermia was found in 105 patients (21.3%; 95% confidence interval, 17.8%-25.2%). The median core temperature was 36.3°C (25th-75th percentiles, 36.0°C-36.7°C). Two independent factors for preoperative hypothermia were identified: male sex and age (>52years). As a consequence of the high incidence of hypothermia before anesthesia, measuring core temperature should be mandatory 60 to 120minutes before induction to identify and provide adequate treatment to hypothermic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

    PubMed

    Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

    2018-05-01

    Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

  3. Npro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites.

    PubMed

    Tamura, Tomokazu; Nagashima, Naofumi; Ruggli, Nicolas; Summerfield, Artur; Kida, Hiroshi; Sakoda, Yoshihiro

    2014-04-17

    Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of pigs. The viral protein Npro of CSFV interferes with alpha- and beta-interferon (IFN-α/β) induction by promoting the degradation of interferon regulatory factor 3 (IRF3). During the establishment of the live attenuated CSF vaccine strain GPE-, Npro acquired a mutation that abolished its capacity to bind and degrade IRF3, rendering it unable to prevent IFN-α/β induction. In a previous study, we showed that the GPE- vaccine virus became pathogenic after forced serial passages in pigs, which was attributed to the amino acid substitutions T830A in the viral proteins E2 and V2475A and A2563V in NS4B. Interestingly, during the re-adaptation of the GPE- vaccine virus in pigs, the IRF3-degrading function of Npro was not recovered. Therefore, we examined whether restoring the ability of Npro to block IFN-α/β induction of both the avirulent and moderately virulent GPE--derived virus would enhance pathogenicity in pigs. Viruses carrying the N136D substitution in Npro regained the ability to degrade IRF3 and suppress IFN-α/β induction in vitro. In pigs, functional Npro significantly reduced the local IFN-α mRNA expression in lymphoid organs while it increased quantities of IFN-α/β in the circulation, and enhanced pathogenicity of the moderately virulent virus. In conclusion, the present study demonstrates that functional Npro influences the innate immune response at local sites of virus replication in pigs and contributes to pathogenicity of CSFV in synergy with viral replication.

  4. Different Expression Patterns of Genes from the Exo-Xis Region of Bacteriophage λ and Shiga Toxin-Converting Bacteriophage Ф24B following Infection or Prophage Induction in Escherichia coli

    PubMed Central

    Bloch, Sylwia; Nejman-Faleńczyk, Bożena; Dydecka, Aleksandra; Łoś, Joanna M.; Felczykowska, Agnieszka; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2014-01-01

    Lambdoid bacteriophages serve as useful models in microbiological and molecular studies on basic biological process. Moreover, this family of viruses plays an important role in pathogenesis of enterohemorrhagic Escherichia coli (EHEC) strains, as they are carriers of genes coding for Shiga toxins. Efficient expression of these genes requires lambdoid prophage induction and multiplication of the phage genome. Therefore, understanding the mechanisms regulating these processes appears essential for both basic knowledge and potential anti-EHEC applications. The exo-xis region, present in genomes of lambdoid bacteriophages, contains highly conserved genes of largely unknown functions. Recent report indicated that the Ea8.5 protein, encoded in this region, contains a newly discovered fused homeodomain/zinc-finger fold, suggesting its plausible regulatory role. Moreover, subsequent studies demonstrated that overexpression of the exo-xis region from a multicopy plasmid resulted in impaired lysogenization of E. coli and more effective induction of λ and Ф24B prophages. In this report, we demonstrate that after prophage induction, the increase in phage DNA content in the host cells is more efficient in E. coli bearing additional copies of the exo-xis region, while survival rate of such bacteria is lower, which corroborated previous observations. Importantly, by using quantitative real-time reverse transcription PCR, we have determined patterns of expressions of particular genes from this region. Unexpectedly, in both phages λ and Ф24B, these patterns were significantly different not only between conditions of the host cells infection by bacteriophages and prophage induction, but also between induction of prophages with various agents (mitomycin C and hydrogen peroxide). This may shed a new light on our understanding of regulation of lambdoid phage development, depending on the mode of lytic cycle initiation. PMID:25310402

  5. Exploring how students think: a new method combining think-aloud and concept mapping protocols.

    PubMed

    Pottier, Pierre; Hardouin, Jean-Benoit; Hodges, Brian D; Pistorius, Marc-Antoine; Connault, Jérome; Durant, Cécile; Clairand, Renaud; Sebille, Véronique; Barrier, Jacques-Henri; Planchon, Bernard

    2010-09-01

    A key element of medical competence is problem solving. Previous work has shown that doctors use inductive reasoning to progress from facts to hypotheses and deductive reasoning to move from hypotheses to the gathering of confirmatory information. No individual assessment method has been designed to quantify the use of inductive and deductive procedures within clinical reasoning. The aim of this study was to explore the feasibility and reliability of a new method which allows for the rapid identification of the style (inductive or deductive) of clinical reasoning in medical students and experts. The study included four groups of four participants. These comprised groups of medical students in Years 3, 4 and 5 and a group of specialists in internal medicine, all at a medical school with a 6-year curriculum in France. Participants were asked to solve four clinical problems by thinking aloud. The thinking expressed aloud was immediately transcribed into concept maps by one or two 'writers' trained to distinguish inductive and deductive links. Reliability was assessed by estimating the inter-writer correlation. The calculated rate of inductive reasoning, the richness score and the rate of exhaustiveness of reasoning were compared according to the level of expertise of the individual and the type of clinical problem. The total number of maps drawn amounted to 32 for students in Year 4, 32 for students in Year 5, 16 for students in Year 3 and 16 for experts. A positive correlation was found between writers (R = 0.66-0.93). Richness scores and rates of exhaustiveness of reasoning did not differ according to expertise level. The rate of inductive reasoning varied as expected according to the nature of the clinical problem and was lower in experts (41% versus 67%). This new method showed good reliability and may be a promising tool for the assessment of medical problem-solving skills, giving teachers a means of diagnosing how their students think when they are confronted with clinical problems.

  6. Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells

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

    Chen, Yue; Zhang, Shunfen; Zhou, Tianyan

    2013-04-15

    Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXRα) in the genistein induction of hSULT2A1. LXRs have been shown to induce expressionmore » of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXRα mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXRα binding to the hSULT2A1 promoter. These results suggest that hLXRα plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT. - Highlights: ► Liver X receptor α mediated genistein induction of hSULT2A1 in Hep G2 cells. ► LXRα and RXRα dimerization further activated this induction. ► Western blot results agreed well with luciferase reporter gene assay results. ► LXRs gene silencing significantly decreased hSULT2A1 expression. ► ChIP analysis suggested that genistein enhances hLXRα binding to the hSULT2A1 promoter.« less

  7. Dual resonant frequencies effects on an induction-based oil palm fruit sensor.

    PubMed

    Harun, Noor Hasmiza; Misron, Norhisam; Mohd Sidek, Roslina; Aris, Ishak; Wakiwaka, Hiroyuki; Tashiro, Kunihisa

    2014-11-19

    As the main exporter in the oil palm industry, the need to improve the quality of palm oil has become the main interest among all the palm oil millers in Malaysia. To produce good quality palm oil, it is important for the miller to harvest a good oil palm Fresh Fruit Bunch (FFB). Conventionally, the main reference used by Malaysian harvesters is the manual grading standard published by the Malaysian Palm Oil Board (MPOB). A good oil palm FFB consists of all matured fruitlets, aged between 18 to 21 weeks of antheses (WAA). To expedite the harvesting process, it is crucial to implement an automated detection system for determining the maturity of the oil palm FFB. Various automated detection methods have been proposed by researchers in the field to replace the conventional method. In our preliminary study, a novel oil palm fruit sensor to detect the maturity of oil palm fruit bunch was proposed. The design of the proposed air coil sensor based on the inductive sensor was further investigated mainly in the context of the effect of coil diameter to improve its sensitivity. In this paper, the sensitivity of the inductive sensor was further examined with a dual flat-type shape of air coil. The dual air coils were tested on fifteen samples of fruitlet from two categories, namely ripe and unripe. Samples were tested within 20 Hz to 10 MHz while evaluations on both peaks were done separately before the gap between peaks was analyzed. A comparative analysis was conducted to investigate the improvement in sensitivity of the induction-based oil palm fruit sensor as compared to previous works. Results from the comparative study proved that the inductive sensor using a dual flat-type shape air coil has improved by up to 167%. This provides an indication in the improvement in the coil sensitivity of the palm oil fruit sensor based on the induction concept.

  8. Dual Resonant Frequencies Effects on an Induction-Based Oil Palm Fruit Sensor

    PubMed Central

    Harun, Noor Hasmiza; Misron, Norhisam; Sidek, Roslina Mohd; Aris, Ishak; Wakiwaka, Hiroyuki; Tashiro, Kunihisa

    2014-01-01

    As the main exporter in the oil palm industry, the need to improve the quality of palm oil has become the main interest among all the palm oil millers in Malaysia. To produce good quality palm oil, it is important for the miller to harvest a good oil palm Fresh Fruit Bunch (FFB). Conventionally, the main reference used by Malaysian harvesters is the manual grading standard published by the Malaysian Palm Oil Board (MPOB). A good oil palm FFB consists of all matured fruitlets, aged between 18 to 21 weeks of antheses (WAA). To expedite the harvesting process, it is crucial to implement an automated detection system for determining the maturity of the oil palm FFB. Various automated detection methods have been proposed by researchers in the field to replace the conventional method. In our preliminary study, a novel oil palm fruit sensor to detect the maturity of oil palm fruit bunch was proposed. The design of the proposed air coil sensor based on the inductive sensor was further investigated mainly in the context of the effect of coil diameter to improve its sensitivity. In this paper, the sensitivity of the inductive sensor was further examined with a dual flat-type shape of air coil. The dual air coils were tested on fifteen samples of fruitlet from two categories, namely ripe and unripe. Samples were tested within 20 Hz to 10 MHz while evaluations on both peaks were done separately before the gap between peaks was analyzed. A comparative analysis was conducted to investigate the improvement in sensitivity of the induction-based oil palm fruit sensor as compared to previous works. Results from the comparative study proved that the inductive sensor using a dual flat-type shape air coil has improved by up to 167%. This provides an indication in the improvement in the coil sensitivity of the palm oil fruit sensor based on the induction concept. PMID:25414970

  9. Predictive model for risk of cesarean section in pregnant women after induction of labor.

    PubMed

    Hernández-Martínez, Antonio; Pascual-Pedreño, Ana I; Baño-Garnés, Ana B; Melero-Jiménez, María R; Tenías-Burillo, José M; Molina-Alarcón, Milagros

    2016-03-01

    To develop a predictive model for risk of cesarean section in pregnant women after induction of labor. A retrospective cohort study was conducted of 861 induced labors during 2009, 2010, and 2011 at Hospital "La Mancha-Centro" in Alcázar de San Juan, Spain. Multivariate analysis was used with binary logistic regression and areas under the ROC curves to determine predictive ability. Two predictive models were created: model A predicts the outcome at the time the woman is admitted to the hospital (before the decision to of the method of induction); and model B predicts the outcome at the time the woman is definitely admitted to the labor room. The predictive factors in the final model were: maternal height, body mass index, nulliparity, Bishop score, gestational age, macrosomia, gender of fetus, and the gynecologist's overall cesarean section rate. The predictive ability of model A was 0.77 [95% confidence interval (CI) 0.73-0.80] and model B was 0.79 (95% CI 0.76-0.83). The predictive ability for pregnant women with previous cesarean section with model A was 0.79 (95% CI 0.64-0.94) and with model B was 0.80 (95% CI 0.64-0.96). For a probability of estimated cesarean section ≥80%, the models A and B presented a positive likelihood ratio (+LR) for cesarean section of 22 and 20, respectively. Also, for a likelihood of estimated cesarean section ≤10%, the models A and B presented a +LR for vaginal delivery of 13 and 6, respectively. These predictive models have a good discriminative ability, both overall and for all subgroups studied. This tool can be useful in clinical practice, especially for pregnant women with previous cesarean section and diabetes.

  10. Spot 42 Small RNA Regulates Arabinose-Inducible araBAD Promoter Activity by Repressing Synthesis of the High-Affinity Low-Capacity Arabinose Transporter

    PubMed Central

    Chen, Jiandong

    2016-01-01

    ABSTRACT The l-arabinose-inducible araBAD promoter (PBAD) enables tightly controlled and tunable expression of genes of interest in a broad range of bacterial species. It has been used successfully to study bacterial sRNA regulation, where PBAD drives expression of target mRNA translational fusions. Here we report that in Escherichia coli, Spot 42 sRNA regulates PBAD promoter activity by affecting arabinose uptake. We demonstrate that Spot 42 sRNA represses araF, a gene encoding the AraF subunit of the high-affinity low-capacity arabinose transporter AraFGH, through direct base-pairing interactions. We further show that endogenous Spot 42 sRNA is sufficient to repress araF expression under various growth conditions. Finally, we demonstrate this posttranscriptional repression has a biological consequence, decreasing the induction of PBAD at low levels of arabinose. This problem can be circumvented using strategies reported previously for avoiding all-or-none induction behavior, such as through constitutive expression of the low-affinity high-capacity arabinose transporter AraE or induction with a higher concentration of inducers. This work adds araF to the set of Spot 42-regulated genes, in agreement with previous studies suggesting that Spot 42, itself negatively regulated by the cyclic AMP (cAMP) receptor protein-cAMP complex, reinforces the catabolite repression network. IMPORTANCE The bacterial arabinose-inducible system is widely used for titratable control of gene expression. We demonstrate here that a posttranscriptional mechanism mediated by Spot 42 sRNA contributes to the functionality of the PBAD system at subsaturating inducer concentrations by affecting inducer uptake. Our finding extends the inputs into the known transcriptional control for the PBAD system and has implications for improving its usage for tunable gene expression. PMID:27849174

  11. Differentiation of monkey embryonic stem cells to hepatocytes by feeder-free dispersion culture and expression analyses of cytochrome p450 enzymes responsible for drug metabolism.

    PubMed

    Maruyama, Junya; Matsunaga, Tamihide; Yamaori, Satoshi; Sakamoto, Sakae; Kamada, Noboru; Nakamura, Katsunori; Kikuchi, Shinji; Ohmori, Shigeru

    2013-01-01

    We reported previously that monkey embryonic stem cells (ESCs) were differentiated into hepatocytes by formation of embryoid bodies (EBs). However, this EB formation method is not always efficient for assays using a large number of samples simultaneously. A dispersion culture system, one of the differentiation methods without EB formation, is able to more efficiently provide a large number of feeder-free undifferentiated cells. A previous study demonstrated the effectiveness of the Rho-associated kinase inhibitor Y-27632 for feeder-free dispersion culture and induction of differentiation of monkey ESCs into neural cells. In the present study, the induction of differentiation of cynomolgus monkey ESCs (cmESCs) into hepatocytes was performed by the dispersion culture method, and the expression and drug inducibility of cytochrome P450 (CYP) enzymes in these hepatocytes were examined. The cmESCs were successfully differentiated into hepatocytes under feeder-free dispersion culture conditions supplemented with Y-27632. The hepatocytes differentiated from cmESCs expressed the mRNAs for three hepatocyte marker genes (α-fetoprotein, albumin, CYP7A1) and several CYP enzymes, as measured by real-time polymerase chain reaction. In particular, the basal expression of cmCYP3A4 (3A8) in these hepatocytes was detected at mRNA and enzyme activity (testosterone 6β-hydroxylation) levels. Furthermore, the expression and activity of cmCYP3A4 (3A8) were significantly upregulated by rifampicin. These results indicated the effectiveness of Y-27632 supplementation for feeder-free dispersed culture and induction of differentiation into hepatocytes, and the expression of functional CYP enzyme(s) in cmESC-derived hepatic cells.

  12. Diversity effect in category-based inductive reasoning of young children: evidence from two methods.

    PubMed

    Zhong, Luojin; Lee, Myung Sook; Huang, Yulan; Mo, Lei

    2014-02-01

    Previous studies have shown that diverse pieces of evidence, rather than similar pieces of evidence, are considered to have greater strength in adults' inductive reasoning. However, this diversity effect is inconsistently recognized by children. Three experiments using the same materials but different tasks examined whether young children consider the diversity principle in their reasoning. Although Experiment 1 applied a data selection task showed five-year-old children in both China and Korea were not sensitive to the diversity of evidence, Experiments 2 and 3 employed an identification task and demonstrated that children as young as five years were sensitive to diverse evidence. These findings indicated that young children, less than nine years of age, may have diversity effect. Methodological and cultural differences were discussed.

  13. Novelty and Inductive Generalization in Human Reinforcement Learning.

    PubMed

    Gershman, Samuel J; Niv, Yael

    2015-07-01

    In reinforcement learning (RL), a decision maker searching for the most rewarding option is often faced with the question: What is the value of an option that has never been tried before? One way to frame this question is as an inductive problem: How can I generalize my previous experience with one set of options to a novel option? We show how hierarchical Bayesian inference can be used to solve this problem, and we describe an equivalence between the Bayesian model and temporal difference learning algorithms that have been proposed as models of RL in humans and animals. According to our view, the search for the best option is guided by abstract knowledge about the relationships between different options in an environment, resulting in greater search efficiency compared to traditional RL algorithms previously applied to human cognition. In two behavioral experiments, we test several predictions of our model, providing evidence that humans learn and exploit structured inductive knowledge to make predictions about novel options. In light of this model, we suggest a new interpretation of dopaminergic responses to novelty. Copyright © 2015 Cognitive Science Society, Inc.

  14. Novelty and Inductive Generalization in Human Reinforcement Learning

    PubMed Central

    Gershman, Samuel J.; Niv, Yael

    2015-01-01

    In reinforcement learning, a decision maker searching for the most rewarding option is often faced with the question: what is the value of an option that has never been tried before? One way to frame this question is as an inductive problem: how can I generalize my previous experience with one set of options to a novel option? We show how hierarchical Bayesian inference can be used to solve this problem, and describe an equivalence between the Bayesian model and temporal difference learning algorithms that have been proposed as models of reinforcement learning in humans and animals. According to our view, the search for the best option is guided by abstract knowledge about the relationships between different options in an environment, resulting in greater search efficiency compared to traditional reinforcement learning algorithms previously applied to human cognition. In two behavioral experiments, we test several predictions of our model, providing evidence that humans learn and exploit structured inductive knowledge to make predictions about novel options. In light of this model, we suggest a new interpretation of dopaminergic responses to novelty. PMID:25808176

  15. Inductive reasoning about causally transmitted properties.

    PubMed

    Shafto, Patrick; Kemp, Charles; Bonawitz, Elizabeth Baraff; Coley, John D; Tenenbaum, Joshua B

    2008-11-01

    Different intuitive theories constrain and guide inferences in different contexts. Formalizing simple intuitive theories as probabilistic processes operating over structured representations, we present a new computational model of category-based induction about causally transmitted properties. A first experiment demonstrates undergraduates' context-sensitive use of taxonomic and food web knowledge to guide reasoning about causal transmission and shows good qualitative agreement between model predictions and human inferences. A second experiment demonstrates strong quantitative and qualitative fits to inferences about a more complex artificial food web. A third experiment investigates human reasoning about complex novel food webs where species have known taxonomic relations. Results demonstrate a double-dissociation between the predictions of our causal model and a related taxonomic model [Kemp, C., & Tenenbaum, J. B. (2003). Learning domain structures. In Proceedings of the 25th annual conference of the cognitive science society]: the causal model predicts human inferences about diseases but not genes, while the taxonomic model predicts human inferences about genes but not diseases. We contrast our framework with previous models of category-based induction and previous formal instantiations of intuitive theories, and outline challenges in developing a complete model of context-sensitive reasoning.

  16. Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies

    PubMed Central

    Lebbé, C.; Weber, J. S.; Maio, M.; Neyns, B.; Harmankaya, K.; Hamid, O.; O'Day, S. J.; Konto, C.; Cykowski, L.; McHenry, M. B.; Wolchok, J. D.

    2014-01-01

    Background This report provides a survival update at a follow-up of >5 years (5.5–6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported. Patients and methods Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025. Results Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%–16.5%, and 15.5%–28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%–49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively. Conclusions At a follow-up of 5–6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS. ClinicalTrials.gov NCT00162123. PMID:25210016

  17. Effect of a Second, Parallel Capacitor on the Performance of a Pulse Inductive Plasma Thruster

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Balla, Joseph V.

    2010-01-01

    Pulsed inductive plasma accelerators are electrodeless space propulsion devices where a capacitor is charged to an initial voltage and is then discharged through an inductive coil that couples energy into the propellant, ionizing and accelerating it to produce thrust. A model that employs a set of circuit equations (as illustrated in Fig. 1a) coupled to a one-dimensional momentum equation has been previously used by Lovberg and Dailey [1] and Polzin et al. [2-4] to model the plasma acceleration process in pulsed inductive thrusters. In this paper an extra capacitor, inductor, and resistor are added to the system in the manner illustrated in the schematic shown in Fig. 1b. If the second capacitor has a smaller value than the initially charged capacitor, it can serve to increase the current rise rate through the inductive coil. Increasing the current rise rate should serve to better ionize the propellant. The equation of motion is solved to find the effect of an increased current rise rate on the acceleration process. We examine the tradeoffs between enhancing the breakdown process (increasing current rise rate) and altering the plasma acceleration process. These results provide insight into the performance of modified circuits in an inductive thruster, revealing how this design permutation can affect an inductive thruster's performance.

  18. Knowledge, expectations, and inductive reasoning within conceptual hierarchies.

    PubMed

    Coley, John D; Hayes, Brett; Lawson, Christopher; Moloney, Michelle

    2004-01-01

    Previous research (e.g. Cognition 64 (1997) 73) suggests that the privileged level for inductive inference in a folk biological conceptual hierarchy does not correspond to the "basic" level (i.e. the level at which concepts are both informative and distinct). To further explore inductive inference within conceptual hierarchies, we examine relations between knowledge of concepts at different hierarchical levels, expectations about conceptual coherence, and inductive inference. In Experiments 1 and 2, 5- and 8-year-olds and adults listed features of living kind (Experiments 1 and 2) and artifact (Experiment 2) concepts at different hierarchical levels (e.g. plant, tree, oak, desert oak), and also rated the strength of generalizations to the same concepts. For living kinds, the level that showed a relative advantage on these two tasks differed; the greatest increase in features listed tended to occur at the life-form level (e.g. tree), whereas the greatest increase in inductive strength tended to occur at the folk-generic level (e.g. oak). Knowledge and induction also showed different developmental trajectories. For artifact concepts, the levels at which the greatest gains in knowledge and induction occurred were more varied, and corresponded more closely across tasks. In Experiment 3, adults reported beliefs about within-category similarity for concepts at different levels of animal, plant and artifact hierarchies, and rated inductive strength as before. For living kind concepts, expectations about category coherence predicted patterns of inductions; knowledge did not. For artifact concepts, both knowledge and expectations predicted patterns of induction. Results suggest that beliefs about conceptual coherence play an important role in guiding inductive inference, that this role may be largely independent of specific knowledge of concepts, and that such beliefs are especially important in reasoning about living kinds.

  19. Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by Induction of CYP1A through the Aromatic Hydrocarbon Receptor

    PubMed Central

    Wang, Ke; Feng, Chenchen; Li, Chenggang; Yao, Jun; Xie, Xiaofeng; Gong, Likun; Luan, Yang; Xing, Guozhen; Zhu, Xue; Qi, Xinming; Ren, Jin

    2015-01-01

    Exposure to aristolochic acid I (AAI) can lead to aristolochic acid nephropathy (AAN), Balkan endemic nephropathy (BEN) and urothelial cancer. The induction of hepatic CYP1A, especially CYP1A2, was considered to detoxify AAI so as to reduce its nephrotoxicity. We previously found that baicalin had the strong ability to induce CYP1A2 expression; therefore in this study, we examined the effects of baicalin on AAI toxicity, metabolism and disposition, as well as investigated the underlying mechanisms. Our toxicological studies showed that baicalin reduced the levels of blood urea nitrogen (BUN) and creatinine (CRE) in AAI-treated mice and attenuated renal injury induced by AAI. Pharmacokinetic analysis demonstrated that baicalin markedly decreased AUC of AAI in plasma and the content of AAI in liver and kidney. CYP1A induction assays showed that baicalin exposure significantly increased the hepatic expression of CYP1A1/2, which was completely abolished by inhibitors of the Aromatic hydrocarbon receptor (AhR), 3ʹ,4ʹ-dimethoxyflavone and resveratrol, in vitro and in vivo, respectively. Moreover, the luciferase assays revealed that baicalin significantly increased the luciferase activity of the reporter gene incorporated with the Xenobiotic response elements recognized by AhR. In summary, baicalin significantly reduced the disposition of AAI and ameliorated AAI-induced kidney toxicity through AhR-dependent CYP1A1/2 induction in the liver. PMID:26204831

  20. Critical role for TNF in the induction of human antigen-specific regulatory T cells by tolerogenic dendritic cells.

    PubMed

    Kleijwegt, Fleur S; Laban, Sandra; Duinkerken, Gaby; Joosten, Antoinette M; Zaldumbide, Arnaud; Nikolic, Tatjana; Roep, Bart O

    2010-08-01

    TNF is a pleiotropic cytokine with differential effects on immune cells and diseases. Anti-TNF therapy was shown to be effective in rheumatoid arthritis but proved inefficient or even detrimental in other autoimmune diseases. We studied the role of TNF in the induction of Ag-specific regulatory T cells (Tregs) by tolerogenic vitamin D3-modulated human dendritic cells (VD3-DCs), which previously were shown to release high amounts of soluble TNF (sTNF) upon maturation with LPS. First, production of TNF by modulated VD3-DCs was analyzed upon maturation with LPS or CD40L with respect to both secreted (cleaved) TNF (sTNF) and expression of the membrane-bound (uncleaved) form of TNF (mTNF). Next, TNF antagonists were tested for their effect on induction of Ag-specific Tregs by modulated DCs and the subsequent functionality of these Tregs. VD3-DCs expressed greater amounts of mTNF than did control DCs (nontreated DCs), independent of the maturation protocol. Inhibition of TNF with anti-TNF Ab (blocking both sTNF and mTNF) during the priming of Tregs with VD3-DCs prevented generation of Tregs and their suppression of proliferation of CD4(+) T cells. In contrast, sTNF receptor II (sTNFRII), mainly blocking sTNF, did not change the suppressive capacity of Tregs. Blocking of TNFRII by anti-CD120b Ab during Treg induction similarly abrogated their subsequent suppressive function. These data point to a specific role for mTNF on VD3-DCs in the induction of Ag-specific Tregs. Interaction between mTNF and TNFRII instructs the induction of suppressive Tregs by VD3-DCs. Anti-TNF therapy may therefore act adversely in different patients or disease pathways.

  1. When Traits Match States: Examining the Associations between Self-Report Trait and State Mindfulness following a State Mindfulness Induction.

    PubMed

    Bravo, Adrian J; Pearson, Matthew R; Wilson, Adam D; Witkiewitz, Katie

    2018-02-01

    Previous research has found inconsistent relationships between trait mindfulness and state mindfulness. To extend previous research, we sought to examine the unique associations between self-report trait mindfulness and state mindfulness by levels of meditation experience (meditation-naïve vs. meditation-experienced) and by mindfulness induction (experimentally induced mindful state vs. control group). We recruited 299 college students (93 with previous mindfulness meditation experience) to participate in an experiment that involved the assessment of five facets of trait mindfulness (among other constructs), followed by a mindfulness induction (vs. control), followed by the assessment of state mindfulness of body and mind. Correlational analyses revealed limited associations between trait mindfulness facets and facets of state mindfulness, and demonstrated that a brief mindfulness exercise focused on bodily sensations and the breath elicited higher state mindfulness of body but not state mindfulness of mind. We found significant interactions such that individuals with previous meditation experience and higher scores on the observing facet of trait mindfulness had the highest levels of state mindfulness of body and mind. Among individuals with meditation experience, the strengths of the associations between observing trait mindfulness and the state mindfulness facets increased with frequency of meditation practice. Some other interactions ran counter to expectations. Overall, the relatively weak associations between trait and state mindfulness demonstrates the need to improve our operationalizations of mindfulness, advance our understanding of how to best cultivate mindfulness, and reappraise the ways in which mindfulness can manifest as a state and as a trait.

  2. High-Resolution THz Measurements of BrO Generated in AN Inductively Coupled Plasma

    NASA Astrophysics Data System (ADS)

    Nemchick, Deacon J.; Drouin, Brian

    2017-06-01

    Building upon the foundation provided by previous work, the X_{1}^{2}Π_{3/2} and X_{2}^{2}Π_{1/2} states of the transient radical, BrO, were interrogated in previously unprobed spectral regions (0.5 to 1.7 THz) by employing JPL developed high-resolution cascaded frequency multiplier sources. Like other members of the halogen monoxides (XO), this species has been the target of several recent atmospheric remote sensing studies and is a known participant in a catalytic ozone degradation cycle. For the current work, BrO is generated in an inductively coupled plasma under dynamic flow conditions and rotational lines are observed directly at their Doppler-limited resolution. New spectral transitions including those owing to both the ground (ν=0) and excited (ν=1 and 2) vibrational states of isotopologues composed of permutations of natural abundance ^{16}O, ^{18}O, ^{79}Br, and ^{81}Br are fit to a global Hamiltonian containing both fine and hyperfine terms. In addition to further refining existing spectroscopic parameters, new observations will be made available to remote detection communities through addition to the JPL catalog. New findings will be discussed along with future plans to extend these studies to other halogen monoxides (X=Cl and I) and the more massive halogen dioxides (OXO & XOO).

  3. Solenoid-free plasma startup in NSTX using transient CHI

    NASA Astrophysics Data System (ADS)

    Raman, R.; Jarboe, T. R.; Mueller, D.; Nelson, B. A.; Bell, M. G.; Bell, R.; Gates, D.; Gerhardt, S.; Hosea, J.; Kaita, R.; Kugel, H.; LeBlanc, B.; Maingi, R.; Maqueda, R.; Menard, J.; Nagata, M.; Ono, M.; Paul, S.; Roquemore, L.; Sabbagh, S.; Soukhanovskii, V.; Taylor, G.

    2009-06-01

    Experiments in NSTX have now demonstrated the coupling of toroidal plasmas produced by the technique of coaxial helicity injection (CHI) to inductive sustainment and ramp-up of the toroidal plasma current. In these discharges, the central Ohmic transformer was used to apply an inductive loop voltage to discharges with a toroidal current of about 100 kA created by CHI. The coupled discharges have ramped up to >700 kA and transitioned into an H-mode demonstrating compatibility of this startup method with conventional operation. The electron temperature in the coupled discharges reached over 800 eV and the resulting plasma had low inductance, which is preferred for long-pulse high-performance discharges. These results from NSTX in combination with the previously obtained record 160 kA non-inductively generated startup currents in an ST or tokamak in NSTX demonstrate that CHI is a viable solenoid-free plasma startup method for future STs and tokamaks.

  4. Ethanol Induction of CYP2A5: Role of CYP2E1-ROS-Nrf2 Pathway

    PubMed Central

    Lu, Yongke; Zhang, Xu Hannah

    2012-01-01

    Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 –/–) mice, suggesting that unlike the CYP2E1-dependent ethanol induction of CYP2A5, ethanol induction of CYP2E1 is not CYP2A5 dependent. Microsomal ethanol oxidation was about 25% lower in Cyp2a5 –/– mice compared with that in WT mice, suggesting that CYP2A5 can oxidize ethanol although to a lesser extent than CYP2E1 does. CYP2A5 was induced by short-term ethanol consumption in human CYP2E1 transgenic knockin (Cyp2e1 –/– KI) mice but not in CYP2E1 knockout (Cyp2e1 –/–) mice. The redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) was also induced by acute ethanol in Cyp2e1 –/– KI mice but not in Cyp2e1 –/– mice. Ethanol induction of CYP2A5 in Nrf2 knockout (Nrf2 –/–) mice was lower compared with that in WT mice, whereas CYP2E1 induction by ethanol was comparable in WT and Nrf2 –/– mice. Antioxidants (N-acetyl-cysteine and vitamin C), which blocked oxidative stress induced by chronic ethanol in WT mice and acute ethanol in Cyp2e1 –/– KI mice, also blunted the induction of CYP2A5 and Nrf2 by ethanol but not the induction of CYP2E1 by ethanol. These results suggest that oxidative stress induced by ethanol via induction of CYP2E1 upregulates Nrf2 activity, which in turn regulates ethanol induction of CYP2A5. Results obtained from primary hepatocytes, mice gavaged with binge ethanol or fed chronic ethanol, show that Nrf2-regulated ethanol induction of CYP2A5 protects against ethanol-induced steatosis. PMID:22552773

  5. Contraintes residuelles et leurs impacts sur l'amorcage de fissures en fatigue de flexion dans des engrenages aeronautiques durcis superficiellement par induction

    NASA Astrophysics Data System (ADS)

    Savaria, Vincent

    The optimization of gearing for aeronautical engines depends on the development of surface hardening processes to significantly improve in-service durability. Induction heating followed by quenching is a treatment increasingly used in this field to improve the fatigue resistance of critical components such as gears. In this context, this thesis studies the impact of the induction process parameters on residual stresses and the effects of those stresses on the bending fatigue of induction hardened gears. Two existing residual stress measurement techniques, X-ray diffraction and the contour method, were adapted for induction hardened components. The residual stress measurement by X-ray diffraction technique has been significantly improved in this thesis by the consideration of the variation of the X-ray elastic constant at different locations in the hardened layer and the development of a finite element based layer removal correction method that enabled more accurate in-depth residual stress measurements in all sort of geometries. The contour method is clearly a powerful tool for residual stress mapping at the core of parts but proved to be inaccurate for near-surface measurements in the case of thin hardened layers. These methods were used to show the effects of several parameters (initial hardness, preheating, final heating, tempering) with discs and aeronautical spur gears. The results indicate that two induction treatments can sometimes produce two different residual stress distributions (amplitude, severity of gradient in the transition zone, etc.) for a similar hardened depth. The bending fatigue of those gears was studied experimentally with a single tooth bending test rig and numerically with the proposition of a fatigue model for the calculation of the bending endurance limit. The calibration of the model was based on fatigue tests results on traction and torsion specimens. Bending fatigue testing results on gears confirmed the overall accuracy of the proposed model predictions. The Crossland criterion without the gradient effect gave better predictions when compared with the experimental results for that particular case. This 3D multiaxial fatigue prediction model represents a significant improvement over previous approaches by the simultaneous consideration of the so-called gradient effect, residual stresses, surface roughness and the variation of properties caused by the surface hardening. The induction treatments used in this study improved the bending fatigue resistance of spur gears by 45 to 71 % depending on the case.

  6. A Retrospective Case-Control Study Evaluating the Role of Mifepristone for Induction of Labor in Women with Previous Cesarean Section.

    PubMed

    Sharma, Chanderdeep; Soni, Anjali; Soni, Pawan K; Verma, Suresh; Verma, Ashok; Gupta, Amit

    2016-10-01

    To investigate the role of "mifepristone" for induction of labor (IOL) in pregnant women with prior cesarean section (CS). In this retrospective study, all pregnant women with prior CS who received oral mifepristone (400 mg) for IOL (as per clear obstetric indications) [group 1] were compared with pregnant women with prior CS who had spontaneous onset of labor (SOL) [group 2], with respect to incidence of vaginal delivery, CS, duration of labor, and various maternal and fetal outcomes. During the study period, 72 women received mifepristone (group 1) for IOL and 346 had SOL (group 2). In group 1 after mifepristone administration, 40 (55.6 %) women had labor onset, and 24 (33.3 %) women had cervical ripening (Bishop Score ≥ 8) within 48 h. There were no statistically significant differences with respect to duration of labor (p value: 0.681), mode of delivery (i.e., normal delivery or CS-p value: 0.076 or 0.120, respectively), or maternal (blood loss or scar dehiscence/rupture uterus), or fetal outcomes (NICU admission) compared to women with previous CS with SOL (group 2). However, the need of oxytocin (p value 0.020) and dose of oxytocin requirement (p value 0.008) were more statistically significant in group 1. Mifepristone may be considered as an agent for IOL in women with prior CS.

  7. Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate

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

    Deng Xue; Department of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575; Yu Zhiqian

    2006-05-15

    Nitrogen-containing bisphosphonates (N-BPs), powerful anti-bone-resorptive drugs, have inflammatory side effects, while histamine is not only an inflammatory mediator, but also an immuno-modifier. In murine models, a single intraperitoneal injection of an N-BP induces various inflammatory reactions, including the induction of the histamine-forming enzyme histidine decarboxylase (HDC) in tissues important in immune responses (such as liver, lungs, spleen, and bone marrow). Lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1 and TNF are also capable of inducing HDC. We reported previously that in mice (i) the inflammatory actions of N-BPs depend on IL-1 (ii) N-BP pretreatment augments both LPS-stimulated IL-1 production and HDCmore » induction, and (iii) the co-administration of clodronate (a non-N-BP) with an N-BP inhibits the latter's inflammatory actions (including HDC induction). Here, we add the new findings that (a) pretreatment with alendronate (a typical N-BP) augments both IL-1- and TNF-induced HDC elevations, (b) LPS pretreatment augments the alendronate-induced HDC elevation, (c) co-administration of clodronate with alendronate abolishes these augmentations, (d) alendronate does not induce HDC in IL-1-deficient mice even if they are pretreated with LPS, and (e) alendronate increases IL-1{beta} in all tissues tested, but not in the serum. These results suggest that (1) there are mutual augmentations between alendronate and immuno-stimulants (IL-1, TNF, and LPS) in HDC induction, (2) tissue IL-1{beta} is important in alendronate-stimulated HDC induction, and (3) combination use of clodronate may have the potential to reduce the inflammatory effects of alendronate (we previously found that clodronate, conveniently, does not inhibit the anti-bone-resorptive activity of alendronate)« less

  8. Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression.

    PubMed

    Nijhoff, M F; Engelse, M A; Dubbeld, J; Braat, A E; Ringers, J; Roelen, D L; van Erkel, A R; Spijker, H S; Bouwsma, H; van der Boog, P J M; de Fijter, J W; Rabelink, T J; de Koning, E J P

    2016-01-01

    Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Improved efficiency and precise temperature control of low-frequency induction-heating pure iron vapor source on ECR ion source

    NASA Astrophysics Data System (ADS)

    Kato, Y.; Takenaka, T.; Yano, K.; Kiriyama, R.; Kurisu, Y.; Nozaki, D.; Muramatsu, M.; Kitagawa, A.; Uchida, T.; Yoshida, Y.; Sato, F.; Iida, T.

    2012-11-01

    Multiply charged ions to be used prospectively are produced from solid pure material in an electron cyclotron resonance ion source (ECRIS). Recently a pure iron source is also required for the production of caged iron ions in the fullerene in order to control cells in vivo in bio-nano science and technology. We adopt directly heating iron rod by induction heating (IH) because it has non-contact with insulated materials which are impurity gas sources. We choose molybdenum wire for the IH coils because it doesn't need water cooling. To improve power efficiency and temperature control, we propose to the new circuit without previously using the serial and parallel dummy coils (SPD) for matching and safety. We made the circuit consisted of inductively coupled coils which are thin-flat and helix shape, and which insulates the IH power source from the evaporator. This coupling coils circuit, i.e. insulated induction heating coil transformer (IHCT), can be move mechanically. The secondary current can be adjusted precisely and continuously. Heating efficiency by using the IHCT is much higher than those of previous experiments by using the SPD, because leakage flux is decreased and matching is improved simultaneously. We are able to adjust the temperature in heating the vapor source around melting point. And then the vapor pressure can be controlled precisely by using the IHCT. We can control ±10K around 1500°C by this method, and also recognize to controlling iron vapor flux experimentally in the extreme low pressures. Now we come into next stage of developing induction heating vapor source for materials with furthermore high temperature melting points above 2000K with the IHCT, and then apply it in our ECRIS.

  10. KSC-06pd0788

    NASA Image and Video Library

    2006-05-06

    KENNEDY SPACE CENTER, FLA. - The stage in the Apollo/Saturn V Center is lined with former NASA astronauts attending the 2006 induction ceremony for the U.S. Astronaut Hall of Fame. All of them had been previously inducted to the U.S. Astronaut Hall of Fame. They came to welcome the inductees for 2006: Henry "Hank" Hartsfield Jr., Brewster H. Shaw Jr. and Charles F. Bolden Jr. The U.S. Astronaut Hall of Fame now includes 63 space explorers. Photo credit: NASA/Kim Shiflett

  11. Enzymatic defenses against the toxicity of oxygen and of streptonigrin in Escherichia coli.

    PubMed

    Hassan, H M; Fridovich, I

    1977-03-01

    Anaerobically grown Escherichia coli K-12 contain only one superoxide dismutase and that is the iron-containing isozyme found in the periplasmic space. Exposure to oxygen caused the induction of a manganese-containing superoxide dismutase and of another, previously undescribed, superoxide dismutase, as well as of catalase and peroxidase. These inductions differed in their responsiveness towards oxygen. Thus the very low levels of oxygen present in deep, static, aerobic cultures were enough for nearly maximal induction of the manganese-superoxide dismutase. In contrast, induction of the new superoxide dismutase, catalase, and peroxidase required the much higher levels of oxygen achieved in vigorously agitated aerobic cultures. Anaerobically grown cells showed a much greater oxygen enhancement of the lethality of streptonigrin than did aerobically grown cells, in accord with the proposal that streptonigrin can serve as an intracellular source of superoxide. Anaerobically grown cells in which enzyme inductions were prevented by puromycin were damaged by exposure to air. This damage was evidenced both as a decline in viable cell count and as structural abnormalities evident under an electron microscope.

  12. The volatile emission of Eurosta solidaginis primes herbivore-induced volatile production in Solidago altissima and does not directly deter insect feeding

    PubMed Central

    2014-01-01

    Background The induction of plant defenses in response to herbivory is well documented. In addition, many plants prime their anti-herbivore defenses following exposure to environmental cues associated with increased risk of subsequent attack, including induced volatile emissions from herbivore-damaged plant tissues. Recently, we showed in both field and laboratory settings that tall goldenrod plants (Solidago altissima) exposed to the putative sex attractant of a specialist gall-inducing fly (Eurosta solidaginis) experienced less herbivory than unexposed plants. Furthermore, we observed stronger induction of the defense phytohormone jasmonic acid in exposed plants compared to controls. These findings document a novel class of plant-insect interactions mediated by the direct perception, by plants, of insect-derived olfactory cues. However, our previous study did not exclude the possibility that the fly emission (or its residue) might also deter insect feeding via direct effects on the herbivores. Results Here we show that the E. solidaginis emission does not (directly) deter herbivore feeding on Cucurbita pepo or Symphyotrichum lateriflorum plants—which have no co-evolutionary relationship with E. solidaginis and thus are not expected to exhibit priming responses to the fly emission. We also document stronger induction of herbivore-induced plant volatiles (HIPV) in S. altissima plants given previous exposure to the fly emission relative to unexposed controls. No similar effect was observed in maize plants (Zea mays), which have no co-evolutionary relationship with E. solidaginis. Conclusions Together with our previous findings, these results provide compelling evidence that reduced herbivory on S. altissima plants exposed to the emission of male E. solidaginis reflects an evolved plant response to olfactory cues associated with its specialist herbivore and does not involve direct effects of the fly emission on herbivore feeding behavior. We further discuss mechanisms by which the priming of HIPV responses documented here might contribute to enhanced S. altissima defense against galling. PMID:24947749

  13. Visualizing fossilization using laser ablation-inductively coupled plasma-mass spectrometry maps of trace elements in Late Cretaceous bones

    USGS Publications Warehouse

    Koenig, A.E.; Rogers, R.R.; Trueman, C.N.

    2009-01-01

    Elemental maps generated by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) provide a previously unavailable high-resolution visualization of the complex physicochemical conditions operating within individual bones during the early stages of diagenesis and fossilization. A selection of LA-ICP-MS maps of bones collected from the Late Cretaceous of Montana (United States) and Madagascar graphically illustrate diverse paths to recrystallization, and reveal unique insights into geochemical aspects of taphonomic history. Some bones show distinct gradients in concentrations of rare earth elements and uranium, with highest concentrations at external bone margins. Others exhibit more intricate patterns of trace element uptake related to bone histology and its control on the flow paths of pore waters. Patterns of element uptake as revealed by LA-ICP-MS maps can be used to guide sampling strategies, and call into question previous studies that hinge upon localized bulk samples of fossilized bone tissue. LA-ICP-MS maps also allow for comparison of recrystallization rates among fossil bones, and afford a novel approach to identifying bones or regions of bones potentially suitable for extracting intact biogeochemical signals. ?? 2009 Geological Society of America.

  14. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

    PubMed

    He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  15. Online Monitoring of Induction Motors

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

    McJunkin, Timothy R.; Agarwal, Vivek; Lybeck, Nancy Jean

    2016-01-01

    The online monitoring of active components project, under the Advanced Instrumentation, Information, and Control Technologies Pathway of the Light Water Reactor Sustainability Program, researched diagnostic and prognostic models for alternating current induction motors (IM). Idaho National Laboratory (INL) worked with the Electric Power Research Institute (EPRI) to augment and revise the fault signatures previously implemented in the Asset Fault Signature Database of EPRI’s Fleet Wide Prognostic and Health Management (FW PHM) Suite software. Induction Motor diagnostic models were researched using the experimental data collected by Idaho State University. Prognostic models were explored in the set of literature and through amore » limited experiment with 40HP to seek the Remaining Useful Life Database of the FW PHM Suite.« less

  16. THE EFFECT OF PENTACHLOROPHENOL ON DNA ADDUCT FORMATION IN C57B1/6 TRP53 +/+ AND C57B16 TRP53 -/- MICE EXPOSED TO BENZO[A]PYRENE MAY BE ASSOCIATED WITH P53 FUNCTION.

    EPA Science Inventory

    Abstract

    Previous studies have shown that pentachlorophenol (PCP) has both potentiative and antagonistic effects on the genotoxicity of benzo[a]pyrene (B[a]P). It has been suggested that these effects are due to inhibition and/or induction of enzymes involved in the biotr...

  17. Development of a High Resolution Liquid Xenon Imaging Telescope for Medium Energy Gamma Ray Astrophysics

    NASA Technical Reports Server (NTRS)

    Aprile, Elena

    1992-01-01

    In the third year of the research project, we have (1) tested a 3.5 liter prototype of the Liquid Xenon Time Projection Chamber, (2) used a prototype having a 4.4 cm drift gap to study the charge and energy resolution response of the 3.5 liter chamber, (3) obtained an energy resolution as good as that previously measured by us using chambers with drift gaps of the order of millimeters, (4) observed the induction signals produced by MeV gamma rays, (4) used the 20 hybrid charge sensitive preamplifiers for a nondestructive readout of the electron image on the induction wires, (5) performed extensive Monte Carlo simulations to obtain results on efficiency, background rejection capability, and source flux sensitivity, and (6) developed a reconstruction algorithm for events with multiple interaction points.

  18. Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

    PubMed

    Fan, C M; Tessier-Lavigne, M

    1994-12-30

    An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.

  19. The Increase in Mannose Receptor Recycling Favors Arginase Induction and Trypanosoma Cruzi Survival in Macrophages

    PubMed Central

    Garrido, Vanina V.; Dulgerian, Laura R.; Stempin, Cinthia C.; Cerbán, Fabio M.

    2011-01-01

    The macrophage mannose receptor (MR) is a pattern recognition receptor of the innate immune system that binds to microbial structures bearing mannose, fucose and N-acetylglucosamine on their surface. Trypanosoma cruzi antigen cruzipain (Cz) is found in the different developmental forms of the parasite. This glycoprotein has a highly mannosylated C-terminal domain that participates in the host-antigen contact. Our group previously demonstrated that Cz-macrophage (Mo) interaction could modulate the immune response against T. cruzi through the induction of a preferential metabolic pathway. In this work, we have studied in Mo the role of MR in arginase induction and in T. cruzi survival using different MR ligands. We have showed that pre-incubation of T. cruzi infected cells with mannose-Bovine Serum Albumin (Man-BSA, MR specific ligand) biased nitric oxide (NO)/urea balance towards urea production and increased intracellular amastigotes growth. The study of intracellular signals showed that pre-incubation with Man-BSA in T. cruzi J774 infected cells induced down-regulation of JNK and p44/p42 phosphorylation and increased of p38 MAPK phosphorylation. These results are coincident with previous data showing that Cz also modifies the MAPK phosphorylation profile induced by the parasite. In addition, we have showed by confocal microscopy that Cz and Man-BSA enhance MR recycling. Furthermore, we studied MR behavior during T. cruzi infection in vivo. MR was up-regulated in F4/80+ cells from T. cruzi infected mice at 13 and 15 days post infection. Besides, we investigated the effect of MR blocking antibody in T. cruzi infected peritoneal Mo. Arginase activity and parasite growth were decreased in infected cells pre-incubated with anti-MR antibody as compared with infected cells treated with control antibody. Therefore, we postulate that during T. cruzi infection, Cz may contact with MR, increasing MR recycling which leads to arginase activity up-regulation and intracellular parasite growth. PMID:22110379

  20. The transcription factor FoxB mediates temporal loss of cellular competence for notochord induction in ascidian embryos.

    PubMed

    Hashimoto, Hidehiko; Enomoto, Takashi; Enomoto, Atsushi; Kumano, Gaku; Nishida, Hiroki

    2011-06-01

    In embryos of the ascidian Halocynthia roretzi, the competence of isolated presumptive notochord blastomeres to respond to fibroblast growth factor (FGF) for induction of the primary notochord decays by 1 hour after cleavage from the 32- to 64-cell stage. This study analyzes the molecular mechanisms responsible for this loss of competence and provides evidence for a novel mechanism. A forkhead family transcription factor, FoxB, plays a role in competence decay by preventing the induction of notochord-specific Brachyury (Bra) gene expression by the FGF/MAPK signaling pathway. Unlike the mechanisms reported previously in other animals, no component in the FGF signal transduction cascade appeared to be lost or inactivated at the time of competence loss. Knockdown of FoxB functions allowed the isolated cells to retain their competence for a longer period, and to respond to FGF with expression of Bra beyond the stage at which competence was normally lost. FoxB acts as a transcription repressor by directly binding to the cis-regulatory element of the Bra gene. Our results suggest that FoxB prevents ectopic induction of the notochord fate within the cells that assume a default nerve cord fate, after the stage when notochord induction has been completed. The merit of this system is that embryos can use the same FGF signaling cascade again for another purpose in the same cell lineage at later stages by keeping the signaling cascade itself available. Temporally and spatially regulated FoxB expression in nerve cord cells was promoted by the ZicN transcription factor and absence of FGF/MAPK signaling.

  1. Anterior visceral endoderm SMAD4 signaling specifies anterior embryonic patterning and head induction in mice.

    PubMed

    Li, Cuiling; Li, Yi-Ping; Fu, Xin-Yuan; Deng, Chu-Xia

    2010-09-27

    SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediated approach. We showed that mutant embryos lack of SMAD4 in the visceral endoderm (Smad4(Co/Co);TTR-Cre) died at E7.5-E9.5 without head-fold and anterior embryonic structures. We demonstrated that TGF-β regulates expression of several genes, such as Hex1, Cer1, and Lim1, in the anterior visceral endoderm (AVE), and the failure of anterior embryonic development in Smad4(Co/Co);TTR-Cre embryos is accompanied by diminished expression of these genes. Consistent with this finding, SMAD4-deficient embryoid bodies showed impaired responsiveness to TGF-β-induced gene expression and morphological changes. On the other hand, embryos carrying Cre-loxP mediated disruption of SMAD4 in the epiblasts exhibited relatively normal mesoderm and head-fold induction although they all displayed profound patterning defects in the later stages of gastrulation. Cumulatively, our data indicate that SMAD4 signaling in the epiblasts is dispensable for mesoderm induction although it remains critical for head patterning, which is significantly different from SMAD4 signaling in the AVE, where it specifies anterior embryonic patterning and head induction.

  2. Anterior Visceral Endoderm SMAD4 Signaling Specifies Anterior Embryonic Patterning and Head Induction in Mice

    PubMed Central

    Li, Cuiling; Li, Yi-Ping; Fu, Xin-Yuan; Deng, Chu-Xia

    2010-01-01

    SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediated approach. We showed that mutant embryos lack of SMAD4 in the visceral endoderm (Smad4Co/Co;TTR-Cre) died at E7.5-E9.5 without head-fold and anterior embryonic structures. We demonstrated that TGF-β regulates expression of several genes, such as Hex1, Cer1, and Lim1, in the anterior visceral endoderm (AVE), and the failure of anterior embryonic development in Smad4Co/Co;TTR-Cre embryos is accompanied by diminished expression of these genes. Consistent with this finding, SMAD4-deficient embryoid bodies showed impaired responsiveness to TGF-β-induced gene expression and morphological changes. On the other hand, embryos carrying Cre-loxP mediated disruption of SMAD4 in the epiblasts exhibited relatively normal mesoderm and head-fold induction although they all displayed profound patterning defects in the later stages of gastrulation. Cumulatively, our data indicate that SMAD4 signaling in the epiblasts is dispensable for mesoderm induction although it remains critical for head patterning, which is significantly different from SMAD4 signaling in the AVE, where it specifies anterior embryonic patterning and head induction. PMID:20941375

  3. Out come of induction of remission in undernourished children with acute lymphoblastic leukaemia.

    PubMed

    Begum, M; Jahan, S; Tawfique, M; Mannan, M A

    2012-10-01

    Acute lymphoblastic leukaemia (ALL) is the most common childhood leukaemia. On the other hand under-nutrition is a common problem in our country. This prospective study was conducted to see the outcome of induction of remission in undernourished children with acute lymphoblastic leukaemia. This study was carried out in the department of Paediatric hematology and oncology of Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period from November 2002 to October 2004. A total of sixty (60) children who were diagnosed as acute lymphoblastic leukaemia in 1 to 15 years of age were included in this study. But the children with previous history of congenital disease and that of chemotherapy or steroid were excluded from this study. Patients were divided into two groups on the basis of Z score of weight for age. Thirty (30) children those with Z score- 2 or less were classified as undernourished and was labeled as Group A and another thirty (30) patient those Z score above-2 were classified as well nourished and was placed in Group B, After inclusion into the study, completion of induction of remission was monitored by physical examination and laboratory investigations. The result showed that mean age in Group A was 77.16 ± 7.07 months and that in Group B was 74.13 ± 5.09 months with male preponderance in both the groups. Mean body weight in Group A was 14.55 ± 0.76 Kg and that in Group B was 21.40 ± 1.05 kg (p<0.001). Children in Group A required 39.06 ± 0.72 days to complete induction but in Group B it required 31.63 ± 0.17 days (p<0.04). Hospital stay in Group A children was 52.10 ± 1.08 days and in Group B 42.37 ± 0.50 (p<0.002). The result suggested that under nutrition has an influence on the out come of induction of remission in undernourished children with acute lymphoblastic leukaemia. So appropriate measures are essential to improve nutritional status of children for successful management of ALL in children.

  4. Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion1

    PubMed Central

    Turner, Michael S.; Kane, Lawrence P.; Morel, Penelope A.

    2009-01-01

    The definitions of tolerogenic vs. immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allo-antigens. However, we have previously reported that mature DC (G4DC) prevented the onset of autoimmune diabetes whereas immature DC (GMDC) were therapeutically ineffective. In this study, islet-specific CD4+ T cells from BDC2.5 TCR Tg mice were stimulated, in the absence of exogenous cytokine, with GMDC or G4DC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both GMDC and G4DC presenting low peptide doses induced weak TCR signaling via the Akt/mTOR pathway, resulting in significant expansion of Foxp3+ Treg. Furthermore, unpulsed G4DC, but not GMDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3neg Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-Tg T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with antigen dose and inversely with Treg expansion. Studies with T cells or DC from IL-6−/− mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low antigen doses. These studies indicate that strength of Akt/mTOR signaling, a critical T cell intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production. PMID:19801514

  5. P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity.

    PubMed

    Silva, Renata; Palmeira, Andreia; Carmo, Helena; Barbosa, Daniel José; Gameiro, Mariline; Gomes, Ana; Paiva, Ana Mafalda; Sousa, Emília; Pinto, Madalena; Bastos, Maria de Lourdes; Remião, Fernando

    2015-10-01

    The induction of P-glycoprotein (P-gp), an ATP-dependent efflux pump, has been proposed as a strategy against the toxicity induced by P-gp substrates such as the herbicide paraquat (PQ). The aim of this study was to screen five newly synthetized thioxanthonic derivatives, a group known to interact with P-gp, as potential inducers of the pump's expression and/or activity and to evaluate whether they would afford protection against PQ-induced toxicity in Caco-2 cells. All five thioxanthones (20 µM) caused a significant increase in both P-gp expression and activity as evaluated by flow cytometry using the UIC2 antibody and rhodamine 123, respectively. Additionally, it was demonstrated that the tested compounds, when present only during the efflux of rhodamine 123, rapidly induced an activation of P-gp. The tested compounds also increased P-gp ATPase activity in MDR1-Sf9 membrane vesicles, indicating that all derivatives acted as P-gp substrates. PQ cytotoxicity was significantly reduced in the presence of four thioxanthone derivatives, and this protective effect was reversed upon incubation with a specific P-gp inhibitor. In silico studies showed that all the tested thioxanthones fitted onto a previously described three-feature P-gp induction pharmacophore. Moreover, in silico interactions between thioxanthones and P-gp in the presence of PQ suggested that a co-transport mechanism may be operating. Based on the in vitro activation results, a pharmacophore model for P-gp activation was built, which will be of further use in the screening for new P-gp activators. In conclusion, the study demonstrated the potential of the tested thioxanthonic compounds in protecting against toxic effects induced by P-gp substrates through P-gp induction and activation.

  6. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, actor and Master of Ceremonies Lance Henriksen (at podium) introduces four newly inducted Space Shuttle astronauts to the audience at their induction ceremony into the U.S. Astronaut Hall of Fame. From left center, they are Story Musgrave, Sally K. Ride, Daniel Brandenstein, and Robert "Hoot" Gibson. Also standing, left, is former astronaut James A. Lovell. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, actor and Master of Ceremonies Lance Henriksen (at podium) introduces four newly inducted Space Shuttle astronauts to the audience at their induction ceremony into the U.S. Astronaut Hall of Fame. From left center, they are Story Musgrave, Sally K. Ride, Daniel Brandenstein, and Robert "Hoot" Gibson. Also standing, left, is former astronaut James A. Lovell. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  7. Outcomes of Induction of Labour in Women with Previous Caesarean Delivery: A Retrospective Cohort Study Using a Population Database

    PubMed Central

    Stock, Sarah J.; Ferguson, Evelyn; Duffy, Andrew; Ford, Ian; Chalmers, James; Norman, Jane E.

    2013-01-01

    Background There is evidence that induction of labour (IOL) around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery). However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39–41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management. Methods and Findings We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981–2007 (n = 46,176). Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401) of women who underwent IOL 39–41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71–0.91]). There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08–1.55]). In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07–0.75]) and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90–1.07] at 40 weeks of 1.08 [0.94–1.23] and at 41 weeks of 0.77 [0.60–1.00]). Conclusions A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications. PMID:23565242

  8. LONGITUDINAL IMPEDANCE OF THE SQUID GIANT AXON

    PubMed Central

    Cole, Kenneth S.; Baker, Richard F.

    1941-01-01

    Longitudinal alternating current impedance measurements have been made on the squid giant axon over the frequency range from 30 cycles per second to 200 kc. per second. Large sea water electrodes were used and the inter-electrode length was immersed in oil. The impedance at high frequency was approximately as predicted theoretically on the basis of the poorly conducting dielectric characteristics of the membrane previously determined. For the large majority of the axons, the impedance reached a maximum at a low frequency and the reactance then vanished at a frequency between 150 and 300 cycles per second. Below this frequency, the reactance was inductive, reaching a maximum and then approaching zero as the frequency was decreased. The inductive reactance is a property of the axon and requires that it contain an inductive structure. The variation of the impedance with interpolar distance indicates that the inductance is in the membrane. The impedance characteristics of the membrane as calculated from the measured longitudinal impedance of the axon may be expressed by an equivalent membrane circuit containing inductance, capacity, and resistance. For a square centimeter of membrane the capacity of 1 µf with dielectric loss is shunted by the series combination of a resistance of 400 ohms and an inductance of one-fifth henry. PMID:19873252

  9. Measurements of reduced corkscrew motion on the ETA-II linear induction accelerator

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

    Allen, S.L.; Brand, H.R.; Chambers, F.W.

    1991-05-01

    The ETA-II linear induction accelerator is used to drive a microwave free electron laser (FEL). Corkscrew motion, which previously limited performance, has been reduced by: (1) an improved pulse distribution system which reduces energy sweep, (2) improved magnetic alignment achieved with a stretched wire alignment technique (SWAT) and (3) a unique magnetic tuning algorithm. Experiments have been carried out on a 20-cell version of ETA-II operating at 1500 A and 2.7 MeV. The measured transverse beam motion is less than 0.5 mm for 40 ns of the pulse, an improvement of a factor of 2 to 3 over previous results.more » Details of the computerized tuning procedure, estimates of the corkscrew phase, and relevance of these results to future FEL experiments are presented. 11 refs.« less

  10. Nonylphenol-mediated CYP induction is PXR-dependent: The use of humanized mice and human hepatocytes suggests that hPXR is less sensitive than mouse PXR to nonylphenol treatment

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

    Mota, Linda C.; Barfield, Christina; Hernandez, Juan P.

    2011-05-01

    Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75 mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined. WT mice treated with NP showed induction of Cyp2b, and male-specificmore » induction of Cyp2c and Cyp3a. CYPs were not induced in PXR-null mice, demonstrating that PXR is necessary for NP-mediated CYP induction. CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating that NP is also a CAR activator. hPXR mice only showed moderate Cyp induction, suggesting that hPXR is not as sensitive to NP as mPXR in vivo. NP-mediated Cyp3a induction from three human hepatocyte donors was not significant, confirming that hPXR is not very sensitive to NP-mediated CYP induction. Lastly, mice with PXR (mPXR and hPXR) showed lower NP serum concentrations than PXR-null mice treated with NP suggesting that PXR plays a role in decreasing liver toxicity by basally regulating phase I-III detoxification enzymes that promote the metabolism and elimination of NP. In summary, PXR is required for NP-mediated CYP-induction, mPXR mediates greater CYP induction than hPXR in vivo, and the presence of PXR, especially mPXR, is associated with altered histopathology and increased clearance of NP.« less

  11. Nonylphenol-mediated CYP induction is PXR-dependent: The use of humanized mice and human hepatocytes suggests that hPXR is less sensitive than mouse PXR to nonylphenol treatment

    PubMed Central

    Mota, Linda C; Barfield, Christina; Hernandez, Juan P; Baldwin, William S.

    2011-01-01

    Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75 mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined. WT mice treated with NP showed induction of Cyp2b, and male-specific induction of Cyp2c and Cyp3a. CYPs were not induced in PXR-null mice, demonstrating that PXR is necessary for NP-mediated CYP induction. CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating NP is also a CAR activator. hPXR mice only showed moderate Cyp induction, suggesting that hPXR is not as sensitive to NP as mPXR in vivo. NP-mediated Cyp3a induction from three human hepatocyte donors was not significant, confirming that hPXR is not very sensitive to NP-mediated CYP induction. Lastly, mice with PXR (mPXR and hPXR) showed lower NP serum concentrations than PXR-null mice treated with NP suggesting that PXR plays a role in decreasing liver toxicity by basally regulating Phase I-III detoxification enzymes that promote the metabolism and elimination of NP. In summary, PXR is required for NP-mediated CYP-induction, and mPXR mediates greater CYP induction than hPXR in vivo, and the presence of PXR, especially mPXR, is associated with altered histopathology and increased clearance of NP. PMID:21376070

  12. An episodic specificity induction enhances means-end problem solving in young and older adults.

    PubMed

    Madore, Kevin P; Schacter, Daniel L

    2014-12-01

    Episodic memory plays an important role not only in remembering past experiences, but also in constructing simulations of future experiences and solving means-end social problems. We recently found that an episodic specificity induction-brief training in recollecting details of past experiences-enhances performance of young and older adults on memory and imagination tasks. Here we tested the hypothesis that this specificity induction would also positively impact a means-end problem-solving task on which age-related changes have been linked to impaired episodic memory. Young and older adults received the specificity induction or a control induction before completing a means-end problem-solving task, as well as memory and imagination tasks. Consistent with previous findings, older adults provided fewer relevant steps on problem solving than did young adults, and their responses also contained fewer internal (i.e., episodic) details across the 3 tasks. There was no difference in the number of other (e.g., irrelevant) steps on problem solving or external (i.e., semantic) details generated on the 3 tasks as a function of age. Critically, the specificity induction increased the number of relevant steps and internal details (but not other steps or external details) that both young and older adults generated in problem solving compared with the control induction, as well as the number of internal details (but not external details) generated for memory and imagination. Our findings support the idea that episodic retrieval processes are involved in means-end problem solving, extend the range of tasks on which a specificity induction targets these processes, and show that the problem-solving performance of older adults can benefit from a specificity induction as much as that of young adults. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  13. An episodic specificity induction enhances means-end problem solving in young and older adults

    PubMed Central

    Madore, Kevin P.; Schacter, Daniel L.

    2014-01-01

    Episodic memory plays an important role not only in remembering past experiences, but also in constructing simulations of future experiences and solving means-end social problems. We recently found that an episodic specificity induction- brief training in recollecting details of past experiences- enhances performance of young and older adults on memory and imagination tasks. Here we tested the hypothesis that this specificity induction would also positively impact a means-end problem solving task on which age-related changes have been linked to impaired episodic memory. Young and older adults received the specificity induction or a control induction before completing a means-end problem solving task as well as memory and imagination tasks. Consistent with previous findings, older adults provided fewer relevant steps on problem solving than did young adults, and their responses also contained fewer internal (i.e., episodic) details across the three tasks. There was no difference in the number of other (e.g., irrelevant) steps on problem solving or external (i.e., semantic) details generated on the three tasks as a function of age. Critically, the specificity induction increased the number of relevant steps and internal details (but not other steps or external details) that both young and older adults generated in problem solving compared with the control induction, as well as the number of internal details (but not external details) generated for memory and imagination. Our findings support the idea that episodic retrieval processes are involved in means-end problem solving, extend the range of tasks on which a specificity induction targets these processes, and show that the problem solving performance of older adults can benefit from a specificity induction as much as that of young adults. PMID:25365688

  14. Liquid-phase oxidation of cyclohexanone over cerium oxide catalyst

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

    Shen, H.C.; Weng, H.S.

    Catalytic oxidation of cyclohexanone in the liquid phase with glacial acetic acid as the solvent over cerium oxide was studied between 5 and 15 atm and 98 and 118 {degrees} C in a batch reactor. The products were adipic acid, glutaric acid, succinic acid, caprolactone, carbon oxides, etc. The reaction undergoes a short induction period prior to a rapid reaction regime. In both regimes, the reaction is independent of oxygen pressure when the system pressure is above 10 atm. The induction period is inversely proportional to both of the catalyst weight and cyclohexanone concentration.During the rapid reaction regime, the reactionmore » rate was found to be proportional to the 0.5 power of the catalyst weight and to the 1.5 power of the cyclohexanone concentration. Reaction mechanisms and rate expressions are proposed. The carbon oxides produced in this study were much lower than those previously reported. The cerium oxide catalyst is stable during the reaction.« less

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

    van den Berg, R.; Brandino, G. P.; El Araby, O.

    In this study, we introduce an integrability-based method enabling the study of semiconductor quantum dot models incorporating both the full hyperfine interaction as well as a mean-field treatment of dipole-dipole interactions in the nuclear spin bath. By performing free induction decay and spin echo simulations we characterize the combined effect of both types of interactions on the decoherence of the electron spin, for external fields ranging from low to high values. We show that for spin echo simulations the hyperfine interaction is the dominant source of decoherence at short times for low fields, and competes with the dipole-dipole interactions atmore » longer times. On the contrary, at high fields the main source of decay is due to the dipole-dipole interactions. In the latter regime an asymmetry in the echo is observed. Furthermore, the non-decaying fraction previously observed for zero field free induction decay simulations in quantum dots with only hyperfine interactions, is destroyed for longer times by the mean-field treatment of the dipolar interactions.« less

  16. Competing interactions in semiconductor quantum dots

    DOE PAGES

    van den Berg, R.; Brandino, G. P.; El Araby, O.; ...

    2014-10-14

    In this study, we introduce an integrability-based method enabling the study of semiconductor quantum dot models incorporating both the full hyperfine interaction as well as a mean-field treatment of dipole-dipole interactions in the nuclear spin bath. By performing free induction decay and spin echo simulations we characterize the combined effect of both types of interactions on the decoherence of the electron spin, for external fields ranging from low to high values. We show that for spin echo simulations the hyperfine interaction is the dominant source of decoherence at short times for low fields, and competes with the dipole-dipole interactions atmore » longer times. On the contrary, at high fields the main source of decay is due to the dipole-dipole interactions. In the latter regime an asymmetry in the echo is observed. Furthermore, the non-decaying fraction previously observed for zero field free induction decay simulations in quantum dots with only hyperfine interactions, is destroyed for longer times by the mean-field treatment of the dipolar interactions.« less

  17. A study of GaN-based LED structure etching using inductively coupled plasma

    NASA Astrophysics Data System (ADS)

    Wang, Pei; Cao, Bin; Gan, Zhiyin; Liu, Sheng

    2011-02-01

    GaN as a wide band gap semiconductor has been employed to fabricate optoelectronic devices such as light-emitting diodes (LEDs) and laser diodes (LDs). Recently several different dry etching techniques for GaN-based materials have been developed. ICP etching is attractive because of its superior plasma uniformity and strong controllability. Most previous reports emphasized on the ICP etching characteristics of single GaN film. In this study dry etching of GaN-based LED structure was performed by inductively coupled plasmas (ICP) etching with Cl2 as the base gas and BCl3 as the additive gas. The effects of the key process parameters such as etching gases flow rate, ICP power, RF power and chamber pressure on the etching properties of GaN-based LED structure including etching rate, selectivity, etched surface morphology and sidewall was investigated. Etch depths were measured using a depth profilometer and used to calculate the etch rates. The etch profiles were observed with a scanning electron microscope (SEM).

  18. Involvement of Cot/Tp12 in bone loss during periodontitis.

    PubMed

    Ohnishi, T; Okamoto, A; Kakimoto, K; Bandow, K; Chiba, N; Matsuguchi, T

    2010-02-01

    Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.

  19. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    PubMed Central

    Roel, María; Rubiolo, Juan A.; Ternon, Eva; Thomas, Olivier P.; Vieytes, Mercedes R.; Botana, Luis M.

    2015-01-01

    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. PMID:26225985

  20. Inductive reasoning and doubt in obsessive compulsive disorder.

    PubMed

    O'Connor, Kieron; Wilson, Samantha; Taillon, Annie; Pélissier, Marie-Claude; Audet, Jean-Sebastien

    2018-06-01

    Previous studies show that individuals with obsessive compulsive disorder (OCD) accord more importance than healthy controls (HC) to alternative conclusions, resulting in increased doubt regarding an initial conclusion. The goal of the present study was to replicate and extend this finding. Eighteen participants diagnosed with OCD and 16 HC completed the Reasoning with Inductive Arguments Task (RIAT), which operationalizes doubt as change in confidence towards a conclusion after alternative conclusions are presented. To examine conditions that facilitate doubt, the impact of alternative conclusions that both supported and contradicted the initial conclusion was compared, as well as the effect of neutral and OCD-relevant item content. Both the OCD and HC groups decreased confidence after contradicting conclusions, but only the HC group increased confidence when presented with supporting conclusions. Furthermore, decrease in confidence in the OCD group correlated with OCD symptom severity. The RIAT could be adapted to better take into account of OCD subtypes. Doubt generation may contribute to obsessional doubting. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. PXR-dependent induction of human CYP3A4 gene expression by organochlorine pesticides.

    PubMed

    Coumoul, Xavier; Diry, Monique; Barouki, Robert

    2002-11-15

    OCP are xenobiotics which display various toxic effects on animal and human health. One of their effects is to bind and activate estrogen receptor alpha (ERalpha). We have previously studied the down-regulation of induced CYP1A1 (cytochrome P450) expression by this class of molecules in mammary carcinoma cells and shown the importance of ERalpha in this process. However, an alternative mechanism was suggested by those experiments in hepatoma cells. In this study, we have performed Northern blot and transient transfection assays in various cell lines and shown that OCP activate human pregnane X receptor (PXR) and subsequent CYP3A4 mRNA expression. This effect is mediated by the distal xenobiotic responsive element modulator of the promoter. The induction of CYP3A4 by OCP was dose-dependent within the 1-10 microM range. The data suggest that chronic exposure to OCP could alter a major metabolite pathway in human liver and putatively modify the pharmacokinetics of drugs and pollutants.

  2. Three-dimensional multiexcitation magnetoacoustic tomography with magnetic induction

    PubMed Central

    Li, Xu; Mariappan, Leo; He, Bin

    2010-01-01

    Magnetoacoustic tomography with magnetic induction (MAT-MI) is a hybrid imaging modality proposed to image electrical conductivity contrast of biological tissue with high spatial resolution. This modality combines magnetic excitations with ultrasound detection through the Lorentz force based coupling mechanism. However, previous studies have shown that MAT-MI method with single type of magnetic excitation can only reconstruct the conductivity boundaries of a sample. In order to achieve more complete conductivity contrast reconstruction, we proposed a multiexcitation MAT-MI approach. In this approach, multiple magnetic excitations using different coil configurations are applied to the object sequentially and ultrasonic signals corresponding to each excitation are collected for conductivity image reconstruction. In this study, we validate the new multiexcitation MAT-MI method for three-dimensional (3D) conductivity imaging through both computer simulations and phantom experiments. 3D volume data are obtained by utilizing acoustic focusing and cylindrical scanning under each magnetic excitation. It is shown in our simulation and experiment results that with a common ultrasound probe that has limited bandwidth we are able to correctly reconstruct the 3D relative conductivity contrast of the imaging object. As compared to those conductivity boundary images generated by previous single-excitation MAT-MI, the new multiexcitation MAT-MI method provides more complete conductivity contrast reconstruction, and therefore, more valuable information in possible clinical and research applications. PMID:21267084

  3. A characterization of the ZFL cell line and primary hepatocytes as in vitro liver cell models for the zebrafish (Danio rerio).

    PubMed

    Eide, Marta; Rusten, Marte; Male, Rune; Jensen, Knut Helge Midtbø; Goksøyr, Anders

    2014-02-01

    The zebrafish (Danio rerio) is a widely used model species in biomedical research. The ZFL cell line, established from zebrafish liver, and freshly isolated primary hepatocytes from zebrafish have been used in several toxicological studies. However, no previous report has compared and characterized these two systems at the level of gene expression. The aim of this study was to evaluate the ZFL cell line in comparison to primary hepatocytes as in vitro models for studying effects of environmental contaminants in zebrafish liver. Using quantitative real-time PCR, the basal level and transcriptional induction potential of key genes involved in toxic responses in the ZFL cell line, primary hepatocytes and whole liver from zebrafish were compared. The study showed that the ZFL cells have lower levels of mRNA of most selected genes compared to zebrafish liver. The induced gene transcription following exposure to ligand was much lower in ZFL cells compared to zebrafish primary hepatocytes at the doses tested. Importantly, oestrogen receptor and vitellogenin genes showed low basal transcription and no induction response in the ZFL cell line. In conclusion, it appears that primary hepatocytes are well suited for studying environmental contaminants including xenoestrogens, but may show large sex-dependent differences in gene transcription. The ZFL cell line shows potential in toxicological studies involving the aryl hydrocarbon receptor pathway. However, low potential for transcriptional induction of genes in general should be expected, especially notable when studying estrogenic responses. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Induction of autophagy by ARHI (DIRAS3) alters fundamental metabolic pathways in ovarian cancer models.

    PubMed

    Ornelas, Argentina; McCullough, Christopher R; Lu, Zhen; Zacharias, Niki M; Kelderhouse, Lindsay E; Gray, Joshua; Yang, Hailing; Engel, Brian J; Wang, Yan; Mao, Weiqun; Sutton, Margie N; Bhattacharya, Pratip K; Bast, Robert C; Millward, Steven W

    2016-10-26

    Autophagy is a bulk catabolic process that modulates tumorigenesis, therapeutic resistance, and dormancy. The tumor suppressor ARHI (DIRAS3) is a potent inducer of autophagy and its expression results in necroptotic cell death in vitro and tumor dormancy in vivo. ARHI is down-regulated or lost in over 60 % of primary ovarian tumors yet is dramatically up-regulated in metastatic disease. The metabolic changes that occur during ARHI induction and their role in modulating death and dormancy are unknown. We employed Nuclear Magnetic Resonance (NMR)-based metabolomic strategies to characterize changes in key metabolic pathways in both cell culture and xenograft models of ARHI expression and autophagy. These pathways were further interrogated by cell-based immunofluorescence imaging, tracer uptake studies, targeted metabolic inhibition, and in vivo PET/CT imaging. Induction of ARHI in cell culture models resulted in an autophagy-dependent increase in lactate production along with increased glucose uptake and enhanced sensitivity to glycolytic inhibitors. Increased uptake of glutamine was also dependent on autophagy and dramatically sensitized cultured ARHI-expressing ovarian cancer cell lines to glutaminase inhibition. Induction of ARHI resulted in a reduction in mitochondrial respiration, decreased mitochondrial membrane potential, and decreased Tom20 staining suggesting an ARHI-dependent loss of mitochondrial function. ARHI induction in mouse xenograft models resulted in an increase in free amino acids, a transient increase in [ 18 F]-FDG uptake, and significantly altered choline metabolism. ARHI expression has previously been shown to trigger autophagy-associated necroptosis in cell culture. In this study, we have demonstrated that ARHI expression results in decreased cellular ATP/ADP, increased oxidative stress, and decreased mitochondrial function. While this bioenergetic shock is consistent with programmed necrosis, our data indicates that the accompanying up-regulation of glycolysis and glutaminolysis is autophagy-dependent and serves to support cell viability rather than facilitate necroptotic cell death. While the mechanistic basis for metabolic up-regulation following ARHI induction is unknown, our preliminary data suggest that decreased mitochondrial function and increased metabolic demand may play a role. These alterations in fundamental metabolic pathways during autophagy-associated necroptosis may provide the basis for new therapeutic strategies for the treatment of dormant ovarian tumors.

  5. Emotional states, attentional resources, and cognitive activity: a preliminary study.

    PubMed

    Versace, R; Monteil, J M; Mailhot, L

    1993-06-01

    This study explored the link between emotional state and attentional resources. A neutral or negative emotional state was induced in 50 subjects, then they performed a path-learning task followed by a word-memorization task while reproducing the prelearned path. Memory performance was assessed on a free-recall test. Analysis indicated that a previous induction of a negative emotional state disrupted path learning. Recall was not significantly affected by the subjects' emotional states, but recall was higher for subjects who had automatized the path prior to memorizing the words.

  6. Inductive knowledge acquisition experience with commercial tools for space shuttle main engine testing

    NASA Technical Reports Server (NTRS)

    Modesitt, Kenneth L.

    1990-01-01

    Since 1984, an effort has been underway at Rocketdyne, manufacturer of the Space Shuttle Main Engine (SSME), to automate much of the analysis procedure conducted after engine test firings. Previously published articles at national and international conferences have contained the context of and justification for this effort. Here, progress is reported in building the full system, including the extensions of integrating large databases with the system, known as Scotty. Inductive knowledge acquisition has proven itself to be a key factor in the success of Scotty. The combination of a powerful inductive expert system building tool (ExTran), a relational data base management system (Reliance), and software engineering principles and Computer-Assisted Software Engineering (CASE) tools makes for a practical, useful and state-of-the-art application of an expert system.

  7. A PBPK Model to Predict Disposition of CYP3A-Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction

    PubMed Central

    Ke, A B; Nallani, S C; Zhao, P; Rostami-Hodjegan, A; Unadkat, J D

    2012-01-01

    Besides logistical and ethical concerns, evaluation of safety and efficacy of medications in pregnant women is complicated by marked changes in pharmacokinetics (PK) of drugs. For example, CYP3A activity is induced during the third trimester (T3). We explored whether a previously published physiologically based pharmacokinetic (PBPK) model could quantitatively predict PK profiles of CYP3A-metabolized drugs during T3, and discern the site of CYP3A induction (i.e., liver, intestine, or both). The model accounted for gestational age-dependent changes in maternal physiological function and hepatic CYP3A activity. For model verification, mean plasma area under the curve (AUC), peak plasma concentration (Cmax), and trough plasma concentration (Cmin) of midazolam (MDZ), nifedipine (NIF), and indinavir (IDV) were predicted and compared with published studies. The PBPK model successfully predicted MDZ, NIF, and IDV disposition during T3. A sensitivity analysis suggested that CYP3A induction in T3 is most likely hepatic and not intestinal. Our PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism. PMID:23835883

  8. Knowledge discovery from structured mammography reports using inductive logic programming.

    PubMed

    Burnside, Elizabeth S; Davis, Jesse; Costa, Victor Santos; Dutra, Inês de Castro; Kahn, Charles E; Fine, Jason; Page, David

    2005-01-01

    The development of large mammography databases provides an opportunity for knowledge discovery and data mining techniques to recognize patterns not previously appreciated. Using a database from a breast imaging practice containing patient risk factors, imaging findings, and biopsy results, we tested whether inductive logic programming (ILP) could discover interesting hypotheses that could subsequently be tested and validated. The ILP algorithm discovered two hypotheses from the data that were 1) judged as interesting by a subspecialty trained mammographer and 2) validated by analysis of the data itself.

  9. Mask induction despite circuit obstruction: an unrecognized hazard of relying on automated machine check technology.

    PubMed

    Yang, Kamie K; Lewis, Ian H

    2014-06-15

    Various equipment malfunctions of anesthesia gas delivery systems have been previously reported. Our profession increasingly uses technology as a means to prevent these errors. We report a case of a near-total anesthesia circuit obstruction that went undetected before the induction of anesthesia despite the use of automated machine check technology. This case highlights that automated machine check modules can fail to detect severe equipment failure and demonstrates how, even in this era of expanding technology, manual checks still remain essential components of safe care.

  10. A critical incident report: Propofol triggered anaphylaxis

    PubMed Central

    Koul, Archna; Jain, Rashmi; Sood, Jayashree

    2011-01-01

    Although propofol is one of the most commonly used drugs for induction of anaesthesia, it is not devoid of anaphylactic potential. Early detection of any suspected anaphylactic reaction during anaesthesia, prompt management, identification of the offending agent and prevention of exposure to the offending agent in the future is the responsibility of the anaesthesiologist. This is a case report of anaphylaxis to propofol at the induction of anaesthesia in a previously non-allergic 56 year-old man, planned to undergo laparoscopic nephrectomy, who responded to epinephrine infusion. PMID:22174476

  11. Impact of novel polymorphisms related to cytotoxicity of cytarabine in the induction treatment of acute myeloid leukemia.

    PubMed

    Megías-Vericat, Juan E; Montesinos, Pau; Herrero, María J; Moscardó, Federico; Bosó, Virginia; Martínez-Cuadrón, David; Poveda, José L; Sanz, Miguel Á; Aliño, Salvador F

    2017-07-01

    Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy and toxicity was analyzed. Six of polymorphisms with clinical significance in the previous study [rs12036333, rs10758713, rs9883101, rs6550826, IRX2: rs2897047, mutated in colorectal cancers (MCC): rs7729269] were analyzed in a cohort of 225 adult patients at initial diagnosis of AML treated with an induction scheme of idarubicin plus cytarabine. The variant alleles of rs12036333 and rs10758713 confirmed the previous associations with lower survival rates. The minor alleles of rs9883101 and rs6550826 were also related to lower survival, in concordance with higher cytarabine-induced cytotoxicity observed in pediatric patients. However, discordant findings between AML adult and pediatric population were observed with IRX2 rs2897047, showing higher survival in heterozygous genotype carriers. The heterozygous genotype of MCC rs7729269 was associated with higher cytarabine-induced toxicities (renal, hepatic, lung, skin toxicities), whereas lower time to thrombocytopenia recovery was associated with the MCC rs7729269 minor allele. This study confirms the influence in survival rates of these polymorphisms in an adult AML population. Novel associations between MCC SNPs and cytarabine toxicities were reported and should be validated in prospective studies involving larger groups of patients.

  12. Live Attenuated Leishmania donovani Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model.

    PubMed

    Banerjee, Antara; Bhattacharya, Parna; Dagur, Pradeep K; Karmakar, Subir; Ismail, Nevien; Joshi, Amritanshu B; Akue, Adovi D; KuKuruga, Mark; McCoy, John Philip; Dey, Ranadhir; Nakhasi, Hira L

    2018-01-01

    No vaccine exists against visceral leishmaniasis. To develop effective vaccines, we have previously reported protective role of live attenuated centrin gene-deleted Leishmania donovani ( LdCen -/- ) parasites through induction of Th1 type immune response in mice, hamsters, and dogs. In this study, we specifically explored the role of Th17 cells in LdCen -/- -induced host protection in mice. Our results showed that compared with wild-type L. donovani infection, LdCen -/- parasites induce significantly higher expression of Th17 differentiation cytokines in splenic dendritic cells. There was also induction of IL-17 and its promoting cytokines in total splenocytes and in both CD4 and CD8 T cells following immunization with LdCen -/- Upon challenge with wild-type parasites, IL-17 and its differentiating cytokines were significantly higher in LdCen -/- -immunized mice compared with nonimmunized mice that resulted in parasite control. Alongside IL-17 induction, we observed induction of IFN-γ-producing Th1 cells as reported earlier. However, Th17 cells are generated before Th1 cells. Neutralization of either IL-17 or IFN-γ abrogated LdCen -/- -induced host protection further confirming the essential role of Th17 along with Th1 cytokines in host protection. Treatment with recombinant IL-23, which is required for stabilization and maintenance of IL-17, heightened Th17, and Tc17 responses in immunized mice splenocytes. In contrast, Th17 response was absent in immunized IL-23R -/- mice that failed to induce protection upon virulent Leishmania challenge suggesting that IL-23 plays an essential role in IL-17-mediated protection by LdCen -/- parasites. This study unveiled the role of IL-23-dependent IL-17 induction in LdCen -/- parasite-induced immunity and subsequent protection against visceral leishmaniasis.

  13. Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis

    PubMed Central

    Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Mehler, Mark F.

    2013-01-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages of neural induction, whereas mHtt enhances this process and promotes precocious neurogenesis and oligodendrocyte progenitor cell elaboration. PMID:23691206

  14. Evaluation of inductively heated ferromagnetic alloy implants for therapeutic interstitial hyperthermia.

    PubMed

    Paulus, J A; Richardson, J S; Tucker, R D; Park, J B

    1996-04-01

    Ferromagnetic alloys heated by magnetic induction have been investigated as interstitial hyperthermia delivery implants for over a decade, utilizing low Curie temperatures to provide thermal self-regulation. The minimally invasive method is attractive for fractionated thermal treatment of tumors which are not easily heated by focused microwave or ultrasound techniques. Past analyses of ferromagnetic seeds by other authors depict poor experimental correlation with theoretical heating predictions. Improvements in computer hardware and commercially available finite element analysis software have simplified the analysis of inductively heated thermal seeds considerably. This manuscript examines end effects of finite length implants and nonlinear magnetic material properties to account for previous inconsistencies. Two alloys, Ni-28 wt% Cu (NiCu) and Pd-6.15 wt% Co (PdCo), were used for comparison of theoretical and experimental calorimetric results. Length to diameter (L/d) ratios of over 20 for cylindrical seeds are necessary for minimization of end effects. Magnetic properties tested for alloys of NiCu and PdCo illustrate considerable nonlinearity of these materials in field strength ranges used for induction heating. Field strength dependent magnetic permeabilities and calorimetric data illustrate that more detailed material information must be included to accurately estimate induction power loss for these implants.

  15. c-fos is induced in the hippocampus during consolidation of sexual imprinting in the zebra finch (Taeniopygia guttata).

    PubMed

    Sadananda, Monika; Bischof, Hans-Joachim

    2004-01-01

    c-fos was used to mark regions of enhanced neuronal activity during sexual imprinting, an early learning process by which information about the prospective sexual partner is acquired and consolidated. In the present study, we demonstrate that the hippocampus, already known for its specialized spatial memory capacities in navigating pigeons and in food-storing birds, depicts a selective differential c-fos induction in a situation shown to lead to sexual imprinting, that is, exposing previously isolated male birds to a female for 1 h. c-fos induction is lateralized, the left hippocampus showing more c-fos activity than the right. Our results would indicate a role for the hippocampus in the consolidation process of imprinting, probably in the transfer of information to the other telencephalic areas that show alterations in synaptic connectivity as a result of consolidation of sexual imprinting.

  16. Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

    PubMed

    Pinkerton, C R; Blanc Vincent, M P; Bergeron, C; Fervers, B; Philip, T

    2000-09-01

    The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy.

  17. First-Year Undergraduate Induction: Who Attends and How Important Is Induction for First Year Attainment?

    ERIC Educational Resources Information Center

    Murtagh, S.; Ridley, A.; Frings, D.; Kerr-Pertic, S.

    2017-01-01

    The first year of study in higher education is a time of major transition for students. While the importance of induction has been widely demonstrated, there is evidence to suggest that not all students benefit equally from participation in induction. This study examined attendance rates at induction, the relationship between induction attendance…

  18. Re-evaluation of rhodopsin's relaxation kinetics determined from femtosecond stimulated Raman lineshapes.

    PubMed

    McCamant, David W

    2011-07-28

    This work presents a theoretical treatment of the vibrational line shape generated in a femtosecond stimulated Raman spectroscopy (FSRS) experiment under conditions in which the probed vibration undergoes a significant frequency shift during its free induction decay. This theory is applied to simulate the FSRS lineshapes previously observed in rhodopsin (Kukura et al. Science 2005, 310, 1006). The previously determined relaxation times for formation of the trans-photoproduct of rhodopsin were calculated using an incorrect equation for the time dependence of the observed frequency shifts. Here the data are reanalyzed by calculation of the corrected frequency sweep occurring during the vibrational free induction decay. It is shown that the calculated frequency shifts and general conclusions of the original work are sound but that the coherent vibrational frequency shifts of the C(10), C(11), and C(12) hydrogen-out-of-plane vibrations occur with a 140 fs time constant rather than the previously reported 325 fs time constant. This time constant provides an important constraint for models of the dynamics of the cis to trans isomerization process. © 2011 American Chemical Society

  19. Metal-metal interaction mediates the iron induction of Drosophila MtnB

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

    Qiang, Wenjia; Huang, Yunpeng; Wan, Zhihui

    Metallothionein (MT) protein families are a class of small and universal proteins rich in cysteine residues. They are synthesized in response to heavy metal stresses to sequester the toxic ions by metal-thiolate bridges. Five MT family members, namely MtnA, MtnB, MtnC, MtnD and MtnE, have been discovered and identified in Drosophila. These five isoforms of MTs are regulated by metal responsive transcription factor dMTF-1 and play differentiated but overlapping roles in detoxification of metal ions. Previous researches have shown that Drosophila MtnB responds to copper (Cu), cadmium (Cd) and zinc (Zn). Interestingly in this study we found that Drosophila MtnBmore » expression also responds to elevated iron levels in the diet. Further investigations revealed that MtnB plays limited roles in iron detoxification, and the direct binding of MtnB to ferrous iron in vitro is also weak. The induction of MtnB by iron turns out to be mediated by iron interference of other metals, because EDTA at even a partial concentration of that of iron can suppress this induction. Indeed, in the presence of iron, zinc homeostasis is altered, as reflected by expression changes of zinc transporters dZIP1 and dZnT1. Thus, iron-mediated MtnB induction appears resulting from interrupted homeostasis of other metals such as zinc, which in turns induced MtnB expression. Metal-metal interaction may more widely exist than we expected. - Highlights: • Metallothionein B expression is regulated by iron in Drosophila melanogaster. • MtnB has limited physiological roles in iron detoxification. • Binding affinity of MtnB to iron is weak in vitro. • Induction of Drosophila MtnB by iron is mediated indirectly through metal-metal interaction.« less

  20. Comparative molecular field analysis to derive pharmacophore maps for induction doses of intravenous anaesthetic agents.

    PubMed

    Sear, J W

    2011-03-01

    The present study examines the molecular basis of induction of anaesthesia by i.v. hypnotic agents using comparative molecular field analysis (CoMFA). ED(50) induction doses for 14 i.v. anaesthetics in human subjects (expressed as molar dose per kilogram body weight) were obtained from the literature. Immobilizing potency data for the same 14 agents (expressed as the EC(50) plasma free drug concentrations that abolish movement in response to a noxious stimulus in 50% patients) were taken from our previous publication. These data were used to form CoMFA models for the two aspects of anaesthetic activity. Molecular alignment was achieved by field-fit minimization techniques. The lead structure for both models was eltanolone. The final CoMFA model for the ED(50) induction dose was based on two latent variables, and explained 99.3% of the variance in observed activities. It showed good intrinsic predictability (cross-validated q(2)=0.849). The equivalent model for immobilizing activity was also based on two latent variables, with r(2)=0.988 and q(2)=0.852. Although there was a correlation between -log ED(50) and -log EC(50) (r(2)=0.779), comparison of the pharmacophore maps showed poor correlation for both electrostatic and steric regions when isocontours were constructed by linking lattice grid points, making the greatest 40% contributions; the relative contributions of electrostatic and steric interactions differing between the models (induction dose: 2.5:1; immobilizing activity 1.8:1). Comparison of two CoMFA activity models shows only small elements of commonality, suggesting that different molecular features may be responsible for these two properties of i.v. anaesthetics.

  1. Measurements and analysis of dynamic effects in the LARP model quadrupole HQ02b during rapid discharge

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

    Sorbi, Massimo; Ambrosio, Giorgio; Bajas, Hugo

    This paper presents the analysis of some quench tests addressed to study the dynamic effects in the 1-m-long 120-mm-aperture Nb 3Sn quadrupole magnet, i.e., HQ02b, designed, fabricated, and tested by the LHC Accelerator Research Program. The magnet has a short sample gradient of 205 T/m at 1.9 K and a peak field of 14.2 T. The test campaign has been performed at CERN in April 2014. In the specific tests, which were dedicated to the measurements of the dynamic inductance of the magnet during the rapid current discharge for a quench, the protection heaters were activated only in some windings,more » in order to obtain the measure of the resistive and inductive voltages separately. The analysis of the results confirms a very low value of the dynamic inductance at the beginning of the discharge, which later approaches the nominal value. Indications of dynamic inductance variation were already found from the analysis of current decay during quenches in the previous magnets HQ02a and HQ02a2; however, with this dedicated test of HQ02b, a quantitative measurement and assessment has been possible. An analytical model using interfilament coupling current influence for the inductance lowering has been implemented in the quench calculation code QLASA, and the comparison with experimental data is given. In conclusion, the agreement of the model with the experimental results is very good and allows predicting more accurately the critical parameters in quench analysis (MIITs, hot spot temperature) for the MQXF Nb3Sn quadrupoles, which will be installed in the High Luminosity LHC.« less

  2. Protein synthesis in TE 671/RD (human rabdomiosarcoma) cells treated with thapsigargin and hyperthermia: impairment of HSP 70 induction.

    PubMed

    Delpino, A; Piselli, P; Mangano, G

    1995-01-01

    In this study we considered the quantitative and qualitative changes of protein synthetic activity occurring in TE 671/RD cells treated with thapsigargin (TG), with hyperthermia (HT) or with a combination of both these agents. In cells treated with TG (100 nM, continuous exposure), the overall protein synthetic activity was initially inhibited but subsequently recovered to about 60% of the initial level. Chronic TG exposure was also able to induce the expression of GRP 78. The rate of synthesis of GRP 78, after a lag period of about 2 h, increased gradually to reach a maximum (9-fold induction) after 6 h of TG-treatment and was then maintained at that level up to 18 h. A weak induction of GRP 94 was observed following 6-8 h of continuous exposure to TG. In cells treated with HT (43 degrees C for 30 min), a typical heat shock response was observed: in particular, the relative rate of synthesis of HSP 70 (the major heat-inducible mammalian heat shock protein) was increased 10-fold over the constitutive level. The heat-promoted induction of HSP 70 was significantly reduced by concomitant or previous exposure to TG. When TG and HT were administred simultaneously, the increase in HSP 70 synthesis was only 4.7-fold over the control level, while in cells pre-treated for 1 h with TG before the hyperthermic challenge the rate of HSP 70 synthesis was only stimulated 2-fold. In both these conditions, by contrast, it was apparent that HT did not affect the TG-promoted induction of GRP 78. The correlations between the TG-induced mobilization of cytosolic Ca2+ and the effects on protein synthesis are discussed.

  3. Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes.

    PubMed

    Rex, Maria; Hilton, Emma; Old, Robert

    2002-03-01

    We have investigated the induction of the six Xenopus nodal-related genes, Xnr1-Xnr6, by maternal determinants. The beta-catenin pathway was modelled by stimulation using Xwnt8, activin-like signalling was modelled by activin, and VegT action was studied by overexpression in animal cap explants. Combinations of factors were examined, and previously unrecognised interactions were revealed in animal caps and whole embryos. For the induction of Xnr5 and Xnr6 in whole embryos, using a beta-catenin antisense morpholino oligonucleotide or a dominant negative XTcf3, we have demonstrated an absolute permissive requirement for the beta-catenin/Tcf pathway, in addition to the requirement for VegT action. In animal caps Xnr5 and Xnr6 are induced in response to VegT overexpression, and this induction is dependent upon the concomitant activation of the beta-catenin pathway that VegT initiates in animal caps. For the induction of Xnr3, VegT interacts negatively so as to inhibit the induction otherwise observed with wnt-signalling alone. The negative effect of VegT is not the result of a general inhibition of wnt-signalling, and does not result from an inhibition of wnt-induced siamois expression. A 294 bp proximal promoter fragment of the Xnr3 gene is sufficient to mediate the negative effect of VegT. Further experiments, employing cycloheximide to examine the dependence of Xnr gene expression upon proteins translated after the mid-blastula stage, demonstrated that Xnrs 4, 5 and 6 are 'primary' Xnr genes whose expression in the late blastula is solely dependent upon factors present before the mid-blastula stage.

  4. Measurements and analysis of dynamic effects in the LARP model quadrupole HQ02b during rapid discharge

    DOE PAGES

    Sorbi, Massimo; Ambrosio, Giorgio; Bajas, Hugo; ...

    2016-06-01

    This paper presents the analysis of some quench tests addressed to study the dynamic effects in the 1-m-long 120-mm-aperture Nb 3Sn quadrupole magnet, i.e., HQ02b, designed, fabricated, and tested by the LHC Accelerator Research Program. The magnet has a short sample gradient of 205 T/m at 1.9 K and a peak field of 14.2 T. The test campaign has been performed at CERN in April 2014. In the specific tests, which were dedicated to the measurements of the dynamic inductance of the magnet during the rapid current discharge for a quench, the protection heaters were activated only in some windings,more » in order to obtain the measure of the resistive and inductive voltages separately. The analysis of the results confirms a very low value of the dynamic inductance at the beginning of the discharge, which later approaches the nominal value. Indications of dynamic inductance variation were already found from the analysis of current decay during quenches in the previous magnets HQ02a and HQ02a2; however, with this dedicated test of HQ02b, a quantitative measurement and assessment has been possible. An analytical model using interfilament coupling current influence for the inductance lowering has been implemented in the quench calculation code QLASA, and the comparison with experimental data is given. In conclusion, the agreement of the model with the experimental results is very good and allows predicting more accurately the critical parameters in quench analysis (MIITs, hot spot temperature) for the MQXF Nb3Sn quadrupoles, which will be installed in the High Luminosity LHC.« less

  5. Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction

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

    Seo, Kyuhwa; Seo, Suho; Han, Jae Yun

    2014-10-15

    Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restoredmore » mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. - Highlights: • Resveratrol decreased methylglyoxal-induced apoptosis. • Resveratrol attenuated GSH depletion and ROS production promoted by methylglyoxal. • Resveratrol restored the mitochondrial function by Sestrin2 induction. • Induction of Sestrin2 prevented methylglyoxal-induced GSH depletion in liver.« less

  6. Cereal crop volatile organic compound induction after mechanical injury, beetle herbivory (Oulema spp.), or fungal infection (Fusarium spp.).

    PubMed

    Piesik, Dariusz; Pańka, Dariusz; Delaney, Kevin J; Skoczek, Agata; Lamparski, Robert; Weaver, David K

    2011-06-15

    Herbivory, mechanical injury or pathogen infestation to vegetative tissues can induce volatile organic compounds (VOCs) production, which can provide defensive functions to injured and uninjured plants. In our studies with 'McNeal' wheat, 'Otana' oat, and 'Harrington' barley, plants that were mechanically injured, attacked by either of two Oulema spp. (melanopus or cyanella) beetles, or infected by one of the three Fusarium spp. (graminearum, avenaceum, or culmorum), had significant VOC induction compared to undamaged plants. Mechanical injury to the main stem or one leaf caused the induction of one green leaf volatile (GLV) - (Z)-3-hexenol, and three terpenes (β-linalool, β-caryophyllene, and α-pinene) with all three grasses; wheat and barley also showed β-linalool oxide induction. The blend of induced VOCs after Fusarium spp. infestation or Oulema spp. herbivory was dominated by GLVs ((Z)-3-hexenal, (E)-2-hexenal, (E)-2-hexenol, (Z)-3-hexenyl acetate, and 1-hexenyl acetate) and β-linalool and β-caryophyllene; beetle herbivory also induced (E)-β-farnesene. Different ratios of individual VOCs were induced between the two Oulema spp. for each cereal grass and different ratios across the three cereals for each beetle species. Also, different ratios of individual VOCs were induced between the three Fusarium spp. for each cereal grass and different ratios across the three cereals for each fungal pathogen species. Our results are preliminary since we could not simultaneously measure VOC induction from controls with each of the ten different injury treatments for each of the three cereals. However, the comparison of mechanical injury, insect herbivory, and fungal infection has not been previously examined with VOC responses from three different plant species within the same family. Also, our work suggests large qualitative and quantitative overlap of VOC induction from plants of all three cereals having beetle herbivory injury when compared to infection injury from necrotrophic fungal pathogens. Copyright © 2010 Elsevier GmbH. All rights reserved.

  7. P143 proteins from heterologous nucleopolyhedroviruses induce apoptosis in BM-N cells derived from the silkworm Bombyx mori.

    PubMed

    Hamajima, Rina; Kobayashi, Michihiro; Ikeda, Motoko

    2017-04-02

    We previously demonstrated that ribosomal RNA (rRNA) of Bombyx mori BM-N cells is rapidly degraded upon infection with heterologous nucleopolyhedroviruses (NPVs), including Autographa californica multiple NPV (AcMNPV), Hyphantria cunea MNPV, Spodoptera exigua MNPV and S. litura MNPV, and that this response is triggered by viral P143 proteins. The transient expression of P143 proteins from heterologous NPVs was also shown to induce apoptosis and caspase-3-like protease activation in BM-N cells. In the present study, we conducted a transient expression assay using BM-N cells expressing mutant AcMNPV P143 (Ac-P143) proteins and demonstrated that five amino acid residues cooperatively participate in Ac-P143 protein-triggered apoptosis of BM-N cells. Notably, these five residues were previously shown to be required for triggering rRNA degradation in BM-N cells. As rRNA degradation in BM-N cells does not result from apoptosis, the present results suggest that Ac-P143-triggered rRNA degradation is the upstream signal for apoptosis induction in BM-N cells. We further showed that P143 protein-triggered apoptosis does not occur in S. frugiperda Sf9 or Lymantria dispar Ld652Y cells, indicating that apoptosis induction by heterologous P143 proteins is a BM-N cell-specific response. In addition, the observed induction of apoptosis in BM-N cells was found to be mediated by activation of the initiator caspase Bm-Dronc. Taken together, these results suggest that BM-N cells evolved a unique antiviral system that recognizes heterologous NPV P143 proteins to induce rRNA degradation and caspase-dependent apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Kinetics of micronucleus induction and cytotoxicity caused by distinct antineoplastics and alkylating agents in vivo.

    PubMed

    Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia

    2014-01-30

    This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Robert "Hoot" Gibson (at podium) addresses the audience at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are actor and Master of Ceremonies Lance Henriksen and former astronaut John H. Glenn. Also being inducted with Gibson are Space Shuttle astronauts Daniel Brandenstein, Story Musgrave, and Sally K. Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

    NASA Image and Video Library

    2003-06-21

    KENNEDY SPACE CENTER, FLA. - At the KSC Visitor Complex, former astronaut Robert "Hoot" Gibson (at podium) addresses the audience at his induction ceremony into the U.S. Astronaut Hall of Fame. Also standing is former astronaut James A. Lovell. Seated on the dais, from left, are actor and Master of Ceremonies Lance Henriksen and former astronaut John H. Glenn. Also being inducted with Gibson are Space Shuttle astronauts Daniel Brandenstein, Story Musgrave, and Sally K. Ride. Conceived by six of the Mercury Program astronauts, the U.S. Astronaut Hall of Fame opened in 1990 to provide a place where space travelers could be remembered for their participation and accomplishments in the U.S. space program. The four new inductees join 48 previously honored astronauts from the ranks of the Gemini, Apollo, Skylab, Apollo-Soyuz, and Space Shuttle programs.

  10. Induction of insulin-producing cells from human pancreatic progenitor cells.

    PubMed

    Noguchi, H; Naziruddin, B; Shimoda, M; Fujita, Y; Chujo, D; Takita, M; Peng, H; Sugimoto, K; Itoh, T; Tamura, Y; Olsen, G S; Kobayashi, N; Onaca, N; Hayashi, S; Levy, M F; Matsumoto, S

    2010-01-01

    We previously established a mouse pancreatic stem cell line without genetic manipulation. In this study, we sought to identify and isolate human pancreatic stem/progenitor cells. We also tested whether growth factors and protein transduction of pancreatic and duodenal homeobox factor-1 (PDX-1) and BETA2/NeuroD into human pancreatic stem/progenitor cells induced insulin or pancreas-related gene expressions. Human pancreata from brain-dead donors were used for islet isolation with the standard Ricordi technique modified by the Edmonton protocol. The cells from a duct-rich population were cultured in several media, based on those designed for mouse pancreatic or for human embryonic stem cells. To induce cell differentiation, cells were cultured for 2 weeks with exendin-4, nicotinamide, keratinocyte growth factor, PDX-1 protein, or BETA2/NeuroD protein. The cells in serum-free media showed morphologies similar to a mouse pancreatic stem cell line, while the cells in the medium for human embryonic stem cells formed fibroblast-like morphologies. The nucleus/cytoplasm ratios of the cells in each culture medium decreased during the culture. The cells stopped dividing after 30 days, suggesting that they had entered senescence. The cells treated with induction medium differentiated into insulin-producing cells, expressing pancreas-related genes. Duplications of cells from a duct-rich population were limited. Induction therapy with several growth factors and transduction proteins might provide a potential new strategy for induction of transplantable insulin-producing cells. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Mechanisms of modafinil: A review of current research

    PubMed Central

    Gerrard, Paul; Malcolm, Robert

    2007-01-01

    The novel wake-promoting agent modafinil has been in use for the treatment of several sleep disorders for a few years and is now undergoing clinical trials for its use in the treatment of stimulant addiction, but its primary mechanism of action remains elusive. Previous laboratory studies have shown that modafinil has antioxidative and neuroprotective effects, which have not previously been suggested to be related to its wake-promoting effects. However, recent research indicates that free radicals may be related to sleep induction as well as cellular damage, suggesting that a common target of action may mediate modafinil’s ability to oppose both of these effects. In this review we summarize and discuss previously published research on modafinil’s neural, cytoprotective, and cognitive effects, and we propose possible primary biochemical targets that could underlie the effects of modafinil observed in these studies. We also suggest neurocognitive mechanisms responsible for modafinil’s cognitive enhancing effects and its therapeutic potential in the treatment of stimulant addiction. PMID:19300566

  12. INDUCTION OF CYP1A1 AD CYP1B1 AND FORMATION OF DNA ADDUCTS IN C57BL/6, BALB/C, AND F1 MICE FOLLOWING IN UTERO EXPOSURE TO 3-METHYLCHOLANTHRENE

    EPA Science Inventory

    Fetal mice are more sensitive to chemical carcinogens than are adults. Previous studies from our laboratory demonstrated differences in the mutational spectrum induced in the Ki-ras gene from lung tumors isolated from [D2 x B6D2F1]F2 mice and Balb/c mice treated in utero with 3�m...

  13. How MMPs Impact Bone Responses to Metastatic Prostate Cancer

    DTIC Science & Technology

    2011-04-30

    various tumor cell types including myeloma ( Barille et al., 1997; Vacca et al., 1998; Barille et al., 1999; Vacca et al., 1999). Previous studies have...useful in vivo mouse model of human multiple myeloma. Hematol. J. 1, 351-356. Barille , S., Akhoundi, C., Collette, M., Mellerin, M. P., Rapp, M. J...activation of proMMP-2, and induction of MMP-1 by myeloma cells. Blood 90, 1649-1655. Barille , S., Bataille, R., Rapp, M. J., Harousseau, J. L. and Amiot, M

  14. Adenovirus-Mediated p202 Gene Transfer in Breast Cancer Gene Therapy

    DTIC Science & Technology

    2005-05-01

    transcriptional regulation of genes important for cell cycle control, differentiation, and apoptosis (1, 3, 4). Our previous studies have shown that p202...leads to induction of p53 and activation of p53 target gene (e.g., p21 CIP 1). 10. The positive regulation of p53 by IFIXcd can be observed only in...cancers. Together, our data suggest that both Ad-p202 and IFIX may be further developed into efficient therapeutic agents for human cancer gene

  15. Induction of a feed forward pro-apoptotic mechanistic loop by nitric oxide in a human breast cancer model.

    PubMed

    Sen, Suvajit; Kawahara, Brian; Fukuto, Jon; Chaudhuri, Gautam

    2013-01-01

    We have previously demonstrated that relatively high concentrations of NO [Nitric Oxide] as produced by activated macrophages induced apoptosis in the human breast cancer cell line, MDA-MB-468. More recently, we also demonstrated the importance of endogenous H2O2 in the regulation of growth in human breast cancer cells. In the present study we assessed the interplay between exogenously administered NO and the endogenously produced reactive oxygen species [ROS] in human breast cancer cells and evaluated the mechanism[s] in the induction of apoptosis. To this end we identified a novel mechanism by which NO down regulated endogenous hydrogen peroxide [H2O2] formation via the down-regulation of superoxide [O2 (.-)] and the activation of catalase. We further demonstrated the existence of a feed forward mechanistic loop involving protein phosphatase 2A [PP2A] and its downstream substrate FOXO1 in the induction of apoptosis and the synthesis of catalase. We utilized gene silencing of PP2A, FOXO1 and catalase to assess their relative importance and key roles in NO mediated apoptosis. This study provides the potential for a therapeutic approach in treating breast cancer by targeted delivery of NO where NO donors and activators of downstream players could initiate a self sustaining apoptotic cascade in breast cancer cells.

  16. Induction of a Feed Forward Pro-Apoptotic Mechanistic Loop by Nitric Oxide in a Human Breast Cancer Model

    PubMed Central

    Sen, Suvajit; Kawahara, Brian; Fukuto, Jon; Chaudhuri, Gautam

    2013-01-01

    We have previously demonstrated that relatively high concentrations of NO [Nitric Oxide] as produced by activated macrophages induced apoptosis in the human breast cancer cell line, MDA-MB-468. More recently, we also demonstrated the importance of endogenous H2O2 in the regulation of growth in human breast cancer cells. In the present study we assessed the interplay between exogenously administered NO and the endogenously produced reactive oxygen species [ROS] in human breast cancer cells and evaluated the mechanism[s] in the induction of apoptosis. To this end we identified a novel mechanism by which NO down regulated endogenous hydrogen peroxide [H2O2] formation via the down-regulation of superoxide [O2 .−] and the activation of catalase. We further demonstrated the existence of a feed forward mechanistic loop involving protein phosphatase 2A [PP2A] and its downstream substrate FOXO1 in the induction of apoptosis and the synthesis of catalase. We utilized gene silencing of PP2A, FOXO1 and catalase to assess their relative importance and key roles in NO mediated apoptosis. This study provides the potential for a therapeutic approach in treating breast cancer by targeted delivery of NO where NO donors and activators of downstream players could initiate a self sustaining apoptotic cascade in breast cancer cells. PMID:23950968

  17. Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones as a general cellular response to stress.

    PubMed

    Jordão, Rita; Campos, Bruno; Lemos, Marco F L; Soares, Amadeu M V M; Tauler, Romà; Barata, Carlos

    2016-06-01

    Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia magna. Previous results characterized gene transcripts of genes encoding and efflux activities of four putative ABCB1 and ABCC transporters that were chemically induced but showed low specificity against model transporter substrates and inhibitors, thus preventing us from distinguishing between activities of different efflux transporter types. In this study we report on the specificity of induction of ABC transporters and of the stress protein hsp70 in clones selected to be genetically resistant to ABCB1 chemical substrates. Clones resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive transcriptional responses of transporter protein coding genes and of putative transporter dye activities. Expression of hsp70 proteins also varied across resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene transporter and of putative dye transporter activity were also induced to a greater extent in the pentachlorophenol resistant clone. Observed higher dye transporter activities in individuals from clones resistant to mitoxantrone and ivermectin were unrelated with transcriptional levels of the studied four abcc and abcb1 transporter genes. These findings suggest that Abcb1 induction in D. magna may be a part of a general cellular stress response. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Isorhamnetin Attenuates Atherosclerosis by Inhibiting Macrophage Apoptosis via PI3K/AKT Activation and HO-1 Induction

    PubMed Central

    Luo, Yun; Sun, Guibo; Dong, Xi; Wang, Min; Qin, Meng; Yu, Yingli; Sun, Xiaobo

    2015-01-01

    Background and Purpose Isorhamnetin (Iso) is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L. Previous studies have revealed its anti-cancer, anti-inflammatory, and anti-oxidant activities. This study investigated the ability of Iso to inhibit oxidized low-density lipoprotein (ox-LDL)-induced cell apoptosis in THP-1-derived macrophages. The effects of Iso on atherosclerosis in vivo were also evaluated in apolipoprotein E knockout (ApoE-/-) mice fed a high fat diet. Methods and Results Iso showed significant inhibitory effects on ox-LDL-induced THP-1-derived macrophage injuries via decreasing reactive oxygen species levels, lipid deposition, and caspase-3 activation, restoring mitochondrial membrane potential, reducing the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells, and regulating apoptosis-related proteins. We also determined the protective effects of Iso by PI3K/AKT activation and HO-1 induction. Iso reduced the atherosclerotic plaque size in vivo in ApoE-/- mice as assessed by oil red O, Sudan IV staining, and CD68-positive cells, and reduced macrophage apoptosis as assessed by caspase-3 and TUNEL assays in lesions. Conclusion In conclusion, our results show that Iso inhibited atherosclerotic plaque development in ApoE-/- mice by PI3K/AKT activation and HO-1 induction. PMID:25799286

  19. Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation.

    PubMed

    Cash, Robin F H; Murakami, Takenobu; Chen, Robert; Thickbroom, Gary W; Ziemann, Ulf

    2016-01-01

    Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS). © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Induction of Haustorium Development by Sphaeropsidones in Radicles of the Parasitic Weeds Striga and Orobanche. A Structure-Activity Relationship Study.

    PubMed

    Fernández-Aparicio, Mónica; Masi, Marco; Maddau, Lucia; Cimmino, Alessio; Evidente, Marco; Rubiales, Diego; Evidente, Antonio

    2016-06-29

    Crop attack by parasitic weeds such as Striga and Orobanche occurs through developmental processes triggered by host chemodetection. Seeds of those weed species remain dormant in the soil until germination is triggered by host root exudates. The development of haustorium, a parasitic plant organ that invades the host to withdraw its nutrients, is also initiated in Orobanchaceae by host molecular cues. The induction of haustorium development by exogenous signals has previously been reported for Striga but not for Orobanche species. In this work, we demonstrate that sphaeropsidone and epi-sphaeropsidone, two phytotoxic cyclohexene oxides isolated from the fungus Diplodia cupressi, a causal agent of cypress canker, induce haustorium development in radicles of the parasitic weeds Striga hermonthica, Orobanche crenata, and Orobanche cumana. This is the first report of chemical stimulation of haustorium development in radicles of Orobanche in the absence of host. In addition, SAR studies were carried out by testing the haustorium-inducing activity of the natural cyclohexene oxides, seven already known and four new hemisynthetic derivatives, in O. cumana, O. crenata, and S. hermonthica, to find a molecular specificity model required for haustorium induction. The results suggested that the haustorium-inducing activity is due to the possibility to convert the natural sphaeropsidone and natural and hemisynthetic derivatives in the corresponding 3-methoxyquinone and that the stereochemistry at C-5 also seems to affect this activity.

  1. Qualitative and quantitative analysis of heparin and low molecular weight heparins using size exclusion chromatography with multiple angle laser scattering/refractive index and inductively coupled plasma/mass spectrometry detectors.

    PubMed

    Ouyang, Yilan; Zeng, Yangyang; Yi, Lin; Tang, Hong; Li, Duxin; Linhardt, Robert J; Zhang, Zhenqing

    2017-11-03

    Heparin, a highly sulfated glycosaminoglycan, has been used as a clinical anticoagulant over 80 years. Low molecular weight heparins (LMWHs), heparins partially depolymerized using different processes, are widely used as clinical anticoagulants. Qualitative molecular weight (MW) and quantitative mass content analysis are two important factors that contribute to LMWH quality control. Size exclusion chromatography (SEC), relying on multiple angle laser scattering (MALS)/refractive index (RI) detectors, has been developed for accurate analysis of heparin MW in the absence of standards. However, the cations, which ion-pair with the anionic polysaccharide chains of heparin and LMWHs, had not been considered in previous reports. In this study, SEC with MALS/RI and inductively coupled plasma/mass spectrometry detectors were used in a comprehensive analytical approach taking both anionic polysaccharide and ion-paired cations heparin products. This approach was also applied to quantitative analysis of heparin and LMWHs. Full profiles of MWs and mass recoveries for three commercial heparin/LMWH products, heparin sodium, enoxaparin sodium and nadroparin calcium, were obtained and all showed higher MWs than previously reported. This important improvement more precisely characterized the MW properties of heparin/LMWHs and potentially many other anionic polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Plasma Measurements in an Integrated-System FARAD Thruster

    NASA Technical Reports Server (NTRS)

    Polzin, K. A.; Rose, M. F.; Miller, R.; Best, S.

    2007-01-01

    Pulsed inductive plasma accelerators are spacecraft propulsion devices in which energy is stored in a capacitor and then discharged through an inductive coil. The device is electrodeless, inducing a current sheet in a plasma located near the face of the coil. The propellant is accelerated and expelled at a high exhaust velocity (order of 10 km/s) through the interaction of the plasma current and the induced magnetic field. The Faraday Accelerator with RF-Assisted Discharge (FARAD) thruster[1,2] is a type of pulsed inductive plasma accelerator in which the plasma is preionized by a mechanism separate from that used to form the current sheet and accelerate the gas. Employing a separate preionization mechanism allows for the formation of an inductive current sheet at much lower discharge energies and voltages than those used in previous pulsed inductive accelerators like the Pulsed Inductive Thruster (PIT). A benchtop FARAD thruster was designed following guidelines and similarity performance parameters presented in Refs. [3,4]. This design is described in detail in Ref. [5]. In this paper, we present the temporally and spatially resolved measurements of the preionized plasma and inductively-accelerated current sheet in the FARAD thruster operating with a Vector Inversion Generator (VIG) to preionize the gas and a Bernardes and Merryman circuit topology to provide inductive acceleration. The acceleration stage operates on the order of 100 J/pulse. Fast-framing photography will be used to produce a time-resolved, global view of the evolving current sheet. Local diagnostics used include a fast ionization gauge capable of mapping the gas distribution prior to plasma initiation; direct measurement of the induced magnetic field using B-dot probes, induced azimuthal current measurement using a mini-Rogowski coil, and direct probing of the number density and electron temperature using triple probes.

  3. Chondrogenesis of Embryonic Stem Cell-Derived Mesenchymal Stem Cells Induced by TGFβ1 and BMP7 Through Increased TGFβ Receptor Expression and Endogenous TGFβ1 Production.

    PubMed

    Lee, Patrick T; Li, Wan-Ju

    2017-01-01

    For decades stem cells have proven to be invaluable to the study of tissue development. More recently, mesenchymal stem cells (MSCs) derived from embryonic stem cells (ESCs) (ESC-MSCs) have emerged as a cell source with great potential for the future of biomedical research due to their enhanced proliferative capability compared to adult tissue-derived MSCs and effectiveness of musculoskeletal lineage-specific cell differentiation compared to ESCs. We have previously compared the properties and differentiation potential of ESC-MSCs to bone marrow-derived MSCs. In this study, we evaluated the potential of TGFβ1 and BMP7 to induce chondrogenic differentiation of ESC-MSCs compared to that of TGFβ1 alone and further investigated the cellular phenotype and intracellular signaling in response to these induction conditions. Our results showed that the expression of cartilage-associated markers in ESC-MSCs induced by the TGFβ1 and BMP7 combination was increased compared to induction with TGFβ1 alone. The TGFβ1 and BMP7 combination upregulated the expression of TGFβ receptor and the production of endogenous TGFβs compared to TGFβ1 induction. The growth factor combination also increasingly activated both of the TGF and BMP signaling pathways, and inhibition of the signaling pathways led to reduced chondrogenesis of ESC-MSCs. Our findings suggest that by adding BMP7 to TGFβ1-supplemented induction medium, ESC-MSC chondrogenesis is upregulated through increased production of endogenous TGFβ and activities of TGFβ and BMP signaling. J. Cell. Biochem. 118: 172-181, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

    PubMed Central

    Sato, Ayako; Kajiya, Hiroshi; Mori, Nana; Sato, Hironobu; Fukushima, Tadao; Kido, Hirofumi

    2017-01-01

    The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration. PMID:28060874

  5. A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma

    PubMed Central

    2013-01-01

    Background A phase II clinical trial previously evaluated the sequential administration of erlotinib after chemotherapy for advanced non-small-cell lung cancer (NSCLC). This current pilot study assessed the feasibility of sequential induction therapy in patients with stage IIB to IIIA NSCLC adenocarcinoma. Methods Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 75 mg/m2 on day 1, followed by oral icotinib (125 mg, three times a day) on days 15 to 28. A repeatcomputed tomography(CT) scan evaluated the response to the induction treatment after two 4-week cycles and eligible patients underwent surgical resection. The primary objective was to assess the objective response rate (ORR), while EGFR and KRAS mutations and mRNA and protein expression levels of ERCC1 and RRM1 were analyzed in tumor tissues and blood samples. Results Eleven patients, most with stage IIIA disease, completed preoperative treatment. Five patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ORR=45%) and six patients underwent resection. Common toxicities included neutropenia, alanine transaminase (ALT) elevation, fatigue, dry skin, rash, nausea, alopecia and anorexia. No serious complications were recorded perioperatively. Three patients had exon 19 deletions and those with EGFR mutations were more likely to achieve a clinical response (P= 0.083). Furthermore, most cases who achieved a clinical response had low levels of ERCC1 expression and high levels of RRM1. Conclusions Two cycles of sequentially administered gemcitabine/cisplatin with icotinib as an induction treatment is a feasible and efficacious approach for stage IIB to IIIA NSCLC adenocarcinoma, which provides evidence for the further investigation of these chemotherapeutic and molecularly targeted therapies. PMID:23621919

  6. Aldosterone acting through the central nervous system sensitizes angiotensin II-induced hypertension.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Roncari, Camila F; Guo, Fang; Johnson, Alan Kim

    2012-10-01

    Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.

  7. Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells

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

    Shibuya, Akiko; Onda, Kenji, E-mail: knjond@toyaku.ac.jp; Kawahara, Hirofumi

    2010-07-30

    Research highlights: {yields} Sofalcone increases HO-1 in gastric epithelial cells. {yields} The induction of HO-1 by sofalcone treatment follows the activation of Nrf2. {yields} The production of VEGF by sofalcone treatment is mediated by HO-1 induction. -- Abstract: Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction inmore » gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.« less

  8. Lack of Pannexin 1 Alters Synaptic GluN2 Subunit Composition and Spatial Reversal Learning in Mice.

    PubMed

    Gajardo, Ivana; Salazar, Claudia S; Lopez-Espíndola, Daniela; Estay, Carolina; Flores-Muñoz, Carolina; Elgueta, Claudio; Gonzalez-Jamett, Arlek M; Martínez, Agustín D; Muñoz, Pablo; Ardiles, Álvaro O

    2018-01-01

    Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity that have been considered as the cellular substrate of memory formation. Although LTP has received considerable more attention, recent evidences indicate that LTD plays also important roles in the acquisition and storage of novel information in the brain. Pannexin 1 (Panx1) is a membrane protein that forms non-selective channels which have been shown to modulate the induction of hippocampal synaptic plasticity. Animals lacking Panx1 or blockade of Pannexin 1 channels precludes the induction of LTD and facilitates LTP. To evaluate if the absence of Panx1 also affects the acquisition of rapidly changing information we trained Panx1 knockout (KO) mice and wild type (WT) littermates in a visual and hidden version of the Morris water maze (MWM). We found that KO mice find the hidden platform similarly although slightly quicker than WT animals, nonetheless, when the hidden platform was located in the opposite quadrant (OQ) to the previous learned location, KO mice spent significantly more time in the previous quadrant than in the new location indicating that the absence of Panx1 affects the reversion of a previously acquired spatial memory. Consistently, we observed changes in the content of synaptic proteins critical to LTD, such as GluN2 subunits of N-methyl-D-aspartate receptors (NMDARs), which changed their contribution to synaptic plasticity in conditions of Panx1 ablation. Our findings give further support to the role of Panx1 channels on the modulation of synaptic plasticity induction, learning and memory processes.

  9. Treatment complications after sequential combination chemotherapy and radiotherapy with or without surgery in previously untreated squamous cell carcinoma of the head and neck

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

    Posner, M.R.; Weichselbaum, R.R.; Fitzgerald, T.J.

    1985-11-01

    One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknownmore » origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.« less

  10. Offline detection of broken rotor bars in AC induction motors

    NASA Astrophysics Data System (ADS)

    Powers, Craig Stephen

    ABSTRACT. OFFLINE DETECTION OF BROKEN ROTOR BARS IN AC INDUCTION MOTORS. The detection of the broken rotor bar defect in medium- and large-sized AC induction machines is currently one of the most difficult tasks for the motor condition and monitoring industry. If a broken rotor bar defect goes undetected, it can cause a catastrophic failure of an expensive machine. If a broken rotor bar defect is falsely determined, it wastes time and money to physically tear down and inspect the machine only to find an incorrect diagnosis. Previous work in 2009 at Baker/SKF-USA in collaboration with the Korea University has developed a prototype instrument that has been highly successful in correctly detecting the broken rotor bar defect in ACIMs where other methods have failed. Dr. Sang Bin and his students at the Korea University have been using this prototype instrument to help the industry save money in the successful detection of the BRB defect. A review of the current state of motor conditioning and monitoring technology for detecting the broken rotor bar defect in ACIMs shows improved detection of this fault is still relevant. An analysis of previous work in the creation of this prototype instrument leads into the refactoring of the software and hardware into something more deployable, cost effective and commercially viable.

  11. Inhibition and induction of aromatase (CYP19) activity by brominated flame retardants in H295R human adrenocortical carcinoma cells.

    PubMed

    Cantón, Rocío F; Sanderson, J Thomas; Letcher, Robert J; Bergman, Ake; van den Berg, Martin

    2005-12-01

    Brominated flame retardants (BFRs) are persistent and ubiquitous chemicals in the environment, and they are found at increasing levels in tissues of wildlife and humans. Previous in vitro studies with the BFR class of polybrominated diphenyl ethers (BDEs) have shown endocrine-disrupting properties. Our study assessed the potential effects of nineteen BDEs, five hydroxylated BDEs (OH-BDEs), one methoxylated BDE (CH(3)O-BDE), tetrabromobisphenol-A (TBBPA), its dibromopropane ether derivative (TBBPA-DBPE), and the brominated phenols/anisols 2,4,6-tribromophenol (TBP), 4-bromophenol (4BP) and 2,4,6-tribromoanisole (TBA) on the catalytic activity of the steroidogenic enzyme aromatase (CYP19) in H295R human adrenocortical carcinoma cells. Effects were studied in the concentration range from 0.5 to 7.5 microM; exposures were for 24 h. Both 6-OH-BDE47 and 6-OH-BDE99 showed an inhibitory effect on aromatase activity at concentrations >2.5 microM and >5 microM, respectively. However, 6-OH-BDE47 also caused a statistically significant increase in cytotoxicity (based on mitochondrial MTT reduction and lactate dehydrogenase-leakage [LDH]) at concentrations >2.5 microM that could explain in part the apparent inhibitory effect on aromatase activity. Compared to 6-OH-BDE47, the methoxy analog (6-CH(3)O-BDE47) did not elicit a cytotoxic effect, whereas significant inhibition of aromatase remained. TBP caused a concentration-dependent induction of aromatase activity between 0.5 and 7.5 microM (with a maximum of 3.8-fold induction at 7.5 microM). This induction was not observed when a OH- group replaced the CH(3)O- group or when bromine atoms adjacent to this OH- group were absent. These in vitro results provide a basis for studies of more detailed structure-activity relationships between these brominated compounds and the modulation of aromatase activity.

  12. Multicharged iron ions produced by using induction heating vapor source.

    PubMed

    Kato, Yushi; Kubo, Takashi; Muramatsu, Masayuki; Tanaka, Kiyokatsu; Kitagawa, Atsushi; Yoshida, Yoshikazu; Asaji, Toyohisa; Sato, Fuminobu; Iida, Toshiyuki

    2008-02-01

    Multiply charged Fe ions are produced from solid pure material in an electron cyclotron resonance (ECR) ion source. We develop an evaporator by using induction heating with an induction coil which is made of bare molybdenum wire partially covered by ceramic beads in vacuum and surrounding and heating directly the pure Fe rod. Heated material has no contact with insulators, so that outgas is minimized. The evaporator is installed around the mirror end plate outside of the ECR plasma with its hole grazing the ECR zone. Helium or argon gas is usually chosen for supporting gas. The multicharged Fe ions up to Fe(13+) are extracted from the opposite side of mirror and against the evaporator, and then multicharged Fe ion beam is formed. We compare production of multicharged iron ions by using this new source with our previous methods.

  13. Rocuronium versus succinylcholine for rapid sequence induction intubation.

    PubMed

    Tran, Diem T T; Newton, Ethan K; Mount, Victoria A H; Lee, Jacques S; Wells, George A; Perry, Jeffrey J

    2015-10-29

    Patients often require a rapid sequence induction (RSI) endotracheal intubation technique during emergencies or electively to protect against aspiration, increased intracranial pressure, or to facilitate intubation. Traditionally succinylcholine has been the most commonly used muscle relaxant for this purpose because of its fast onset and short duration; unfortunately, it can have serious side effects. Rocuronium has been suggested as an alternative to succinylcholine for intubation. This is an update of our Cochrane review published first in 2003 and then updated in 2008 and now in 2015. To determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during RSI intubation. In our initial review we searched all databases until March 2000, followed by an update to June 2007. This latest update included searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015 ) for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) relating to the use of rocuronium and succinylcholine. We included foreign language journals and handsearched the references of identified studies for additional citations. We included any RCT or CCT that reported intubating conditions in comparing the use of rocuronium and succinylcholine for RSI or modified RSI in any age group or clinical setting. The dose of rocuronium was at least 0.6 mg/kg and succinylcholine was at least 1 mg/kg. Two authors (EN and DT) independently extracted data and assessed methodological quality for the 'Risk of bias' tables. We combined the outcomes in Review Manager 5 using a risk ratio (RR) with a random-effects model. The previous update (2008) had identified 53 potential studies and included 37 combined for meta-analysis. In this latest update we identified a further 13 studies and included 11, summarizing the results of 50 trials including 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions: RR 0.86 (95% confidence interval (CI) 0.81 to 0.92; n = 4151) and clinically acceptable intubation conditions (RR 0.97, 95% CI 0.95 to 0.99; n = 3992, 48 trials). A high incidence of detection bias amongst the trials coupled with significant heterogeneity provides moderate-quality evidence for these conclusions, which are unchanged from the previous update. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: RR 0.81 (95% CI: 0.73 to 0.88; n = 2302, 28 trials). In the previous update, we had concluded that propofol was the superior induction agent with succinylcholine. There were no reported incidences of severe adverse outcomes. We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2 mg/kg rocuronium; however, succinylcholine was clinically superior as it has a shorter duration of action. Succinylcholine created superior intubation conditions to rocuronium in achieving excellent and clinically acceptable intubating conditions.

  14. Worrying about the Future: An Episodic Specificity Induction Impacts Problem Solving, Reappraisal, and Well-Being

    PubMed Central

    Jing, Helen G.; Madore, Kevin P.; Schacter, Daniel L.

    2015-01-01

    Previous research has demonstrated that an episodic specificity induction – brief training in recollecting details of a recent experience – enhances performance on various subsequent tasks thought to draw upon episodic memory processes. Existing work has also shown that mental simulation can be beneficial for emotion regulation and coping with stressors. Here we focus on understanding how episodic detail can affect problem solving, reappraisal, and psychological well-being regarding worrisome future events. In Experiment 1, an episodic specificity induction significantly improved participants’ performance on a subsequent means-end problem solving task (i.e., more relevant steps) and an episodic reappraisal task (i.e., more episodic details) involving personally worrisome future events compared with a control induction not focused on episodic specificity. Imagining constructive behaviors with increased episodic detail via the specificity induction was also related to significantly larger decreases in anxiety, perceived likelihood of a bad outcome, and perceived difficulty to cope with a bad outcome, as well as larger increases in perceived likelihood of a good outcome and indicated use of active coping behaviors compared with the control. In Experiment 2, we extended these findings using a more stringent control induction, and found preliminary evidence that the specificity induction was related to an increase in positive affect and decrease in negative affect compared with the control. Our findings support the idea that episodic memory processes are involved in means-end problem solving and episodic reappraisal, and that increasing the episodic specificity of imagining constructive behaviors regarding worrisome events may be related to improved psychological well-being. PMID:26820166

  15. High intensity ion beams from an atmospheric pressure inductively coupled plasma

    NASA Astrophysics Data System (ADS)

    Al Moussalami, S.; Chen, W.; Collings, B. A.; Douglas, D. J.

    2002-02-01

    This work is directed towards substantially improving the sensitivity of an inductively coupled plasma mass spectrometer (ICP-MS). Ions produced in the ICP at atmospheric pressure have been extracted with comparatively high current densities. The conventional approach to ion extraction, based on a skimmed molecular beam, has been abandoned, and a high extraction field arrangement has been adopted. Although the new approach is not optimized, current densities more than 180 times greater than that of a conventional interface have been extracted and analyte sensitivities ˜10-100× greater than those reported previously for quadrupole ICP-MS have been measured.

  16. Pinch current limitation effect in plasma focus

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

    Lee, S.; Saw, S. H.; INTI International University College, 71800 Nilai

    The Lee model couples the electrical circuit with plasma focus dynamics, thermodynamics, and radiation. It is used to design and simulate experiments. A beam-target mechanism is incorporated, resulting in realistic neutron yield scaling with pinch current and increasing its versatility for investigating all Mather-type machines. Recent runs indicate a previously unsuspected 'pinch current limitation' effect. The pinch current does not increase beyond a certain value however low the static inductance is reduced to. The results indicate that decreasing the present static inductance of the PF1000 machine will neither increase the pinch current nor the neutron yield, contrary to expectations.

  17. The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial.

    PubMed

    Ronchetti, Katherine; Tame, Jo-Dee; Paisey, Christopher; Thia, Lena P; Doull, Iolo; Howe, Robin; Mahenthiralingam, Eshwar; Forton, Julian T

    2018-06-01

    Pathogen surveillance is challenging but crucial in children with cystic fibrosis-who are often non-productive of sputum even if actively coughing-because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage. This prospective internally controlled interventional trial was done at the Children's Hospital for Wales (Cardiff, UK) in children with cystic fibrosis aged between 6 months and 18 years. Samples from cough swab, sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage were matched for within-patient comparisons. Primary outcomes were comparative pathogen yield between sputum induction and cough swab for stage 1, and between sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage for stage 2. Data were analysed as per protocol. This study is registered with the UK Clinical Research Network (14615) and with the International Standard Randomised Controlled Trial Network Registry (12473810). Between Jan 23, 2012, and July 4, 2017, 124 patients were prospectively recruited to the trial and had 200 sputum induction procedures for stage 1. 167 (84%) procedures were successful and the procedure was well tolerated. Of the 167 paired samples, 63 (38%) sputum-induction samples were pathogen positive compared with 24 (14%) cough swabs (p<0·0001; odds ratio [OR] 7·5; 95% CI 3·19-17·98). More pathogens were isolated from sputum induction than cough swab (79 [92%] of 86 vs 27 [31%] of 86; p<0·0001). For stage 2, 35 patients had a total of 41 paired sputum-induction and bronchoalveolar lavage procedures. Of the 41 paired samples, 28 (68%) were positive for at least one of the concurrent samples. 39 pathogens were isolated. Sputum induction identified 27 (69%) of the 39 pathogens, compared with 22 (56%; p=0·092; OR 3·3, 95% CI 0·91-12·11) on single-lobe, 28 (72%; p=1·0; OR 1·1, 95% CI 0·41-3·15) on two-lobe, and 33 (85%; p=0·21; OR 2·2, 95% CI 0·76-6·33) on six-lobe bronchoalveolar lavage. Sputum induction is superior to cough swab for pathogen detection, is effective at sampling the lower airway, and is a credible surrogate for bronchoalveolar lavage in symptomatic children. A substantial number of bronchoscopies could be avoided if sputum induction is done first and pathogens are appropriately treated. Both sputum induction and six-lobe bronchoalveolar lavage provide independent, sizeable gains in pathogen detection compared with the current gold-standard two-lobe bronchoalveolar lavage. We propose that sputum induction and six-lobe bronchoalveolar lavage combined are used as standard of care for comprehensive lower airway pathogen detection in children with cystic fibrosis. Health and Care Research Wales-Academic Health Science Collaboration and Wellcome Trust Institutional Strategic Support Fund. Copyright © 2018 The Author(s). Published by Elsevier Ltd. Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

  18. Developing Attitudinal Metrics for Induction-Year Agricultural Education Teachers

    ERIC Educational Resources Information Center

    Rayfield, John; McKim, Billy R.; Lawrence, Shannon; Stair, Kristin

    2014-01-01

    This study was part of a larger regional study of induction-year agricultural education teachers in three Western states. Studies have purported that attitude toward teaching is important for understanding and helping induction-year teachers. Thus, developing an instrument to assess induction-year agricultural education teachers' attitudes toward…

  19. Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC) Theory of Emotionality

    PubMed Central

    Zhan, Jun; Tang, Fan; He, Mei; Fan, Jin; Xiao, Jing; Liu, Chang; Luo, Jing

    2017-01-01

    Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC), which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC) relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA) proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017). In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR) which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger. PMID:29249998

  20. Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics.

    PubMed

    Koltin, Dror; Sung, Lillian; Naqvi, Ahmed; Urbach, Stacey L

    2012-09-01

    Medication induced diabetes (MID) during induction therapy (MIDi) in patients with acute lymphoblastic leukemia (ALL) is not well characterized in children, with recent studies yielding conflicting results. The purpose of the study was to describe the prevalence of MIDi and risk factors for its development. We retrospectively gathered demographic, disease course and treatment data on 363 patients aged 1 to 17.9 years diagnosed with ALL at a pediatric tertiary care hospital between 1998 and 2005. MIDi was defined as blood glucose ≥200 mg/dL (11.1 mmol/L) on at least 2 separate days during induction. Fifty-seven subjects (15.7%) developed MIDi during the study period. Patients ≥10 years were more likely to develop MIDi than those <10 years (odds ratio [OR] 9.6, 95% confidence interval [CI] 5.1-17.8). BMI percentile among those with MIDi (mean ± SD 58.2 ± 31.0) did not differ from those without MIDi (52.2 ± 32.0, P = 0.429). The presence of Trisomy 21 (OR 3.6, 95% CI 1.1-11.4, P = 0.030) and CNS involvement at diagnosis (OR 3.8, 95% CI 1.4-10.1, P = 0.009) were associated with an increased risk of MIDi. After adjustment for potential confounding variables, age ≥10 years and the presence of CNS disease at diagnosis remained significantly associated with MIDi. Older age and CNS involvement at diagnosis increase the risk of MIDi. In contrast to previous studies, higher BMI was not associated with MIDi in our population.

  1. Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC) Theory of Emotionality.

    PubMed

    Zhan, Jun; Tang, Fan; He, Mei; Fan, Jin; Xiao, Jing; Liu, Chang; Luo, Jing

    2017-01-01

    Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC), which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC) relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of "sadness counteracts anger" (SCA) proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017). In this study, we experimentally examined the MPMC hypothesis that "anger counteracts rumination" (ACR) which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger.

  2. A Resonant Damping Study Using Piezoelectric Materials

    NASA Technical Reports Server (NTRS)

    Min, J. B.; Duffy, K. P.; Choi, B. B.; Morrison, C. R.; Jansen, R. H.; Provenza, A. J.

    2008-01-01

    Excessive vibration of turbomachinery blades causes high cycle fatigue (HCF) problems requiring damping treatments to mitigate vibration levels. Based on the technical challenges and requirements learned from previous turbomachinery blade research, a feasibility study of resonant damping control using shunted piezoelectric patches with passive and active control techniques has been conducted on cantilever beam specimens. Test results for the passive damping circuit show that the optimum resistive shunt circuit reduces the third bending resonant vibration by almost 50%, and the optimum inductive circuit reduces the vibration by 90%. In a separate test, active control reduced vibration by approximately 98%.

  3. Relational complexity modulates activity in the prefrontal cortex during numerical inductive reasoning: an fMRI study.

    PubMed

    Feng, Xiao; Peng, Li; Chang-Quan, Long; Yi, Lei; Hong, Li

    2014-09-01

    Most previous studies investigating relational reasoning have used visuo-spatial materials. This fMRI study aimed to determine how relational complexity affects brain activity during inductive reasoning, using numerical materials. Three numerical relational levels of the number series completion task were adopted for use: 0-relational (e.g., "23 23 23"), 1-relational ("32 30 28") and 2-relational ("12 13 15") problems. The fMRI results revealed that the bilateral dorsolateral prefrontal cortex (DLPFC) showed enhanced activity associated with relational complexity. Bilateral inferior parietal lobule (IPL) activity was greater during the 1- and 2-relational level problems than during the 0-relational level problems. In addition, the left fronto-polar cortex (FPC) showed selective activity during the 2-relational level problems. The bilateral DLPFC may be involved in the process of hypothesis generation, whereas the bilateral IPL may be sensitive to calculation demands. Moreover, the sensitivity of the left FPC to the multiple relational problems may be related to the integration of numerical relations. The present study extends our knowledge of the prefrontal activity pattern underlying numerical relational processing. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial.

    PubMed

    Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Opheim, Arild; Krajci, Peter; Sharma-Haase, Kamni; Benth, Jūratė Šaltytė; Tanum, Lars; Kunoe, Nikolaj

    2018-05-28

    This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility. In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment. Five urban, out-patient addiction clinics in Norway. Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX. XR-NTX administrated as intramuscular injections (380 mg) every fourth week. Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week. Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids. Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment. © 2018 Society for the Study of Addiction.

  5. Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients.

    PubMed

    Kim, Inho; Koh, Youngil; Yoon, Sung-Soo; Park, Seonyang; Kim, Byoung Kook; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Cheong, June-Won; Lee, Hong-Kee; Kim, Sung-Hyun; Kim, Hyuk; Joo, Young Don; Lee, Sang-Min; Won, Jong-Ho; Park, Sung-Kyu; Hong, Dae-Sik; Kim, Se-Hyung; Sohn, Sang Kyun; Kim, Chul-Soo; Park, Eunkyung; Kim, Min Kyoung; Park, Moo Rim; Lee, Je-Hwan; Min, Yoo Hong

    2013-01-01

    We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Copyright © 2012 Wiley Periodicals, Inc.

  6. Costs and benefits of jasmonic acid induced responses in soybean.

    PubMed

    Accamando, A K; Cronin, J T

    2012-06-01

    In response to herbivory, plants have evolved defense strategies to reduce herbivore preference and performance. A strategy whereby defenses are induced only upon herbivory can mitigate costs of defense when herbivores are scarce. Although costs and benefits of induced responses are generally assumed, empirical evidence for many species is lacking. Soybean (Glycine max L. Merr.) has emerged as a model species with which to address questions about induced responses. To our knowledge, this is the first study to examine the fitness costs and benefits of jasmonic acid-induced responses by soybean in the absence and presence of soybean loopers (Chrysodeix includens Walker) (Lepidoptera: Noctuidae). In a greenhouse experiment we demonstrated that soybean induction was costly. Induced plants produced 10.1% fewer seeds that were 9.0% lighter, and had 19.2% lower germination rates than noninduced plants. However, induction provided only modest benefits to soybeans. In a choice experiment, soybean loopers significantly preferred leaves from noninduced plants, consuming 62% more tissue than from induced plants. Soybean loopers that fed on plants that were previously subjected to treatment with jasmonic acid matured at the same rate and to the same size as those that fed on control plants. However, at high conspecific density, soybean looper survivorship was reduced by 44% on previously induced relative to control plants. Reduced soybean looper preference and survivorship did not translate into fitness benefits for soybeans. Our findings support theoretical predictions of costly induced defenses and highlight the importance of considering the environmental context in studies of plant defense.

  7. Local induction of calcium phosphate formation on TiO2 coatings on titanium via surface treatment with a CO2 laser.

    PubMed

    Moritz, N; Jokinen, M; Peltola, T; Areva, S; Yli-Urpo, A

    2003-04-01

    Sol-gel-derived TiO(2) coatings are known to promote bonelike hydroxyapatite formation on their surfaces in vitro and in vivo. Hydroxyapatite integrates into bone tissue. In some clinical applications, the surface of an implant is simultaneously interfaced with soft and hard tissues, so it should match the properties of both. A new method is introduced for treating the coatings locally in a controlled manner. The local densification of sol-gel-derived titania coatings on titanium substrates with a CO(2) laser was studied in terms of the in vitro calcium phosphate-inducting properties. CO(2)-laser-treated multilayer coatings were compared with furnace-fired coatings prepared with the same recipe and previously shown to be bioactive. Additionally, local areas of furnace-fired multilayer coatings (previously shown to be bioactive in vitro) were further laser-treated to achieve various properties in the same implant. Topological surface properties were examined with atomic force microscopy. The formation of hydroxyapatite was studied with Fourier transform infrared and scanning electron microscopy energy-dispersive X-ray analysis. The results show that calcium phosphate formation can be adjusted locally by laser treatment. Calcium phosphate is a bonelike hydroxyapatite. The local treatment of sol-gel-derived coatings with a CO(2) laser is a promising technique for creating implants with various properties to interface different tissues and a possible way of coating implants that do not tolerate furnace firing. Copyright 2003 Wiley Periodicals, Inc.

  8. Models of performance of evolutionary program induction algorithms based on indicators of problem difficulty.

    PubMed

    Graff, Mario; Poli, Riccardo; Flores, Juan J

    2013-01-01

    Modeling the behavior of algorithms is the realm of evolutionary algorithm theory. From a practitioner's point of view, theory must provide some guidelines regarding which algorithm/parameters to use in order to solve a particular problem. Unfortunately, most theoretical models of evolutionary algorithms are difficult to apply to realistic situations. However, in recent work (Graff and Poli, 2008, 2010), where we developed a method to practically estimate the performance of evolutionary program-induction algorithms (EPAs), we started addressing this issue. The method was quite general; however, it suffered from some limitations: it required the identification of a set of reference problems, it required hand picking a distance measure in each particular domain, and the resulting models were opaque, typically being linear combinations of 100 features or more. In this paper, we propose a significant improvement of this technique that overcomes the three limitations of our previous method. We achieve this through the use of a novel set of features for assessing problem difficulty for EPAs which are very general, essentially based on the notion of finite difference. To show the capabilities or our technique and to compare it with our previous performance models, we create models for the same two important classes of problems-symbolic regression on rational functions and Boolean function induction-used in our previous work. We model a variety of EPAs. The comparison showed that for the majority of the algorithms and problem classes, the new method produced much simpler and more accurate models than before. To further illustrate the practicality of the technique and its generality (beyond EPAs), we have also used it to predict the performance of both autoregressive models and EPAs on the problem of wind speed forecasting, obtaining simpler and more accurate models that outperform in all cases our previous performance models.

  9. Beginning Teacher Induction in the State of Colorado

    ERIC Educational Resources Information Center

    Bierbaum, Myra Desha

    2016-01-01

    The purpose of the study was to gain a deeper understanding of teacher induction in the state of Colorado. The guiding question for the study was "What components do Colorado school districts include as part of their beginning teacher induction?" The study examined the implementation of nine teacher induction components: orientation,…

  10. Conditions that influence the response to Fgf during otic placode induction

    PubMed Central

    Padanad, Mahesh S.; Bhat, Neha; Guo, BiWei; Riley, Bruce B.

    2016-01-01

    Despite the vital importance of Fgf for otic induction, previous attempts to study otic induction through Fgf misexpression have yielded widely varying and contradictory results. There are also discrepancies regarding the ability of Fgf to induce otic tissue in ectopic locations, raising questions about the sufficiency of Fgf and the degree to which other local factors enhance or restrict otic potential. Using heat shock-inducible transgenes to misexpress Fgf3 or Fgf8 in zebrafish, we found that the stage, distribution and level of misexpression strongly influence the response to Fgf. Fgf misexpression during gastrulation can inhibit or promote otic development, depending on context, whereas misexpression after gastrulation leads to expansion of otic markers throughout preplacodal ectoderm surrounding the head. Elevated Fgf also expands expression of the putative competence factor Foxi1, which is required for Fgf to expand other otic markers. Misexpression of downstream factors Pax2a or Pax8 also expands otic markers but cannot bypass the requirement for Fgf or Foxi1. Co-misexpression of Pax2/8 with Fgf8 potentiates formation of ectopic otic vesicles expressing a full range of otic markers. These findings document the variables critically affecting the response to Fgf and clarify the roles of foxi1 and pax2/8 in the otic response. PMID:22327005

  11. The diversity effect of inductive reasoning under segment manipulation of complex cognition.

    PubMed

    Chen, Antao; Li, Hong; Feng, Tingyong; Gao, Xuemei; Zhang, Zhongming; Li, Fuhong; Yang, Dong

    2005-12-01

    The present study proposed the idea of segment manipulation of complex cognition (SMCC), and technically made it possible the quantitative treatment and systematical manipulation on the premise diversity. The segment manipulation of complex cognition divides the previous inductive strengths judgment task into three distinct steps, attempting to particularly distinguish the psychological processes and their rules. The results in Experiment 1 showed that compared with the traditional method, the quantitative treatment and systematical manipulation of SMCC on the diversity did not change the task's nature, and remain rational and a good measurement of inductive strength judgment. The results in Experiment 2 showed that the participants' response rules in the triple-step task were expected from our proposal, and that in Step 2 the "feeling of surprise" (FOS), which seems implausible but predicted from the diversity premises, was measured, and its component might be the critical part that produced the diversity effect. The "feeling of surprise" may reflect the impact of emotion on cognition, representing a strong revision to premise probability principle of pure rational hypothesis proposed by Lo et al., and its roles in the diversity effect are worthy of further research. In this regards were discussed the mistakes that the premise probability principle makes when it takes posterity probability as prior probability.

  12. Testing the cognitive catalyst model of rumination with explicit and implicit cognitive content.

    PubMed

    Sova, Christopher C; Roberts, John E

    2018-06-01

    The cognitive catalyst model posits that rumination and negative cognitive content, such as negative schema, interact to predict depressive affect. Past research has found support for this model using explicit measures of negative cognitive content such as self-report measures of trait self-esteem and dysfunctional attitudes. The present study tested whether these findings would extend to implicit measures of negative cognitive content such as implicit self-esteem, and whether effects would depend on initial mood state and history of depression. Sixty-one undergraduate students selected on the basis of depression history (27 previously depressed; 34 never depressed) completed explicit and implicit measures of negative cognitive content prior to random assignment to a rumination induction followed by a distraction induction or vice versa. Dysphoric affect was measured both before and after these inductions. Analyses revealed that explicit measures, but not implicit measures, interacted with rumination to predict change in dysphoric affect, and these interactions were further moderated by baseline levels of dysphoria. Limitations include the small nonclinical sample and use of a self-report measure of depression history. These findings suggest that rumination amplifies the association between explicit negative cognitive content and depressive affect primarily among people who are already experiencing sad mood. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Animal models in the research of abdominal aortic aneurysms development.

    PubMed

    Patelis, N; Moris, D; Schizas, D; Damaskos, C; Perrea, D; Bakoyiannis, C; Liakakos, T; Georgopoulos, S

    2017-12-20

    Abdominal aortic aneurysm (AAA) is a prevalent and potentially life threatening disease. Many animal models have been developed to simulate the natural history of the disease or test preclinical endovascular devices and surgical procedures. The aim of this review is to describe different methods of AAA induction in animal models and report on the effectiveness of the methods described in inducing an analogue of a human AAA. The PubMed database was searched for publications with titles containing the following terms "animal" or "animal model(s)" and keywords "research", "aneurysm(s)", "aorta", "pancreatic elastase", "Angiotensin", "AngII" "calcium chloride" or "CaCl(2)". Starting date for this search was set to 2004, since previously bibliography was already covered by the review of Daugherty and Cassis (2004). We focused on animal studies that reported a model of aneurysm development and progression. A number of different approaches of AAA induction in animal models has been developed, used and combined since the first report in the 1960's. Although specific methods are successful in AAA induction in animal models, it is necessary that these methods and their respective results are in line with the pathophysiology and the mechanisms involved in human AAA development. A researcher should know the advantages/disadvantages of each animal model and choose the appropriate model.

  14. Gamma-interferon causes a selective induction of the lysosomal proteases, cathepsins B and L, in macrophages

    NASA Technical Reports Server (NTRS)

    Lah, T. T.; Hawley, M.; Rock, K. L.; Goldberg, A. L.

    1995-01-01

    Previous studies have indicated that acid-optimal cysteine proteinase(s) in the endosomal-lysosomal compartments, cathepsins, play a critical role in the proteolytic processing of endocytosed proteins to generate the antigenic peptides presented to the immune system on major histocompatibility complex (MHC) class II molecules. The presentation of these peptides and the expression of MHC class II molecules by macrophages and lymphocytes are stimulated by gamma-interferon (gamma-IFN). We found that treatment of human U-937 monocytes with gamma-IFN increased the activities and the content of the two major lysosomal cysteine proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked immunosorbant assays (ELISA) and immunoblotting showed that this cytokine increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this fraction was not significantly altered by gamma-IFN treatment. An induction of cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells. These results suggest coordinate regulation in monocytes of the expression of cathepsins B and L and MHC class II molecules. Presumably, this induction of cysteine proteases contributes to the enhancement of antigen presentation by gamma-IFN.

  15. Production in stirred-tank bioreactor of recombinant bovine chymosin B by a high-level expression transformant clone of Pichia pastoris.

    PubMed

    Noseda, Diego Gabriel; Recúpero, Matías; Blasco, Martín; Bozzo, Joaquín; Galvagno, Miguel Ángel

    2016-07-01

    An intense screening of Pichia pastoris clones transformed with the gene of bovine chymosin under methanol-inducible AOX1 promoter was performed, obtaining a transformant clone with a higher milk-clotting activity value in comparison with our previous studies. The scaling of recombinant-chymosin production was carried out by a fed-batch strategy in a stirred-tank bioreactor using biodiesel-byproduct crude glycerol as the carbon source and pure methanol for the induction of chymosin expression, achieving a biomass concentration of 158 g DCW/L and a maximum coagulant activity of 192 IMCU/ml after 120 h of methanol induction. Recombinant bovine chymosin was purified from bioreactor-fermentation culture by a procedure including anion-exchange chromatography which allowed obtaining heterologous chymosin with high level of purity and activity; suggesting that this downstream step could be scaled up in a successful manner for chymosin purification. Thermoestability assay permitted to establish that unformulated recombinant chymosin could be stored at 5 °C without decrease of enzyme activity throughout at least 120 days. Finally, reiterative methanol-inductions of recombinant chymosin expression in bioreactor demonstrated that the reutilization of cell biomass overcame the low enzyme productivity usually reached by P. pastoris system. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Laboratory-Model Integrated-System FARAD Thruster

    NASA Technical Reports Server (NTRS)

    Polzin, K.A.; Best, S.; Miller, R.; Rose, M.F.; Owens, T.

    2008-01-01

    Pulsed inductive plasma accelerators are spacecraft propulsion devices in which energy is stored in a capacitor and then discharged through an inductive coil. The device is electrodeless, inducing a plasma current sheet in propellant located near the face of the coil. The propellant is accelerated and expelled at a high exhaust velocity (order of 10 km/s) through the interaction of the plasma current with an induced magnetic field. The Faraday Accelerator with RF-Assisted Discharge (FARAD) thruster [1,2] is a type of pulsed inductive plasma accelerator in which the plasma is preionized by a mechanism separate from that used to form the current sheet and accelerate the gas. Employing a separate preionization mechanism in this manner allows for the formation of an inductive current sheet at much lower discharge energies and voltages than those found in previous pulsed inductive accelerators like the Pulsed Inductive Thruster (PIT). In a previous paper [3], the authors presented a basic design for a 100 J/pulse FARAD laboratory-version thruster. The design was based upon guidelines and performance scaling parameters presented in Refs. [4, 5]. In this paper, we expand upon the design presented in Ref. [3] by presenting a fully-assembled and operational FARAD laboratory-model thruster and addressing system and subsystem-integration issues (concerning mass injection, preionization, and acceleration) that arose during assembly. Experimental data quantifying the operation of this thruster, including detailed internal plasma measurements, are presented by the authors in a companion paper [6]. The thruster operates by first injecting neutral gas over the face of a flat, inductive acceleration coil and at some later time preionizing the gas. Once the gas is preionized current is passed through the acceleration coil, inducing a plasma current sheet in the propellant that is accelerated away from the coil through electromagnetic interaction with the time-varying magnetic field. Neutral gas is injected over the face of the acceleration coil through a fast-acting valve that feeds a central distribution manifold. The thruster is designed to preionize the gas using an RF-frequency ringing signal produced by a discharging Vector Inversion Generator (VIG). The acceleration stage consists of a multiple-turn, multiple-strand spiral induction coil (see Fig. 1, left panel) and is designed for operation at discharge energies on the order of 100 J/pulse. Several different pulsed power train modules can be used to drive current through the acceleration coil. One such power train is based upon the Bernardes and Merryman circuit topology, which restricts voltage reversal on the capacitor banks and can be clamped to eliminate current reversal in the coil. A second option is a pulse-compression-ring power train (see Fig. 1, right panel), which takesa temporally broad, low current pulse and transforms it into a short, high current pulse.

  17. A transcription activator-like effector (TALE) induction system mediated by proteolysis.

    PubMed

    Copeland, Matthew F; Politz, Mark C; Johnson, Charles B; Markley, Andrew L; Pfleger, Brian F

    2016-04-01

    Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications owing to their customizable DNA-binding specificity. In this work we expanded the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded after induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator-agnostic.

  18. A transcription activator-like effector induction system mediated by proteolysis

    PubMed Central

    Copeland, Matthew F.; Politz, Mark C.; Johnson, Charles B.; Markley, Andrew L.; Pfleger, Brian F.

    2016-01-01

    Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications due to their customizable DNA binding specificity. In this work we expand the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded following the induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator agnostic. PMID:26854666

  19. Carbon-free induction furnace

    DOEpatents

    Holcombe, Cressie E.; Masters, David R.; Pfeiler, William A.

    1985-01-01

    An induction furnace for melting and casting highly pure metals and alloys such as uranium and uranium alloys in such a manner as to minimize contamination of the melt by carbon derived from the materials and the environment within the furnace. The subject furnace is constructed of carbon free materials and is housed within a conventional vacuum chamber. The furnace comprises a ceramic oxide crucible for holding the charge of metal or alloy. The heating of the crucible is achieved by a plasma-sprayed tungsten susceptor surrounding the crucible which, in turn, is heated by an RF induction coil separated from the susceptor by a cylinder of inorganic insulation. The furnace of the present invention is capable of being rapidly cycled from ambient temperatures to about 1650.degree. C. for effectively melting uranium and uranium alloys without the attendant carbon contamination problems previously encountered when using carbon-bearing furnace materials.

  20. Non-carbon induction furnace

    DOEpatents

    Holcombe, C.E.; Masters, D.R.; Pfeiler, W.A.

    1984-01-06

    The present invention is directed to an induction furnace for melting and casting highly pure metals and alloys such as uranium and uranium alloys in such a manner as to minimize contamination of the melt by carbon derived from the materials and the environment within the furnace. The subject furnace is constructed of non-carbon materials and is housed within a conventional vacuum chamber. The furnace comprises a ceramic oxide crucible for holding the charge of metal or alloys. The heating of the crucible is achieved by a plasma-sprayed tungsten susceptor surrounding the crucible which, in turn, is heated by an rf induction coil separated from the susceptor by a cylinder of inorganic insulation. The furnace of the present invention is capable of being rapidly cycled from ambient temperatures to about 1650/sup 0/C for effectively melting uranium and uranium alloys without the attendant carbon contamination problems previously encountered when using carbon-bearing furnace materials.

  1. NMR spectroscopy of single sub-nL ova with inductive ultra-compact single-chip probes

    PubMed Central

    Grisi, Marco; Vincent, Franck; Volpe, Beatrice; Guidetti, Roberto; Harris, Nicola; Beck, Armin; Boero, Giovanni

    2017-01-01

    Nuclear magnetic resonance (NMR) spectroscopy enables non-invasive chemical studies of intact living matter. However, the use of NMR at the volume scale typical of microorganisms is hindered by sensitivity limitations, and experiments on single intact organisms have so far been limited to entities having volumes larger than 5 nL. Here we show NMR spectroscopy experiments conducted on single intact ova of 0.1 and 0.5 nL (i.e. 10 to 50 times smaller than previously achieved), thereby reaching the relevant volume scale where life development begins for a broad variety of organisms, humans included. Performing experiments with inductive ultra-compact (1 mm2) single-chip NMR probes, consisting of a low noise transceiver and a multilayer 150 μm planar microcoil, we demonstrate that the achieved limit of detection (about 5 pmol of 1H nuclei) is sufficient to detect endogenous compounds. Our findings suggest that single-chip probes are promising candidates to enable NMR-based study and selection of microscopic entities at biologically relevant volume scales. PMID:28317887

  2. Illness perceptions or recurrence risk perceptions: What comes first? A longitudinal cross-lagged examination among cardiac patients.

    PubMed

    Peleg, Shira; Drori, Erga; Banai, Shmuel; Finkelstein, Ariel; Shiloh, Shoshana

    2016-05-01

    Previous research suggested that illness perceptions provide the basis for illness risk perceptions through an inductive reasoning process. This study aimed to assess the direction of relationships between illness and recurrence risk perceptions over time, among cardiac patients. A longitudinal study was conducted among 138 patients undergoing coronary angioplasty. Self-report questionnaires measured perceived recurrence risk and illness perceptions one day and one month after catheterisation. Cross-lagged Panel Model Analyses revealed that higher perceptions of timeline, consequences and emotional representations of illness at hospitalisation were associated with higher recurrence risk perceptions one month later. Perceived personal control was the only illness perception with bi-directional associations: higher perceived personal control at hospitalisation was associated with higher recurrence risk perceptions one month later; and higher recurrence risk perceptions at hospitalisation was associated with lower personal control one month later. The findings suggest that the associations between recurrence risk and illness perceptions can only partly be explained by inductive reasoning. Halo effects and defensive processes are suggested as complementary explanations for the observed associations between risk and illness perceptions.

  3. Ruminative and mindful self-focused attention in borderline personality disorder.

    PubMed

    Sauer, Shannon E; Baer, Ruth A

    2012-10-01

    The current study investigated the short-term effects of mindful and ruminative forms of self-focused attention on a behavioral measure of distress tolerance in individuals with borderline personality disorder (BPD) who had completed an angry mood induction. Participants included 40 individuals who met criteria for BPD and were currently involved in mental health treatment. Each completed an individual 1-hr session. Following an angry mood induction, each participant was randomly assigned to engage in ruminative or mindful self-focus for several minutes. All participants then completed the computerized Paced Auditory Serial Addition Test (PASAT-C), a behavioral measure of willingness to tolerate distress in the service of goal-directed behavior. The mindfulness group persisted significantly longer than the rumination group on the distress tolerance task and reported significantly lower levels of anger following the self-focus period. Results are consistent with previous studies in suggesting that distinct forms of self-focused attention have distinct outcomes and that, for people with BPD, mindful self-observation is an adaptive alternative to rumination when feeling angry. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  4. Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation

    PubMed Central

    Xie, Luokun; Li, Wenjun; Winters, Ali; Yuan, Fang; Jin, Kunlin; Yang, Shaohua

    2013-01-01

    Methylene blue has been shown to be neuroprotective in multiple experimental neurodegenerative disease models. However, the mechanisms underlying the neuroprotective effects have not been fully elucidated. Previous studies have shown that macroautophagy has multiple beneficial roles for maintaining normal cellular homeostasis and that induction of macroautophagy after myocardial ischemia is protective. In the present study we demonstrated that methylene blue could protect HT22 hippocampal cell death induced by serum deprivation, companied by induction of macroautophagy. We also found that methylene blue-mediated neuroprotection was abolished by macroautophagy inhibition. Interestingly, 5′ adenosine monophosphate-activated protein kinase (AMPK) signaling, but not inhibition of mammalian target of rapamycin signaling, was activated at 12 and 24 h after methylene blue treatment in a dose-dependent manner. Methylene blue-induced macroautophagy was blocked by AMPK inhibitor. Consistent with in vitro data, macroautophagy was induced in the cortex and hippocampus of mouse brains treated with methylene blue. Our findings suggest that methylene blue-induced neuroprotection is mediated, at least in part, by macroautophagy though activation of AMPK signaling. PMID:23653592

  5. Methylene blue induces macroautophagy through 5' adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation.

    PubMed

    Xie, Luokun; Li, Wenjun; Winters, Ali; Yuan, Fang; Jin, Kunlin; Yang, Shaohua

    2013-01-01

    Methylene blue has been shown to be neuroprotective in multiple experimental neurodegenerative disease models. However, the mechanisms underlying the neuroprotective effects have not been fully elucidated. Previous studies have shown that macroautophagy has multiple beneficial roles for maintaining normal cellular homeostasis and that induction of macroautophagy after myocardial ischemia is protective. In the present study we demonstrated that methylene blue could protect HT22 hippocampal cell death induced by serum deprivation, companied by induction of macroautophagy. We also found that methylene blue-mediated neuroprotection was abolished by macroautophagy inhibition. Interestingly, 5' adenosine monophosphate-activated protein kinase (AMPK) signaling, but not inhibition of mammalian target of rapamycin signaling, was activated at 12 and 24 h after methylene blue treatment in a dose-dependent manner. Methylene blue-induced macroautophagy was blocked by AMPK inhibitor. Consistent with in vitro data, macroautophagy was induced in the cortex and hippocampus of mouse brains treated with methylene blue. Our findings suggest that methylene blue-induced neuroprotection is mediated, at least in part, by macroautophagy though activation of AMPK signaling.

  6. Acute aerobic exercise helps overcome emotion regulation deficits.

    PubMed

    Bernstein, Emily E; McNally, Richard J

    2017-06-01

    Although colloquial wisdom and some studies suggest an association between regular aerobic exercise and emotional well-being, the nature of this link remains poorly understood. We hypothesised that aerobic exercise may change the way people respond to their emotions. Specifically, we tested whether individuals experiencing difficulties with emotion regulation would benefit from a previous session of exercise and show swifter recovery than their counterparts who did not exercise. Participants (N = 80) completed measures of emotion response tendencies, mood, and anxiety, and were randomly assigned to either stretch or jog for 30 minutes. All participants then underwent the same negative and positive mood inductions, and reported their emotional responses. Analyses showed that more perceived difficulty generating regulatory strategies and engaging in goal-directed behaviours after the negative mood induction predicted more intense and persistent negative affect in response to the stressor, as would be expected. Interactions revealed that aerobic exercise attenuated these effects. Moderate aerobic exercise may help attenuate negative emotions for participants initially experiencing regulatory difficulties. This study contributes to the literature on aerobic exercise's therapeutic effects with experimental data, specifically in the realm of emotional processing.

  7. Predicting who will drop out of nursing courses: a machine learning exercise.

    PubMed

    Moseley, Laurence G; Mead, Donna M

    2008-05-01

    The concepts of causation and prediction are different, and have different implications for practice. This distinction is applied here to studies of the problem of student attrition (although it is more widely applicable). Studies of attrition from nursing courses have tended to concentrate on causation, trying, largely unsuccessfully, to elicit what causes drop out. However, the problem may more fruitfully be cast in terms of predicting who is likely to drop out. One powerful method for attempting to make predictions is rule induction. This paper reports the use of the Answer Tree package from SPSS for that purpose. The main data set consisted of 3978 records on 528 nursing students, split into a training set and a test set. The source was standard university student records. The method obtained 84% sensitivity, 70% specificity, and 94% accuracy on previously unseen cases. The method requires large amounts of high quality data. When such data are available, rule induction offers a way to reduce attrition. It would be desirable to compare its results with those of predictions made by tutors using more informal conventional methods.

  8. Enhancing memory and imagination improves problem solving among individuals with depression.

    PubMed

    McFarland, Craig P; Primosch, Mark; Maxson, Chelsey M; Stewart, Brandon T

    2017-08-01

    Recent work has revealed links between memory, imagination, and problem solving, and suggests that increasing access to detailed memories can lead to improved imagination and problem-solving performance. Depression is often associated with overgeneral memory and imagination, along with problem-solving deficits. In this study, we tested the hypothesis that an interview designed to elicit detailed recollections would enhance imagination and problem solving among both depressed and nondepressed participants. In a within-subjects design, participants completed a control interview or an episodic specificity induction prior to completing memory, imagination, and problem-solving tasks. Results revealed that compared to the control interview, the episodic specificity induction fostered increased detail generation in memory and imagination and more relevant steps on the problem-solving task among depressed and nondepressed participants. This study builds on previous work by demonstrating that a brief interview can enhance problem solving among individuals with depression and supports the notion that episodic memory plays a key role in problem solving. It should be noted, however, that the results of the interview are relatively short-lived.

  9. Induction and prevention of micronuclei and chromosomal aberrations in cultured human lymphocytes exposed to the light of halogen tungsten lamps.

    PubMed

    D'Agostini, F; Caimo, A; De Filippi, S; De Flora, S

    1999-07-01

    Previous studies have shown that the light emitted by halogen tungsten lamps contains UV radiation in the UV-A, UV-B and UV-C regions, induces mutations and irreparable DNA damage in bacteria, enhances the frequency of micronuclei in cultured human lymphocytes and is potently carcinogenic to the skin of hairless mice. The present study showed that the light emitted by an uncovered, traditional halogen lamp induces a significant, dose-related and time-related increase not only in micronuclei but also in chromosome-type aberrations, such as breaks, and even more in chromatid-type aberrations, such as isochromatid breaks, exchanges and isochromatid/chromatid interchanges, all including gaps or not, in cultured human lymphocytes. All these genotoxic effects were completely prevented by shielding the same lamp with a silica glass cover, blocking UV radiation. A new model of halogen lamp, having the quartz bulb treated in order to reduce the output of UV radiation, was considerably less genotoxic than the uncovered halogen lamp, yet induction of chromosomal alterations was observed at high illuminance levels.

  10. Differences in the induction of cytochrome P450 3A4 by taxane anticancer drugs, docetaxel and paclitaxel, assessed employing primary human hepatocytes.

    PubMed

    Nallani, Srikanth C; Goodwin, Bryan; Buckley, Arthur R; Buckley, Donna J; Desai, Pankaj B

    2004-09-01

    The induction of cytochrome P450 (CYP) 3A4 by drugs and other xenobiotics is a common cause of serious drug interactions. The aim of this study was to comparatively examine the effects of paclitaxel and docetaxel, two structurally related taxane anticancer agents, on the activity and expression of hepatic CYP3A4. Employing primary cultures of human hepatocytes from multiple donors, we investigated the differences in the magnitude of CYP3A4 induction and relative accumulation of paclitaxel and docetaxel. The CYP3A4 activity of intact hepatocytes was measured as the rate of testosterone 6beta-hydroxylation. The CYP3A4-specific immunoreactive protein and mRNA levels were measured employing Western blot and Northern blot analysis, respectively. Furthermore, employing cell-based reporter gene assay in CV-1 cells, we evaluated the capacity of paclitaxel and docetaxel to activate human pregnane X receptor (hPXR), an orphan nuclear receptor that plays a key role in the transcriptional regulation of CYP3A4. In concurrence with previous reports, we observed that paclitaxel potently induced CYP3A4 activity and expression in hepatocytes treated for 48-96 h. However, docetaxel did not increase the activity or the CYP3A4 immunoreactive protein levels for treatment periods up to 96 h. A marginal increase in the CYP3A4 mRNA levels was observed in cells treated with higher levels (5 and 10 microM) of docetaxel. Furthermore, while paclitaxel effectively activated hPXR (the half-maximal effective concentration, EC50, being about 5.2 microM), docetaxel weakly activated hPXR, and moreover the activation occurred only at high concentrations relative to paclitaxel. A comparison of the cellular concentrations of paclitaxel and docetaxel, in the cell culture models employed for evaluating CYP3A4 induction and hPXR activation, revealed that the intracellular paclitaxel levels were three-fold higher than that of docetaxel. Thus, it appears that both pharmacokinetic (drug concentration) and pharmacodynamic differences (hPXR activation) may account for the observed differences in CYP3A induction by paclitaxel and docetaxel. Our studies suggest that docetaxel has markedly reduced propensity to cause drug interactions that may entail hepatic CYP3A4 induction.

  11. Factors determining the smooth flow and the non-operative time in a one-induction room to one-operating room setting

    PubMed Central

    Mulier, Jan P; De Boeck, Liesje; Meulders, Michel; Beliën, Jeroen; Colpaert, Jan; Sels, Annabel

    2015-01-01

    Rationale, aims and objectives What factors determine the use of an anaesthesia preparation room and shorten non-operative time? Methods A logistic regression is applied to 18 751 surgery records from AZ Sint-Jan Brugge AV, Belgium, where each operating room has its own anaesthesia preparation room. Surgeries, in which the patient's induction has already started when the preceding patient's surgery has ended, belong to a first group where the preparation room is used as an induction room. Surgeries not fulfilling this property belong to a second group. A logistic regression model tries to predict the probability that a surgery will be classified into a specific group. Non-operative time is calculated as the time between end of the previous surgery and incision of the next surgery. A log-linear regression of this non-operative time is performed. Results It was found that switches in surgeons, being a non-elective surgery as well as the previous surgery being non-elective, increase the probability of being classified into the second group. Only a few surgery types, anaesthesiologists and operating rooms can be found exclusively in one of the two groups. Analysis of variance demonstrates that the first group has significantly lower non-operative times. Switches in surgeons, anaesthesiologists and longer scheduled durations of the previous surgery increases the non-operative time. A switch in both surgeon and anaesthesiologist strengthens this negative effect. Only a few operating rooms and surgery types influence the non-operative time. Conclusion The use of the anaesthesia preparation room shortens the non-operative time and is determined by several human and structural factors. PMID:25496600

  12. Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression

    PubMed Central

    Mocking, Roel J T; van Wingen, Guido; Martens, Suzanne; Ruhé, Henricus G; Schene, Aart H

    2017-01-01

    Abstract Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = −0.21, P = 0.046) and rumination (r = −0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission. PMID:28981917

  13. Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression.

    PubMed

    Figueroa, Caroline A; Mocking, Roel J T; van Wingen, Guido; Martens, Suzanne; Ruhé, Henricus G; Schene, Aart H

    2017-11-01

    Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = -0.21, P = 0.046) and rumination (r = -0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission. © The Author (2017). Published by Oxford University Press.

  14. Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells.

    PubMed

    Dong, Yinhui; Yin, Shutao; Song, Xinhua; Huo, Yazhen; Fan, Lihong; Ye, Min; Hu, Hongbo

    2016-04-01

    Curcumin-based structural modification for developing more effective curcumin analogues has been drawning increasing attention. As alternative approach, using LC/MS guided purification, we previously obtained a series of novel natural terpene-conjugated curcuminoids from turmeric, and some of them exhibited even more potent anti-cancer activity against multiple types of cancer cells than curcumin. The purpose of this follow-up study was designed to decipher the mechanisms involved in anti-cancer activity of these novel curcumin analogues. Apoptosis was evaluated using sub-G1 analysis by flow cytometry and Cell Death ELISA Kit. Changes of protein expression were analyzed by western blotting. RNA interference was employed to inhibit expression of specific protein. We found that bisabolocurcumin ether (T1) and demethoxybisabolocurcumin ether (T2) were able to trigger much stronger apoptosis induction in multiple types of cancer cells than curcumin, which was attributed to persistent and stronger ROS generation. ROS induction by T1 resulted in activation of p38/H2AX axis and p53. Inhibition of p38/H2AX led to a significant reduction of apoptosis, whereas inactivation of p53 caused a dramatically enhanced H2AX phosphorylation and apoptosis induction, suggesting activation of p38/H2AX contributed to apoptosis induction by T1, whereas p53 activation protected novel curcumins-induced apoptosis via suppression of H2AX activation. Our findings provide mechanistic support for the potential use of terpene-conjugated curcuminoids as a novel class of cancer chemopreventive agents. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  15. The activation of c-Jun NH2-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells

    PubMed Central

    2014-01-01

    Background c-Jun NH2-terminal kinases (JNKs) are strongly activated by a stressful cellular environment, such as chemotherapy and oxidative stress. Autophagy is a protein-degradation system in which double-membrane vacuoles called autophagosomes are formed. The autophagy-related gene Beclin 1 plays a key role in this process. We previously found that autophagy was induced by dihydroartemisinin (DHA) in pancreatic cancer cells. However, little is known about the complex relationship between ROS, JNK activation, autophagy induction, and Beclin 1 expression. Methods Cell viability and CCK-8 assays were carried out to determine the cell proliferation; small interfering RNAs (siRNAs) were used to knockdown c-Jun NH2-terminal kinases (JNK1/2) genes; western blot was performed to detect the protein expression of LC3, JNK, Beclin 1, caspase 3 and β-actin; production of intracellular ROS was analyzed using FACS flow cytometry; autophagy induction was confirmed by electron microscopy. Results In the present study, we explored the role of DHA and Beclin 1 expression in autophagy. DHA-treated cells showed autophagy characteristics, and DHA also activated the JNK pathway and up-regulated the expression of Beclin 1. Conversely, blocking JNK signaling inhibited Beclin 1 up-regulation. JNK activation was found to primarily depend on reactive oxygen species (ROS) resulting from the DHA treatment. Moreover, JNK pathway inhibition and Beclin 1 silencing prevented the induction of DHA-induced autophagy. Conclusions These results suggest that the induction of autophagy by DHA is required for JNK-mediated Beclin 1 expression. PMID:24438216

  16. Iron triggers λSo prophage induction and release of extracellular DNA in Shewanella oneidensis MR-1 biofilms.

    PubMed

    Binnenkade, Lucas; Teichmann, Laura; Thormann, Kai M

    2014-09-01

    Prophages are ubiquitous elements within bacterial chromosomes and affect host physiology and ecology in multiple ways. We have previously demonstrated that phage-induced lysis is required for extracellular DNA (eDNA) release and normal biofilm formation in Shewanella oneidensis MR-1. Here, we investigated the regulatory mechanisms of prophage λSo spatiotemporal induction in biofilms. To this end, we used a functional fluorescence fusion to monitor λSo activation in various mutant backgrounds and in response to different physiological conditions. λSo induction occurred mainly in a subpopulation of filamentous cells in a strictly RecA-dependent manner, implicating oxidative stress-induced DNA damage as the major trigger. Accordingly, mutants affected in the oxidative stress response (ΔoxyR) or iron homeostasis (Δfur) displayed drastically increased levels of phage induction and abnormal biofilm formation, while planktonic cells were not or only marginally affected. To further investigate the role of oxidative stress, we performed a mutant screen and identified two independent amino acid substitutions in OxyR (T104N and L197P) that suppress induction of λSo by hydrogen peroxide (H2O2). However, λSo induction was not suppressed in biofilms formed by both mutants, suggesting a minor role of intracellular H2O2 in this process. In contrast, addition of iron to biofilms strongly enhanced λSo induction and eDNA release, while both processes were significantly suppressed at low iron levels, strongly indicating that iron is the limiting factor. We conclude that uptake of iron during biofilm formation triggers λSo-mediated lysis of a subpopulation of cells, likely by an increase in iron-mediated DNA damage sensed by RecA. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. Glucocorticoid Induction of Occludin Expression and Endothelial Barrier Requires Transcription Factor p54 NONO

    PubMed Central

    Keil, Jason M.; Liu, Xuwen; Antonetti, David A.

    2013-01-01

    Purpose. Glucocorticoids (GCs) effectively reduce retinal edema and induce vascular barrier properties but possess unwanted side effects. Understanding GC induction of barrier properties may lead to more effective and specific therapies. Previous work identified the occludin enhancer element (OEE) as a GC-responsive cis-element in the promoters of multiple junctional genes, including occludin, claudin-5, and cadherin-9. Here, we identify two OEE-binding factors and determine their contribution to GC induction of tight junction (TJ) gene expression and endothelial barrier properties. Methods. OEE-binding factors were isolated from human retinal endothelial cells (HREC) using DNA affinity purification followed by MALDI-TOF MS/MS. Chromatin immunoprecipitation (ChIP) assays determined in situ binding. siRNA was used to evaluate the role of trans-acting factors in transcription of TJ genes in response to GC stimulation. Paracellular permeability was determined by quantifying flux through a cell monolayer, whereas transendothelial electrical resistance (TER) was measured using the ECIS system. Results. MS/MS analysis of HREC nuclear extracts identified the heterodimer of transcription factors p54/NONO (p54) and polypyrimidine tract-binding protein-associated splicing factor (PSF) as OEE-binding factors, which was confirmed by ChIP assay from GC-treated endothelial cells and rat retina. siRNA knockdown of p54 demonstrated that this factor is necessary for GC induction of occludin and claudin-5 expression. Further, p54 knockdown ablated the pro-barrier effects of GC treatment. Conclusions. p54 is essential for GC-mediated expression of occludin, claudin-5, and barrier induction, and the p54/PSF heterodimer may contribute to normal blood-retinal barrier (BRB) induction in vivo. Understanding the mechanism of GC induction of BRB properties may provide novel therapies for macular edema. PMID:23640037

  18. Glucocorticoid induction of occludin expression and endothelial barrier requires transcription factor p54 NONO.

    PubMed

    Keil, Jason M; Liu, Xuwen; Antonetti, David A

    2013-06-12

    Glucocorticoids (GCs) effectively reduce retinal edema and induce vascular barrier properties but possess unwanted side effects. Understanding GC induction of barrier properties may lead to more effective and specific therapies. Previous work identified the occludin enhancer element (OEE) as a GC-responsive cis-element in the promoters of multiple junctional genes, including occludin, claudin-5, and cadherin-9. Here, we identify two OEE-binding factors and determine their contribution to GC induction of tight junction (TJ) gene expression and endothelial barrier properties. OEE-binding factors were isolated from human retinal endothelial cells (HREC) using DNA affinity purification followed by MALDI-TOF MS/MS. Chromatin immunoprecipitation (ChIP) assays determined in situ binding. siRNA was used to evaluate the role of trans-acting factors in transcription of TJ genes in response to GC stimulation. Paracellular permeability was determined by quantifying flux through a cell monolayer, whereas transendothelial electrical resistance (TER) was measured using the ECIS system. MS/MS analysis of HREC nuclear extracts identified the heterodimer of transcription factors p54/NONO (p54) and polypyrimidine tract-binding protein-associated splicing factor (PSF) as OEE-binding factors, which was confirmed by ChIP assay from GC-treated endothelial cells and rat retina. siRNA knockdown of p54 demonstrated that this factor is necessary for GC induction of occludin and claudin-5 expression. Further, p54 knockdown ablated the pro-barrier effects of GC treatment. p54 is essential for GC-mediated expression of occludin, claudin-5, and barrier induction, and the p54/PSF heterodimer may contribute to normal blood-retinal barrier (BRB) induction in vivo. Understanding the mechanism of GC induction of BRB properties may provide novel therapies for macular edema.

  19. Experimental evaluation of analyte excitation mechanisms in the inductively coupled plasma

    NASA Astrophysics Data System (ADS)

    Lehn, Scott A.; Hieftje, Gary M.

    2003-10-01

    The inductively coupled plasma (ICP) is a justifiably popular source for atomic emission spectrometry. However, despite its popularity, the ICP is still only partially understood. Even the mechanisms of analyte excitation remain unclear; some energy levels are quite clearly populated by charge transfer while others might be populated by electron-ion recombination, by electron impact, or by Penning processes. Distinguishing among these alternatives is possible by means of a steady-state kinetics approach that examines correlations between the emission of a selected atom, ion, or level and the local number densities of species assumed to produce the excitation. In an earlier investigation, strong correlations were found between either calcium atom or ion emission and selected combinations of calcium atom or ion number densities and electron number densities in the plasma. However, all radially resolved data employed in the earlier study were produced from Abel inversion and from measurements that were crude by today's standards. Now, by means of tomographic imaging, laser-saturated atomic fluorescence, and Thomson and Rayleigh scattering, it is possible to measure the required radially resolved data without Abel inversion and with far greater fidelity. The correlations previously studied for calcium have been investigated with these more reliable data. Ion-electron recombination, either radiative or with argon as a third body, was determined to be the most likely excitation mechanism for calcium atom, while electron impact appeared to be the most important process to produce excite-state calcium ions. These results were consistent with the previous study. However, the present study suggests that collisional deactivation, rather than radiative decay, is the most likely mode of returning both calcium atoms and ions to the ground state.

  20. Analysis of repair and PCNA complex formation induced by ionizing radiation in human fibroblast cell lines.

    PubMed

    Karmakar, P; Balajee, A S; Natarajan, A T

    2001-05-01

    Proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerase delta and epsilon, is involved in both DNA replication and repair. Previous studies in vitro have demonstrated the requirement of PCNA in the resynthesis step of nucleotide excision repair (NER) and base excision repair (BER). Using a native chromatin template isolated under near physiological conditions, we have analysed the involvement of PCNA in the BER pathway in different NER defective human cell lines. The repair sites and PCNA were visualized by indirect immunolabelling followed by fluorescence microscopy. The results indicate that exposure to X-rays triggers the induction of PCNA in all the three human fibroblast cell lines studied, namely normal, xeroderma pigmentosum group A (XP-A) and Cockayne syndrome group B (CS-B). In all the cell lines, induction of PCNA and repair patches occurred in a dose- and time-dependent fashion. Induction of repair patches in NER-deficient XP-A cells suggests that the X-ray-induced lesions are largely repaired via the BER pathway involving PCNA as one of the key components of this pathway. X-ray-induced repair synthesis was greatly inhibited by treatment of cells with DNA polymerase inhibitors aphidicolin and cytosine arabinoside. Interestingly, inhibition of repair resynthesis did not affect the intensity of PCNA staining in X-irradiated cells indicating that the PCNA may be required for the BER pathway at a step preceding the resynthesis step.

  1. Evaluation of Granulated Lactose as a Carrier for Dry Powder Inhaler Formulations 2: Effect of Drugs and Drug Loading.

    PubMed

    Du, Ping; Du, Ju; Smyth, Hugh D C

    2017-01-01

    Previously, granulated lactose carriers were shown to improve uniformity and aerosolization of a low-dose model drug. In the present study, the blending uniformity and aerosol dispersion performance were assessed for 2 model drugs salbutamol sulfate (SS) and rifampicin (RIF), blended at high loadings (10% or 30% drug) with granulated lactose carriers. The model drug powders differed in particle size distribution, morphology, density, and surface energies. Content uniformity of RIF blends was better than that of SS. Aerosolization studies showed that all blend formulations had acceptable emitted fractions (>70%). The SS blends showed low induction-port deposition (6%-10%) compared to RIF (5%-30%). This difference was greater at high flow rates. At 90 L/min, the low induction port deposition of SS blends allowed high fine particle fraction (FPF) of 73%-81%, whereas the FPF of the RIF blends was around 43%-45% with higher induction port deposition. However, SS blends exhibited strong flow rate-dependent performance. Increasing the flow rate from 30 L/min to 90 L/min increased SS FPF from approximately 20% to 80%. Conversely, RIF blends were flow rate and drug loading independent. It was concluded that the aerosolization of high drug-loaded dry powder inhaler formulations using granulated lactose, particularly flow rate dependency, varies with active pharmaceutical ingredient properties. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  2. Osteoblasts extracellular matrix induces vessel like structures through glycosylated collagen I

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

    Palmieri, D.; Valli, M.; Viglio, S.

    2010-03-10

    Extracellular matrix (ECM) plays a fundamental role in angiogenesis affecting endothelial cells proliferation, migration and differentiation. Vessels-like network formation in vitro is a reliable test to study the inductive effects of ECM on angiogenesis. Here we utilized matrix deposed by osteoblasts as substrate where the molecular and structural complexity of the endogenous ECM is preserved, to test if it induces vessel-like network formation by endothelial cells in vitro. ECM is more similar to the physiological substrate in vivo than other substrates previously utilized for these studies in vitro. Osteogenic ECM, prepared in vitro from mature osteoblasts at the phase ofmore » maximal deposition and glycosylation of collagen I, induces EAhy926, HUVEC, and HDMEC endothelial cells to form vessels-like structures and promotes the activation of metalloproteinase-2 (MMP-2); the functionality of the p-38/MAPK signaling pathway is required. Osteogenic ECM also induces a transient increase of CXCL12 and a decrease of the receptor CXCR4. The induction of vessel-like networks is dependent from proper glycosylation of collagens and does not occur on osteogenic ECMs if deglycosylated by -galactosidase or on less glycosylated ECMs derived from preosteoblasts and normal fibroblasts, while is sustained on ECM from osteogenesis imperfecta fibroblasts only when their mutation is associated with over-glycosylation of collagen type I. These data support that post-translational glycosylation has a role in the induction in endothelial cells in vitro of molecules conductive to self-organization in vessels-like structures.« less

  3. Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies.

    PubMed

    Simpson, S A; Alexander, D J; Reed, C J

    2005-04-01

    We have previously developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to determine whether heat shock protein (HSP) 70 is induced in this model following exposure to carbon tetrachloride (CCl4), dimethyl adipate (DMA), methyl iodide (CH3I) or paracetamol, and whether HSP70 can also be induced in the nasal cavity in vivo. Intracellular ATP was significantly depleted in ethmoturbinates incubated for 4 h with the toxins (0-100 mM; EC50 concentrations: CCl4 32 mM, DMA 3 mM, CH3I 1.5 mM, paracetamol 70 mM), but there was little induction of HSP70. Turbinates were then incubated for 1 h with CCl4 (5 mM), DMA (1.5 mM), CH3I (0.57 mM) or paracetamol (30 mM) and allowed to recover for up to 24 h. Treatment with CCl4, DMA or paracetamol resulted in 250-300% induction of HSP70. Male rats were administered a single oral dose of CCl4 (1600 mg/kg) and killed 16 h later. Degenerative lesions (epithelial undulation and hydropic vacuolation) were evident in the olfactory epithelium, and immunohistochemical analysis of HSP70 revealed increased staining in, or proximate to, areas of damage. Thus, HSP70 can be induced in the olfactory epithelium both in vitro and in vivo.

  4. Experimentally induced hyperchloremic and DL-lactic acidosis in calves: an attempt to study the effects of oral rehydration on acid-base status.

    PubMed

    Schwedhelm, L; Kirchner, D; Klaus, B; Bachmann, L

    2013-04-01

    Many diarrheic calves suffer from metabolic acidosis, which is commonly treated by oral rehydration therapy. Oral rehydration solutions can be prepared in water, milk, or milk replacer. Therefore, the aim of the study was to verify dietary effects of water- or milk replacer-based oral rehydration solutions on parameters of acid-base balance in calves with experimentally induced hyperchloremic and dl-lactate acidosis. In 12 calves, hyperchloremic or dl-lactate acidosis was induced by HCl or dl-lactic acid infusions according to protocols outlined in previous literature. Immediately after induction, the calves were fed with milk replacer or water- or milk replacer-based oral rehydration solutions, or remained fasting, respectively. Blood samples were taken to monitor acid-base status over an experimental period of 4h. Using the protocols, all calves revealed a manifest hyperchloremic or dl-lactate acidosis. Because of high infusion volumes, plasma volume was expanded and effects of feeding regimens on blood parameters were rare. Unexpected clinical aberrations occurred after repeated induction of dl-lactate acidosis: all calves developed a thrombophlebitis of the jugular vein, whereas HCl infusion had no effect on endothelium. Induction of acidosis via infusion is not suitable to study dietary effects. A protocol to induce acidosis and dehydration simultaneously is required to duplicate the metabolic conditions of diarrheic calves. In further investigations, attention should be focused on effects of d-lactate or its metabolites on endothelial tissue. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. DNA DAMAGE INDUCED BY METHYLATED TRIVALENT ARSENICALS IS MEDIATED BY REACTIVE OXYGEN SPECIES

    EPA Science Inventory

    Abstract
    Arsenic is a human carcinogen; however, the mechanisms of arsenic's induction of carcinogenic effects have not been identified clearly. We have shown previously that monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII ) are genotoxic and can damage supe...

  6. High-kinetic inductance additive manufactured superconducting microwave cavity

    NASA Astrophysics Data System (ADS)

    Holland, Eric T.; Rosen, Yaniv J.; Materise, Nicholas; Woollett, Nathan; Voisin, Thomas; Wang, Y. Morris; Torres, Sharon G.; Mireles, Jorge; Carosi, Gianpaolo; DuBois, Jonathan L.

    2017-11-01

    Investigations into the microwave surface impedance of superconducting resonators have led to the development of single photon counters that rely on kinetic inductance for their operation, while concurrent progress in additive manufacturing, "3D printing," opens up a previously inaccessible design space for waveguide resonators. In this manuscript, we present results from the synthesis of these two technologies in a titanium, aluminum, vanadium (Ti-6Al-4V) superconducting radio frequency resonator which exploits a design unattainable through conventional fabrication means. We find that Ti-6Al-4V has two distinct superconducting transition temperatures observable in heat capacity measurements. The higher transition temperature is in agreement with DC resistance measurements, while the lower transition temperature, not previously known in the literature, is consistent with the observed temperature dependence of the superconducting microwave surface impedance. From the surface reactance, we extract a London penetration depth of 8 ± 3 μm—roughly an order of magnitude larger than other titanium alloys and several orders of magnitude larger than other conventional elemental superconductors.

  7. The treatment of tumors by the induction of anemia and irradiation in hyperbaric oxygen

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

    Sealy, R.; Jacobs, P.; Wood, L.

    1989-08-01

    Because increased effects have been achieved when murine tumors are irradiated after a period of hypoxia and because of anecdotal clinical experiences of an improved result after irradiation of previously anemic patients in hyperbaric oxygen, the relationship between irradiation and increased survival was investigated in seventy-two patients with advanced head and neck or cervical cancer. Anemia was achieved by means of a two-stage isovolemic venesection maintained for seventy-two hours, hemoglobin was returned to a normal level, and treatment in hyperbaric oxygen was started. Marked tumor shrinkage after the induction of anemia and before radiotherapy was seen and was probably disease,more » site, and hemoglobin level related. As a result, a possible new approach to cancer therapy is suggested. After completion of therapy, the 1-year disease-free survival for patients with head and neck and cervical cancer was not improved, but the 21-month survival for cervical cancer was improved. Further studies are strongly urged.« less

  8. CD30 induction of human immunodeficiency virus gene transcription is mediated by TRAF2

    PubMed Central

    Tsitsikov, Erdyni N.; Wright, Dowain A.; Geha, Raif S.

    1997-01-01

    CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily expressed on activated T and B lymphocytes and natural killer cells. Ligation of CD30 was previously shown to induce NF-κB activation and HIV expression in chronically infected T lymphocytes. In this study, we report that two members of the TNFR-associated factor (TRAF) family of proteins, TRAF1 and TRAF2, independently bind to the intracellular domain of CD30 (CD30IC). Transient overexpression of TRAF2, but not TRAF1, induced NF-κB activation and HIV-1-long terminal repeat-driven transcription in the T cell line, KT3. Moreover, dominant negative mutants consisting of the TRAF domain of TRAF1 and TRAF2 inhibited CD30 induction of NF-κB activation and HIV-1 transcription. These results suggest that CD30 ligation may enhance the expression of HIV via TRAF-2-mediated activation of NF-κB. PMID:9037063

  9. [Vitamin para-aminobenzoic acid inhibits development of SOS function in tif-1 mutants of Escherichia coli at nonpermissive temperatures].

    PubMed

    Vasil'eva, S V; Gorb, T E; Rapoport, I A

    1983-12-01

    The development of "SOS" inducible functions in lysogenic and non-lysogenic strains of Escherichia coli tif-1 sfiA11 (lambda) at nonpermissive temperature of 42 degrees C was strongly suppressed by para-aminobenzoic acid (PABA). The rate of prophage lambda induction decreased 400 times, as compared to the control level; the efficiency of W-reactivation of UV-irradiated phage lambda decreased 37.5 to 16%. PABA also inhibited to some extent (1.5 times) the process of inducible recombination on the RecF pathway. The processes of spontaneous lambda induction and W-reactivation, as well as spontaneous recombination on RecBC and RecF pathways, were not influenced by PABA. The above data are in accordance with previous studies of PABA action when the manifestation of "SOS" functions was induced by chemical mutagens. The action of PABA has been tentatively interpreted on the basis of negative control of "SOS" repair pathway.

  10. Phytohormones in Japanese mugwort gall induction by a gall-inducing gall midge.

    PubMed

    Tanaka, Yuichiro; Okada, Koichi; Asami, Tadao; Suzuki, Yoshihito

    2013-01-01

    A variety of insect species induce galls on host plants. Liquid chromatographic/tandem mass spectrometric analyses showed that a gall midge (Rhopalomyia yomogicola) that induces galls on Artemisia princeps contained high levels of indole-3-acetic acid and cytokinins. The gall midge larvae also synthesized indole-3-acetic acid from tryptophan. Close observation of gall tissue sections indicated that the larval chamber was surrounded by layers of cells having secondary cell walls with extensive lignin deposition, except for the part of the gall that constituted the feeding nutritive tissue which was composed of small cells negatively stained for lignin. The differences between these two types of tissue were confirmed by an expression analysis of the genes involved in the synthesis of the secondary cell wall. Phytohormones may have functioned in maintaining the feeding part of the gall as fresh nutritive tissue. Together with the results in our previous study, those presented here suggest the importance of phytohormones in gall induction.

  11. Off-line monitoring of bacterial stress response during recombinant protein production using an optical biosensor.

    PubMed

    Vostiar, Igor; Tkac, Jan; Mandenius, Carl-Fredrik

    2004-07-15

    A surface plasmon resonance (SPR) biosensor was used to monitor the profiles of the heat-shock protein (DnaK) and the expression of a heterologous protein to map the dynamics of the cellular stress response in Escherichia coli. As expression system was used an E. coli strain overproducing human recombinant superoxide dismutase (rhSOD). Expression of DnaK showed complex patterns differing with strength of induction. The strong up-regulation of DnaK expression was observed in all cultivations which over-produced of rhSOD. Similar patterns were not observed in non-induced reference cultures. Differences in DnaK concentration profiles were correlated with induction strength. Presented data, carried out in shake flask and glucose limited fed-batch cultivation, show a good consistency with previously published transcriptional profiling results and provide complementary information to understand stress response related to overproduction of recombinant protein. The study also demonstrates the feasibility of using the SPR as a two channel protein array for monitoring of intracellular components.

  12. Molecular-targeted antitumor agents. 19. Furospongolide from a marine Lendenfeldia sp. sponge inhibits hypoxia-inducible factor-1 activation in breast tumor cells.

    PubMed

    Liu, Yang; Liu, Rui; Mao, Shui-Chun; Morgan, J Brian; Jekabsons, Mika B; Zhou, Yu-Dong; Nagle, Dale G

    2008-11-01

    A natural product chemistry-based approach was employed to discover small-molecule inhibitors of the important tumor-selective molecular target hypoxia-inducible factor-1 (HIF-1). Bioassay-guided isolation of an active lipid extract of a Saipan collection of the marine sponge Lendenfeldia sp. afforded the terpene-derived furanolipid furospongolide as the primary inhibitor of hypoxia-induced HIF-1 activation (IC(50) 2.9 μM, T47D breast tumor cells). The active component of the extract also contained one new cytotoxic scalarane sesterterpene and two previously reported scalaranes. Furospongolide blocked the induction of the downstream HIF-1 target secreted vascular endothelial growth factor (VEGF) and was shown to suppress HIF-1 activation by inhibiting the hypoxic induction of HIF-1α protein. Mechanistic studies indicate that furospongolide inhibits HIF-1 activity primarily by suppressing tumor cell respiration via the blockade of NADH-ubiquinone oxidoreductase (complex I)-mediated mitochondrial electron transfer.

  13. Transcriptional activation by heat and cold of a thiol protease gene in tomato. [Lycopersicon esculentum

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

    Schaffer, M.A.; Fischer, R.L.

    We previously determined that low temperature induces the accumulation in tomato (Lycopersicon esculentum) fruit of a cloned mRNA, designated C14, encoding a polypeptide related to thiol proteases. We now demonstrate that C14 mRNA accumulation is a response common to both high (40{degree}C) and low (4{degree}C) temperature stresses. Exposure of tomato fruit to 40{degree}C results in the accumulation of C14 mRNA, by 8 hours. This response is more rapid than that to 4{degree}C, but slower than the induction of many heat shock messages by 40{degree}C, and therefore unique. We have also studied the mechanism by which heat and cold exposure activatemore » C14 gene expression. Both high and low temperature regulate protease gene expression through transcriptional induction of a single C14 gene. A hypothesis for the function of C14 thiol protease gene expression in response to heat and cold is discussed.« less

  14. Memory Reconsolidation Interference as an Emerging Treatment for Emotional Disorders: Strengths, Limitations, Challenges and Opportunities

    PubMed Central

    Beckers, Tom; Kindt, Merel

    2016-01-01

    Experimental research on emotional memory reconsolidation interference, or the induction of amnesia for previously established emotional memory, has a long tradition, but the potential of that research for the development of novel interventions to treat psychological disorders has been recognized only recently. Here we provide an overview of basic research and clinical studies on emotional memory reconsolidation interference. We point out specific advantages of interventions based on memory reconsolidation interference over traditional treatment for emotional disorders. We also explain how findings from basic research suggest limitations and challenges to clinical translation that may help to understand why clinical trials have met with mixed success so far and how their success can be increased. In closing, we preview new intervention approaches beyond the induction of amnesia that the phenomenon of memory reconsolidation may afford for alleviating the burden imposed by emotional memories and comment on theoretical controversies regarding the nature of memory reconsolidation. PMID:28375725

  15. Heavy ion action on yeast cells: Inhibition of ribosomal-RNA synthesis, loss of colony forming ability and induction of mutants

    NASA Astrophysics Data System (ADS)

    Kiefer, J.; Rase, S.; Schöpfer, F.; Schneider, E.; Weber, K.; Kraft, G.

    The action of heavy ions (Ar to U) accelerated to specific energies up to about 10 MeV/u (u=atomic mass unit) on different functions of yeast cells was studied. Ribosomal-RNA synthesis is inhibited according to a single-hit mechanism. Inactivation cross-sections were linearly related to the ratio of the squares of the effective charge Z* and the velocity of the ions. It is concluded from the analysis that the range of the most energetic δ-electrons is larger than previously assumed. There is no such dependence for survival and induction of mutants. In both cases cross-sections increase with the ion's specific-energy indicating an important contribution of long-range δ-electrons. The analysis shows that diploid yeast is not killed by a single-hit mechanism even by very heavy ions if the track width is too small. The relative importance of the penumbral region is even more pronounced with the more sensitive strains.

  16. 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.

  17. Ibrutinib improves the development of acute lymphoblastic leukemia by activating endoplasmic reticulum stress-induced cell death.

    PubMed

    Li, Zhaohui; Wu, Jia; Sheng, Lei

    2018-05-01

    The current study mainly aims to evaluate the effects of ibrutinib on endoplasmic reticulum stress (ERS)-induced apoptosis in Reh cells, which may shed light on the treatment of acute lymphoblastic leukemia (ALL) among children. In line with previous studies, our data show that ibrutinib significantly suppressed Reh cell viability in a time- and dose-dependent manner. We further evaluated the role of ibrutinib on Reh cell colony formation and apoptosis. Ibrutinib inhibited clonogenic capacity and induced Reh cell apoptosis, suggesting an anti-tumor effects of ibrutinib in the progression of ALL. Further study showed that ibrutinib treatment increased ERS-related protein expression, including Bip, ATF4 and CHOP, suggesting the induction of ER-stress in Reh cells. More importantly, once ER-stress was suppressed by tauroursodeoxycholic acid (TUDCA), an ER-stress inhibitor, the upregulation of Bip, ATF4, CHOP, cleaved-caspase3 and cleaved-PARP after ibrutinib treatment was partially reversed, suggesting that induction of ALL cell apoptosis by ibrutinib was partially attributed to activation of ER stress. In summary, we showed novel data that ER-stress induced cell apoptosis plays a key role in the therapeutic effects of ibrutinib on ALL cell malignancies.

  18. Sevoflurane and bradycardia in infants with trisomy 21: A case report and review of the literature.

    PubMed

    Walia, Hina; Ruda, James; Tobias, Joseph D

    2016-01-01

    Various perioperative concerns have been reported in patients with trisomy 21 including associated congenital heart disease, atlantoaxial instability, tracheal and subglottic stenosis, a predisposition to respiratory complications, hypothyroidism, and macroglossia leading to sleep disordered breathing. The recent literature has also suggested a propensity for the development of significant bradycardia during inhalation induction with sevoflurane. We present a 2-year-old girl with trisomy 21 who developed the rapid onset of bradycardia during anesthetic induction with sevoflurane. Previous reports are reviewed, postulated mechanisms discussed, and preventative strategies presented. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit.

    PubMed

    Wada, Ken-Ichi; Hosokawa, Kazuo; Ito, Yoshihiro; Maeda, Mizuo

    2015-11-01

    We previously reported a direct cytoplasmic transfer method using a microfluidic device, in which cell fusion was induced through a microslit (slit-through-fusion) by the Sendai virus envelope (HVJ-E) to prevent nuclear mixing. However, the method was impractical due to low efficiency of slit-through-fusion formation and insufficient prevention of nuclear mixing. The purpose of this study was to establish an efficient method for inducing slit-through-fusion without nuclear mixing. We hypothesized that modulation of cytoskeletal component can decrease nuclear migration through the microslit considering its functions. Here we report that supplementation with Y-27632, a specific ROCK inhibitor, significantly enhances cell fusion induction and prevention of nuclear mixing. Supplementation with Y-27632 increased the formation of slit-through-fusion efficiency by more than twofold. Disruption of F-actin by Y-27632 prevented nuclear migration between fused cells through the microslit. These two effects of Y-27632 led to promotion of the slit-through-fusion without nuclear mixing with a 16.5-fold higher frequency compared to our previous method (i.e., cell fusion induction by HVJ-E without supplementation with Y-27632). We also confirmed that mitochondria were successfully transferred to the fusion partner under conditions of Y-27632 supplementation. These findings demonstrate the practicality of our cell fusion system in producing direct cytoplasmic transfer between live cells. © 2015 Wiley Periodicals, Inc.

  20. Ultrasound cervical length measurement in prediction of labor induction outcome.

    PubMed

    Kehila, M; Abouda, H S; Sahbi, K; Cheour, H; Chanoufi, M Badis

    2016-05-17

    Induction of labor is one of the most common procedures in modern obstetrics, with an incidence of approximately 20% of all deliveries. Not all of these inductions result in vaginal delivery; some lead to cesarean sections, either for emergency reasons or for failed induction. That's why, It seems necessary to outline strategies for the improvement of the success rate of induced deliveries. Traditionally, the identification of women in whom labor induction is more likely to be successful is based on the Bishop score. However, several studies have shown it to be subjective, with high variation and a poor predictor of the outcome of labor induction. Transvaginal sonography for cervical measurement can be a more objective criterion in assessing the success of labor induction. Many studies have been done recently to compare cervical measurement and Bishop Score in labor induction.This paper reviewed the literature that evaluated sonographic cervical length measurement to predict induction of labor outcome.

  1. Propofol Induction's Effect on Cardiac Function

    ClinicalTrials.gov

    2015-03-31

    This Study Was Focused to Evaluate Feasibility of Doppler Tissue Monitoring During the Induction Anesthesia,; and Evaluate Routine Propofol Induction's Effect on Myocardial Tissue Motion, Using Non-invasive Doppler Tissue and 2D Speckle Tracking Imaging.; This is the First Study, to Our Knowledge, Which Has Evaluated the Possible Impact of Propofol Induction on LV Function.

  2. Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo.

    PubMed Central

    Truss, M; Bartsch, J; Schelbert, A; Haché, R J; Beato, M

    1995-01-01

    Hormonal induction of the mouse mammary tumour virus (MMTV) promoter is mediated by interactions between hormone receptors and other transcription factors bound to a complex array of sites. Previous results suggested that access to these sites is modulated by their precise organization into a positioned regulatory nucleosome. Using genomic footprinting, we show that MMTV promoter DNA is rotationally phased in intact cells containing either episomal or chromosomally integrated proviral fragments. Prior to induction there is no evidence for factors bound to the promoter. Following progesterone induction of cells with high levels of receptor, genomic footprinting detects simultaneous protection over the binding sites for hormone receptors, NF-I and the octamer binding proteins. Glucocorticoid or progestin induction leads to a characteristic chromatin remodelling that is independent of ongoing transcription. The centre of the regulatory nucleosome becomes more accessible to DNase I and restriction enzymes, but the limits of the nucleosome are unchanged and the 145 bp core region remains protected against micrococcal nuclease digestion. Thus, the nucleosome covering the MMTV promoter is neither removed nor shifted upon hormone induction, and all relevant transcription factors bind to the surface of the rearranged nucleosome. Since these factors cannot bind simultaneously to free DNA, maintainance of the nucleosome may be required for binding of factors to contiguous sites. Images PMID:7737125

  3. The Skn7 Response Regulator of Saccharomyces cerevisiae Interacts with Hsf1 In Vivo and Is Required for the Induction of Heat Shock Genes by Oxidative Stress

    PubMed Central

    Raitt, Desmond C.; Johnson, Anthony L.; Erkine, Alexander M.; Makino, Kozo; Morgan, Brian; Gross, David S.; Johnston, Leland H.

    2000-01-01

    The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress. PMID:10888672

  4. Role of human pregnane X receptor in tamoxifen- and 4-hydroxytamoxifen-mediated CYP3A4 induction in primary human hepatocytes and LS174T cells.

    PubMed

    Sane, Rucha S; Buckley, Donna J; Buckley, Arthur R; Nallani, Srikanth C; Desai, Pankaj B

    2008-05-01

    Previously we observed that the antiestrogens tamoxifen and 4-hydroxytamoxifen (4OHT) induce CYP3A4 in primary human hepatocytes and activate human pregnane X receptor (PXR) in cell-based reporter assays. Given the complex cross-talk between nuclear receptors, tissue-specific expression of CYP3A4, and the potential for tamoxifen and 4OHT to interact with a myriad of receptors, this study was undertaken to gain mechanistic insights into the inductive effects of tamoxifen and 4OHT. First, we observed that transfection of the primary cultures of human hepatocytes with PXR-specific small interfering RNA reduced the PXR mRNA expression and the extent of CYP3A4 induction by tamoxifen and 4OHT by 50%. Second, in LS174T colon carcinoma cells, which were observed to have significantly lower PXR expression relative to human hepatocytes, neither tamoxifen nor 4OHT induced CYP3A4. Third, N-desmethyltamoxifen, which did not induce CYP3A4 in human hepatocytes, also did not activate PXR in LS174T cells. We then used cell-based reporter assay to evaluate the effects of other receptors such as glucocorticoid receptor GR alpha and estrogen receptor ER alpha on the transcriptional activation of PXR. The cotransfection of GR alpha in LS174T cells augmented PXR activation by tamoxifen and 4OHT. On the other hand, the presence of ER alpha inhibited PXR-mediated basal activation of CYP3A4 promoter, possibly via competing for common cofactors such as steroid receptor coactivator 1 and glucocorticoid receptor interacting protein 1. Collectively, our findings suggest that the CYP3A4 induction by tamoxifen and 4OHT is primarily mediated by PXR but the overall stoichiometry of other nuclear receptors and transcription cofactors also contributes to the extent of the inductive effect.

  5. Role of FGF and noggin in neural crest induction.

    PubMed

    Mayor, R; Guerrero, N; Martínez, C

    1997-09-01

    A study of the molecules noggin and fibroblast growth factor (FGF) and its receptor in the induction of the prospective neural crest in Xenopus laevis embryos has been carried out, using the expression of the gene Xslu as a marker for the neural crest. We show that when a truncated FGF receptor (XFD) was expressed ectopically in order to block FGF signaling Xslu expression was inhibited. The effect of XFD on Xslu was specific and could be reversed by the coinjection of the wild-type FGF receptor (FGFR). Inhibition of Xslu expression by XFD is not a consequence of neural plate inhibition, as was shown by analyzing Xsox-2 expression. When ectoderm expressing XFD was transplanted into the prospective neural fold region of embryos Xslu induction was inhibited. The neural crest can also be induced by an interaction between neural plate and epidermis. As this induction is suppressed by the presence of XFD in the neural plate and not in the epidermis, it suggests that the neural crest is induced by FGF from the epidermis. However, treatment of neural plate with FGF was not able to induce Xslug expression, showing that in addition to FGF other non-FGF factors are also required. Previously we have suggested that the ectopic ventral expression of Xslu produced by overexpression of noggin mRNA resulted from an interaction of noggin with a ventral signal. Overexpression of XFD inhibits this effect, suggesting that FGF could be one component involved in this ventral signaling. Overexpression of FGFR produced a remarkable increase in the expression of Xslu in the posterior neural folds and around the blastopore. Injections in different blastomeres of the embryo suggest that the target cells of this effect are the ventral cells. Finally, we proposed a model in which the induction of the neural crests at the border of the neural plate requires functional FGF signaling, which possibly interacts with a neural inducer such as noggin.

  6. DNA DAMAGE INDUCED BY METHYLATED TRIVALENT ARSENICALS IS MEDIATED BY REACTIVE OXYGEN SPECIES

    EPA Science Inventory

    Abstract

    Arsenic is a human carcinogen; however; the mechanisms of arsenic's induction of carcinogenic effects have not been identified clearly. We have shown previously that
    monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMA III) are genotoxic and can d...

  7. TRACE ANALYSIS OF FLUORESCEIN-DERIVATIZED PHENOXY ACID HERBICIDES BY MICELLAR ELECTROKINETIC CHROMATOGRAPHY WITH LASER-INDUCTED FLUORESCENCE DETECTION

    EPA Science Inventory

    Micellar electrokinetic chromatography (MEKC) with laser-induced fluorescence (LIF) detection was used for the trace analysis of phenoxy acid herbicides. Capillary electrophoresis (CE) with LIF detection, which has not previously been used for pesticide analysis, overcomes the po...

  8. A Retrospective, Multicenter Study of the Tolerance of Induction Chemotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Radiotherapy With Concomitant Cetuximab in 46 Cases of Squamous Cell Carcinoma of the Head and Neck

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

    Buiret, Guillaume, E-mail: guillaume.buiret@laposte.ne; Service de biostatistique, Hospices Civils de Lyon, Lyon; Combe, Claire

    2010-06-01

    Purpose: To investigate, in a multicenter study, the tolerance of induction chemotherapy (ICT) and external radiotherapy (ERT) with concomitant cetuximab in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Clinical data from 46 patients with Stage III or IV nonmetastatic SCCHN who received docetaxel, cisplatin, and 5-fluorouracil as ICT, followed by ERT with concomitant cetuximab, were retrospectively analyzed. Clinical safety (weight, allergy, mucositis, and dermatitis) and paraclinical safety (levels of hemoglobin, polynuclear neutrophils, and creatinine clearance) were studied. The primary objective was the proportion of patients who completed the protocol. Results:more » The percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.6%. Induction chemotherapy was better tolerated than that previously reported. The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalization (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment, although Grade 4 dermatitis was not experienced. There were no allergic reactions to cetuximab. Conclusion: The completed protocol rate for SCCHN patients receiving ICT and ERT with concomitant cetuximab is high and the toxicity acceptable. Future improvements to protocol will be possible through early action and systematic implementation of nutritional support coupled with antibiotic treatment upon the first signs of radiodermatitis. These data could be useful for prospective studies on the safety and efficacy of this protocol.« less

  9. Brain mechanisms underlying the impact of attachment-related stress on social cognition

    PubMed Central

    Nolte, Tobias; Bolling, Danielle Z.; Hudac, Caitlin M.; Fonagy, Peter; Mayes, Linda; Pelphrey, Kevin A.

    2013-01-01

    Mentalizing, in particular the successful attribution of complex mental states to others, is crucial for navigating social interactions. This ability is highly influenced by external factors within one's daily life, such as stress. We investigated the impact of stress on the brain basis of mentalization in adults. Using a novel modification of the Reading the Mind in the Eyes Test (RMET-R) we compared the differential effects of two personalized stress induction procedures: a general stress induction (GSI) and an attachment-related stress induction (ASI). Participants performed the RMET-R at baseline and after each of the two inductions. Baseline results replicated and extended previous findings regarding the neural correlates of the RMET-R. Additionally, we identified brain regions associated with making complex age judgments from the same stimuli. Results after stress exposure showed that the ASI condition resulted in reduced mentalization-related activation in the left posterior superior temporal sulcus (STS), left inferior frontal gyrus and left temporoparietal junction (TPJ). Moreover, the left middle frontal gyrus and left anterior insula showed greater functional connectivity to the left posterior STS after the ASI. Our findings indicate that attachment-related stress has a unique effect on the neural correlates of mentalization. PMID:24348364

  10. A taxonomy of inductive problems.

    PubMed

    Kemp, Charles; Jern, Alan

    2014-02-01

    Inductive inferences about objects, features, categories, and relations have been studied for many years, but there are few attempts to chart the range of inductive problems that humans are able to solve. We present a taxonomy of inductive problems that helps to clarify the relationships between familiar inductive problems such as generalization, categorization, and identification, and that introduces new inductive problems for psychological investigation. Our taxonomy is founded on the idea that semantic knowledge is organized into systems of objects, features, categories, and relations, and we attempt to characterize all of the inductive problems that can arise when these systems are partially observed. Recent studies have begun to address some of the new problems in our taxonomy, and future work should aim to develop unified theories of inductive reasoning that explain how people solve all of the problems in the taxonomy.

  11. On rules of induction and the raven paradox in Bayesian confirmation theory

    NASA Astrophysics Data System (ADS)

    Afshar, H. M.; Sunehag, P.

    2014-12-01

    Confirmation theory is studying how one can confirm a universal statement like "All ravens are black". Early authors discussed how one's degree of belief in such a statement should change with new evidence and suggested various rules of induction. Nicod's Condition (NC) says that the claim that all F are G is supported by observing a previously unseen object that is both F and G. Hempel pointed out that NC implies the paradoxical conclusion that observing a white sock supports that all ravens are black. In our time, confirmation is studied by using subjective conditional probability as degrees of belief with Kolmogorov's axioms as the main rules of induction. The old rules and problems of induction are, however, still studied within the probabilistic framework. We consider a setting where the number of individuals having a particular property is given and find that NC can contradict a simpler principle, namely projectability (PJ) which says that if we observe an object with property ψ then other objects are also more likely to have property ψ. We find that intuition can side with either one depending on the situation. We suggest that a more appropriate formalization of the intuition behind NC is the weaker principle of reasoning by analogy (RA). RA says that if we see an object that is F and G and we know that another object is F, then it is more likely to also be G. Projectability might still be considered valid for relatively uninformed a priori beliefs. If one decides that a principle like projectability is valid for confirmation in an uninformed situation, it provides a test that an a priori distribution must satisfy. Hence, decreasing the arbitrariness of the choice of measure. Further, by considering background knowledge saying only how many ravens there are in the world we conclude that if someone accepts the projectability principle, an agent will not increment the belief that all ravens are black when having observed a white sock. Most Bayesian approaches have so far derived a small increment in confirmation by relying on some particular a priori measure. A conclusion rejected by common sense. We here resolve the contradiction by formally identifying the natural background knowledge considered and the inductive rule that the a priori belief should comply with in the situation at hand. The original paradox is dispelled by rejecting NC.

  12. The external amino acid signaling pathway promotes activation of Stp1 and Uga35/Dal81 transcription factors for induction of the AGP1 gene in Saccharomyces cerevisiae.

    PubMed Central

    Abdel-Sater, Fadi; Iraqui, Ismaïl; Urrestarazu, Antonio; André, Bruno

    2004-01-01

    Yeast cells respond to the presence of amino acids in their environment by inducing transcription of several amino acid permease genes including AGP1, BAP2, and BAP3. The signaling pathway responsible for this induction involves Ssy1, a permease-like sensor of external amino acids, and culminates with proteolytic cleavage and translocation to the nucleus of the zinc-finger proteins Stp1 and Stp2, the lack of which abolishes induction of BAP2 and BAP3. Here we show that Stp1-but not Stp2-plays an important role in AGP1 induction, although significant induction of AGP1 by amino acids persists in stp1 and stp1 stp2 mutants. This residual induction depends on the Uga35/Dal81 transcription factor, indicating that the external amino acid signaling pathway activates not only Stp1 and Stp2, but also another Uga35/Dal81-dependent transcriptional circuit. Analysis of the AGP1 gene's upstream region revealed that Stp1 and Uga35/Dal81 act synergistically through a 21-bp cis-acting sequence similar to the UAS(AA) element previously found in the BAP2 and BAP3 upstream regions. Although cells growing under poor nitrogen-supply conditions display much higher induction of AGP1 expression than cells growing under good nitrogen-supply conditions, the UAS(AA) itself is totally insensitive to nitrogen availability. Nitrogen-source control of AGP1 induction is mediated by the GATA factor Gln3, likely acting through adjacent 5'-GATA-3' sequences, to amplify the positive effect of UAS(AA). Our data indicate that Stp1 may act in combination with distinct sets of transcription factors, according to the gene context, to promote induction of transcription in response to external amino acids. The data also suggest that Uga35/Dal81 is yet another transcription factor under the control of the external amino acid sensing pathway. Finally, the data show that the TOR pathway mediating global nitrogen control of transcription does not interfere with the external amino acid signaling pathway. PMID:15126393

  13. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

    PubMed

    Sandborn, William J; Su, Chinyu; Sands, Bruce E; D'Haens, Geert R; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

    2017-05-04

    Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.).

  14. Effect of the St. John's wort constituent hyperforin on docetaxel metabolism by human hepatocyte cultures.

    PubMed

    Komoroski, Bernard J; Parise, Robert A; Egorin, Merrill J; Strom, Stephen C; Venkataramanan, Raman

    2005-10-01

    St. John's wort is a commonly used herbal medication that increases cytochrome P450 3A (CYP3A) activity. Because docetaxel is inactivated by CYP3A, we studied the effects of the St. John's wort constituent hyperforin on docetaxel metabolism in a human hepatocyte model. Hepatocytes, isolated from three donor livers, were exposed to hyperforin (0.1, 0.5, or 1.5 micromol/L) or rifampin (10 micromol/L) for 48 hours. After 48 hours, hyperforin- or rifampin-containing medium was replaced with medium containing 100 micromol/L docetaxel. After 1 hour, docetaxel metabolism was characterized by liquid chromatography-tandem mass spectrometry. Subsequent incubations characterized the specific cytochrome P450s that produced the docetaxel metabolites observed in hepatocyte incubations. Rifampin induced docetaxel metabolism 6.8- to 32-fold above docetaxel metabolism in control cultures. Hyperforin induced docetaxel metabolism in all three hepatocyte preparations. Hyperforin induction was dose-dependent and, at maximum, was 2.6- to 7-fold greater than that in controls. Docetaxel metabolites identified in rifampin- and hyperforin-treated hepatocyte preparations included the previously described tert-butyl-hydroxylated metabolite and two previously unidentified metabolites involving hydroxylation on the baccatin ring. CYP3A4 produced the tert-butyl-hydroxylated metabolite and the two ring-hydroxylated metabolites. CYP2C8 produced one of the newly described ring-hydroxylated metabolites. Exposure to the St. John's wort constituent hyperforin induces docetaxel metabolism in vitro. This implies that subtherapeutic docetaxel concentrations may result when docetaxel is administered to patients using St. John's wort on a chronic basis. The results also show induction of previously undescribed metabolic pathways for docetaxel, one of which may be analogous to the known 6-alpha-hydroxylation of paclitaxel by CYP2C8.

  15. Vadose Zone Transport Field Study: Status Report

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

    Gee, Glendon W.; Ward, Anderson L.

    2001-11-30

    Studies were initiated at the Hanford Site to evaluate the process controlling the transport of fluids in the vadose zone and to develop a reliable database upon which vadose-zone transport models can be calibrated. These models are needed to evaluate contaminant migration through the vadose zone to underlying groundwaters at Hanford. A study site that had previously been extensively characterized using geophysical monitoring techniques was selected in the 200 E Area. Techniques used previously included neutron probe for water content, spectral gamma logging for radionuclide tracers, and gamma scattering for wet bulk density. Building on the characterization efforts of themore » past 20 years, the site was instrumented to facilitate the comparison of nine vadose-zone characterization methods: advanced tensiometers, neutron probe, electrical resistance tomography (ERT), high-resolution resistivity (HRR), electromagnetic induction imaging (EMI), cross-borehole radar (XBR), and cross-borehole seismic (XBS). Soil coring was used to obtain soil samples for analyzing ionic and isotopic tracers.« less

  16. WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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

    Grassberger, C; Paganetti, H

    Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumedmore » to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation could minimize the probability of resistance, increasing tumor control significantly.« less

  17. Epstein-Barr Virus MicroRNA miR-BART20-5p Suppresses Lytic Induction by Inhibiting BAD-Mediated caspase-3-Dependent Apoptosis

    PubMed Central

    Kim, Hyoji; Choi, Hoyun

    2015-01-01

    ABSTRACT Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with a variety of tumor types. EBV can establish latency or undergo lytic replication in host cells. In general, EBV remains latent in tumors and expresses a limited repertoire of latent proteins to avoid host immune surveillance. When the lytic cycle is triggered by some as-yet-unknown form of stimulation, lytic gene expression and progeny virus production commence. Thus far, the exact mechanism of EBV latency maintenance and the in vivo triggering signal for lytic induction have yet to be elucidated. Previously, we have shown that the EBV microRNA miR-BART20-5p directly targets the immediate early genes BRLF1 and BZLF1 as well as Bcl-2-associated death promoter (BAD) in EBV-associated gastric carcinoma. In this study, we found that both mRNA and protein levels of BRLF1 and BZLF1 were suppressed in cells following BAD knockdown and increased after BAD overexpression. Progeny virus production was also downregulated by specific knockdown of BAD. Our results demonstrated that caspase-3-dependent apoptosis is a prerequisite for BAD-mediated EBV lytic cycle induction. Therefore, our data suggest that miR-BART20-5p plays an important role in latency maintenance and tumor persistence of EBV-associated gastric carcinoma by inhibiting BAD-mediated caspase-3-dependent apoptosis, which would trigger immediate early gene expression. IMPORTANCE EBV has an ability to remain latent in host cells, including EBV-associated tumor cells hiding from immune surveillance. However, the exact molecular mechanisms of EBV latency maintenance remain poorly understood. Here, we demonstrated that miR-BART20-5p inhibited the expression of EBV immediate early genes indirectly, by suppressing BAD-induced caspase-3-dependent apoptosis, in addition to directly, as we previously reported. Our study suggests that EBV-associated tumor cells might endure apoptotic stress to some extent and remain latent with the aid of miR-BART20-5p. Blocking the expression or function of BART20-5p may expedite EBV-associated tumor cell death via immune attack and apoptosis. PMID:26581978

  18. Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b1

    PubMed Central

    Doherty, Melissa; Osborne, Douglas G.; Browning, Diana L.; Parker, David C.; Wetzel, Scott A.

    2010-01-01

    CD4+ T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with antigen in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study we anergized primary murine CD4+ T cells by incubation of costimulation-deficient, transfected fibroblast APC. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic cSMAC and pSMAC domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the pSMAC and the cSMAC of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance and/or induction. PMID:20207996

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

    Moon, Yuseok; Yang, Hyun; Kim, Yung Bu

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and inflammation and have also received considerable attention because of their preventive effects against human cancer. However, the drug application is sometimes limited by the severe gastrointestinal ulcers and mucosal complications. In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an immediate inducible factor, early growth response gene 1 (EGR-1). Previously we reported that sulindac sulfide can suppress tumor cell invasion by inducing EGR-1. Extending the previous study, EGR-1 induction by sulindac sulfide was observed both in the non-transformedmore » and transformed human intestinal epithelial cell lines. In terms of signaling pathway, ERK1/2 MAP kinases and its substrate Elk-1 transcription factor were involved in the sulindac sulfide-induced EGR-1 gene expression. Moreover, sulindac sulfide stimulated the nuclear translocation of the transcription factor EGR-1, which was also mediated by ERK1/2 signaling pathway. The roles of EGR-1 signals in the apoptotic cell death were assessed in the intestinal epithelial cells. Suppression of EGR-1 expression retarded cellular growth and colony forming activity in the intestinal epithelial cells. Moreover, induced EGR-1 ameliorated sulindac sulfide-mediated apoptotic cell death and enhanced the cellular survival. Taken all together, sulindac sulfide activated ERK1/2 MAP kinases which then mediated EGR-1 induction and nuclear translocation, all of which played important roles in the cellular survival from NSAID-mediated cytotoxicity in the human intestinal epithelial cells, implicating the protective roles of EGR-1 in the NSAID-mediated mucosal injuries.« less

  20. Mechanism of the stationary canalicular excretion of tributylmethyl ammonium in rats with a CCl4-induced acute hepatic injury.

    PubMed

    Choi, Min-Koo; Song, Im-Sook; Park, So-Ra; Hong, Soon-Sun; Kim, Dae-Duk; Chung, Suk-Jae; Shim, Chang-Koo

    2005-02-01

    The in vivo canalicular excretion clearance of tributylmethyl ammonium (TBuMA), a P-glycoprotein (P-gp) substrate, was previously reported to be unaffected by the induction of an experimental hepatic injury (EHI) by CCl(4) despite the increased expression of P-gp in the EHI liver. The objective of this study, therefore, was to elucidate the mechanism for the unchanged canalicular excretion clearance of TBuMA in EHI rats. TBuMA uptake was increased in cLPM vesicles from EHI rats compared with that from control rats. The total bile salt concentration in EHI liver was significantly reduced compared with that in a control liver. Because, in our previous studies, the uptake of TBuMA by cLPM vesicles was found to be significantly enhanced in the presence of bile salts, the reduction in bile salt levels in the EHI liver may be related to the unaltered TBuMA clearance. Despite the fact that the uptake of TBuMA by cLPM vesicles was increased by the addition of an EHI liver extract, the extent of the increase was comparatively less compared to the addition of a control liver extract. The in vivo excretion clearance of TBuMA was increased in a taurodeoxycholate dose-dependent manner in EHI rats. These observations suggest, therefore, that despite the induction of P-gp expression by the EHI, the in vivo canalicular excretion clearance of TBuMA remains unaltered as the result of an offset by reduced levels of bile salt(s). Copyright 2004 Wiley-Liss, Inc.

  1. Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants.

    PubMed

    Knuf, Markus; Pankow-Culot, Heidemarie; Grunert, Detlef; Rapp, Michael; Panzer, Falko; Köllges, Ralph; Fanic, Aurélie; Habib, Ahsan; Borys, Dorota; Dieussaert, Ilse; Schuerman, Lode

    2012-01-01

    Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

  2. Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

    PubMed

    Madas, Balázs G

    2016-09-01

    There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

  3. Simulator test to study hot-flow problems related to a gas cooled reactor

    NASA Technical Reports Server (NTRS)

    Poole, J. W.; Freeman, M. P.; Doak, K. W.; Thorpe, M. L.

    1973-01-01

    An advance study of materials, fuel injection, and hot flow problems related to the gas core nuclear rocket is reported. The first task was to test a previously constructed induction heated plasma GCNR simulator above 300 kW. A number of tests are reported operating in the range of 300 kW at 10,000 cps. A second simulator was designed but not constructed for cold-hot visualization studies using louvered walls. A third task was a paper investigation of practical uranium feed systems, including a detailed discussion of related problems. The last assignment resulted in two designs for plasma nozzle test devices that could be operated at 200 atm on hydrogen.

  4. Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.

    PubMed

    Cavé, Hélène; Suciu, Stefan; Preudhomme, Claude; Poppe, Bruce; Robert, Alain; Uyttebroeck, Anne; Malet, Michèle; Boutard, Patrick; Benoit, Yves; Mauvieux, Laurent; Lutz, Patrick; Méchinaud, Françoise; Grardel, Nathalie; Mazingue, Francoise; Dupont, Madeleine; Margueritte, Geneviève; Pages, Marie-Pierre; Bertrand, Yves; Plouvier, Emmanuel; Brunie, Ghislaine; Bastard, Christian; Plantaz, Dominique; Vande Velde, Isabel; Hagemeijer, Anne; Speleman, Frank; Lessard, Michel; Otten, Jacques; Vilmer, Etienne; Dastugue, Nicole

    2004-01-15

    In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (+/- SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (+/- 8.1%) and 68.3% (+/- 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (+/- 8.5%) and 75.3% (+/- 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.

  5. Cesarean section trends in the Nordic Countries - a comparative analysis with the Robson classification.

    PubMed

    Pyykönen, Aura; Gissler, Mika; Løkkegaard, Ellen; Bergholt, Thomas; Rasmussen, Steen C; Smárason, Alexander; Bjarnadóttir, Ragnheiður I; Másdóttir, Birna B; Källén, Karin; Klungsoyr, Kari; Albrechtsen, Susanne; Skjeldestad, Finn E; Tapper, Anna-Maija

    2017-05-01

    The cesarean rates are low but increasing in most Nordic countries. Using the Robson classification, we analyzed which obstetric groups have contributed to the changes in the cesarean rates. Retrospective population-based registry study including all deliveries (3 398 586) between 2000 and 2011 in Denmark, Finland, Iceland, Norway and Sweden. The Robson group distribution, cesarean rate and contribution of each Robson group were analyzed nationally for four 3-year time periods. For each country, we analyzed which groups contributed to the change in the total cesarean rate. Between the first and the last time period studied, the total cesarean rates increased in Denmark (16.4 to 20.7%), Norway (14.4 to 16.5%) and Sweden (15.5 to 17.1%), but towards the end of our study, the cesarean rates stabilized or even decreased. The increase was explained mainly by increases in the absolute contribution from R5 (women with previous cesarean) and R2a (induced labor on nulliparous). In Finland, the cesarean rate decreased slightly (16.5 to 16.2%) mainly due to decrease among R5 and R6-R7 (breech presentation, nulliparous/multiparous). In Iceland, the cesarean rate decreased in all parturient groups (17.6 to 15.3%), most essentially among nulliparous women despite the increased induction rates. The increased total cesarean rates in the Nordic countries are explained by increased cesarean rates among nulliparous women, and by an increased percentage of women with previous cesarean. Meanwhile, induction rates on nulliparous increased significantly, but the impact on the total cesarean rate was unclear. The Robson classification facilitates benchmarking and targeting efforts for lowering the cesarean rates. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  6. Using Implicit Instructional Cues to Influence False Memory Induction

    ERIC Educational Resources Information Center

    Cirelli, Laura K.; Dickinson, Joël; Poirier, Marie

    2015-01-01

    Previous research has shown that explicit cues specific to the encoding process (endogenous) or characteristic of the stimuli themselves (exogenous) can be used to direct a reader's attentional resources towards either relational or item-specific information. By directing attention to relational information (and therefore away from item-specific…

  7. THE IDENTIFICATION AND CHARACTERIZATION OF AN LGE-INDUCING PROTEIN IN METARHIZIUM ANISOPLIAE EXTRACT

    EPA Science Inventory

    Molds are ubiquitous components of the indoor environment and have been associated with exacerbation of asthma as well as a number of other health effects. Their contribution to the induction of allergic asthma is less certain. Previously, we have shown that BALB/c mice exposed...

  8. Being Influenced or Being an Influence: New Teachers' Induction Experiences

    ERIC Educational Resources Information Center

    Keay, Jeanne

    2009-01-01

    This article draws on and develops the outcomes of previous research which concluded that school subject departments provide the setting for influential professional development and that experienced teachers strongly influence their newly qualified colleagues. The findings of two subsequent research projects, which used this as a starting point,…

  9. EFFECTS OF SIZE FRACTIONATED AMBIENT PM SAMPLES ON INDUCTION OF PULMONARY ALLERGY IN MICE

    EPA Science Inventory


    There is increasing evidence that exposure to certain air pollutants including ozone and diesel exhaust can enhance allergic sensitization to allergens. Previous work from our laboratory has shown that exposure to residual oil fly ash or its associated transition metals can ...

  10. Pseudocontingencies and Choice Behavior in Probabilistic Environments with Context-Dependent Outcomes

    ERIC Educational Resources Information Center

    Meiser, Thorsten; Rummel, Jan; Fleig, Hanna

    2018-01-01

    Pseudocontingencies are inferences about correlations in the environment that are formed on the basis of statistical regularities like skewed base rates or varying base rates across environmental contexts. Previous research has demonstrated that pseudocontingencies provide a pervasive mechanism of inductive inference in numerous social judgment…

  11. Modeling the toxicokinetics of 24-hour toluene exposure in rats, impact of activity patterns and enzyme induction

    EPA Science Inventory

    Toluene, a solvent used in numerous consumer and industrial applications, exerts its critical effects on the brain and nervous system following inhalation exposure. Our previously published PBPK model successfully predicted toluene concentrations in blood and brain over a range o...

  12. The Control of Human Aggression: An Incompatible Response Strategy.

    ERIC Educational Resources Information Center

    Baron, Robert A.

    This is a brief report discussing ways of dealing with aggression in individuals. The author feels that previous approaches, such as catharsis or punishment, have proved inadequate, and that a more successful approach to reducing aggression involves the induction of incompatible reactions among aggressors. In the author's opinion, when angry…

  13. Activation of ERK signaling and induction of colon cancer cell death by piperlongumine

    USDA-ARS?s Scientific Manuscript database

    Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objectiv...

  14. The Exclusive Induction of Extinction Is Gated by BDNF

    ERIC Educational Resources Information Center

    Kirtley, Anne; Thomas, Kerrie L.

    2010-01-01

    We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268…

  15. A prospective pilot study of Dilapan-S compared with Propess for induction of labour at 41+ weeks in nulliparous pregnancy.

    PubMed

    Crosby, David A; O'Reilly, Claire; McHale, Helen; McAuliffe, Fionnuala M; Mahony, Rhona

    2017-12-21

    The incidence of labour induction has risen worldwide over the past decade, and this may contribute to the rising caesarean delivery rate. The mechanisms for induction of labour are generally divided into two categories: mechanical and pharmacological. The objective of this study was to determine if mechanical induction with Dilapan-S is an acceptable, safe method of induction of labour in post-dates uncomplicated nulliparous pregnancy. This was a single-centre prospective observational pilot study trial. Fifty-two low-risk nulliparous women with an unfavourable cervix, scheduled for induction of labour for post-dates ≥ 41 weeks gestation, were offered induction of labour with Dilapan-S or Propess from May 2016 until November 2016. The primary outcomes measured were compliance to study protocol and maternal (infection, hyperstimulation) and neonatal outcomes (Apgar score at birth). The secondary outcome measures included change in Bishop's score and caesarean delivery rate. Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S in all but one woman. There were no differences in maternal and neonatal primary outcomes between the groups. There were no cases in either arm of hyperstimulation with either induction method. No difference between the groups was noted in the caesarean delivery rate nor in the mean change in Bishop's score. Dilapan-S is an acceptable, safe form of induction of labour in post-dates uncomplicated nulliparous pregnancy. No cases of hyperstimulation were found, and therefore, Dilapan-S may be a suitable option for outpatient induction of labour in low-risk post-dates nulliparas.

  16. Conditions that influence the response to Fgf during otic placode induction.

    PubMed

    Padanad, Mahesh S; Bhat, Neha; Guo, Biwei; Riley, Bruce B

    2012-04-01

    Despite the vital importance of Fgf for otic induction, previous attempts to study otic induction through Fgf misexpression have yielded widely varying and contradictory results. There are also discrepancies regarding the ability of Fgf to induce otic tissue in ectopic locations, raising questions about the sufficiency of Fgf and the degree to which other local factors enhance or restrict otic potential. Using heat shock-inducible transgenes to misexpress Fgf3 or Fgf8 in zebrafish, we found that the stage, distribution and level of misexpression strongly influence the response to Fgf. Fgf misexpression during gastrulation can inhibit or promote otic development, depending on context, whereas misexpression after gastrulation leads to expansion of otic markers throughout preplacodal ectoderm surrounding the head. Elevated Fgf also expands expression of the putative competence factor Foxi1, which is required for Fgf to expand other otic markers. Misexpression of downstream factors Pax2a or Pax8 also expands otic markers but cannot bypass the requirement for Fgf or Foxi1. Co-misexpression of Pax2/8 with Fgf8 potentiates formation of ectopic otic vesicles expressing a full range of otic markers. These findings document the variables critically affecting the response to Fgf and clarify the roles of foxi1 and pax2/8 in the otic response. © 2012 Elsevier Inc. All rights reserved.

  17. A PBPK Model to Predict Disposition of CYP3A-Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction.

    PubMed

    Ke, A B; Nallani, S C; Zhao, P; Rostami-Hodjegan, A; Unadkat, J D

    2012-09-26

    Besides logistical and ethical concerns, evaluation of safety and efficacy of medications in pregnant women is complicated by marked changes in pharmacokinetics (PK) of drugs. For example, CYP3A activity is induced during the third trimester (T3). We explored whether a previously published physiologically based pharmacokinetic (PBPK) model could quantitatively predict PK profiles of CYP3A-metabolized drugs during T3, and discern the site of CYP3A induction (i.e., liver, intestine, or both). The model accounted for gestational age-dependent changes in maternal physiological function and hepatic CYP3A activity. For model verification, mean plasma area under the curve (AUC), peak plasma concentration (Cmax), and trough plasma concentration (Cmin) of midazolam (MDZ), nifedipine (NIF), and indinavir (IDV) were predicted and compared with published studies. The PBPK model successfully predicted MDZ, NIF, and IDV disposition during T3. A sensitivity analysis suggested that CYP3A induction in T3 is most likely hepatic and not intestinal. Our PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e3; doi:10.1038/psp.2012.2; advance online publication 26 September 2012.

  18. Radioprotection of Human Cell Nuclear DNA by Polyamines: Radiosensitivity of Chromatin is Influenced by Tightly Bound Spermine

    NASA Technical Reports Server (NTRS)

    Warters, Raymond L.; Newton, Gerald L.; Olive, Peggy L.; Fahey, Robert C.

    1999-01-01

    The polyamines putrescine (PUT) and spermine (SPM) were examined for their ability to protect human cell Deoxyribonucleic Acid (DNA) against the formation of radiation-induced double-strand breaks (DSBs). As observed previously, under conditions where polyamines were shown to be almost completely absent, association with nuclear matrix protein into a nucleoid, and organization into chromatin structure, protected DNA from induction of DSBs by factors of 4.5 and 95, respectively. At concentrations below 1 mM, PUT or SPM provided equivalent levels of protection to deproteinized nuclear DNA, consistent with their capacity to scavenge radiation-induced radicals. At constant ionic strength, 5 mM SPM protected deproteinized DNA and nucleoid DNA and DNA in nuclear chromatin by factors of 100 and 26, respectively. At 5 mM, SPM provided 15 times greater protection of deproteinized DNA than did PUT. Under physiologically relevant conditions, 5 mM SPM protected DNA in the intact nucleus from the induction of DSBs by a factor of 2 relative to DNA in the absence of SPM. Studies of SPM binding during cellular fractionation revealed that a significant fraction of the cellular SPM is tightly bound in the nucleus but can be removed by extended washing. Thus the association of SPM with nuclear chromatin appears to be a significant contributor to the resistance of the cell's DNA to the induction of DSBs.

  19. Enhanced induction of microspore embryogenesis after n-butanol treatment in wheat (Triticum aestivum L.) anther culture.

    PubMed

    Soriano, M; Cistué, L; Castillo, A M

    2008-05-01

    The aim of this study was the improvement of embryo production in wheat anther culture. Three butanol alcohols, n-butanol, sec-butanol and tert-butanol, were evaluated for their effect on microspore embryogenesis in two spring cultivars of wheat, Pavon and Caramba. Application of n-butanol, at 0.1 and 0.2% (v/v) in the induction media for 5 h, highly improved embryo production in both cultivars. Sec- and tert-butanol performed similarly to control plates. Regeneration ability was unaffected by any butyl-alcohol treatment. As a consequence of the higher embryo production after n-butanol treatment, the number of green regenerated plants increased up to five times in cultivar Pavon and up to three times in cultivar Caramba. The percentage of green plants was improved or unaffected by the treatment. Doubled haploid plant production was between 2 and 4 times higher after n-butanol treatment than in control plates. Therefore, n-butanol was successfully applied in the production of wheat doubled haploids. This primary alcohol is known as an activator of phospholipase D and has been previously reported to disrupt cortical microtubules and detach them from the plasma membrane in plants. Its effects on androgenetic induction could confirm the importance of microtubule regulation in plant cell fate, specifically in microspore development. A possible implication of phospholipase D is discussed.

  20. Identification of an activator protein required for the induction of fruA, a gene essential for fruiting body development in Myxococcus xanthus

    PubMed Central

    Ueki, Toshiyuki; Inouye, Sumiko

    2003-01-01

    Myxococcus xanthus exhibits social behavior and multicellular development. FruA is an essential transcription factor for fruiting body development in M. xanthus. In the present study, the upstream promoter region was found to be necessary for the induction of fruA expression during development. A cis-acting element required for the induction was identified and was located between nucleotides –154 and –107 with respect to the transcription initiation site. In addition, it was found that two binding sites exist within this element of the fruA promoter. By using DNA affinity column chromatography containing the cis-acting element, a fruA promoter-binding protein was purified. The purified protein was shown by N-terminal sequence analysis to be identical to MrpC, a protein identified previously by transposon insertion mutagenesis as an essential locus for fruiting body development [Sun, H. & Shi, W. (2001) J. Bacteriol. 183, 4786–4795]. Furthermore, fruA mRNA was not detectable in the mrpC::km strain, demonstrating that MrpC is essential for fruA expression. Moreover, mutational analysis of the binding sites for MrpC in the fruA promoter indicates that binding of MrpC activates transcription of fruA in vivo. This report provides evidence for a direct molecular interaction involved in temporally regulated gene expression in M. xanthus. PMID:12851461

  1. Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway

    PubMed Central

    Potu, Harish; Peterson, Luke F.; Pal, Anupama; Verhaegen, Monique; Cao, Juxiang; Talpaz, Moshe; Donato, Nicholas J.

    2014-01-01

    Usp5 is a deubiquitinase (DUB) previously shown to regulate unanchored polyubiquitin (Ub) chains, p53 transcriptional activity and double-strand DNA repair. In BRAF mutant melanoma cells, Usp5 activity was suppressed by BRAF inhibitor (vemurafenib) in sensitive but not in acquired or intrinsically resistant cells. Usp5 knockdown overcame acquired vemurafenib resistance and sensitized BRAF and NRAS mutant melanoma cells to apoptosis initiated by MEK inhibitor, cytokines or DNA-damaging agents. Knockdown and overexpression studies demonstrated that Usp5 regulates p53 (and p73) levels and alters cell growth and cell cycle distribution associated with p21 induction. Usp5 also regulates the intrinsic apoptotic pathway by modulating p53-dependent FAS expression. A small molecule DUB inhibitor (EOAI3402143) phenocopied the FAS induction and apoptotic sensitization of Usp5 knockdown and fully blocked melanoma tumor growth in mice. Overall, our results demonstrate that BRAF activates Usp5 to suppress cell cycle checkpoint control and apoptosis by blocking p53 and FAS induction; all of which can be restored by small molecule-mediated Usp5 inhibition. These results suggest that Usp5 inhibition can provide an alternate approach in recovery of diminished p53 (or p73) function in melanoma and can add to the targeted therapies already used in the treatment of melanoma. PMID:24980819

  2. c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-beta signaling in diffuse-type gastric carcinoma.

    PubMed

    Kiyono, Kunihiko; Suzuki, Hiroshi I; Morishita, Yasuyuki; Komuro, Akiyoshi; Iwata, Caname; Yashiro, Masakazu; Hirakawa, Kosei; Kano, Mitsunobu R; Miyazono, Kohei

    2009-10-01

    c-Ski, originally identified as a proto-oncogene product, is an important negative regulator of transforming growth factor (TGF)-beta family signaling through interaction with Smad2, Smad3, and Smad4. High expression of c-Ski has been found in some cancers, including gastric cancer. We previously showed that disruption of TGF-beta signaling by dominant-negative TGF-beta type II receptor in a diffuse-type gastric carcinoma model accelerated tumor growth through induction of tumor angiogenesis by decreased expression of the anti-angiogenic factor thrombospondin (TSP)-1. Here, we examined the function of c-Ski in human diffuse-type gastric carcinoma OCUM-2MLN cells. Overexpression of c-Ski inhibited TGF-beta signaling in OCUM-2MLN cells. Interestingly, c-Ski overexpression resulted in extensive acceleration of the growth of subcutaneous xenografts in BALB/c nu/nu female mice (6 weeks of age). Similar to tumors expressing dominant-negative TGF-beta type II receptor, histochemical studies revealed less fibrosis and increased angiogenesis in xenografted tumors expressing c-Ski compared to control tumors. Induction of TSP-1 mRNA by TGF-beta was attenuated by c-Ski in vitro, and expression of TSP-1 mRNA was decreased in tumors expressing c-Ski in vivo. These findings suggest that c-Ski overexpression promotes the growth of diffuse-type gastric carcinoma through induction of angiogenesis.

  3. Induction of L-phenylalanine ammonia-lyase during utilization of phenylalanine as a carbon or nitrogen source in Rhodotorula glutinis

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

    Marusich, W.C.; Jensen, R.A.; Zamir, L.O.

    Rhodotorula glutinis is a convenient source of L-phenylalanine ammonia-lyase, an enzyme that is useful as a biochemical reagent in the assay of L-phenylalanine. There have been previous descriptions of induced lyase production in complex medium where induction occurs late in exponential growth, suggesting a role in secondary metabolism such as is the case in higher plants. A higher specific activity of L-phenylalanine ammonia-lyase (sixfold higher than in complex medium) can be obtained during midexponential growth in a defined medium containing L-phenylalanine as the sole source of carbon. L-phenylalanine will also induce lyase synthesis during exponential growth in minimal medium inmore » which L-phenylalanine is the sole source of nitrogen. The appearance of lyase in complex medium supplemented with L-phenylalanine is probably triggered fortuitously by exhaustion late in growth of a prime source of nitrogen. In this study, R. glutinis appeared to express a single lyase enzyme, regardless of whether induction was nitrogen signaled or carbon signaled. Thin-layer chromatographic analysis of ether extracts prepared fom cultures induced with doubly labeled (U-/sup 14/C; ring-4-/sup 3/H) L-phenylalanine provided evidence of a catabolic sequence containing cinnamic acid, benzoic acid, and 4-hydroxybenzoic acid as degradative intermediates. 3,4-Dihydroxybenzoic acid was not identified as a catabolic intermediate.« less

  4. Induction of L-phenylalanine ammonia-lyase during utilization of phenylalanine as a carbon or nitrogen source in Rhodotorula glutinis.

    PubMed Central

    Marusich, W C; Jensen, R A; Zamir, L O

    1981-01-01

    Rhodotorula glutinis is a convenient source of L-phenylalanine ammonia-lyase, an enzyme that is useful as a biochemical reagent in the assay of L-phenylalanine. There have been previous descriptions of induced lyase production in complex medium where induction occurs late in exponential growth, suggesting a role in secondary metabolism such as is the case in higher plants. A higher specific activity of L-phenylalanine ammonia-lyase (sixfold higher than a complex medium) can be obtained during midexponential growth in a defined medium containing L-phenylalanine as the sole source of carbon. L-Phenylalanine will also induce lyase synthesis during exponential growth in minimal in which L-phenylalanine is the sole source of nitrogen. The appearance of lyase in complex medium supplemented with L-phenylalanine is probably triggered fortuitously by exhaustion late in growth of a prime source of nitrogen. In this study, R. glutinis appeared to express a single lyase enzyme, regardless of whether induction was nitrogen signaled or carbon signaled. Thin-layer chromatographic analysis of ether extracts prepared from cultures induced with doubly labeled (U-14C; ring-4-3H) L-phenylalanine provided evidence of a catabolic sequence containing cinnamic acid, benzoic acid, and 4-hydroxybenzoic acid as degradative intermediates. 3,4-Dihydroxybenzoic acid was not identified as a catabolic intermediate. PMID:7195398

  5. Immunohistochemical analysis of cytochrome P4501A induction in organs and cell types of Rivulus marmoratus exposed to waterborne 2,3,7,8-tetrachlorodibenzo-p-dioxin

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

    Stegeman, J.; Smolowitz, R.; Burnett, K.

    1994-12-31

    Identifying target cells and organs is critical to establishing the sites and mechanisms of toxicity of Ah-receptor agonists. Previous studies have described the localization of CYPLA induced in multiple organs of fish exposed to Ah-receptor agonists. Here the authors compare the responses in multiple cell types and organs of small fish (Rivulus) exposed to waterborne TCDD. Adult fish were exposed to TCDD at concentrations from 0.01 to 10 ng/liter for 48 hours, then prepared and analyzed by immunohistochemistry with monoclonal antibody to teleost CYPIAI. At the highest dose profound induction was detected in virtually every organ. Structures staining intensely were:more » nasal and cephalic chemoreceptors, including sensory and basal cells; superficial cells in skin and pharynx; cartilage cells (chondrocytes) in the head, gills, growth plates and fins; epithelial and endothelial cells of liver, gut, kidney, and gill; pseudobranch vessels and glandular cells; eye lens epithelium; endothelium in vessels of eye, brain, skin, muscle, thymus and gonad. Lesser concentrations of TCDD elicited less strong responses, and control fish showed mild staining only in cartilage structures. The dose-dependent patterns of induction differed between different cell types. Responsive cells identified is these fish indicate sites where toxicity associated with Ah-receptor agonists or with CYPLA function may be expressed.« less

  6. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

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

    Takeda, Kazuyo; Adhikari, Rewati; Yamada, Kenneth M.

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1),more » an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.« less

  7. Induction-related cost of patients with acute myeloid leukaemia in France.

    PubMed

    Nerich, Virginie; Lioure, Bruno; Rave, Maryline; Recher, Christian; Pigneux, Arnaud; Witz, Brigitte; Escoffre-Barbe, Martine; Moles, Marie-Pierre; Jourdan, Eric; Cahn, Jean Yves; Woronoff-Lemsi, Marie-Christine

    2011-04-01

    The economic profile of acute myeloid leukaemia (AML) is badly known. The few studies published on this disease are now relatively old and include small numbers of patients. The purpose of this retrospective study was to evaluate the induction-related cost of 500 patients included in the AML 2001 trial, and to determine the explanatory factors of cost. "Induction" patient's hospital stay from admission for "induction" to discharge after induction. The study was performed from the French Public Health insurance perspective, restrictive to hospital institution costs. The average management of a hospital stay for "induction" was evaluated according to the analytical accounting of Besançon University Teaching Hospital and the French public Diagnosis-Related Group database. Multiple linear regression was used to search for explanatory factors. Only direct medical costs were included: treatment and hospitalisation. Mean induction-related direct medical cost was estimated at €41,852 ± 6,037, with a mean length of hospital stay estimated at 36.2 ± 10.7 days. After adjustment for age, sex and performance status, only two explanatory factors were found: an additional induction course and salvage course increased induction-related cost by 38% (± 4) and 15% (± 1) respectively, in comparison to one induction. These explanatory factors were associated with a significant increase in the mean length of hospital stay: 45.8 ± 11.6 days for 2 inductions and 38.5 ± 15.5 if the patient had a salvage course, in comparison to 32.9 ± 7.7 for one induction (P < 10⁻⁴). This result is robust and was confirmed by sensitivity analysis. Consideration of economic constraints in health care is now a reality. Only the control of length of hospital stay may lead to a decrease in induction-related cost for patients with AML.

  8. Particle-in-cell simulations of electron beam control using an inductive current divider

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

    Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.

    2015-11-15

    Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam's return current. The current divider concept was proposed and studied theoretically in a previous publication [Swanekamp et al., Phys. Plasmas 22, 023107 (2015)]. A central post carries a portion of the return current (I{sub 1}), while the outer conductor carries the remainder (I{sub 2}) with the injected beam current given by I{sub b} = I{sub 1} + I{sub 2}. The simulations are in agreement withmore » the theory which predicts that the total force on the beam trajectory is proportional to (I{sub 2}−I{sub 1}) and the force on the beam envelope is proportional to I{sub b}. Independent control over both the current density and the beam angle at the target is possible by choosing the appropriate current-divider geometry. The root-mean-square (RMS) beam emittance (ε{sub RMS}) varies as the beam propagates through the current divider to the target. For applications where control of the beam trajectory is desired and the current density at the target is similar to the current density at the entrance foil, there is a modest 20% increase in ε{sub RMS} at the target. For other applications where the beam is pinched to a current density ∼5 times larger at the target, ε{sub RMS} is 2–3 times larger at the target.« less

  9. Alterations in expression pattern of splicing factors in epithelial ovarian cancer and its clinical impact.

    PubMed

    Iborra, Severine; Hirschfeld, Marc; Jaeger, Markus; Zur Hausen, Axel; Braicu, Iona; Sehouli, Jalid; Gitsch, Gerald; Stickeler, Elmar

    2013-07-01

    Alternative splicing represents an important nuclear mechanism in the posttranscriptional regulation of gene expression, which is frequently altered during tumorigenesis. Previously, we described marked changes in alternative splicing of the CD44 gene in ovarian and breast cancer as well as specific induction of distinct splicing factors during tumor development. The present study was focused on the expression profiles of different splicing factors, including classical serine-arginine (SR) proteins including ASF/SF2, hTra2β1, hTra2α, and Y-box-binding protein (YB-1) in physiological and malignant epithelial ovarian tissue to evaluate their expression pattern with regard to tumor development and disease progression. Expression levels of the different splicing factors were analyzed in physiological epithelial ovarian tissue samples, primary tumors, and metastatic samples of patients with a diagnosis of epithelial ovarian cancer using quantified reverse transcription polymerase chain reaction analysis. We examined more closely the splicing factor hTra2β1 using Western blot analysis and immunohistochemistry. The analysis revealed a marked and specific induction of ASF/SF2, SRp20, hTra2β1, and YB-1 in primary tumors as well as in their metastatic sites. However, in our patient cohort, no induction was seen for the other investigated splicing factors SRp55, SRp40, and hTra2α. Our results suggest a specific induction of distinct splicing factors in ovarian cancer tumorigenesis. The involvement of hTra2β1, YB-1, SRp20, and ASF/SF2 in exon recognition and alternative splicing may be important for gene regulation of alternatively spliced genes like CD44 with potential functional consequences in this tumor type leading to progression and metastasis.

  10. Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy.

    PubMed

    Touitou, Valerie; Johnson, Mary A; Guo, Yan; Miller, Neil R; Bernstein, Steven L

    2013-11-11

    Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. TOXICITY was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

  11. Support vector inductive logic programming outperforms the naive Bayes classifier and inductive logic programming for the classification of bioactive chemical compounds.

    PubMed

    Cannon, Edward O; Amini, Ata; Bender, Andreas; Sternberg, Michael J E; Muggleton, Stephen H; Glen, Robert C; Mitchell, John B O

    2007-05-01

    We investigate the classification performance of circular fingerprints in combination with the Naive Bayes Classifier (MP2D), Inductive Logic Programming (ILP) and Support Vector Inductive Logic Programming (SVILP) on a standard molecular benchmark dataset comprising 11 activity classes and about 102,000 structures. The Naive Bayes Classifier treats features independently while ILP combines structural fragments, and then creates new features with higher predictive power. SVILP is a very recently presented method which adds a support vector machine after common ILP procedures. The performance of the methods is evaluated via a number of statistical measures, namely recall, specificity, precision, F-measure, Matthews Correlation Coefficient, area under the Receiver Operating Characteristic (ROC) curve and enrichment factor (EF). According to the F-measure, which takes both recall and precision into account, SVILP is for seven out of the 11 classes the superior method. The results show that the Bayes Classifier gives the best recall performance for eight of the 11 targets, but has a much lower precision, specificity and F-measure. The SVILP model on the other hand has the highest recall for only three of the 11 classes, but generally far superior specificity and precision. To evaluate the statistical significance of the SVILP superiority, we employ McNemar's test which shows that SVILP performs significantly (p < 5%) better than both other methods for six out of 11 activity classes, while being superior with less significance for three of the remaining classes. While previously the Bayes Classifier was shown to perform very well in molecular classification studies, these results suggest that SVILP is able to extract additional knowledge from the data, thus improving classification results further.

  12. Induction of hepatic and renal ornithine decarboxylase by cobalt and other metal ions in rats.

    PubMed Central

    Yoshida, T; Numazawa, S; Kuroiwa, Y

    1986-01-01

    We previously showed that Cd2+ is able to induce hepatic and renal ornithine decarboxylase (ODC). In addition to Cd2+, the administration of Co2+ and other metal ions such as Se2+, Zn2+ and Cr2+ produced a significant increase of hepatic and/or renal ODC activity. Of the metal ions used in this study, Co2+ produced the greatest increase of ODC activity. The maximum increases in hepatic and renal ODC activity, to respectively 70 and 14 times the control values in male rats, were observed 6 h after the administration of Co2+. A similar response was seen in the liver, but not in the kidney, of female rats. Thereafter, ODC activity gradually returned to control values in the liver, but it was profoundly decreased to 7% of the control value at 24 h in the kidney. The pretreatment of animals with either actinomycin D or cycloheximide almost completely blocked the Co2+-mediated increase of ODC activity. Co2+ complexed with either cysteine or glutathione (GSH) failed to induce ODC. Depletion of hepatic GSH content by treatment of rats with diethyl maleate greatly enhanced the inducing effect of Co2+ on ODC. The inhibitors of ODC, 1,3-diaminopropane and alpha-difluoromethylornithine, were able to inhibit the induction of the enzyme, without affecting the induction of haem oxygenase by Co2+. Methylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, significantly inhibited the Co2+-mediated induction of both ODC and haem oxygenase. It is suggested that the inducing effects of Co2+ on ODC and haem oxygenase are brought about in a similar manner. PMID:3754136

  13. Differential induction of antioxidant stilbenoids in hairy roots of Vitis rotundifolia treated with methyl jasmonate and hydrogen peroxide.

    PubMed

    Nopo-Olazabal, Cesar; Condori, Jose; Nopo-Olazabal, Luis; Medina-Bolivar, Fabricio

    2014-01-01

    Stilbenoids are polyphenolic phytoalexins that exhibit potential health applications in humans. Hairy root cultures of muscadine grape (Vitis rotundifolia Michx.) were used to study the biochemical and molecular regulation of stilbenoid biosynthesis upon treatment with 100 μM methyl jasmonate (MeJA) or 10 mM hydrogen peroxide (H2O2) over a 96-h period. Resveratrol, piceid, and ε-viniferin were identified in higher concentrations in the tissue whereas resveratrol was the most abundant stilbenoid in the medium under either treatment. An earlier increase in resveratrol accumulation was observed for the MeJA-treated group showing a maximum at 12 h in the tissue and 18 h in the medium. Furthermore, the antioxidant capacity of extracts from the tissue and medium was determined by the 2,2'-azinobis[3-ethylbenzthiazoline sulfonic acid] (ABTS) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays showing correlation with the stilbenoid content. Fourteen candidate reference genes for qPCR were tested under the described experimental conditions and resulted in the selection of 5 reference genes. Quantitative analyses of transcripts for phenylalanine ammonia-lyase (PAL), resveratrol synthase (RS), and two stilbene synthases (STS and STS2) showed the highest RNA level induction at 3 h for both treatments with a higher induction for the MeJA treatment. In contrast, the flavonoid-related chalcone synthase (CHS) transcripts showed induction and a decrease in expression for MeJA and H2O2 treatments, respectively. The observed responses could be related to an oxidative burst triggered by the exposure to abiotic stressor compounds with signaling function such as MeJA and H2O2 which have been previously related to the synthesis of secondary metabolites. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends

    NASA Technical Reports Server (NTRS)

    Lobrich, M.; Rydberg, B.; Cooper, P. K.; Chatterjee, A. (Principal Investigator)

    1995-01-01

    An assay that allows measurement of absolute induction frequencies for DNA double-strand breaks (dsbs) in defined regions of the genome and that quantitates rejoining of correct DNA ends has been used to study repair of dsbs in normal human fibroblasts after x-irradiation. The approach involves hybridization of single-copy DNA probes to Not I restriction fragments separated according to size by pulsed-field gel electrophoresis. Induction of dsbs is quantitated from the decrease in the intensity of the hybridizing restriction fragment and an accumulation of a smear below the band. Rejoining of dsbs results in reconstitution of the intact restriction fragment only if correct DNA ends are joined. By comparing results from this technique with results from a conventional electrophoresis assay that detects all rejoining events, it is possible to quantitate the misrejoining frequency. Three Not I fragments on the long arm of chromosome 21 were investigated with regard to dsb induction, yielding an identical induction rate of 5.8 X 10(-3) break per megabase pair per Gy. Correct dsb rejoining was measured for two of these Not I fragments after initial doses of 80 and 160 Gy. The misrejoining frequency was about 25% for both fragments and was independent of dose. This result appears to be representative for the whole genome as shown by analysis of the entire Not I fragment distribution. The correct rejoining events primarily occurred within the first 2 h, while the misrejoining kinetics included a much slower component, with about half of the events occurring between 2 and 24 h. These misrejoining kinetics are similar to those previously reported for production of exchange aberrations in interphase chromosomes.

  15. Oral administration with diosgenin enhances the induction of intestinal T helper 1-like regulatory T cells in a murine model of food allergy.

    PubMed

    Huang, Chung-Hsiung; Wang, Chia-Chi; Lin, Yu-Chin; Hori, Masatoshi; Jan, Tong-Rong

    2017-01-01

    Although the development of T helper (Th)1-like regulatory T (Treg) cells under Th1 inflammatory conditions has been reported, the role of Th1-like Treg cells in Th2 allergic responses remains mostly unclear. We previously demonstrated that diosgenin, the major sapogenin contained in the Chinese yam, attenuated food allergy and augmented Th1 and Treg immune responses. In this study, we hypothesized that diosgenin may enhance the induction of Th1-like Treg cells in the gut of mice with food allergy. Ovalbumin (OVA)-sensitized BALB/c mice were gavaged daily with diosgenin and received repeatedly intragastric ovalbumin challenges to induce intestinal allergic responses. The induction of Foxp3 + Treg cells co-expressing Th1-type transcription factors, cytokines and chemokines in the intestine was examined, and the mRNA expression of the chemokines corresponding to Th1-like Treg cells was measured. Diosgenin administration increased the number of Foxp3 + Treg cells co-expressing Th1 markers, including CCR5, CXCR3, IFN-γ and T-bet in the intestine, and enhanced populations of Foxp3 + IFN-γ + and Foxp3 + T-bet + cells that expressed the regulatory cytokine IL-10 in the Peyer's patches. Diosgenin also augmented the intestinal expression of CXCR3, CCL3, and CXCL10. Concordantly, diosgenin increased the number of CXCR3 + Foxp3 + IL-10 cells in the Peyer's patches. Our data demonstrated the enhanced induction of Th1-like Treg cells in allergic mice treated with diosgenin, providing evidence to suggest a role for Th1-like Treg cells in diosgenin-mediated anti-allergic effects against Th2-type allergy. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Killing of Human Melanoma Cells Induced by Activation of Class I Interferon–Regulated Signaling Pathways via MDA-7/IL-24

    PubMed Central

    Ekmekcioglu, Suhendan; Mumm, John B.; Udtha, Malini; Chada, Sunil; Grimm, Elizabeth A.

    2008-01-01

    Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1–regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN alfa) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of Class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN beta induction followed by IRF regulation and TRAIL/FasL system activation. PMID:18511292

  17. Stress disrupts the reconsolidation of fear memories in men.

    PubMed

    Meir Drexler, Shira; Wolf, Oliver T

    2017-03-01

    Reconsolidation is a post-retrieval process of restabilization of the memory trace. Previous findings from our group suggest that cortisol, a glucocorticoid hormone secreted in response to stress, enhances the reconsolidation of fear memories in healthy men. Cortisol effect was found to be very specific, enhancing only the fear memory that was reactivated (i.e. retrieved), but not the non-reactivated memory. In the current study we aimed to investigate the effects of psychosocial stress, a more ecologically valid intervention, on fear memory reconsolidation in men. Using a similar design, we expected stress induction to have comparable effects to those of cortisol intake. During the three testing days, the participants went through (1) fear acquisition, (2) stress induction and memory reactivation (or the corresponding control conditions), (3) fear extinction, reinstatement and reinstatement test. Salivary cortisol, blood pressure measures and subjective ratings confirmed the success of the stress induction. Skin conductance response, serving as a measure of conditioned fear, confirmed acquisition, fear retrieval, and extinction in all groups. In the three control groups (where either reactivation, stress, or both components were missing) reinstatement effects were seen as expected. Yet in contrast to the hypothesis, the target group (i.e. combining reactivation and stress) showed no reinstatement to any of the stimuli. Stress induction is thus suggested to have a general impairing effect on the reconsolidation of fear memories. The unique characteristic of the stress response and experience compared to a pharmacological intervention are proposed as possible explanations to the findings. This disruptive effect of stress on fear memory reconsolidation may have potential therapeutic implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.

    PubMed

    Chen, Ting; Gu, Chengxin; Xue, Cailin; Yang, Tao; Zhong, Yun; Liu, Shiming; Nie, Yuqiang; Yang, Hui

    2017-01-01

    Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.

  19. L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

    PubMed

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

    PubMed

    Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

    2013-03-15

    This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

  1. Pulsed laser illumination of photovoltaic cells

    NASA Technical Reports Server (NTRS)

    Yater, Jane A.; Lowe, Roland A.; Jenkins, Phillip P.; Landis, Geoffrey A.

    1995-01-01

    In future space missions, free electron lasers (FEL) may be used to illuminate photovoltaic receivers to provide remote power. Both the radio-frequency (RF) and induction FEL produce pulsed rather than continuous output. In this work we investigate cell response to pulsed laser light which simulates the RF FEL format. The results indicate that if the pulse repetition is high, cell efficiencies are only slightly reduced compared to constant illumination at the same wavelength. The frequency response of the cells is weak, with both voltage and current outputs essentially dc in nature. Comparison with previous experiments indicates that the RF FEL pulse format yields more efficient photovoltaic conversion than does an induction FEL format.

  2. Pulsed laser illumination of photovoltaic cells

    NASA Technical Reports Server (NTRS)

    Yater, Jane A.; Lowe, Roland A.; Jenkins, Phillip P.; Landis, Geoffrey A.

    1994-01-01

    In future space missions, free electron lasers (FEL) may be used to illuminate photovoltaic array receivers to provide remote power. Both the radio-frequency (RF) and induction FEL provide FEL produce pulsed rather than continuous output. In this work we investigate cell response to pulsed laser light which simulates the RF FEL format. The results indicate that if the pulse repetition is high, cell efficiencies are only slightly reduced compared to constant illumination at the same wavelength. The frequency response of the cells is weak, with both voltage and current outputs essentially dc in nature. Comparison with previous experiments indicates that the RF FEL pulse format yields more efficient photovoltaic conversion than does an induction FEL pulse format.

  3. Imaging of Selenium by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in 2-D Electrophoresis Gels and Biological Tissues.

    PubMed

    Cruz, Elisa Castañeda Santa; Susanne Becker, J; Sabine Becker, J; Sussulini, Alessandra

    2018-01-01

    Selenium and selenoproteins are important components of living organisms that play a role in different biological processes. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful analytical technique that has been employed to obtain distribution maps of selenium in biological tissues in a direct manner, as well as in selenoproteins, previously separated by their molecular masses and isoelectric points using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In this chapter, we present the protocols to perform LA-ICP-MS imaging experiments, allowing the distribution visualization and determination of selenium and/or selenoproteins in biological systems.

  4. Broadband parametric amplifiers based on nonlinear kinetic inductance artificial transmission lines

    NASA Astrophysics Data System (ADS)

    Chaudhuri, S.; Li, D.; Irwin, K. D.; Bockstiegel, C.; Hubmayr, J.; Ullom, J. N.; Vissers, M. R.; Gao, J.

    2017-04-01

    We present broadband parametric amplifiers based on the kinetic inductance of superconducting NbTiN thin films in an artificial (lumped-element) transmission line architecture. We demonstrate two amplifier designs implementing different phase matching techniques: periodic impedance loading and resonator phase shifters placed periodically along the transmission line. Our design offers several advantages over previous CPW-based amplifiers, including intrinsic 50 Ω characteristic impedance, natural suppression of higher pump harmonics, lower required pump power, and shorter total trace length. Experimental realizations of both versions of the amplifiers are demonstrated. With a transmission line length of 20 cm, we have achieved gains of 15 dB over several GHz of bandwidth.

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

    Chesnokov, E. N., E-mail: chesnok@kinetics.nsc.ru; Novosibirsk State University, Novosibirsk 630090; Kubarev, V. V.

    Using the pulses of terahertz free electron laser and ultra-fast Schottky diode detectors, we observed the coherent transients within a free induction decay of gaseous nitrogen dioxide NO{sub 2}. The laser excited different sub-bands of rotation spectra of NO{sub 2} containing about 50–70 lines. The free induction signal continued more than 30 ns and consisted of many echo-like bursts duration about 0.2 ns. Unlike the similar effect observed previously for linear and symmetric top molecules, the sequence of echo bursts is not periodic. The values for delay of individual echo are stable, and the set of these delays can be considered asmore » a “molecular fingerprint” in the time domain.« less

  6. Minimally-invasive Laser Ablation Inductively Coupled Plasma Mass Spectrometry analysis of model ancient copper alloys

    NASA Astrophysics Data System (ADS)

    Walaszek, Damian; Senn, Marianne; Wichser, Adrian; Faller, Markus; Wagner, Barbara; Bulska, Ewa; Ulrich, Andrea

    2014-09-01

    This work describes an evaluation of a strategy for multi-elemental analysis of typical ancient bronzes (copper, lead bronze and tin bronze) by means of laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS).The samples originating from archeological experiments on ancient metal smelting processes using direct reduction in a ‘bloomery’ furnace as well as historical casting techniques were investigated with the use of the previously proposed analytical procedure, including metallurgical observation and preliminary visual estimation of the homogeneity of the samples. The results of LA-ICPMS analysis were compared to the results of bulk composition obtained by X-ray fluorescence spectrometry (XRF) and by inductively coupled plasma mass spectrometry (ICPMS) after acid digestion. These results were coherent for most of the elements confirming the usefulness of the proposed analytical procedure, however the reliability of the quantitative information about the content of the most heterogeneously distributed elements was also discussed in more detail.

  7. The application of magnetic gradiometry and electromagnetic induction at a former radioactive waste disposal site.

    PubMed

    Rucker, Dale Franklin

    2010-04-01

    A former radioactive waste disposal site is surveyed with two non-intrusive geophysical techniques, including magnetic gradiometry and electromagnetic induction. Data were gathered over the site by towing the geophysical equipment mounted to a non-electrically conductive and non-magnetic fibre-glass cart. Magnetic gradiometry, which detects the location of ferromagnetic material, including iron and steel, was used to map the existence of a previously unknown buried pipeline formerly used in the delivery of liquid waste to a number of surface disposal trenches and concrete vaults. The existence of a possible pipeline is reinforced by historical engineering drawing and photographs. The electromagnetic induction (EMI) technique was used to map areas of high and low electrical conductivity, which coincide with the magnetic gradiometry data. The EMI also provided information on areas of high electrical conductivity unrelated to a pipeline network. Both data sets demonstrate the usefulness of surface geophysical surveillance techniques to minimize the risk of exposure in the event of future remediation efforts.

  8. 3-Decylcatechol induces autophagy-mediated cell death through the IRE1α/JNK/p62 in hepatocellular carcinoma cells

    PubMed Central

    Kim, Jin-A; Jo, In-Hwa; Han, Yeon Soo; Jo, Yong Hun; Kim, Kwang-Youn; Seo, Young-Kyo; Moon, Jae-Hak; Jung, Chang Hwa; Jeon, Tae-Il

    2017-01-01

    The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation. The autophagy inhibitor, chloroquine, suppressed autolysosome formation and cell death induction by DC, indicating an autophagic cell death. Interestingly, DC also activated the endoplasmic reticulum (ER) stress response that promotes autophagy via p62 transcriptional activation involving the inositol-requiring enzyme 1α/c-Jun N-terminal kinase/c-jun pathway. We also show that cytosolic calcium mobilization is necessary for the ER stress response and autophagy induction by DC. These findings reveal a novel mechanism by which this urushiol derivative induces autophagic cell death in HCC. PMID:28938597

  9. Dendritic spine dynamics in synaptogenesis after repeated LTP inductions: Dependence on pre-existing spine density

    PubMed Central

    Oe, Yuki; Tominaga-Yoshino, Keiko; Hasegawa, Sho; Ogura, Akihiko

    2013-01-01

    Not only from our daily experience but from learning experiments in animals, we know that the establishment of long-lasting memory requires repeated practice. However, cellular backgrounds underlying this repetition-dependent consolidation of memory remain largely unclear. We reported previously using organotypic slice cultures of rodent hippocampus that the repeated inductions of LTP (long-term potentiation) lead to a slowly developing long-lasting synaptic enhancement accompanied by synaptogenesis distinct from LTP itself, and proposed this phenomenon as a model system suitable for the analysis of the repetition-dependent consolidation of memory. Here we examined the dynamics of individual dendritic spines after repeated LTP-inductions and found the existence of two phases in the spines' stochastic behavior that eventually lead to the increase in spine density. This spine dynamics occurred preferentially in the dendritic segments having low pre-existing spine density. Our results may provide clues for understanding the cellular bases underlying the repetition-dependent consolidation of memory. PMID:23739837

  10. Proceedings of the Workshop on Change of Representation and Problem Reformulation

    NASA Technical Reports Server (NTRS)

    Lowry, Michael R.

    1992-01-01

    The proceedings of the third Workshop on Change of representation and Problem Reformulation is presented. In contrast to the first two workshops, this workshop was focused on analytic or knowledge-based approaches, as opposed to statistical or empirical approaches called 'constructive induction'. The organizing committee believes that there is a potential for combining analytic and inductive approaches at a future date. However, it became apparent at the previous two workshops that the communities pursuing these different approaches are currently interested in largely non-overlapping issues. The constructive induction community has been holding its own workshops, principally in conjunction with the machine learning conference. While this workshop is more focused on analytic approaches, the organizing committee has made an effort to include more application domains. We have greatly expanded from the origins in the machine learning community. Participants in this workshop come from the full spectrum of AI application domains including planning, qualitative physics, software engineering, knowledge representation, and machine learning.

  11. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants

    PubMed Central

    De Rosa, Veronica; Galgani, Mario; Porcellini, Antonio; Colamatteo, Alessandra; Santopaolo, Marianna; Zuchegna, Candida; Romano, Antonella; De Simone, Salvatore; Procaccini, Claudio; La Rocca, Claudia; Carrieri, Pietro Biagio; Maniscalco, Giorgia Teresa; Salvetti, Marco; Buscarinu, Maria Chiara; Franzese, Adriana; Mozzillo, Enza; La Cava, Antonio; Matarese, Giuseppe

    2016-01-01

    Human regulatory T cells (Treg cells) that develop from conventional T cells (Tconv cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced Treg cells (iTreg cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iTreg cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2–related suppressive activity of iTreg cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of Treg cells in health and in autoimmunity. PMID:26414764

  12. New method for solving inductive electric fields in the non-uniformly conducting ionosphere

    NASA Astrophysics Data System (ADS)

    Vanhamäki, H.; Amm, O.; Viljanen, A.

    2006-10-01

    We present a new calculation method for solving inductive electric fields in the ionosphere. The time series of the potential part of the ionospheric electric field, together with the Hall and Pedersen conductances serves as the input to this method. The output is the time series of the induced rotational part of the ionospheric electric field. The calculation method works in the time-domain and can be used with non-uniform, time-dependent conductances. In addition, no particular symmetry requirements are imposed on the input potential electric field. The presented method makes use of special non-local vector basis functions called the Cartesian Elementary Current Systems (CECS). This vector basis offers a convenient way of representing curl-free and divergence-free parts of 2-dimensional vector fields and makes it possible to solve the induction problem using simple linear algebra. The new calculation method is validated by comparing it with previously published results for Alfvén wave reflection from a uniformly conducting ionosphere.

  13. Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning.

    PubMed

    Léger, Sophie; Brand, Michael

    2002-11-01

    The vertebrate inner ear develops from initially 'simple' ectodermal placode and vesicle stages into the complex three-dimensional structure which is necessary for the senses of hearing and equilibrium. Although the main morphological events in vertebrate inner ear development are known, the genetic mechanisms controlling them are scarcely understood. Previous studies have suggested that the otic placode is induced by signals from the chordamesoderm and the hindbrain, notably by fibroblast growth factors (Fgfs) and Wnt proteins. Here we study the role of Fgf8 as a bona-fide hindbrain-derived signal that acts in conjunction with Fgf3 during placode induction, maintenance and otic vesicle patterning. Acerebellar (ace) is a mutant in the fgf8 gene that results in a non-functional Fgf8 product. Homozygous mutants for acerebellar (ace) have smaller ears that typically have only one otolith, abnormal semi-circular canals, and behavioral defects. Using gene expression markers for the otic placode, we find that ace/fgf8 and Fgf-signaling are required for normal otic placode formation and maintenance. Conversely, misexpression of fgf8 or Fgf8-coated beads implanted into the vicinity of the otic placode can increase ear size and marker gene expression, although competence to respond to the induction appears restricted. Cell transplantation experiments and expression analysis suggest that Fgf8 is required in the hindbrain in the rhombomere 4-6 area to restore normal placode development in ace mutants, in close neighbourhood to the forming placode, but not in mesodermal tissues. Fgf3 and Fgf8 are expressed in hindbrain rhombomere 4 during the stages that are critical for placode induction. Joint inactivation of Fgf3 and Fgf8 by mutation or antisense-morpholino injection causes failure of placode formation and results in ear-less embryos, mimicking the phenotype we observe after pharmacological inhibition of Fgf-signaling. Fgf8 and Fgf3 together therefore act during induction and differentiation of the ear placode. In addition to the early requirement for Fgf signaling, the abnormal differentiation of inner ear structures and mechanosensory hair cells in ace mutants, pharmacological inhibition of Fgf signaling, and the expression of fgf8 and fgf3 in the otic vesicle demonstrate independent Fgf function(s) during later development of the otic vesicle and lateral line organ. We furthermore addressed a potential role of endomesomerm by studying mzoep mutant embryos that are depleted of head endomesodermal tissue, including chordamesoderm, due to a lack of Nodal-pathway signaling. In these embryos, early placode induction proceeds largely normally, but the ear placode extends abnormally to midline levels at later stages, suggesting a role for the midline in restricting placode development to dorsolateral levels. We suggest a model of zebrafish inner ear development with several discrete steps that utilize sequential Fgf signals during otic placode induction and vesicle patterning. Copyright 2002 Elsevier Science Ireland Ltd.

  14. Pregnancy outcomes of induced labor in women with previous cesarean section: a systematic review and meta-analysis.

    PubMed

    Rossi, A C; Prefumo, Federico

    2015-02-01

    To systematically review the literature about maternal and neonatal outcomes following induction of labor (IOL) and spontaneous labor (SL) in women with previous cesarean section (PCS). PubMed, Medline, EMBASE, Cochrane library searches; January 2000-February 2013. women attempting labor after PCS, singleton term pregnancies. Women undergoing IOL were compared with women in SL. Method for induction, mode of delivery, uterine rupture/dehiscence, post-partum hemorrhage, emergency hysterectomy and any maternal or neonatal morbidity and mortality were analyzed. MOOSE guidelines were followed. Interstudies heterogeneity was tested. A random effect model was generated if heterogeneity was >25 %. Pooled odds ratio with 95 % confidence interval (OR, 95 % CI) were calculated. Eight articles included 4,038 women with IOL (23.2 %) and 13,374 women with SL (76.8 %). IOL was associated with a lower incidence of vaginal delivery (OR 0.66; 95 % CI 0.55-0.80) and higher rates of cesarean section (OR 1.52; 95 % CI 1.26-1.83), uterine rupture/dehiscence (OR 1.62; 95 % CI 1.13-2.31), and post-partum hemorrhage (OR 1.57; 95 % CI 1.20-2.04), although hysterectomy was similar between the two groups (OR 2.60; 95 % CI 0.52-13.1). Neonatal morbidity was similar after IOL or SL (OR 1.13; 95 % CI 0.75-1.69). Induction of labor increases the risk of uterine rupture/dehiscence and of repeat cesarean section.

  15. The association of panic and hyperventilation with psychogenic non-epileptic seizures: A systematic review and meta-analysis.

    PubMed

    Indranada, Alaric M; Mullen, Saul A; Duncan, Roderick; Berlowitz, David J; Kanaan, Richard A A

    2018-07-01

    Psychogenic Non-Epileptic Seizures (PNES) are events that appear epileptic but are instead thought to have a psychological origin. Increased rates of several psychiatric disorders have been reported in PNES, including anxiety and panic disorders. Some theories suggest panic and/or hyperventilation have aetiological roles in PNES, though these remain unproven. We conducted a systematic review of associations of panic and hyperventilation with PNES using Ovid Medline and PubMed, and a meta-analysis where appropriate. We found eighteen studies reporting rates of panic in PNES and eight studies reporting hyperventilation. The reported rate of panic attacks in PNES ranged from 17% to 83%, with physical symptoms more commonly reported, and affective symptoms less so. 'Dizziness or light-headedness' was found to be more prevalent than 'fear of dying' by random-effects meta-analysis (68% vs. 23%). A proportion meta-analysis found a weighted occurrence of 20% of panic disorder in PNES. A pooled meta-analytic rate of PNES events following voluntary hyperventilation induction was 30%, while the clinically observed rates of peri-ictal hyperventilation in PNES without induction varied from 15 to 46%. Previous studies have reported moderate rates of association of panic in PNES, though the proportions varied considerably across the literature, with physical symptoms more commonly reported than affective. Hyperventilation is an effective inducer of PNES events in a minority, and can be observed occurring in a minority of patients without induction. These results support an important, albeit not essential, role for panic and hyperventilation in the pathogenesis of PNES events. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  16. Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.

    PubMed

    Lokhandwala, Shehnaz; Waghela, Suryakant D; Bray, Jocelyn; Martin, Cameron L; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R; Mwangi, Duncan; Dominowski, Paul J; Foss, Dennis L; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G; Brake, David; Neilan, John; Mwangi, Waithaka

    2016-11-01

    The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ + ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Up-regulation of human prostaglandin reductase 1 improves the efficacy of hydroxymethylacylfulvene, an antitumor chemotherapeutic agent.

    PubMed

    Yu, Xiang; Erzinger, Melanie M; Pietsch, Kathryn E; Cervoni-Curet, Frances N; Whang, John; Niederhuber, John; Sturla, Shana J

    2012-11-01

    Prostaglandin reductase 1 (PTGR1) is a highly inducible enzyme with enone reductase activity. Previous studies demonstrated the role of rat PTGR1 in the activation of acylfulvene analogs, a class of antitumor natural product derivatives. Of these, hydroxymethylacylfulvene (HMAF) was in advanced clinical development for the treatment of advanced solid tumors, including prostate, ovarian, and pancreatic cancers. However, the efficiency of human PTGR1 in activating acylfulvenes and its potential to enhance therapeutic efficacy have remained uncharacterized. In this study, human PTGR1 was polymerase chain reaction-cloned and purified. Conversion of HMAF to its cellular metabolite by the purified enzyme proceeded at a 20-fold higher rate than with the rat variant of the enzyme. The Km was 4.9 μM, which was 40-fold lower than for the rat variant and similar to the therapeutic dose. Human cell lines, including colon cancer lines, were transfected with a vector containing rat PTGR1 or human PTGR1, and cell viability was examined after dosing with HMAF. New data obtained in this study suggest that transfection with human PTGR1, or its induction in colon and liver cancer cell lines with 1,2-dithiol-3-thione, enhances susceptibility to the cytotoxic influences of HMAF by 2- to 10-fold. Furthermore, similar or enhanced enzyme induction and HMAF toxicity results from preconditioning cancer cells with the bioactive food components curcumin and resveratrol. The functional impact of PTGR1 induction in human cells and chemical-based strategies for its activation can provide important knowledge for the design of clinical strategies involving reductively activated cytotoxic chemotherapeutics.

  18. Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens

    PubMed Central

    Waghela, Suryakant D.; Bray, Jocelyn; Martin, Cameron L.; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R.; Mwangi, Duncan; Dominowski, Paul J.; Foss, Dennis L.; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G.; Brake, David; Neilan, John

    2016-01-01

    The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ+) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. PMID:27628166

  19. Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells

    PubMed Central

    Lukiw, Walter J.; Pogue, Aileen I.

    2007-01-01

    Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death. PMID:17629564

  20. Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

    PubMed

    van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

    2001-11-01

    Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

  1. Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species.

    PubMed

    Zhang, Aifeng; Sheng, Yuqing; Zou, Mingchang

    2017-03-01

    Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. c-Met and its ligand hepatocyte growth factor/scatter factor regulate mature B cell survival in a pathway induced by CD74.

    PubMed

    Gordin, Maya; Tesio, Melania; Cohen, Sivan; Gore, Yael; Lantner, Frida; Leng, Lin; Bucala, Richard; Shachar, Idit

    2010-08-15

    The signals regulating the survival of mature splenic B cells have become a major focus in recent studies of B cell immunology. Durable B cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. In this study, we describe a novel biological mechanism involved in mature B cell homeostasis, the hepatocyte growth factor/scatter factor (HGF)/c-Met pathway. We demonstrate that c-Met activation by HGF leads to a survival cascade, whereas its blockade results in induction of mature B cell death. Our results emphasize a unique and critical function for c-Met signaling in the previously described macrophage migration inhibitory factor/CD74-induced survival pathway. Macrophage migration inhibitory factor recruits c-Met to the CD74/CD44 complex and thereby enables the induction of a signaling cascade within the cell. This signal results in HGF secretion, which stimulates the survival of the mature B cell population in an autocrine manner. Thus, the CD74-HGF/c-Met axis defines a novel physiologic survival pathway in mature B cells, resulting in the control of the humoral immune response.

  3. Chemical and toxicological characterizations of hydraulic fracturing flowback and produced water.

    PubMed

    He, Yuhe; Flynn, Shannon L; Folkerts, Erik J; Zhang, Yifeng; Ruan, Dongliang; Alessi, Daniel S; Martin, Jonathan W; Goss, Greg G

    2017-05-01

    Hydraulic fracturing (HF) has emerged as a major method of unconventional oil and gas recovery. The toxicity of hydraulic fracturing flowback and produced water (HF-FPW) has not been previously reported and is complicated by the combined complexity of organic and inorganic constituents in HF fluids and deep formation water. In this study, we characterized the solids, salts, and organic signatures in an HF-FPW sample from the Duvernay Formation, Alberta, Canada. Untargeted HPLC-Orbitrap revealed numerous unknown dissolved polar organics. Among the most prominent peaks, a substituted tri-phenyl phosphate was identified which is likely an oxidation product of a common polymer antioxidant. Acute toxicity of zebrafish embryo was attributable to high salinity and organic contaminants in HF-FPW with LC50 values ranging from 0.6% to 3.9%, depending on the HF-FPW fractions and embryo developmental stages. Induction of ethoxyresorufin-O-deethylase (EROD) activity was detected, due in part to polycyclic aromatic hydrocarbons (PAHs), and suspended solids might have a synergistic effect on EROD induction. This study demonstrates that toxicological profiling of real HF-FPW sample presents great challenges for assessing the potential risks and impacts posed by HF-FPW spills. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Optimal Control of Inspired Perfluorocarbon Temperature for Ultrafast Hypothermia Induction by Total Liquid Ventilation in an Adult Patient Model.

    PubMed

    Nadeau, Mathieu; Sage, Michael; Kohlhauer, Matthias; Mousseau, Julien; Vandamme, Jonathan; Fortin-Pellerin, Etienne; Praud, Jean-Paul; Tissier, Renaud; Walti, Herve; Micheau, Philippe

    2017-12-01

    Recent preclinical studies have shown that therapeutic hypothermia induced in less than 30 min by total liquid ventilation (TLV) strongly improves the survival rate after cardiac arrest. When the lung is ventilated with a breathable perfluorocarbon liquid, the inspired perfluorocarbon allows us to control efficiently the cooling process of the organs. While TLV can rapidly cool animals, the cooling speed in humans remains unknown. The objective is to predict the efficiency and safety of ultrafast cooling by TLV in adult humans. It is based on a previously published thermal model of ovines in TLV and the design of a direct optimal controller to compute the inspired perfluorocarbon temperature profile. The experimental results in an adult sheep are presented. The thermal model of sheep is subsequently projected to a human model to simulate the optimal hypothermia induction and its sensitivity to physiological parameter uncertainties. The results in the sheep showed that the computed inspired perfluorocarbon temperature command can avoid arterial temperature undershoot. The projection to humans revealed that mild hypothermia should be ultrafast (reached in fewer than 3 min (-72 °C/h) for the brain and 20 min (-10 °C/h) for the entire body). The projection to human model allows concluding that therapeutic hypothermia induction by TLV can be ultrafast and safe. This study is the first to simulate ultrafast cooling by TLV in a human model and is a strong motivation to translate TLV to humans to improve the quality of life of postcardiac arrest patients.

  5. Correlation between hepatocarcinogenic effect of estragole and its influence on glucocorticoid induction of liver-specific enzymes and activities of FOXA and HNF4 transcription factors in mouse and rat liver.

    PubMed

    Kaledin, V I; Pakharukova, M Yu; Pivovarova, E N; Kropachev, K Yu; Baginskaya, N V; Vasilieva, E D; Ilnitskaya, S I; Nikitenko, E V; Kobzev, V F; Merkulova, T I

    2009-04-01

    It is known that the carcinogenic effect of estragole, a component of essential oils of many spicy plants, is characterized by species, tissue, and sex specificity. It causes mainly liver tumors in female mice but is not carcinogenic for male mice and for rats. In this work, the estragole hepatocarcinogenicity was shown for female mice of previously not studied ICR line. The strict correlation between estragole hepatocarcinogenicity and its ability to decrease the level of glucocorticoid induction of liver-specific enzymes tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) was found. Inhibition of TAT and TO inducibility by estragole takes place only in female mice but not in male mice and in rats. Studying the estragole effect on DNA-binding activity of transcription factors, present mainly in liver and regulating expression of genes encoding liver-specific proteins, has shown that estragole decreases FOXA and HNF4 activities but not activities of C/EBP and HNF1, and this happens only in female mice, for which this substance is hepatocarcinogen, but not in male mice and in rats. Pentachlorophenol, preventing hepatocarcinogenic effect of estragole, abolishes inhibitory influence of the latter on the TAT and TO glucocorticoid induction and restores DNA-binding activity of FOXA and HNF4. Thus, a correlation was revealed between the estragole hepatocarcinogenic effect and decrease in DNA-binding activity of transcription factors FOXA and HNF4, which might be indicative of the role of these factors in tumor suppression mechanisms in liver.

  6. Cellular Pathway(S) of Antigen Processing and Presentation in Fish APC: Endosomal Involvement and Cell-Free Antigen Presentation

    PubMed Central

    Vallejo, Abbe N.; Miller, Norman W.; Harvey, Nancy E.; Cuchens, Marvin A.; Warr, Gregory W.

    1992-01-01

    Studies were conducted to address further the role(s) of antigen processing and presentation in the induction of immune responses in a phylogenetically lower vertebrate, specifically a teleost, the channel catfish. In particular, studies were aimed at determining the subcellular compartments involved in antigen degradation by channel catfish antigen-presenting cells (APC) as well as ascertaining the reexpression of immunogenic peptides on the surfaces of APC. The results showed that exogenous protein antigens were actively endocytosed by APC as detected by flow cytometry. Use of radiolabeled antigen and subcellular fractionation protocols also showed that antigen localized in endosomes/lysosomes. Furthermore, there was an apparent redistribution of antigen between these organelles and the plasma membrane during the course of antigen pulsing. Functional assays for the induction of in vitro antigen-specific proliferation of immune catfish peripheral blood leukocytes (PBL) showed that membrane preparations from antigen-pulsed autologous APC were highly stimulatory. The magnitude of responses elicited with such membrane preparations was very similar to that of PBL cultures stimulated with native antigen-pulsed and fixed intact APC or prefixed intact APC incubated with a peptide fragment of the nominal antigen. Current data further corroborate our previous findings that steps akin to antigen processing and presentation are clearly important in the induction of immune responses in lower vertebrates like fish, in a manner similar to that seen in mammalian systems. Consequently, it would appear that many immune functions among the diverse taxa of vertebrates are remarkably conserved. PMID:1343103

  7. Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid β-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPK.

    PubMed

    Li, Li; Du, Ji-Kun; Zou, Li-Yi; Wu, Tie; Lee, Yong-Woo; Kim, Yong-Ho

    2013-01-01

    Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced A β 25 ‒ 35-induced cytotoxicity in PC12 cells. Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro. Pretreatment of cells with D diminished intracellular generation of ROS in response to A β 25 ‒ 35. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against A β 25 ‒ 35-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in A β 25 ‒ 35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury. Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression. While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells. Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against A β 25 ‒ 35-induced cell death. These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from A β 25 ‒ 35-induced oxidative cytotoxicity.

  8. Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid β-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPK

    PubMed Central

    Li, Li; Du, Ji-kun; Zou, Li-yi; Wu, Tie; Lee, Yong-woo; Kim, Yong-ho

    2013-01-01

    Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced Aβ 25‒35-induced cytotoxicity in PC12 cells. Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro. Pretreatment of cells with D diminished intracellular generation of ROS in response to Aβ 25‒35. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against Aβ 25‒35-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in Aβ 25‒35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury. Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression. While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells. Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against Aβ 25‒35-induced cell death. These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from Aβ 25‒35-induced oxidative cytotoxicity. PMID:23762139

  9. Hypervigilance and avoidance in visual attention in children with social phobia.

    PubMed

    Seefeldt, Wiebke L; Krämer, Martina; Tuschen-Caffier, Brunna; Heinrichs, Nina

    2014-03-01

    Attentional bias towards threat in socially anxious adults is well documented; however, research on this bias in children with social phobia is rather scarce. The present study investigates whether the hypervigilance-avoidance hypothesis also applies to children with social phobia. Thirty children (aged 8-12) with social phobia and 43 control children participated in an eye-tracking experiment while their attentional distribution was recorded. Social anxiety was induced in half of the children before the eye-tracking task. Stimuli were presented for 3000 ms, and bias scores for initial fixations and the time span of attention were assessed. Results indicated initial vigilance towards angry faces for all children independent of anxiety induction, while hypervigilance (but not avoidance) was only established in children with social phobia for angry-neutral face pairs and with social fears induced. Self-report measures of anxiety correlated with bias towards threat with more pronounced associations occurring in the anxiety induction condition. We did not record reaction times simultaneously which limits the opportunity to compare our results to some previous studies which focused on this variable as an indicator of attention. Cognitive biases in elementary school children (between 8 and 12 years) relate to hypervigilant rather than to avoidant information processing. Attentional distribution varies over time. Differences between clinical anxious and healthy children seem to be modified by anxiety induction, symptom severity and contextual stimuli, such as the emotional valence of a face and the context in which the threat stimulus appears. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Development and validation of the Pediatric Anesthesia Behavior score--an objective measure of behavior during induction of anesthesia.

    PubMed

    Beringer, Richard M; Greenwood, Rosemary; Kilpatrick, Nicky

    2014-02-01

    Measuring perioperative behavior changes requires validated objective rating scales. We developed a simple score for children's behavior during induction of anesthesia (Pediatric Anesthesia Behavior score) and assessed its reliability, concurrent validity, and predictive validity. Data were collected as part of a wider observational study of perioperative behavior changes in children undergoing general anesthesia for elective dental extractions. One-hundred and two healthy children aged 2-12 were recruited. Previously validated behavioral scales were used as follows: the modified Yale Preoperative Anxiety Scale (m-YPAS); the induction compliance checklist (ICC); the Pediatric Anesthesia Emergence Delirium scale (PAED); and the Post-Hospitalization Behavior Questionnaire (PHBQ). Pediatric Anesthesia Behavior (PAB) score was independently measured by two investigators, to allow assessment of interobserver reliability. Concurrent validity was assessed by examining the correlation between the PAB score, the m-YPAS, and the ICC. Predictive validity was assessed by examining the association between the PAB score, the PAED scale, and the PHBQ. The PAB score correlated strongly with both the m-YPAS (P < 0.001) and the ICC (P < 0.001). PAB score was significantly associated with the PAED score (P = 0.031) and with the PHBQ (P = 0.034). Two independent investigators recorded identical PAB scores for 94% of children and overall, there was close agreement between scores (Kappa coefficient of 0.886 [P < 0.001]). The PAB score is simple to use and may predict which children are at increased risk of developing postoperative behavioral disturbance. This study provides evidence for its reliability and validity. © 2013 John Wiley & Sons Ltd.

  11. Urokinase plasminogen activator mRNA is induced by IL-1alpha and TNF-alpha in in vitro acantholysis.

    PubMed

    Feliciani, Claudio; Toto, Paola; Wang, Binghe; Sauder, Daniel N; Amerio, Pierluigi; Tulli, Antonio

    2003-08-01

    The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1alpha and TNF-alpha are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1alpha and TNF-alpha are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1alpha, TNF-alpha and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1alpha, TNF-alpha and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1alpha/TNF-alpha mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-1alpha, anti-TNF-alpha and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1alpha and anti-TNF-alpha antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1alpha/TNF-alpha mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction.

  12. Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams

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

    Chaudhary, Pankaj; Marshall, Thomas I.; Currell, Frederick J.

    Purpose: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. Methods and Materials: Human skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, andmore » distal positions of SOBP and the entrance and peak position for the pristine beam. Results: A significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci. Conclusions: The DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions.« less

  13. Operational Characteristics and Plasma Measurements in a Low-Energy FARAD Thruster

    NASA Technical Reports Server (NTRS)

    Polzin, K. A.; Best, S.; Rose, M. F.; Miller, R.; Owens, T.

    2008-01-01

    Pulsed inductive plasma accelerators are spacecraft propulsion devices in which energy is stored in a capacitor and then discharged through an inductive coil. The device is electrodeless, inducing a plasma current sheet in propellant located near the face of the coil. The propellant is accelerated and expelled at a high exhaust velocity (order of 10 km/s) through the interaction of the plasma current with an induced magnetic field. The Faraday Accelerator with RF-Assisted Discharge (FARAD) thruster is a type of pulsed inductive plasma accelerator in which the plasma is preionized by a mechanism separate from that used to form the current sheet and accelerate the gas. Employing a separate preionization mechanism in this manner allows for the formation of an inductive current sheet at much lower discharge energies and voltages than those found in previous pulsed inductive accelerators like the Pulsed Inductive Thruster (PIT). In this paper, we present measurements aimed at quantifying the thruster's overall operational characteristics and providing additional insight into the nature of operation. Measurements of the terminal current and voltage characteristics during the pulse help quantify the output of the pulsed power train driving the acceleration coil. A fast ionization gauge is used to measure the evolution of the neutral gas distribution in the accelerator prior to a pulse. The preionization process is diagnosed by monitoring light emission from the gas using a photodiode, and a time-resolved global view of the evolving, accelerating current sheet is obtained using a fast-framing camera. Local plasma and field measurements are obtained using an array of intrusive probes. The local induced magnetic field and azimuthal current density are measured using B-dot probes and mini-Rogowski coils, respectively. Direct probing of the number density and electron temperature is performed using a triple probe.

  14. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

    PubMed

    Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

    2016-06-01

    A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

  15. The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT.

    PubMed Central

    Masuda, E S; Tokumitsu, H; Tsuboi, A; Shlomai, J; Hung, P; Arai, K; Arai, N

    1993-01-01

    Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in T cells is activated by the combination of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187), which mimic antigen stimulation through the T-cell receptor. We have previously shown that a fragment containing bp -95 to +27 of the mouse GM-CSF promoter can confer inducibility to reporter genes in the human Jurkat T-cell line. Here we use an in vitro transcription system to demonstrate that a cis-acting element (positions -54 to -40), referred to as CLE0, is a target for the induction signals. We observed induction with templates containing intact CLE0 but not with templates with deleted or mutated CLE0. We also observed that two distinct signals were required for the stimulation through CLE0, since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction. Stimulation probably was mediated by CLE0-binding proteins because depletion of these proteins specifically reduced GM-CSF transcription. One of the binding factors possessed biochemical and immunological features identical to those of the transcription factor AP1. Another factor resembled the T-cell-specific factor NFAT. The characteristics of these two factors are consistent with their involvement in GM-CSF induction. The presence of CLE0-like elements in the promoters of interleukin-3 (IL-3), IL-4, IL-5, GM-CSF, and NFAT sites in the IL-2 promoter suggests that the factors we detected, or related factors that recognize these sites, may account for the coordinate induction of these genes during T-cell activation. Images PMID:8246960

  16. Carprofen Induction of p75NTR Dependent Apoptosis via the p38 MAPK Pathway in Prostate Cancer Cells

    PubMed Central

    Khwaja, Fatima S.; Quann, Emily J.; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel

    2008-01-01

    The p75NTR functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we demonstrated that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in several prostate cancer cell lines leading to p75NTR mediated decreased survival. Utilizing the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico data base of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75NTR levels and inhibition of cell survival. Prostate (PC-3, DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75NTR associated loss of survival than breast (MCF7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant negative form of p75NTR prior to carprofen treatment partially rescued cell survival demonstrating a cause and effect relationship between carprofen induction of p75NTR levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF7 and 3T3 cells. Furthermore, siRNA knockdown of the p38 MAPK protein prevented induction of p75NTR by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 minute. Expression of a dominant negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75NTR protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75NTR dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. PMID:18974393

  17. Wnt and Notch Pathways Have Interrelated Opposing Roles on Prostate Progenitor Cell Proliferation and Differentiation

    PubMed Central

    Shahi, Payam; Seethammagari, Mamatha R.; Valdez, Joseph M.; Xin, Li; Spencer, David M.

    2011-01-01

    Tissue stem cells are capable of both self-renewal and differentiation to maintain a constant stem cell population and give rise to the plurality of cells within a tissue. Wnt signaling has been previously identified as a key mediator for the maintenance of tissue stem cells; however, possible cross-regulation with other developmentally critical signaling pathways involved in adult tissue homeostasis, such as Notch, is not well understood. By using an in vitro prostate stem cell colony (“prostasphere”) formation assay and in vivo prostate reconstitution experiments, we demonstrate that Wnt pathway induction on Sca-1+ CD49f+ basal/stem cells (B/SCs) promotes expansion of the basal epithelial compartment with noticeable increases in “triple positive” (cytokeratin [CK] 5+, CK8+, p63+) prostate progenitor cells, concomitant with upregulation of known Wnt target genes involved in cell-cycle induction. Moreover, Wnt induction affects expression of epithelial-to-mesenchymal transition signature genes, suggesting a possible mechanism for priming B/SC to act as potential tumor-initiating cells. Interestingly, induction of Wnt signaling in B/SCs results in downregulation of Notch1 transcripts, consistent with its postulated antiproliferative role in prostate cells. In contrast, induction of Notch signaling in prostate progenitors inhibits their proliferation and disrupts prostasphere formation. In vivo prostate reconstitution assays further demonstrate that induction of Notch in B/SCs disrupts proper acini formation in cells expressing the activated Notch1 allele, Notch-1 intracellular domain. These data emphasize the importance of Wnt/Notch cross-regulation in adult stem cell biology and suggest that Wnt signaling controls the proliferation and/or maintenance of epithelial progenitors via modulation of Notch signaling. PMID:21308863

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

    Wieneke, N.; Neuschaefer-Rube, F.; Bode, L.M.

    Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feedback-controlled regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase II enzymes of xenobiotic metabolism. We have recently shown, that PPAR{alpha} agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPAR{alpha} agonist could enhance the phenobarbital-dependentmore » acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPAR{alpha} agonist WY14643 to a larger extent than after induction with either compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UGT1A10. The PPAR{alpha}-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-induced reduction in energy expenditure by fatty acids as natural PPAR{alpha} ligands. The synergism of the PPAR{alpha} agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics.« less

  19. A Novel Pheromone Quorum-Sensing System Controls the Development of Natural Competence in Streptococcus thermophilus and Streptococcus salivarius▿ †

    PubMed Central

    Fontaine, Laetitia; Boutry, Céline; de Frahan, Marie Henry; Delplace, Brigitte; Fremaux, Christophe; Horvath, Philippe; Boyaval, Patrick; Hols, Pascal

    2010-01-01

    In streptococcal species, the key step of competence development is the transcriptional induction of comX, which encodes the alternative sigma factor σX, which positively regulates genes necessary for DNA transformation. In Streptococcus species belonging to the mitis and mutans groups, induction of comX relies on the activation of a three-component system consisting of a secreted pheromone, a histidine kinase, and a response regulator. In Streptococcus thermophilus, a species belonging to the salivarius group, the oligopeptide transporter Ami is essential for comX expression under competence-inducing conditions. This suggests a different regulation pathway of competence based on the production and reimportation of a signal peptide. The objective of our work was to identify the main actors involved in the early steps of comX induction in S. thermophilus LMD-9. Using a transcriptomic approach, four highly induced early competence operons were identified. Among them, we found a Rgg-like regulator (Ster_0316) associated with a nonannotated gene encoding a 24-amino-acid hydrophobic peptide (Shp0316). Through genetic deletions, we showed that these two genes are essential for comX induction. Moreover, addition to the medium of synthetic peptides derived from the C-terminal part of Shp0316 restored comX induction and transformation of a Shp0316-deficient strain. These peptides also induced competence in S. thermophilus and Streptococcus salivarius strains that are poorly transformable or not transformable. Altogether, our results show that Ster_0316 and Shp0316, renamed ComRS, are the two members of a novel quorum-sensing system responsible for comX induction in species from the salivarius group, which differs from the classical phosphorelay three-component system identified previously in streptococci. PMID:20023010

  20. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

    PubMed Central

    O'Leary, Jacqueline G.; Samaniego, Millie; Barrio, Marta Crespo; Potena, Luciano; Zeevi, Adriana; Djamali, Arjang; Cozzi, Emanuele

    2016-01-01

    Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID:26680372

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