Nuclear NF-κB contributes to chlorpyrifos-induced apoptosis through p53 signaling in human neural precursor cells.

PubMed

Lee, Jeong Eun; Lim, Mi Sun; Park, Jae Hyeon; Park, Chang Hwan; Koh, Hyun Chul

2014-05-01

Chlorpyrifos (CPF) is one of the most widely used organophosphate insecticides with several harmful effects, including neurotoxicity. Although many studies have addressed the neurotoxicity induced by CPF, most data on neurodevelopmental damage was obtained from animal models. We are the first group to use human neural precursor cells (hNPCs) derived from human embryonic stem cells (hESCs) as a developing neuron model to evaluate the mechanisms involved in CPF-induced neurotoxicity. CPF was cytotoxic to these cells in a concentration-dependent manner, as shown by decreased cell viability and increased lactate dehydrogenase release. Furthermore, CPF reduced the expression of AKT and ERK proteins which are involved in intracellular survival pathways. Exposure of hNPCs to CPF led to the production of reactive oxygen species (ROS), and the antioxidant N-acetyl-cystein (NAC) attenuated ROS production induced by CPF. In addition, CPF increased cytochrome c release into the cytosol and activated caspase-9 and -3, indicating that cell death induced by CPF was due to apoptosis in hNPCs. Consistent with these findings, CPF treatment reduced the level of Bcl-2 protein and increased the level of Bax protein. Especially, CPF increased the translocation of BAX into the mitochondria. CPF also induced nuclear accumulation of NF-κB and p53 proteins in a concentration-dependent manner, and their inhibitors attenuated CPF-induced cytotoxicity. In addition, an inhibitor of NF-κB nuclear translocation blocked the increase of p53 in CPF-treated hNPCs. These findings show that CPF induced hNPCs death in part through NF-κB activation via ROS generation, enabling the interaction of p53 with Bcl-2 and Bax and subsequent release of cytochrome c. Collectively, these results represent a unique molecular characterization of CPF-induced cytotoxicity in hNPCs. These data suggest that CPF may affect neurodevelopment in a manner similar to that of several known and suspected neurotoxicants. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring - a mouse study.

PubMed

Venerosi, Aldina; Tait, Sabrina; Stecca, Laura; Chiarotti, Flavia; De Felice, Alessia; Cometa, Maria Francesca; Volpe, Maria Teresa; Calamandrei, Gemma; Ricceri, Laura

2015-04-02

Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides worldwide. Epidemiological studies on pregnant women and their children suggest a link between in utero CPF exposure and delay in psychomotor and cognitive maturation. A large number of studies in animal models have shown adverse effects of CPF on developing brain and more recently on endocrine targets. Our aim was to determine if developmental exposure to CPF affects social responsiveness and associated molecular neuroendocrine markers at adulthood. Pregnant CD1 outbred mice were fed from gestational day 15 to lactation day 14 with either a CPF-added (equivalent to 6 mg/kg/bw/day during pregnancy) or a standard diet. We then assessed in the offspring the long-term effects of CPF exposure on locomotion, social recognition performances and gene expression levels of selected neurondocrine markers in amygdala and hypothalamus. No sign of CPF systemic toxicity was detected. CPF induced behavioral alterations in adult offspring of both sexes: CPF-exposed males displayed enhanced investigative response to unfamiliar social stimuli, whereas CPF-exposed females showed a delayed onset of social investigation and lack of reaction to social novelty. In parallel, molecular effects of CPF were sex dimorphic: in males CPF increased expression of estrogen receptor beta in hypothalamus and decreased oxytocin expression in amygdala; CPF increased vasopressin 1a receptor expression in amygdala in both sexes. These data indicate that developmental CPF affects mouse social behavior and interferes with development of sex-dimorphic neuroendocrine pathways with potential disruptive effects on neuroendocrine axes homeostasis. The route of exposure selected in our study corresponds to relevant human exposure scenarios, our data thus supports the view that neuroendocrine effects, especially in susceptible time windows, should deserve more attention in risk assessment of OP insecticides.

Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

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

Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.

Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare themore » pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.« less

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

PubMed Central

Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

2015-01-01

Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

Cpf1-Database: web-based genome-wide guide RNA library design for gene knockout screens using CRISPR-Cpf1.

PubMed

Park, Jeongbin; Bae, Sangsu

2018-03-15

Following the type II CRISPR-Cas9 system, type V CRISPR-Cpf1 endonucleases have been found to be applicable for genome editing in various organisms in vivo. However, there are as yet no web-based tools capable of optimally selecting guide RNAs (gRNAs) among all possible genome-wide target sites. Here, we present Cpf1-Database, a genome-wide gRNA library design tool for LbCpf1 and AsCpf1, which have DNA recognition sequences of 5'-TTTN-3' at the 5' ends of target sites. Cpf1-Database provides a sophisticated but simple way to design gRNAs for AsCpf1 nucleases on the genome scale. One can easily access the data using a straightforward web interface, and using the powerful collections feature one can easily design gRNAs for thousands of genes in short time. Free access at http://www.rgenome.net/cpf1-database/. sangsubae@hanyang.ac.kr.

Characteristics of total gaseous mercury (TGM) concentrations in an industrial complex in South Korea: impacts from local sources

NASA Astrophysics Data System (ADS)

Seo, Yong-Seok; Jeong, Seung-Pyo; Holsen, Thomas M.; Han, Young-Ji; Choi, Eunhwa; Park, Eun Ha; Kim, Tae Young; Eum, Hee-Sang; Park, Dae Gun; Kim, Eunhye; Kim, Soontae; Kim, Jeong-Hun; Choi, Jaewon; Yi, Seung-Muk

2016-08-01

Total gaseous mercury (TGM) concentrations were measured every 5 min in Pohang, Gyeongsangbuk-do, Korea, during summer (17-23 August 2012), fall (9-17 October 2012), winter (22-29 January 2013), and spring (26 March-3 April 2013) to (1) characterize the hourly and seasonal variations of atmospheric TGM concentrations; (2) identify the relationships between TGM and co-pollutants; and (3) identify likely source directions and locations of TGM using the conditional probability function (CPF), conditional bivariate probability function (CBPF) and total potential source contribution function (TPSCF). The TGM concentration was statistically significantly highest in fall (6.7 ± 6.4 ng m-3), followed by spring (4.8 ± 4.0 ng m-3), winter (4.5 ± 3.2 ng m-3) and summer (3.8 ± 3.9 ng m-3). There was a weak but statistically significant negative correlation between the TGM concentration and ambient air temperature (r = -0.08, p<0.05). Although the daytime temperature (14.7 ± 10.0 °C) was statistically significantly higher than that in the nighttime (13.0 ± 9.8 °C) (p<0.05), the daytime TGM concentration (5.3 ± 4.7 ng m-3) was statistically significantly higher than that in the nighttime (4.7 ± 4.7 ng m-3) (p<0.01), possibly due to local emissions related to industrial activities and activation of local surface emission sources. The observed ΔTGM / ΔCO was significantly lower than that of Asian long-range transport, but similar to that of local sources in Korea and in US industrial events, suggesting that local sources are more important than those of long-range transport. CPF, CBPF and TPSCF indicated that the main sources of TGM were iron and manufacturing facilities, the hazardous waste incinerators and the coastal areas.

Effect of modulated-frequency and modulated-intensity transcutaneous electrical nerve stimulation after abdominal surgery: a randomized controlled trial.

PubMed

Tokuda, Mitsunori; Tabira, Kazuyuki; Masuda, Takashi; Nishiwada, Takashi; Shomoto, Koji

2014-07-01

This study aimed to evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) for treatment of postoperative pain and pulmonary functions (vital capacity [VC]; cough peak flow, [CPF]) in patients who underwent abdominal surgery. Forty-eight patients were randomly allocated to receive TENS, placebo TENS, or no TENS (control) 1 hour a day for 3 days postoperatively. A 0-100 visual analog scale was used to assess pain at preintervention, mid-intervention, and postintervention on the third postoperative day. Pulmonary functions (VC, CPF) were evaluated by spirometer at preoperation (baseline) and at preintervention, mid-intervention, and postintervention on the third postoperative day. One-way analysis of variance was used to assess differences between groups at baseline. Mann-Whitney test was used to compare the control group with the placebo-TENS and TENS group, at each assessment timepoint. Two-way analysis of variance and Bonferroni post hoc test assessed the difference between the 2 (placebo-TENS×TENS) groups. A value of P<0.01 was considered statistically significant. The baselines were not significantly different between any groups. The TENS group had significant reductions in postoperative pain compared with the placebo group (P<0.01) and control group (P<0.01). There was also improvement in pulmonary functions (VC, CPF) at mid-TENS and post-TENS, but not in the placebo-TENS (P<0.01) or control groups (P<0.01). TENS is a valuable treatment to alleviate postoperative pain and improve pulmonary functions (ie, VC, CPF) in patients following abdominal surgery.

Theoretical study of the electric dipole moment function of the ClO molecule

NASA Technical Reports Server (NTRS)

Pettersson, L. G. M.; Langhoff, S. R.; Chong, D. P.

1986-01-01

The potential energy function and electric dipole moment function (EDMF) are computed for ClO X 2Pi using several different techniques to include electron correlation. The EDMF is used to compute Einstein coefficients, vibrational lifetimes, and dipole moments in higher vibrational levels. The band strength of the 1-0 fundamental transition is computed to be 12 + or - 2 per sq cm atm determined from infrared heterodyne spectroscopy. The theoretical methods used include SCF, CASSCF, multireference singles plus doubles configuration interaction (MRCI) and contracted CI, coupled pair functional (CPF), and a modified version of the CPF method. The results obtained using the different methods are critically compared.

Engineered Cpf1 variants with altered PAM specificities.

PubMed

Gao, Linyi; Cox, David B T; Yan, Winston X; Manteiga, John C; Schneider, Martin W; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-08-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ∼11 bp.

Engineered Cpf1 variants with altered PAM specificities increase genome targeting range

PubMed Central

Gao, Linyi; Cox, David B.T.; Yan, Winston X.; Manteiga, John C.; Schneider, Martin W.; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-01-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells1–7. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS7 assay indicated that these variants retain high DNA targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately three-fold in human coding sequences to one cleavage site per ~11 bp. PMID:28581492

In vitro enantioselective pharmacodynamics of Carprofen and Flunixin-meglumine in feedlot cattle.

PubMed

Miciletta, M; Cuniberti, B; Barbero, R; Re, G

2014-02-01

The activity of the anti-inflammatory agents Flunixin-meglumine (FLU), RS (±) Carprofen (CPF) and S (+) CPF on bovine cyclooxygenases (COXs) has been characterized in feedlot calves using an in vitro whole blood model. The drugs showed equivalent efficacy in their inhibitory activity on COXs, and the rank order of potency for both COX-1 and COX-2 inhibition was FLU > S (+) CPF > RS (±) CPF. Our results indicated that FLU is a nonselective inhibitor of bovine COXs, whereas RS (±) CPF and S (+) CPF exhibited different degrees of preferential inhibition of COX-2 isoenzyme. The rank order of IC50 COX-1: IC50 COX-2 potency ratios was in fact S (+) CPF (51.882) > RS (±) CPF (13.964) > FLU (0.606), and the calculated percentage inhibition of COX-1 corresponding to COX-2 inhibition values comprised between 80% and 95% was comprised between 57.697 and 79.865 for FLU, 33.373 and 51.319 for RS (±) CPF, and 0.230 and 4.622 for S (+) CPF, respectively. These findings are discussed in relation to the prediction of the clinical relevance of COX inhibition by the test drugs in cattle. © 2013 John Wiley & Sons Ltd.

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

Lee, Jeong Eun; Hanyang Biomedical Research Institute, Seoul; Park, Jae Hyeon

Oxidative stress can lead to expression of inflammatory transcription factors, which are important regulatory elements in the induction of inflammatory responses. One of the transcription factors, nuclear transcription factor kappa-B (NF-κB) plays a significant role in the inflammation regulatory process. Inflammatory cell death has been implicated in neuronal cell death in some neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying apoptosis initiated by chlorpyrifos (CPF)-mediated oxidative stress. Based on the cytotoxic mechanism of CPF, we examined the neuroprotective effects of rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, against CPF-induced neuronalmore » cell death. The treatment of SH-SY5Y cells with CPF induced oxidative stress. In addition, CPF activated the p38, JNK and ERK mitogen-activated protein kinases (MAPKs), and induced increases in the inflammatory genes such as COX-2 and TNF-α. CPF also induced nuclear translocation of NF-κB and inhibitors of NF-κB abolished the CPF-induced COX-2 expression. Pretreatment with RGZ significantly reduced ROS generation and enhanced HO-1 expression in CPF-exposed cells. RGZ blocked the activation of both p38 and JNK signaling, while ERK activation was strengthened. RGZ also attenuated CPF-induced cell death through the reduction of NF-κB-mediated proinflammatory factors. Results from this study suggest that RGZ may exert an anti-apoptotic effect against CPF-induced cytotoxicity by attenuation of oxidative stress as well as inhibition of the inflammatory cascade via inactivation of signaling by p38 and JNK, and NF-κB. - Highlights: • CPF induces apoptotic cell death in SH-SY5Y cells • ROS involved in CPF-mediated apoptotic cell death • Inflammation involved in CPF-mediated apoptotic cell death • Rosiglitazone modulates ROS and inflammatory response in CPF-treated cells.« less

Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

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

Park, Jae Hyeon; Hanyang Biomedical Research Institute, Seoul; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul

Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition,more » we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by apoptosis ► CPF induces autophagy in SH-SY5Y cells ► Autophagy regulates CPF-induced apoptosis in SH-SY5Y cells.« less

Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

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

Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.

Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urinemore » along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF metabolism was not affected by repeated treatments with ethanol or both ethanol and nicotine. When compared with a previous study of nicotine and CPF exposure, there were no apparent additional exacerbating effects due to ethanol co-exposure.« less

Use of the challenge point framework to guide motor learning of stepping reactions for improved balance control in people with stroke: a case series.

PubMed

Pollock, Courtney L; Boyd, Lara A; Hunt, Michael A; Garland, S Jayne

2014-04-01

Stepping reactions are important for walking balance and community-level mobility. Stepping reactions of people with stroke are characterized by slow reaction times, poor coordination of motor responses, and low amplitude of movements, which may contribute to their decreased ability to recover their balance when challenged. An important aspect of rehabilitation of mobility after stroke is optimizing the motor learning associated with retraining effective stepping reactions. The Challenge Point Framework (CPF) is a model that can be used to promote motor learning through manipulation of conditions of practice to modify task difficulty, that is, the interaction of the skill of the learner and the difficulty of the task to be learned. This case series illustrates how the retraining of multidirectional stepping reactions may be informed by the CPF to improve balance function in people with stroke. Four people (53-68 years of age) with chronic stroke (>1 year) and mild to moderate motor recovery received 4 weeks of multidirectional stepping reaction retraining. Important tenets of motor learning were optimized for each person during retraining in accordance with the CPF. Participants demonstrated improved community-level walking balance, as determined with the Community Balance and Mobility Scale. These improvements were evident 1 year later. Aspects of balance-related self-efficacy and movement kinematics also showed improvements during the course of the intervention. The application of CPF motor learning principles in the retraining of stepping reactions to improve community-level walking balance in people with chronic stroke appears to be promising. The CPF provides a plausible theoretical framework for the progression of functional task training in neurorehabilitation.

Coherence penalty functional: A simple method for adding decoherence in Ehrenfest dynamics

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

Akimov, Alexey V., E-mail: alexvakimov@gmail.com, E-mail: oleg.prezhdo@rochester.edu; Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973; Long, Run

2014-05-21

We present a new semiclassical approach for description of decoherence in electronically non-adiabatic molecular dynamics. The method is formulated on the grounds of the Ehrenfest dynamics and the Meyer-Miller-Thoss-Stock mapping of the time-dependent Schrödinger equation onto a fully classical Hamiltonian representation. We introduce a coherence penalty functional (CPF) that accounts for decoherence effects by randomizing the wavefunction phase and penalizing development of coherences in regions of strong non-adiabatic coupling. The performance of the method is demonstrated with several model and realistic systems. Compared to other semiclassical methods tested, the CPF method eliminates artificial interference and improves agreement with the fullymore » quantum calculations on the models. When applied to study electron transfer dynamics in the nanoscale systems, the method shows an improved accuracy of the predicted time scales. The simplicity and high computational efficiency of the CPF approach make it a perfect practical candidate for applications in realistic systems.« less

Binary mixtures of azinphos-methyl oxon and chlorpyrifos oxon produce in vitro synergistic cholinesterase inhibition in Planorbarius corneus.

PubMed

Cacciatore, Luis Claudio; Kristoff, Gisela; Verrengia Guerrero, Noemí R; Cochón, Adriana C

2012-07-01

In this study, the cholinesterase (ChE) and carboxylesterase (CES) activities present in whole organism homogenates from Planorbarius corneus and their in vitro sensitivity to organophosphorous (OP) pesticides were studied. Firstly, a characterization of ChE and CES activities using different substrates and selective inhibitors was performed. Secondly, the effects of azinphos-methyl oxon (AZM-oxon) and chlorpyrifos oxon (CPF-oxon), the active oxygen analogs of the OP insecticides AZM and CPF, on ChE and CES activities were evaluated. Finally, it was analyzed whether binary mixtures of the pesticide oxons cause additive, antagonistic or synergistic ChE inhibition in P. corneus homogenates. The results showed that the extracts of P. corneus preferentially hydrolyzed acetylthiocholine (AcSCh) over propionylthiocholine (PrSCh) and butyrylthiocholine (BuSCh). Besides, AcSCh hydrolyzing activity was inhibited by low concentrations of BW284c51, a selective inhibitor of AChE activity, and also by high concentrations of substrate. These facts suggest the presence of a typical AChE activity in this species. However, the different dose-response curves observed with BW284c51 when using PrSCh or BuSCh instead of AcSCh suggest the presence of at least another ChE activity. This would probably correspond to an atypical BuChE. Regarding CES activity, the highest specific activity was obtained when using 2-naphthyl acetate (2-NA), followed by 1-naphthyl acetate (1-NA); p-nitrophenyl acetate (p-NPA), and p-nitrophenyl butyrate (p-NPB). The comparison of the IC(50) values revealed that, regardless of the substrate used, CES activity was approximately one order of magnitude more sensitive to AZM-oxon than ChE activity. Although ChE activity was very sensitive to CPF-oxon, CES activity measured with 1-NA, 2-NA, and p-NPA was poorly inhibited by this pesticide. In contrast, CES activity measured with p-NPB was equally sensitive to CPF-oxon than ChE activity. Several specific binary combinations of AZM-oxon and CPF-oxon caused a synergistic effect on the ChE inhibition in P. corneus homogenates. The degree of synergism tended to increase as the ratio of AZM-oxon to CPF-oxon decreased. These results suggest that synergism is likely to occur in P. corneus snails exposed in vivo to binary mixtures of the OPs AZM and CPF. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells.

PubMed

Saulsbury, Marilyn D; Heyliger, Simone O; Wang, Kaiyu; Johnson, Deadre J

2009-05-02

There are increasing concerns regarding the relative safety of chlorpyrifos (CPF) to various facets of the environment. Although published works suggest that CPF is relatively safe in adult animals, recent evidence indicates that juveniles, both animals and humans, may be more sensitive to CPF toxicity than adults. In young animals, CPF is neurotoxic and mechanistically interferes with cellular replication and cellular differentiation, which culminates in the alteration of synaptic neurotransmission in neurons. However, the effects of CPF on glial cells are not fully elucidated. Here we report that chlorpyrifos is toxic to oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases in 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA) and dihydroethidium (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF toxicity is associated with nuclear condensation and elevation of caspase 3/7 activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and cholinergic receptor antagonists' atropine and mecamylamine failed to protect oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH) depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor L-NAME partially protected progenitors and the non-specific antioxidant vitamin E (alpha-tocopherol) completely spared cells from injury. Collectively, this data suggests that CPF induced toxicity is independent of cholinergic stimulation and is most likely caused by the induction of oxidative stress.

Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

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

Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita

2006-10-01

This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted inmore » any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some compensatory process(es) downstream from synaptic neurotransmitter accumulation limits the expression of toxicity following acute CPF exposure.« less

Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats

PubMed Central

Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique

2016-01-01

Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure. PMID:27760213

Efficient and accurate local approximations to coupled-electron pair approaches: An attempt to revive the pair natural orbital method

NASA Astrophysics Data System (ADS)

Neese, Frank; Wennmohs, Frank; Hansen, Andreas

2009-03-01

Coupled-electron pair approximations (CEPAs) and coupled-pair functionals (CPFs) have been popular in the 1970s and 1980s and have yielded excellent results for small molecules. Recently, interest in CEPA and CPF methods has been renewed. It has been shown that these methods lead to competitive thermochemical, kinetic, and structural predictions. They greatly surpass second order Møller-Plesset and popular density functional theory based approaches in accuracy and are intermediate in quality between CCSD and CCSD(T) in extended benchmark studies. In this work an efficient production level implementation of the closed shell CEPA and CPF methods is reported that can be applied to medium sized molecules in the range of 50-100 atoms and up to about 2000 basis functions. The internal space is spanned by localized internal orbitals. The external space is greatly compressed through the method of pair natural orbitals (PNOs) that was also introduced by the pioneers of the CEPA approaches. Our implementation also makes extended use of density fitting (or resolution of the identity) techniques in order to speed up the laborious integral transformations. The method is called local pair natural orbital CEPA (LPNO-CEPA) (LPNO-CPF). The implementation is centered around the concepts of electron pairs and matrix operations. Altogether three cutoff parameters are introduced that control the size of the significant pair list, the average number of PNOs per electron pair, and the number of contributing basis functions per PNO. With the conservatively chosen default values of these thresholds, the method recovers about 99.8% of the canonical correlation energy. This translates to absolute deviations from the canonical result of only a few kcal mol-1. Extended numerical test calculations demonstrate that LPNO-CEPA (LPNO-CPF) has essentially the same accuracy as parent CEPA (CPF) methods for thermochemistry, kinetics, weak interactions, and potential energy surfaces but is up to 500 times faster. The method performs best in conjunction with large and flexible basis sets. These results open the way for large-scale chemical applications.

Efficient and accurate local approximations to coupled-electron pair approaches: An attempt to revive the pair natural orbital method.

PubMed

Neese, Frank; Wennmohs, Frank; Hansen, Andreas

2009-03-21

Coupled-electron pair approximations (CEPAs) and coupled-pair functionals (CPFs) have been popular in the 1970s and 1980s and have yielded excellent results for small molecules. Recently, interest in CEPA and CPF methods has been renewed. It has been shown that these methods lead to competitive thermochemical, kinetic, and structural predictions. They greatly surpass second order Moller-Plesset and popular density functional theory based approaches in accuracy and are intermediate in quality between CCSD and CCSD(T) in extended benchmark studies. In this work an efficient production level implementation of the closed shell CEPA and CPF methods is reported that can be applied to medium sized molecules in the range of 50-100 atoms and up to about 2000 basis functions. The internal space is spanned by localized internal orbitals. The external space is greatly compressed through the method of pair natural orbitals (PNOs) that was also introduced by the pioneers of the CEPA approaches. Our implementation also makes extended use of density fitting (or resolution of the identity) techniques in order to speed up the laborious integral transformations. The method is called local pair natural orbital CEPA (LPNO-CEPA) (LPNO-CPF). The implementation is centered around the concepts of electron pairs and matrix operations. Altogether three cutoff parameters are introduced that control the size of the significant pair list, the average number of PNOs per electron pair, and the number of contributing basis functions per PNO. With the conservatively chosen default values of these thresholds, the method recovers about 99.8% of the canonical correlation energy. This translates to absolute deviations from the canonical result of only a few kcal mol(-1). Extended numerical test calculations demonstrate that LPNO-CEPA (LPNO-CPF) has essentially the same accuracy as parent CEPA (CPF) methods for thermochemistry, kinetics, weak interactions, and potential energy surfaces but is up to 500 times faster. The method performs best in conjunction with large and flexible basis sets. These results open the way for large-scale chemical applications.

Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

PubMed

López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

2016-03-01

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

Biosensors for detecting stress in developing embryos

NASA Astrophysics Data System (ADS)

Purdey, Malcolm S.; Saini, Avishkar; McLennan, Hanna J.; Pullen, Benjamin J.; Schartner, Erik P.; Sutton-McDowall, Melanie L.; Thompson, Jeremy G.; Monro, Tanya M.; Nicholls, Stephen J.; Abell, Andrew D.

2016-12-01

Reactive Oxygen Species (ROS) cause DNA damage and defective function in sperm and also affects the developmental competence of embryos. It is therefore critical to monitor ROS in sperm, oocytes and developing embryos. In particular, hydrogen peroxide (H2O2) is a ROS important to normal cell function and signalling as well as its role in oxidative stress. Here we report the development of a fluorescent sensor for H2O2 using carboxyperoxyfluor-1 (CPF1) in solution and attached to a glass slide or multi-mode optical fibre. CPF1 increases in fluorescence upon reaction with H2O2 to non-invasively detect H2O2 near developing embryos. These probes are constructed by immobilising CPF1 to the optical fibre tip a polyacrylamide layer. Also reported is a new dual optical fibre sensor for detecting both H2O2 and pH that is functional at biologically concentrations of H2O2 and can sense pH to 0.1 units. This research shows promise for the use of optical fibre sensors for monitoring the health of developing embryos. Furthermore, these sensors are applicable for use beyond embryos such as detecting stress in endothelial cells involved in cardiovascular dysfunction.

Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage.

PubMed

Hassani, S; Sepand, M R; Jafari, A; Jaafari, J; Rezaee, R; Zeinali, M; Tavakoli, F; Razavi-Azarkhiavi, K

2015-06-01

There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn., which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues. © The Author(s) 2014.

Hybridization between the African clawed frogs Xenopus laevis and Xenopus muelleri (Pipidae) increases the multiplicity of antimicrobial peptides in skin secretions of female offspring.

PubMed

Mechkarska, Milena; Meetani, Mohammed; Michalak, Pawel; Vaksman, Zalman; Takada, Koji; Conlon, J Michael

2012-09-01

Peptidomic analysis was used to compare the distribution of host-defense peptides in norepinephrine-stimulated skin secretions from laboratory-generated female F1 hybrids of the common clawed frog Xenopus laevis (Daudin, 1802) and Mueller's clawed frog Xenopus muelleri (Peters, 1844) with the corresponding distribution in skin secretions from the parent species. A total of 18 peptides were identified in secretions from the hybrid frogs. Eleven peptides (magainin-1, magainin-2, CPF-1, CPF-3, CPF-4, CPF-5, CPF-6, CPF-7, XPF-1, XPF-2, and PGLa) were identified in secretions of both the hybrids and X. laevis. Four peptides (magainin-M1, XPF-M1, CPF-M1, and tigerinin-M1) were previously found in skin secretions of X. muelleri but magainin-M2 and CPF-M2 from X. muelleri were not detected. Three previously undescribed peptides (magainin-LM1, PGLa-LM1, and CPF-LM1) were purified from the secretions of the hybrid frogs that were not detected in secretions from either X. laevis or X. muelleri. Magainin-LM1 differs from magainin-2 from X. laevis by a single amino acid substitution (Gly(13)→Ala) but PGLa-LM1 and CPF-LM1 differ appreciably in structure from orthologs in the parent species. CPF-LM1 shows potent, broad-spectrum antimicrobial activity and is hemolytic. The data indicate that hybridization increases the multiplicity of skin host-defense peptides in skin secretions. As the female F1 hybrids are fertile, hybridization may represent an adaptive strategy among Xenopus species to increase protection against pathogenic microorganisms in the environment. Copyright © 2012 Elsevier Inc. All rights reserved.

Chlorpyrifos promotes colorectal adenocarcinoma H508 cell growth through the activation of EGFR/ERK1/2 signaling pathway but not cholinergic pathway.

PubMed

Suriyo, Tawit; Tachachartvanich, Phum; Visitnonthachai, Daranee; Watcharasit, Piyajit; Satayavivad, Jutamaad

2015-12-02

Aside from the effects on neuronal cholinergic system, epidemiological studies suggest an association between chlorpyrifos (CPF) exposure and cancer risk. This in vitro study examined the effects of CPF and its toxic metabolite, chlorpyrifos oxon (CPF-O), on the growth of human colorectal adenocarcinoma H508, colorectal adenocarcinoma HT-29, normal colon epithelial CCD841, liver hepatocellular carcinoma HepG2, and normal liver hepatocyte THLE-3 cells. The results showed that CPF (5-100 μM) concentration-dependently increased viability of H508 and CCD841 cells in serum-free conditions. This increasing trend was not found in HT-29, HepG2 and THLE-3 cells. In contrast, CPF-O (50-100 μM) reduced the viability of all cell lines. Cell cycle analysis showed the induction of cells in the S phase, and EdU incorporation assay revealed the induction of DNA synthesis in CPF-treated H508 cells indicating that CPF promotes cell cycle progression. Despite the observation of acetylcholinesterase activity inhibition and reactive oxygen species (ROS) generation, atropine (a non-selective muscarinic acetylcholine receptor antagonist) and N-acetylcysteine (a potent antioxidant) failed to inhibit the growth-promoting effect of CPF. CPF increased the phosphorylation of epidermal growth factor receptor (EGFR) and its downstream effector, extracellular signal regulated kinase (ERK1/2), in H508 cells. AG-1478 (a specific EGFR tyrosine kinase inhibitor) and U0126 (a specific MEK inhibitor) completely mitigated the growth promoting effect of CPF. Altogether, these results suggest that EGFR/ERK1/2 signaling pathway but not cholinergic pathway involves in CPF-induced colorectal adenocarcinoma H508 cell growth. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

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

Wang, Tingting; Zhao, Ling; Liu, Mengyu

Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increasedmore » glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo and in vitro. • Hydrogen molecules have direct effect on the modulation of AChE activity in vitro.« less

Changes in Composition and Function of Human Intestinal Microbiota Exposed to Chlorpyrifos in Oil as Assessed by the SHIME® Model

PubMed Central

Reygner, Julie; Joly Condette, Claire; Bruneau, Aurélia; Delanaud, Stéphane; Rhazi, Larbi; Depeint, Flore; Abdennebi-Najar, Latifa; Bach, Veronique; Mayeur, Camille; Khorsi-Cauet, Hafida

2016-01-01

The presence of pesticide residues in food is a public health problem. Exposure to these substances in daily life could have serious effects on the intestine—the first organ to come into contact with food contaminants. The present study investigated the impact of a low dose (1 mg/day in oil) of the pesticide chlorpyrifos (CPF) on the community structure, diversity and metabolic response of the human gut microbiota using the SHIME® model (six reactors, representing the different parts of the gastrointestinal tract). The last three reactors (representing the colon) were inoculated with a mixture of feces from human adults. Three time points were studied: immediately before the first dose of CPF, and then after 15 and 30 days of CPF-oil administration. By using conventional bacterial culture and molecular biology methods, we showed that CPF in oil can affect the gut microbiota. It had the greatest effects on counts of culturable bacteria (with an increase in Enterobacteria, Bacteroides spp. and clostridia counts, and a decrease in bifidobacterial counts) and fermentative activity, which were colon-segment-dependent. Our results suggest that: (i) CPF in oil treatment affects the gut microbiota (although there was some discordance between the culture-dependent and culture-independent analyses); (ii) the changes are “SHIME®-compartment” specific; and (iii) the changes are associated with minor alterations in the production of short-chain fatty acids and lactate. PMID:27827942

Effects of chlorpyrifos on the transcription of CYP3A cDNA, activity of acetylcholinesterase, and oxidative stress response of goldfish (Carassius auratus).

PubMed

Ma, Junguo; Liu, Yang; Niu, Daichun; Li, Xiaoyu

2015-04-01

Chlorpyrifos (CPF) is the widely used organophosphate pesticide in agriculture throughout the world. It has been found that CPF is relatively safe to human but highly toxic to fish. In this study, acute toxicity of CPF on goldfish was determined and then the transcription of goldfish cytochrome P450 (CYP) 3A was evaluated after 96 h of CPF exposure at concentrations of 15.3 [1/10 50% lethal concentration (LC50 )] or 51 μg L(-1) (1/3 LC50 ) of CPF. Meanwhile, the enzymatic activities of acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT), total antioxidant activity (T-AOC), and the contents of malondialdehyde (MDA) in the liver or brain of goldfish were also determined. The results of acute toxicity testing showed that the 96-h LC50 of CPF to the goldfish was 153 μg L(-1) . Moreover, a length sequence of 1243 bp CYP3A cDNA encoding for 413 amino acids from goldfish liver was cloned. Polymerase chain reaction results reveal that CPF exposure downregulates CYP 3A transcription in goldfish liver, suggesting that goldfish CYP 3A may be not involved in CPF bioactivation. Finally, the results of biochemical assays indicate that 96 h of CPF exposure remarkably inhibits AChE activity in fish liver or brain, alters hepatic antioxidant enzyme activities, decreases brain T-AOC, and causes lipid peroxidation in fish liver. These results suggest that oxidative stress might be involved in CPF toxicity on goldfish. Copyright © 2013 Wiley Periodicals, Inc.

High time-resolved elemental components in fine and coarse particles in the Pearl River Delta region of Southern China: Dynamic variations and effects of meteorology.

PubMed

Zhou, Shengzhen; Davy, Perry K; Wang, Xuemei; Cohen, Jason Blake; Liang, Jiaquan; Huang, Minjuan; Fan, Qi; Chen, Weihua; Chang, Ming; Ancelet, Travis; Trompetter, William J

2016-12-01

Hourly-resolved PM 2.5 and PM 10-2.5 samples were collected in the industrial city Foshan in the Pearl River Delta region, China. The samples were subsequently analyzed for elemental components and black carbon (BC). A key purpose of the study was to understand the composition of particulate matter (PM) at high-time resolution in a polluted urban atmosphere to identify key components contributing to extreme PM concentration events and examine the diurnal chemical concentration patterns for air quality management purposes. It was found that BC and S concentrations dominated in the fine mode, while elements with mostly crustal and oceanic origins such as Si, Ca, Al and Cl were found in the coarse size fraction. Most of the elements showed strong diurnal variations. S did not show clear diurnal variations, suggesting regional rather than local origin. Based on empirical orthogonal functions (EOF) method, 3 forcing factors were identified contributing to the extreme events of PM 2.5 and selected elements, i.e., urban direct emissions, wet deposition and a combination of coarse mode sources. Conditional probability functions (CPF) were performed using wind profiles and elemental concentrations. The CPF results showed that BC and elemental Cl, K, Fe, Cu and Zn in the fine mode were mostly from the northwest, indicating that industrial emissions and combustion were the main sources. For elements in the coarse mode, Si, Al, K, Ca, Fe and Ti showed similar patterns, suggesting same sources such as local soil dust/construction activities. Coarse elemental Cl was mostly from the south and southeast, implying the influence of marine aerosol sources. For other trace elements, we found vanadium (V) in fine PM was mainly from the sources located to the southeast of the measuring site. Combined with CPF results of S and V in fine PM, we concluded shipping emissions were likely an important elemental emission source. Copyright © 2016. Published by Elsevier B.V.

Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury

PubMed Central

Wang, Lu; Espinoza, Herbert M.; MacDonald, James W.; Bammler, Theo K.; Williams, Chase R.; Yeh, Andrew; Louie, Ke’ale W.; Marcinek, David J.; Gallagher, Evan P.

2016-01-01

Pacific salmon exposed to sublethal concentrations of organophosphate pesticides (OP) have impaired olfactory function that can lead to loss of behaviors that are essential for survival. These exposures often involve mixtures and can occur at levels below those which inhibit acetylcholinesterase (AChE). In this study, juvenile Coho salmon were exposed for 24 h to either 0.1, 0.5, or 2.5 ppb chlorpyrifos (CPF), 2, 10, or 50 ppb malathion (MAL), or binary mixtures of 0.1 CPF:2 ppb MAL, 0.5 CPF:10 ppb MAL, or 2.5 CPF:10 ppb MAL to mimic single and binary environmental exposures. Microarray analysis of olfactory rosettes from pesticide-exposed salmon revealed differentially expressed genes involved in nervous system function and signaling, aryl hydrocarbon receptor signaling, xenobiotic metabolism, and mitochondrial dysfunction. Coho exposed to OP mixtures exhibited a more pronounced loss in detection of a predatory olfactory cue relative to those exposed to single compounds, whereas respirometry experiments demonstrated that exposure to OPs, individually and in mixtures, reduced maximum respiratory capacity of olfactory rosette mitochondria. The observed molecular, biochemical, and behavioral effects occurred largely in the absence of effects on brain AChE. In summary, our results provide new insights associated with the sublethal neurotoxic effects of OP mixtures relevant to environmental exposures involving molecular and cellular pathways of injury to the salmon olfactory system that underlie neurobehavioral injury. PMID:26494550

Design and assessment of engineered CRISPR-Cpf1 and its use for genome editing.

PubMed

Li, Bin; Zeng, Chunxi; Dong, Yizhou

2018-05-01

Cpf1, a CRISPR endonuclease discovered in Prevotella and Francisella 1 bacteria, offers an alternative platform for CRISPR-based genome editing beyond the commonly used CRISPR-Cas9 system originally discovered in Streptococcus pyogenes. This protocol enables the design of engineered CRISPR-Cpf1 components, both CRISPR RNAs (crRNAs) to guide the endonuclease and Cpf1 mRNAs to express the endonuclease protein, and provides experimental procedures for effective genome editing using this system. We also describe quantification of genome-editing activity and off-target effects of the engineered CRISPR-Cpf1 in human cell lines using both T7 endonuclease I (T7E1) assay and targeted deep sequencing. This protocol enables rapid construction and identification of engineered crRNAs and Cpf1 mRNAs to enhance genome-editing efficiency using the CRISPR-Cpf1 system, as well as assessment of target specificity within 2 months. This protocol may also be appropriate for fine-tuning other types of CRISPR systems.

Corrosion Product Film-Induced Stress Facilitates Stress Corrosion Cracking

PubMed Central

Wang, Wenwen; Zhang, Zhiliang; Ren, Xuechong; Guan, Yongjun; Su, Yanjing

2015-01-01

Finite element analyses were conducted to clarify the role of corrosion product films (CPFs) in stress corrosion cracking (SCC). Flat and U-shaped edge-notched specimens were investigated in terms of the CPF-induced stress in the metallic substrate and the stress in the CPF. For a U-shaped edge-notched specimen, the stress field in front of the notch tip is affected by the Young’s modulus of the CPF and the CPF thickness and notch geometry. The CPF-induced tensile stress in the metallic substrate is superimposed on the applied load to increase the crack tip strain and facilitate localized plasticity deformation. In addition, the stress in the CPF surface contributes to the rupture of the CPFs. The results provide physical insights into the role of CPFs in SCC. PMID:26066367

Prenatal Organophosphates Exposure Alternates the Cleavage Plane Orientation of Apical Neural Progenitor in Developing Neocortex

PubMed Central

Chen, Xiao-Ping; Chen, Wei-Feng; Wang, Da-Wei

2014-01-01

Prenatal organophosphate exposure elicits long-term brain cytoarchitecture and cognitive function impairments, but the mechanism underlying the onset and development of neural progenitors remain largely unclear. Using precise positioned brain slices, we observed an alternated cleavage plane bias that emerged in the mitotic neural progenitors of embryonal neocortex with diazinion (DZN) and chlorpyrifos (CPF) pretreatment. In comparison with the control, DZN and CPF treatment induced decrease of vertical orientation, increase of oblique orientation, and increase of horizontal orientation. That is, the cleavage plane orientation bias had been rotated from vertical to horizontal after DZN and CPF treatment. Meanwhile, general morphology and mitotic index of the progenitors were unchanged. Acephate (ACP), another common organophosphate, had no significant effects on the cleavage plane orientation, cell morphology and mitotic index. These results represent direct evidence for the toxicity mechanism in onset multiplication of neural progenitors. PMID:24740262

Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells.

PubMed

Park, Jae Hyeon; Lee, Jeong Eun; Shin, In Chul; Koh, Hyun Chul

2013-04-01

Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

The clinical effect of acellular dermal matrix on gingival thickness and root coverage compared to coronally positioned flap alone.

PubMed

Woodyard, James G; Greenwell, Henry; Hill, Margaret; Drisko, Connie; Iasella, John M; Scheetz, James

2004-01-01

The primary aim of this randomized, controlled, blinded, clinical investigation was to compare the coronally positioned flap (CPF) plus an acellular dermal matrix (ADM) allograft to CPF alone to determine their effect on gingival thickness and percent root coverage. Twenty-four subjects with one Miller Class I or II buccal recession defect of > or = 3 mm were treated with a CPF plus ADM or a CPF alone. Multiple additional recession sites were treated with the same flap procedure, and all sites were studied for 6 months. Tissue thickness was measured at the sulcus base and at the mucogingival junction of all teeth, with an SDM ultrasonic gingival thickness meter. For the ADM sites, mean initial recession of 3.46 mm was reduced to 0.04 mm for defect coverage of 3.42 mm or 99% (P < 0.05). For the CPF group, mean initial recession of 3.27 mm was reduced to 1.08 mm for defect coverage of 2.19 mm or 67% (P < 0.05). The difference between ADM and CPF groups was statistically significant (P < 0.05). Marginal soft-tissue thickness was increased by 0.40 mm (P < 0.05) for the ADM group, whereas the CPF group remained essentially unchanged. Keratinized tissue was increased for the ADM group by 0.81 mm (P < 0.05), whereas the CPF group increased by 0.33 mm (P > 0.05). No additional root coverage was gained due to creeping attachment between 2 and 6 months for either group. Treatment with a CPF plus an ADM allograft significantly increased gingival thickness when compared with a CPF alone. Recession defect coverage was significantly improved with the use of ADM.

Comparison of polyurethane foam and XAD-2 sampling matrices to measure airborne organophosphorus pesticides and their oxygen analogs in an agricultural community

PubMed Central

Armstrong, Jenna L.; Fenske, Richard A.; Yost, Michael G.; Tchong-French, Maria; Yu, Jianbo

2013-01-01

Side-by-side active air sampling for the organophosphorus (OP) pesticide, chlorpyrifos (CPF) and its oxygen analog, chlorpyrifos-oxon (CPF-O) was conducted with two recommended air sampling matrices: OSHA Versatile Sampling (OVS) tubes with XAD-2 resin, polyurethane foam (PUF) tubes, and passive PUF deposition disks. The study compared the proportion of artificially transformed CPF-O in the laboratory and in the field during a tree fruit application in Washington State. Lab results demonstrated that the NIOSH-recommended OVS tubes artificially transformed up to 32% of CPF to CPF-O during the sampling process, whereas PUF tubes had little to no artificial transformation (≤ 0.1%). In the field, the proportion of CPF-O in the sample was significantly higher on OVS tubes than on PUF tubes (p < 0.001), confirming that OVS tubes were converting a significant portion of CPF to CPF-O. In addition, PUF tubes reported measurable levels CPF-O in the field even when no artificial transformation was expected. We conclude that the PUF matrix is the superior sampling medium for OP oxygen analogs when compared to XAD-2 resin. Community-located PUF tube samples 24 hours post-application had considerably higher levels CPF-O (16–21 ng/m3) than near field samples during application (2–14 ng/m3), suggesting that the oxygen analog is volatile and formed during atmospheric transport. It is recommended that worker and community risk assessments begin to take into consideration the presence of the more toxic oxygen analogs when measuring for OP pesticide mixtures. PMID:23466277

Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

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

Lee, Jeong Eun; Hanyang Biomedical Research Institute, Seoul; Park, Jae Hyeon

2012-09-01

Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity asmore » well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.« less

The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

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

Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.

2007-12-01

There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactationalmore » exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.« less

Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a).

PubMed

Singh, Digvijay; Mallon, John; Poddar, Anustup; Wang, Yanbo; Tippana, Ramreddy; Yang, Olivia; Bailey, Scott; Ha, Taekjip

2018-05-22

CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.

The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis.

PubMed

Li, Diqiu; Huang, Qingchun; Lu, Miaoqing; Zhang, Lei; Yang, Zhichuan; Zong, Mimi; Tao, Liming

2015-09-01

The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, γH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of γH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

How safe is the use of chlorpyrifos: Revelations through its effect on layer birds.

PubMed

Singh, P P; Kumar, Ashok; Chauhan, R S; Pankaj, P K

2016-07-01

The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF) insecticide after oral administration in layer chickens. A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose) for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

CRISPR-Cpf1 assisted genome editing of Corynebacterium glutamicum

PubMed Central

Jiang, Yu; Qian, Fenghui; Yang, Junjie; Liu, Yingmiao; Dong, Feng; Xu, Chongmao; Sun, Bingbing; Chen, Biao; Xu, Xiaoshu; Li, Yan; Wang, Renxiao; Yang, Sheng

2017-01-01

Corynebacterium glutamicum is an important industrial metabolite producer that is difficult to genetically engineer. Although the Streptococcus pyogenes (Sp) CRISPR-Cas9 system has been adapted for genome editing of multiple bacteria, it cannot be introduced into C. glutamicum. Here we report a Francisella novicida (Fn) CRISPR-Cpf1-based genome-editing method for C. glutamicum. CRISPR-Cpf1, combined with single-stranded DNA (ssDNA) recombineering, precisely introduces small changes into the bacterial genome at efficiencies of 86–100%. Large gene deletions and insertions are also obtained using an all-in-one plasmid consisting of FnCpf1, CRISPR RNA, and homologous arms. The two CRISPR-Cpf1-assisted systems enable N iterative rounds of genome editing in 3N+4 or 3N+2 days. A proof-of-concept, codon saturation mutagenesis at G149 of γ-glutamyl kinase relieves L-proline inhibition using Cpf1-assisted ssDNA recombineering. Thus, CRISPR-Cpf1-based genome editing provides a highly efficient tool for genetic engineering of Corynebacterium and other bacteria that cannot utilize the Sp CRISPR-Cas9 system. PMID:28469274

Gene repression via multiplex gRNA strategy in Y. lipolytica.

PubMed

Zhang, Jin-Lai; Peng, Yang-Zi; Liu, Duo; Liu, Hong; Cao, Ying-Xiu; Li, Bing-Zhi; Li, Chun; Yuan, Ying-Jin

2018-04-20

The oleaginous yeast Yarrowia lipolytica is a promising microbial cell factory due to their biochemical characteristics and native capacity to accumulate lipid-based chemicals. To create heterogenous biosynthesis pathway and manipulate metabolic flux in Y. lipolytica, numerous studies have been done for developing synthetic biology tools for gene regulation. CRISPR interference (CRISPRi), as an emerging technology, has been applied for specifically repressing genes of interest. In this study, we established CRISPRi systems in Y. lipolytica based on four different repressors, that was DNase-deactivated Cpf1 (dCpf1) from Francisella novicida, deactivated Cas9 (dCas9) from Streptococcus pyogenes, and two fusion proteins (dCpf1-KRAB and dCas9-KRAB). Ten gRNAs that bound to different regions of gfp gene were designed and the results indicated that there was no clear correlation between the repression efficiency and targeting sites no matter which repressor protein was used. In order to rapidly yield strong gene repression, a multiplex gRNAs strategy based on one-step Golden-brick assembly technology was developed. High repression efficiency 85% (dCpf1) and 92% (dCas9) were achieved in a short time by making three different gRNAs towards gfp gene simultaneously, which avoided the need of screening effective gRNA loci in advance. Moreover, two genes interference including gfp and vioE and three genes repression including vioA, vioB and vioE in protodeoxy-violaceinic acid pathway were also realized. Taken together, successful CRISPRi-mediated regulation of gene expression via four different repressors dCpf1, dCas9, dCpf1-KRAB and dCas9-KRAB in Y. lipolytica is achieved. And we demonstrate a multiplexed gRNA targeting strategy can efficiently achieve transcriptional simultaneous repression of several targeted genes and different sites of one gene using the one-step Golden-brick assembly. This timesaving method promised to be a potent transformative tool valuable for metabolic engineering, synthetic biology, and functional genomic studies of Y. lipolytica.

The Two Cryptochrome/Photolyase Family Proteins Fulfill Distinct Roles in DNA Photorepair and Regulation of Conidiation in the Gray Mold Fungus Botrytis cinerea

PubMed Central

Cohrs, Kim C.

2017-01-01

ABSTRACT The plant-pathogenic leotiomycete Botrytis cinerea is known for the strict regulation of its asexual differentiation programs by environmental light conditions. Sclerotia are formed in constant darkness; black/near-UV (NUV) light induces conidiation; and blue light represses both differentiation programs. Sensing of black/NUV light is attributed to proteins of the cryptochrome/photolyase family (CPF). To elucidate the molecular basis of the photoinduction of conidiation, we functionally characterized the two CPF proteins encoded in the genome of B. cinerea as putative positive-acting components. B. cinerea CRY1 (BcCRY1), a cyclobutane pyrimidine dimer (CPD) photolyase, acts as the major enzyme of light-driven DNA repair (photoreactivation) and has no obvious role in signaling. In contrast, BcCRY2, belonging to the cry-DASH proteins, is dispensable for photorepair but performs regulatory functions by repressing conidiation in white and especially black/NUV light. The transcription of bccry1 and bccry2 is induced by light in a White Collar complex (WCC)-dependent manner, but neither light nor the WCC is essential for the repression of conidiation through BcCRY2 when bccry2 is constitutively expressed. Further, BcCRY2 affects the transcript levels of both WCC-induced and WCC-repressed genes, suggesting a signaling function downstream of the WCC. Since both CPF proteins are dispensable for photoinduction by black/NUV light, the origin of this effect remains elusive and may be connected to a yet unknown UV-light-responsive system. IMPORTANCE Botrytis cinerea is an economically important plant pathogen that causes gray mold diseases in a wide variety of plant species, including high-value crops and ornamental flowers. The spread of disease in the field relies on the formation of conidia, a process that is regulated by different light qualities. While this feature has been known for a long time, we are just starting to understand the underlying molecular mechanisms. Conidiation in B. cinerea is induced by black/near-UV light, whose sensing is attributed to the action of cryptochrome/photolyase family (CPF) proteins. Here we report on the distinct functions of two CPF proteins in the photoresponse of B. cinerea. While BcCRY1 acts as the major photolyase in photoprotection, BcCRY2 acts as a cryptochrome with a signaling function in regulating photomorphogenesis (repression of conidiation). PMID:28667107

Chlorpyrifos pollution: its effect on brain acetylcholinesterase activity in rat and treatment of polluted soil by indigenous Pseudomonas sp.

PubMed

Sharma, Shelly; Singh, Partap Bir; Chadha, Pooja; Saini, Harvinder Singh

2017-01-01

The study was aimed to evaluate the levels of chlorpyrifos (CPF) pollution in agricultural soil of Punjab, India, its detrimental effects on acetylcholinesterase (AChE) activity in rat brain and bioremediation of soils polluted with CPF using indigenous and adapted bacterial lab isolate. The analysis revealed that soil samples of Bathinda and Amritsar regions are highly contaminated with chlorpyrifos showing 19 to 175 mg/kg concentrations of CPF. The non-targeted animals may get poisoned with CPF by its indirect dermal absorption, inhalation of toxic fumes and regular consumption of soiled food grains. The study indicated that even the lowermost concentrations of CPF, 19 and 76 mg/kg of soil found in the Amritsar and Bathinda regions respectively can significantly inhibit the AChE activity in rat brain within 24 h of its treatment. This represents the antagonistic effect of CPF on AChE which is a prime neurotransmitter present in all living beings including humans. In light of this, an attempt was made to remediate the polluted soil, a major reservoir of CPF, using Pseudomonas sp. (ChlD), an indigenous bacterial isolate. The culture efficiently degraded 10 to 100 mg/kg chlorpyrifos supplemented in the soil and utilized it as sole source of carbon and energy for its growth. Thus, this study provides a detailed insight regarding the level of CPF pollution in Punjab, its detrimental effects on mammals and bio-based solution to remediate the sites polluted with CPF.

Postnatal chlorpyrifos exposure and apolipoprotein E (APOE) genotype differentially affect cholinergic expression and developmental parameters in transgenic mice.

PubMed

Basaure, Pia; Guardia-Escote, Laia; Cabré, Maria; Peris-Sampedro, Fiona; Sánchez-Santed, Fernando; Domingo, José L; Colomina, Maria Teresa

2018-05-03

Chlorpyrifos (CPF) is one of the most commonly used organophosphate pesticides in the world. Our previous results described that apolipoprotein E (APOE) polymorphisms are a source of individual differences in susceptibility to CPF. The aim of this study was to assess the physical and biochemical effects of postnatal exposure to CPF in the apoE targeted replacement mouse model. Mice were exposed to CPF at 0 or 1 mg/kg/day from postnatal day 10-15. Physical development, plasma and forebrain cholinesterase (ChE) activity and gene expression in liver and forebrain were evaluated. CPF exposure delays physical maturation and decreases the expression of choline acetyltransferase, α4-subunit and the α7 receptor. CPF decreases the expression of vesicular acetylcholine transporter (VAChT) mRNA in the forebrain only in apoE3 mice. The expression of paraoxonase-2 in the forebrain was also influenced by APOE genotype and CPF. Differences between genotypes were observed in litter size, ChE activity, expression of butyrylcholinesterase and paraoxonase-1 in liver and variants of acetylcholinesterase, VAChT and the α7 receptor in the forebrain. These results support that there are different vulnerabilities to postnatal CPF exposure according to the APOE polymorphism, which in turn affects the cholinergic system and defenses to oxidative stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Esterases activity in the axolotl Ambystoma mexicanum exposed to chlorpyrifos and its implication to motor activity.

PubMed

Robles-Mendoza, Cecilia; Zúñiga-Lagunes, Sebastian R; Ponce de León-Hill, Claudia A; Hernández-Soto, Jesús; Vanegas-Pérez, Cecilia

2011-10-01

The axolotl Ambystoma mexicanum is a neotenic salamander considered a good biological model due to its ability to regenerate limbs, tail, brain and heart cells. Nevertheless, severe reduction of A. mexicanum wild populations in the lacustrine area of Xochimilco, the natural habitat of the axolotl, could be related to several environmental pressures as the presence of organophosphate pesticides (OPPs), intensively applied in agricultural activities in Xochimilco. Thus the aim of this study was to evaluate the effect of environmentally realistic chlorpyrifos (CPF) concentrations, a OPP commonly used in this zone, on esterases activity (acetylcholinesterase and carboxylesterase) and bioconcentration of CPF and to relate them with the motor activity of A. mexicanum juveniles. Axolotls were exposed 48 h to 0.05 and 0.1mg CPF/L, and the responses were evaluated at the end of the CPF exposure. Results suggest that CPF is bioconcentrated into axolotls and that the CPF internal concentrations are related with the observed inhibition activity of AChE (>50%) and CbE (≈ 50%). CPF concentration responsible of the inhibition of the 50% of AChE activity (IC50) was estimated in 0.04 mg CPF/L; however IC50 for CbE activity was not possible to calculate since inhibition levels were lower than 50%, results that suggest a higher resistance of CbE enzymatic activity to CPF. However, motor activity was a more sensitive endpoint to CPF poisoning since time that axolotls spent active and walking, frequency and speed of swimming, frequency of prey attack were reduced >90% of control groups. The motor activity alterations in the axolotl could be related with the registered esterases inhibition. Thus important alterations on axolotls were identified even at short time and low concentrations of CPF exposure. Also, it was possible to link biochemical responses as esterases activity with higher levels of biological organization as behavior. This study provides tools for the regulation of the use of organophosphorus pesticides in the natural habitat of the axolotl. Copyright © 2011 Elsevier B.V. All rights reserved.

Drug-protein interactions assessed by fluorescence measurements in the real complexes and in model dyads

NASA Astrophysics Data System (ADS)

Vayá, Ignacio; Pérez-Ruiz, Raúl; Lhiaubet-Vallet, Virginie; Jiménez, M. Consuelo; Miranda, Miguel A.

2010-02-01

In the present work, a systematic fluorescence study on supramolecular systems using two serum albumins (HSA or BSA) as hosts and the nonsteroidal antiinflammatory drugs carprofen (CPF) or naproxen (NPX) as guests has been undertaken. In parallel, model dyads containing Tyr or Trp covalently linked to CPF or NPX have also been investigated. In HSA/(S)-CPF and BSA/(S)-CPF ( λexc = 266 nm), at 1:1 M ratio, an important degree (more than 40%) of singlet-singlet energy transfer (SSET) was observed to take place. The distance ( r) calculated for energy transfer from the SAs to (S)-CPF through a FRET mechanism was found to be ca. 21 Å. In the case of HSA/(S)-NPX and BSA/(S)-NPX, energy transfer occurred to a lower extent (ca. 7%), and r was determined as ca. 24 Å. In order to investigate the possible excited state interactions between bound ligands and the relevant amino acids present in the protein binding sites, four pairs of model dyads were designed and synthesised, namely ( S, S)-TyrCPF, ( S, R)-TyrCPF, ( S, S)-TrpCPF, ( S, R)-TrpCPF, ( S, S)-TyrNPX, ( S, R)-TyrNPX, ( S, S)-TrpNPX and ( S, R)-TrpNPX. A complete SSET was observed from Tyr or Trp to CPF, since no contribution from the amino acids was present in the emission of the dyads. Likewise, a very efficient Tyr or Trp to NPX energy transfer was observed. Remarkably, in ( S, S)-TrpNPX and ( S, R)-TrpNPX a configuration-dependent reduction in the emission intensity was observed, revealing a strong and stereoselective intramolecular quenching. This effect can be attributed to exciplex formation and is dynamic in nature, as the fluorescence lifetimes were much shorter in ( S, R)- and ( S, S)-TrpNPX (1.5 and 3.1 ns, respectively) than in (S)-NPX (11 ns).

Structural Basis for the Altered PAM Recognition by Engineered CRISPR-Cpf1.

PubMed

Nishimasu, Hiroshi; Yamano, Takashi; Gao, Linyi; Zhang, Feng; Ishitani, Ryuichiro; Nureki, Osamu

2017-07-06

The RNA-guided Cpf1 nuclease cleaves double-stranded DNA targets complementary to the CRISPR RNA (crRNA), and it has been harnessed for genome editing technologies. Recently, Acidaminococcus sp. BV3L6 (AsCpf1) was engineered to recognize altered DNA sequences as the protospacer adjacent motif (PAM), thereby expanding the target range of Cpf1-mediated genome editing. Whereas wild-type AsCpf1 recognizes the TTTV PAM, the RVR (S542R/K548V/N552R) and RR (S542R/K607R) variants can efficiently recognize the TATV and TYCV PAMs, respectively. However, their PAM recognition mechanisms remained unknown. Here we present the 2.0 Å resolution crystal structures of the RVR and RR variants bound to a crRNA and its target DNA. The structures revealed that the RVR and RR variants primarily recognize the PAM-complementary nucleotides via the substituted residues. Our high-resolution structures delineated the altered PAM recognition mechanisms of the AsCpf1 variants, providing a basis for the further engineering of CRISPR-Cpf1. Copyright © 2017 Elsevier Inc. All rights reserved.

The Conspicuity of CRISPR-Cpf1 System as a Significant Breakthrough in Genome Editing.

PubMed

Bayat, Hadi; Modarressi, Mohammad Hossein; Rahimpour, Azam

2018-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) is a microbial adaptive immune system. CRISPR-Cas systems are classified into two main classes and six types. Cpf1 is a putative type V (class II) CRISPR effector, which has revolutionized the genome editing approaches through multiple distinct features such as using T-rich protospacer-adjacent motif, applying a short guide RNA lacking trans-activating crRNA, introducing a staggered double-strand break, and possessing RNA processing activity in addition to DNA nuclease activity. In the present review, we attempt to highlight most recent advances in CRISPR-Cpf1 (CRISPR-Cas12a) system in particular, considering ground expeditions of the nature and the biology of this system, introducing novel Cpf1 variants that have broadened the versatility and feasibility of CRISPR-Cpf1 system, and lastly the great impact of the CRISPR-Cpf1 system on the manipulation of the genome of prokaryotic, mammalian, and plant models is summarized. With regard to recent developments in utilizing the CRISPR-Cpf1 system in genome editing of various organisms, it can be concluded with confidence that this system is a reliable molecular toolbox of genome editing approaches.

CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration.

PubMed

Koo, Taeyoung; Park, Sung Wook; Jo, Dong Hyun; Kim, Daesik; Kim, Jin Hyoung; Cho, Hee-Yeon; Kim, Jeungeun; Kim, Jeong Hun; Kim, Jin-Soo

2018-05-10

LbCpf1, derived from Lachnospiraceae bacterium ND2006, is a CRISPR RNA-guided endonuclease and holds promise for therapeutic applications. Here we show that LbCpf1 can be used for therapeutic gene editing in a mouse model of age-related macular degeneration (AMD). The intravitreal delivery of LbCpf1, targeted to two angiogenesis-associated genes encoding vascular endothelial growth factor A (Vegfa) and hypoxia inducing factor 1a (Hif1a), using adeno-associated virus, led to efficient gene disruption with no apparent off-target effects in the retina and retinal pigment epithelium (RPE) cells. Importantly, LbCpf1 targeted to Vegfa or Hif1a in RPE cells reduced the area of laser-induced choroidal neovascularization as efficiently as aflibercept, an anti-VEGF drug currently used in the clinic, without inducing cone dysfunction. Unlike aflibercept, LbCpf1 targeted to Vegfa or Hif1a achieved a long-term therapeutic effect on CNV, potentially avoiding repetitive injections. Taken together, these results indicate that LbCpf1-mediated in vivo genome editing to ablate pathologic angiogenesis provides an effective strategy for the treatment of AMD and other neovascularization-associated diseases.

Theoretical Study of the Electric Dipole Moment Function of the CIO Molecule

NASA Technical Reports Server (NTRS)

Pettersson, Lars G. M.; Langhoff, Stephen R.; Chong, Delano P.

1986-01-01

The potential energy function and electric dipole moment function (EDMF) are computed for CIO Chi(sup 2)Pi using several different techniques to include electron correlation. The EDMF is used to compute Einstein coefficients, vibrational lifetimes, and dipole moments in higher vibrational levels. Remaining questions concerning the position of the maximum of the EDMF may be resolved through experimental measurement of dipole moments of higher vibrational levels. The band strength of the 1-0 fundamental transition is computed to be 12 +/- 2 /sq cm atm in good agreement with three experimental values, but larger than a recent value of 5 /sq cm atm determined from infrared heterodyne spectroscopy. The theoretical methods used include SCF, CASSCF, multireference singles plus doubles configuration interaction (MRCI) and contracted CI, coupled pair functional (CPF), and a modified version of the CPF method. The results obtained using the different methods are critically compared.

Deep learning improves prediction of CRISPR-Cpf1 guide RNA activity.

PubMed

Kim, Hui Kwon; Min, Seonwoo; Song, Myungjae; Jung, Soobin; Choi, Jae Woo; Kim, Younggwang; Lee, Sangeun; Yoon, Sungroh; Kim, Hyongbum Henry

2018-03-01

We present two algorithms to predict the activity of AsCpf1 guide RNAs. Indel frequencies for 15,000 target sequences were used in a deep-learning framework based on a convolutional neural network to train Seq-deepCpf1. We then incorporated chromatin accessibility information to create the better-performing DeepCpf1 algorithm for cell lines for which such information is available and show that both algorithms outperform previous machine learning algorithms on our own and published data sets.

A patient-centered clinical evaluation of acellular dermal matrix graft in the treatment of gingival recession defects.

PubMed

Mahajan, Ajay; Dixit, Jaya; Verma, Umesh Pratap

2007-12-01

The present randomized controlled trial was conducted to evaluate acellular dermal matrix (ADM) graft in terms of patient satisfaction and its effectiveness and efficiency in the treatment of gingival recession. Fourteen patients (seven males and seven females) with Miller Class I and II recessions > or =3 mm participated in this 6-month clinical study. They were assigned randomly to the ADM group (ADM graft and coronally positioned flap [CPF]) or the CPF group (CPF alone). Results were evaluated based on parameters measuring patient satisfaction and clinical outcomes associated with the two treatment procedures. Significance was set at P <0.05. The mean recession was 4.0 +/- 1.0 mm and 3.7 +/- 0.7 mm for the ADM and CPF groups, respectively. For the ADM group, the defect coverage was 3.85 +/- 0.89 mm or 97.14% compared to the CPF group, in which the defect coverage was 2.85 +/- 0.89 mm or 77.42%. The difference between the two groups was statistically significant (P <0.05). There were no statistically significant differences between the two groups in the remaining clinical parameters and overall patient satisfaction except in criteria related to patient comfort and cost effectiveness, in which CPF alone produced significantly better results (P <0.03). ADM graft is significantly superior with regard to effectiveness and efficiency in the treatment of gingival recession than CPF alone. CPF emerges as a better option than ADM graft in terms of cost effectiveness and patient comfort.

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

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

Ellison, Corie A., E-mail: cellison@buffalo.edu; Crane, Alice L., E-mail: alcrane@buffalo.edu; Bonner, Matthew R., E-mail: mrbonner@buffalo.edu

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase)more » and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.« less

PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION FOR A BINARY MIXTURE OF CHLORPYRIFOS AND DIAZINON IN THE RAT

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

Timchalk, Chuck; Poet, Torka S.; Hinman, Melissa N.

2005-05-15

Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE) by their oxon metabolites. The pharmacokinetic and pharmacodynamic impact of acute binary exposures to CPF and DZN in rats were evaluated in this study. Rats were orally administered CPF, DZN or a CPF/DZN mixture (0, 15, 30 or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12 and 24 h post-dosing, urine was also collected at 24 h. Chlorpyrifos, DZNmore » and their respective metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP) were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBCs and plasma. Co-exposure to CPF/DZN at 15/15 mg/kg, did not appreciably alter the pharmacokinetics of CPF, DZN or their metabolites in blood; whereas, a 60/60 mg/kg dose resulted in a transient increase in Cmax, AUC, and decreased clearance of both compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and co-exposures. The overall potency for ChE inhibition was greater for CPF than DZN and the binary mixture response appeared to be strongly influenced by CPF. A comparison of the ChE binary response at the low dose (15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These are the first reported experiments we are aware of that characterize both the pharmacokinetic and pharmacodynamic interactions between CPF and DZN in the rat, and will be used to further develop a binary physiologically based pharmacokinetic and pharmacodynamic model for mixtures.« less

Isolation and characterisation of in vitro and cellular free radical scavenging peptides from corn peptide fractions.

PubMed

Wang, Liying; Ding, Long; Wang, Ying; Zhang, Yan; Liu, Jingbo

2015-02-16

Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) were investigated. Results indicated that CPF1 (molecular weight less than 1 kDa) and CPF2 (molecular weight between 1 and 3 kDa) exhibited good hydroxyl radical, superoxide anion radical and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) diammonium salt (ABTS) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Meanwhile, the in vitro radical scavenging activity of CPF1 was slightly higher than that of CPF2. Both CPF1 and CPF2 also exhibited significant cytoprotective effects and intracellular reactive oxygen species scavenging activity in Caco-2 cells exposed to hydrogen peroxide (H2O2). The amino acid composition analysis revealed that the CPF were rich in hydrophobic amino acids, which comprised of more than 45% of total amino acids. An antioxidant peptide sequence of Tyr-Phe-Cys-Leu-Thr (YFCLT) was identified from CPF1 using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI TOF/TOF MS). The YFCLT exhibited excellent ABTS radical scavenging activity with a 50% effective concentration (EC50) value of 37.63 µM, which was much lower than that of Trolox. In conclusion, corn gluten meal might be a good source to prepare antioxidant peptides.

Ultraviolet Photolysis of Chlorpyrifos: Developmental Neurotoxicity Modeled in PC12 Cells

PubMed Central

Slotkin, Theodore A.; Seidler, Frederic J.; Wu, Changlong; MacKillop, Emiko A.; Linden, Karl G.

2009-01-01

Background Ultraviolet photodegradation products from pesticides form both in the field and during water treatment. Objectives We evaluated the photolytic breakdown of the organophosphate pesticide chlorpyrifos (CPF) in terms of both the chemical entities generated by low-pressure ultraviolet C irradiation and their potential as developmental neurotoxicants. Methods We separated by-products using high-performance liquid chromatography and characterized them by gas chromatography/mass spectrometry. We assessed neurotoxicity in neuronotypic PC12 cells, both in the undifferentiated state and during differentiation. Results Photodegradation of CPF in methanol solution generated CPF oxon and trichloropyridinol, products known to retain developmental neurotoxicant actions, as well as a series of related organophosphate and phosphorothionate derivatives. Exposure conditions that led to 50% degradation of CPF thus did not reduce developmental neurotoxicity. The degradation mixture inhibited DNA synthesis in undifferentiated cells to the same extent as native CPF. In differentiating cells, the products likewise retained the full ability to elicit shortfalls in cell number and corresponding effects on cell growth and neurite formation. When the exposure was prolonged to the point where 70% of the CPF was degraded, the adverse effects on PC12 cells were no longer evident; however, these conditions were sufficiently severe to generate toxic products from the methanol vehicle. Conclusions Our results indicate that field conditions or remediation treatments that degrade a significant proportion of the CPF do not necessarily produce inactive products and, indeed, may elicit formation of even more toxic chemicals that are more water soluble and thus have greater field mobility than CPF itself. PMID:19337505

Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats.

PubMed

Abolaji, Amos O; Ojo, Mercy; Afolabi, Tosin T; Arowoogun, Mary D; Nwawolor, Darlinton; Farombi, Ebenezer O

2017-05-25

Chlorpyrifos (CPF) is an organophosphorus pesticide widely used in agricultural applications and household environments. 6-Gingerol-rich fraction from Zingiber officinale (Ginger, 6-GRF) has been reported to possess potent anti-oxidative, anti-inflammatory and anti-apoptotic properties. Here, we investigated the protective properties of 6-GRF on CPF-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Five groups of rats containing 14 rats/group received corn oil (control), CPF (5 mg/kg), 6-GRF (100 mg/kg), CPF (5 mg/kg) + 6-GRF (50 mg/kg) and CPF (5 mg/kg) + 6-GRF (100 mg/kg) through gavage once per day for 35 days respectively. The results showed that 6-GRF protected against CPF-induced increases in oxidative stress ((hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA)), inflammatory (myeloperoxidase (MPO), nitric oxide (NO) and tumour necrosis factor-α (TNF- α)), and apoptotic (caspase-3) markers. Also, 6-GRF improved the activities of antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) as well as glutathione (GSH) level in the brain, ovary and uterus of rats exposed to CPF (p < 0.05). Overall, the protective effects of 6-GRF on CPF-induced toxicity in the brain and reproductive organs of rats may be due to its potent antioxidative, anti-inflammatory and antiapoptotic properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

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

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron

2011-11-15

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemicalmore » changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and cannabinoid CB1 receptor knockout littermates responded similarly to the toxic effects of chlorpyrifos. Black-Right-Pointing-Pointer OP-induced changes in acetylcholine release appeared sensitive to modulation by CB1-mediated endocannabinoid signaling.« less

A Structure Standard for Archival Context: EAC-CPF Is Here

ERIC Educational Resources Information Center

Dryden, Jean

2010-01-01

The archival community's new descriptive standard, "Encoded Archival Context" for Corporate Bodies, Persons, and Families (EAC-CPF), supports the sharing of descriptions of records creators and is a significant addition to the suite of standards for archival description. EAC-CPF is a data structure standard similar to its older sibling EAD…

78 FR 21123 - Charlotte Pipe and Foundry; Analysis to Aid Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... Agreement'') from Charlotte Pipe and Foundry Company (hereinafter ``CP&F'') and its wholly-owned subsidiary... the following allegations. A. The Respondents CP&F is a privately-held corporation with its principal place of business located at 2109 Randolph Road, Charlotte, NC 28207. CP&F is one of the largest...

Chlorpyrifos PBPK/PD model for multiple routes of exposure.

PubMed

Poet, Torka S; Timchalk, Charles; Hotchkiss, Jon A; Bartels, Michael J

2014-10-01

1. Chlorpyrifos (CPF) is an important pesticide used to control crop insects. Human Exposures to CPF will occur primarily through oral exposure to residues on foods. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model has been developed that describes the relationship between oral, dermal and inhalation doses of CPF and key events in the pathway for cholinergic effects. The model was built on a prior oral model that addressed age-related changes in metabolism and physiology. This multi-route model was developed in rats and humans to validate all scenarios in a parallelogram design. 2. Critical biological effects from CPF exposure require metabolic activation to CPF oxon, and small amounts of metabolism in tissues will potentially have a great effect on pharmacokinetics and pharmacodynamic outcomes. Metabolism (bioactivation and detoxification) was therefore added in diaphragm, brain, lung and skin compartments. Pharmacokinetic data are available for controlled human exposures via the oral and dermal routes and from oral and inhalation studies in rats. The validated model was then used to determine relative dermal versus inhalation uptake from human volunteers exposed to CPF in an indoor scenario.

Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

PubMed Central

2009-01-01

Background Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Methods Late gestational exposure [gestational day (GD) 14–17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs) 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10). Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. Results As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking) and explorative (wall rearing) responses. Conclusion Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants. PMID:19331648

Sex-dimorphic effects of gestational exposure to the organophosphate insecticide chlorpyrifos on social investigation in mice.

PubMed

De Felice, Alessia; Venerosi, Aldina; Ricceri, Laura; Sabbioni, Mara; Scattoni, Maria Luisa; Chiarotti, Flavia; Calamandrei, Gemma

2014-01-01

Several pieces of evidence from animal and human studies indicate that the organophosphate insecticide chlorpyrifos (CPF) acts as a developmental neurotoxicant at environmentally relevant doses, and it is possibly endowed with endocrine-disrupting activity. Data collected in rodent models show that developmental exposure to CPF at sub-toxic doses induces long-lasting and sex-dimorphic changes in social and investigative responses in exposed offspring. The aim of this study was to evaluate the effects of gestational CPF treatment on social and olfactory discrimination in adult mice of both sexes. Pregnant CD1 out-bred mice were exposed to CPF per os on gestational days (GD) 14-17 at the sub-toxic dose of 6 mg/kg/bw. At adulthood, male and female offspring underwent the same experimental paradigms, namely i) a social discrimination test where mice were presented with a simultaneous binary choice between a novel conspecific and a familiar one, and ii) an olfactory habituation/dishabituation test to evaluate their capability to discriminate between odors with different eco-ethological salience (non-social vs. social odors). Results showed that in the social discrimination test prenatal CPF primarily affected the female sex by raising the investigation time in females to the same levels as found in vehicle- and CPF-exposed males. The ability to discriminate between a familiar and a novel social mate was not affected by CPF in either sex. In the olfactory habituation/dishabituation test, mice of both sexes successfully discriminated non-social from social odors regardless of the prenatal treatment received. These results confirm previous evidence indicating that developmental exposure to CPF causes long-lasting and sex-dimorphic changes in responsiveness to social cues, in the absence of significant impairment of social and olfactory discrimination capacity. These findings are discussed within the framework of recent data pointing to the limbic/hypothalamic circuitry and steroid hormonal regulations as possible targets for CPF neurotoxicity. Copyright © 2014. Published by Elsevier Inc.

Prenatal Exposure of Guinea Pigs to the Organophosphorus Pesticide Chlorpyrifos Disrupts the Structural and Functional Integrity of the Brain

PubMed Central

Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Pescrille, Joseph D.; Todd, Spencer W.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

2015-01-01

This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (20 mg/kg, s.c.) or vehicle (peanut oil) once per day for ten consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40–45 post-natal days (PND) using the Morris Water Maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T2-weighted anatomical scans and Diffusion Kurtosis Imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of pre-natal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment. PMID:25704171

Ambient PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in Changhua County, central Taiwan: Seasonal variation, source apportionment and cancer risk assessment.

PubMed

Chen, Yu-Cheng; Chiang, Hung-Che; Hsu, Chin-Yu; Yang, Tzu-Ting; Lin, Tzu-Yu; Chen, Mu-Jean; Chen, Nai-Tzu; Wu, Yuh-Shen

2016-11-01

This study investigates PM 2.5 -bound PAHs for rural sites (Dacheng and Fangyuan) positioned close to heavy air-polluting industries in Changhua County, central Taiwan. A total of 113 PM 2.5 samples with 22 PAHs collected from 2014 to 2015 were analyzed, and Positive Matrix Factorization (PMF) and diagnostic ratios of PAHs were applied to quantify potential PAH sources. The influences of local and regional sources were also explored using the conditional probability function (CPF) and potential source contribution function (PSCF) with PMF-modeled results, respectively. Annual mean concentrations of total PAHs were 2.91 ± 1.34 and 3.04 ± 1.40 ng/m 3 for Dacheng and Fangyuan, respectively, and their corresponding BaP eq were measured at 0.534 ± 0.255 and 0.563 ± 0.273 ng/m 3 in concentration. Seasonal variations with higher PAHs found for the winter than for the spring and summer were observed for both sites. The lifetime excess cancer risk (ECR) from inhalation exposure to PAHs was recorded as 4.7 × 10 -5 overall. Potential sources of PM 2.5 -bound PAHs include unburned petroleum and traffic emissions (42%), steel industry and coal combustion (31%), and petroleum and oil burning (27%), and unburned petroleum and traffic emission could contribute the highest ECR (2.4 × 10 -5 ). The CPF results show that directional apportionment patterns were consistent with the actual locations of local PAH sources. The PSCF results indicate that mainly northeastern regions of China have contributed elevated PM 2.5 -bound PAHs from long-range transports. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential risks of dietary exposure to chlorpyrifos and cypermethrin from their use in fruit/vegetable crops and beef cattle productions.

PubMed

Ferré, Daniela M; Quero, Arnoldo A M; Hernández, Antonio F; Hynes, Valentina; Tornello, Marcelo J; Lüders, Carlos; Gorla, Nora B M

2018-04-18

The active ingredients (a.i.) used as pesticides vary across regions. Diet represents the main source of chronic exposure to these chemicals. The aim of this study was to look at the pesticides applied in fruit, vegetable, and beef cattle productions in Mendoza (Argentina), to identify those that were simultaneously used by the three production systems. Local individuals (n = 160), involved in these productions, were interviewed. Glyphosate was the a.i. most often used by fruit-vegetable producers, and ivermectin by beef cattle producers. Chlorpyrifos (CPF) and cypermethrin (CYP) were the only a.i. used by the three production systems. The survey revealed that CPF, CYP, alpha CYP, and CPF+CYP were used by 22, 16, 4, and 20% of the fruit and vegetable producers, respectively. Regarding beef cattle, CYP was used by 90% of producers, CYP + CPF formulation by 8%, and alpha CYP by 2%. The second approach of this study was to search the occurrence of CYP and CPF residues in food commodities analyzed under the National Plan for Residue Control (2012-2015). CYP residues found above the LOD were reported in 4.0% and CPF in 13.4% of the vegetable samples tested, as well as in 1.2 and 28.8%, respectively, of the fruit samples tested. Regarding beef cattle, CYP residues were reported in 2.3% and organophosphates (as a general pesticide class) in 13.5% of samples tested. In conclusion, consumers may be exposed simultaneously to CPF and CYP, from fruits, vegetables, and beef intake. Accordingly, the policy for pesticide residues in food and human risk assessment should account for the combined exposure to CPF and CYP. Moreover, appropriate toxicological studies of this mixture (including genotoxicity) are warranted.

SN56 neuronal cell death after 24 h and 14 days chlorpyrifos exposure through glutamate transmission dysfunction, increase of GSK-3β enzyme, β-amyloid and tau protein levels.

PubMed

Moyano, Paula; Frejo, María Teresa; Anadon, María José; García, José Manuel; Díaz, María Jesús; Lobo, Margarita; Sola, Emma; García, Jimena; Del Pino, Javier

2018-06-01

Chlorpyrifos (CPF) is an organophosphate insecticide described to induce cognitive disorders, both after acute and repeated administration. However, the mechanisms through which it induces these effects are unknown. CPF has been reported to produce basal forebrain cholinergic neuronal cell death, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Neuronal cell death was partially mediated by oxidative stress generation, P75 NTR and α 7 -nAChRs gene expression alteration triggered through acetylcholinesterase (AChE) variants disruption, suggesting other mechanisms are involved. In this regard, CPF induces Aβ and tau proteins production and activation of GSK3β enzyme and alters glutamatergic transmission, which have been related with basal forebrain cholinergic neuronal cell death and development of cognitive disorders. According to these data, we hypothesized that CPF induces basal forebrain cholinergic neuronal cell death through induction of Aβ and tau proteins production, activation of GSK-3β enzyme and disruption of glutamatergic transmission. We evaluated this hypothesis in septal SN56 basal forebrain cholinergic neurons, after 24 h and 14 days CPF exposure. This study shows that CPF increases glutamate levels, upregulates GSK-3β gene expression, and increases the production of Aβ and phosphorylated tau proteins and all these effects reduced cell viability. CPF increases glutaminase activity and upregulates the VGLUT1 gene expression, which could mediate the disruption of glutamatergic transmission. Our present results provide new understanding of the mechanisms contributing to the harmful effects of CPF, and its possible relevance in the pathogenesis of neurodegenerative diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Chlorpyrifos is estrogenic and alters embryonic hatching, cell proliferation and apoptosis in zebrafish.

PubMed

Yu, Kaimin; Li, Guochao; Feng, Weimin; Liu, Lili; Zhang, Jiayu; Wu, Wei; Xu, Lei; Yan, Yanchun

2015-09-05

The potential interference of endocrine disrupting chemicals (EDCs) on aquatic animals and humans has drawn wide attention in recent years. Reports have shown that some organophosphorus pesticides were a kind of EDCs, but their effects on fish species are still under research. In present study, flow cytometry data of HEC-1B cell line showed that chlorpyrifos (CPF) could increase cell proliferation index like 17β-estradiol (E2), but the effect of CPF was weaker than of E2 in the same concentration. Moreover, CPF altered the expression pattern of estrogen-responsive gene VTG and ERα in zebrafish embryos. When exposed to CPF at various concentrations (0, 0.10, 0.25, 0.50, 0.75 and 1.00mg/L) for 48h during the embryo stage, compared with controls, the hatching rate of treated groups significantly increased at the same time and the hatching rate of embryos was proportional to CPF concentration. The mRNA expression levels of c-myc, cyclin D1, Bax and Bcl-2, which are closely related to cell proliferation and cell apoptosis, were disturbed by CPF in zebrafish embryos after exposure treated for 48h. In addition, acridine orange (AO) staining of zebrafish embryos showed that cell apoptosis was appeared in the 0.75, 1.00mg/L CPF treated groups. Taken together, the results obtained in the present study indicated that chlorpyrifos is estrogenic and alters embryonic hatching, cell proliferation and apoptosis in zebrafish. Copyright © 2015. Published by Elsevier Ireland Ltd.

Apolipoprotein E (APOE) genotype and the pesticide chlorpyrifos modulate attention, motivation and impulsivity in female mice in the 5-choice serial reaction time task.

PubMed

Peris-Sampedro, Fiona; Reverte, Ingrid; Basaure, Pia; Cabré, Maria; Domingo, José L; Colomina, Maria Teresa

2016-06-01

Organophosphate pesticides - and chlorpyrifos (CPF) in particular - contribute to a wide range of neurobehavioural disorders. Most experimental research focuses on learning and memory processes, while other behaviours remain understudied. The isoforms of the human apolipoprotein E (apoE) confer different cognitive skills on their carriers, but data on this topic are still limited. The current study was performed to assess whether the APOE genotypic variability differently modulates the effects of CPF on attentional performance, inhibitory control and motivation. Human apoE targeted replacement adult female mice (apoE2, apoE3 and apoE4) were trained to stably perform the 5-choice serial reaction time task (5-CSRTT). Animals were then subjected to daily dietary CPF (3.75 mg/kg body weight) for 4 weeks. After CPF exposure, we established a 4-week CPF-free period to assess recovery. All individuals acquired the task, apoE2 mice showed enhanced learning, while apoE4 mice displayed increased premature and perseverative responding. This genotype-dependent lack of inhibitory control was reversed by CPF. Overall, the pesticide induced protracted impairments in sustained attention and motivation, and it reduced anticipatory responding. ApoE3 mice exhibited delayed attentional disruptions throughout the wash-out period. Taken together, these findings provide notable evidence on the emergence of CPF-related attentional and motivational deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

CHLORPYRIFOS AND 3,5,6 TRICHLORO-2-PYRIDINOL DISTRIBUTION IN RAT BLOOD AND BRAIN DURING CHRONIC DIETARY AND REPEATED HIGH LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS.

EPA Science Inventory

The aim of this study was to determine the concentrations of an organophosphorus pesticide, chlorpyrifos (CPF), and the metabolite 3,5,6 trichloro-2-pyridinol (TCP) in tissues from rats exposed to long-term, low-dose CPF. Adult, Long-Evans male rats received CPF for one year at ...

Spectro-temporal characterization of the photoactivation mechanism of two new oxidized cryptochrome/photolyase photoreceptors.

PubMed

Brazard, Johanna; Usman, Anwar; Lacombat, Fabien; Ley, Christian; Martin, Monique M; Plaza, Pascal; Mony, Laetitia; Heijde, Marc; Zabulon, Gérald; Bowler, Chris

2010-04-07

The photoactivation dynamics of two new flavoproteins (OtCPF1 and OtCPF2) of the cryptochrome photolyase family (CPF), belonging to the green alga Ostreococcus tauri , was studied by broadband UV-vis femtosecond absorption spectroscopy. Upon excitation of the protein chromophoric cofactor, flavin adenine dinucleotide in its oxidized form (FAD(ox)), we observed in both cases the ultrafast photoreduction of FAD(ox): in 390 fs for OtCPF1 and 590 fs for OtCPF2. Although such ultrafast electron transfer has already been reported for other flavoproteins and CPF members, the present result is the first demonstration with full spectral characterization of the mechanism. Analysis of the photoproduct spectra allowed identifying tryptophan as the primary electron donor. This residue is found to be oxidized to its protonated radical cation form (WH(*+)), while FAD(ox) is reduced to FAD(*-). Subsequent kinetics were observed in the picosecond and subnanosecond regime, mostly described by a biexponential partial decay of the photoproduct transient signal (9 and 81 ps for OtCPF1, and 13 and 340 ps for OtCPF2), with reduced spectral changes, while a long-lived photoproduct remains in the nanosecond time scale. We interpret these observations within the model proposed by the groups of Brettel and Vos, which describes the photoreduction of FADH(*) within E. coli CPD photolyase (EcCPD) as a sequential electron transfer along a chain of three tryptophan residues, although in that case the rate limiting step was the primary photoreduction in 30 ps. In the present study, excitation of FAD(ox) permitted to reveal the following steps and spectroscopically assign them to the hole-hopping process along the tryptophan chain, accompanied by partial charge recombination at each step. In addition, structural analysis performed by homology modeling allowed us to propose a tentative structure of the relative orientations of FAD and the conserved tryptophan triad. The results of preliminary transient anisotropy measurements performed on OtCPF2 finally showed good compatibility with the oxidation of the distal tryptophan residue (WH(351)) in 340 ps, hence, with the overall Brettel-Vos mechanism.

Theoretical study of the dipole moments of selected alkaline-earth halides

NASA Technical Reports Server (NTRS)

Langhoff, S. R.; Bauschlicher, C. W., Jr.; Partridge, H.; Ahlrichs, R.

1986-01-01

Ab initio calculations at the self-consistent-field (SCF), singles-plus-doubles configuration-interaction (SDCI), and coupled-pair functional (CPF) level, are reported for the dipole moments and dipole derivatives of the X2Sigma(+) ground states of BeF, BeCl, MgF, MgCl, CaF, CaCl, and SrF. For comparison, analogous calculations are performed for the X1Sigma(+) state of KCl. The CPF results are found to be in remarkably better agreement with experiment than are the SCF and SDCI results. Apparently higher excitations are required to properly describe the radial extent along the bond axis of the remaining valence electron on the alkaline-earth metal.

Chlorpyrifos and lambda cyhalothrin-induced oxidative stress in human erythrocytes.

PubMed

Deeba, Farah; Raza, Irum; Muhammad, Noor; Rahman, Hazir; Ur Rehman, Zia; Azizullah, Azizullah; Khattak, Baharullah; Ullah, Farman; Daud, M K

2017-04-01

Pesticides are one of the most potentially harmful chemicals introduced into the environment, and their adverse impacts on non-target organisms can be significant. The present study was conducted to shed light on effects of locally used insecticides chlorpyrifos (CPF) and lambda cyhalothrin (LCT) on oxidative stress biomarkers in human erythrocytes. The activity of catalase (CAT), superoxide dismutase (SOD), and protein contents as well as the levels of malondialdehyde (MDA) and osmotic fragility (OF) were measured in human erythrocytes exposed to CPF at concentrations of 0, 100, 500, 1000, and 2000 ppm and LCT at concentrations of 0, 100, 300, 600, and 800 ppm for 1 h and 3 h at 37°C. MDA levels and OF of erythrocytes were significantly higher in erythrocytes incubated with CPF and LCT at increasing concentrations of both insecticides and increased incubation time. However, erythrocyte CAT and SOD activities were decreased at all concentrations of CPF and LCT tested. Protein oxidation products were decreased at lower doses of CPF (100 and 500 ppm); at higher doses (1000 and 2000 ppm), total protein content was increased compared with control. In contrast LCT was associated with decreased in protein contents at all the concentrations. These results clearly demonstrated that CPF and LCT can induce oxidative stress in human erythrocytes ( in vitro).

Highly Concentrated Preterm Formula as an Alternative to Powdered Human Milk Fortifier: A Randomized Controlled Trial.

PubMed

Willeitner, Andrea; Anderson, Michael; Lewis, Jami

2017-11-01

The aim of the study was to assess clinical feasibility and tolerance of concentrated preterm formula at 30 kcal/oz (CPF30) to fortify human milk to a caloric density of 24 kcal/oz, compared to conventional powdered human milk fortifier (PHMF). Very low birth weight neonates were stratified by birth weight and randomized to receive human milk fortification using CPF30 or PHMF. Infants were monitored from first introduction of human milk fortification, until fortified feeds were well tolerated. Primary outcome was weight gain; secondary outcomes included other measures of feeding intolerance (residual gastric aspirates, feeds held, prokinetic therapy), sepsis, and death. The clinical and study personnel were blinded to the intervention. No significant differences in weight gain or other measures of feeding tolerance were demonstrated between CPF30 and PHMF. Macronutrient intake was similar between both groups. Infants with a birth weight of ≥ 1000 g who received CPF30, experienced fewer days NPO (nil per os; nothing per mouth) and a trend toward lower incidence of NEC, compared with those who received PHMF.. The amount of human milk consumed was significantly lower in the CPF30 group. Both fortifiers were similarly well tolerated. Fortification of human milk with CPF30 is a safe and feasible alternative to conventional PHMF.

Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?

PubMed Central

Horton, Megan K.; Kahn, Linda G.; Perera, Frederica; Barr, Dana Boyd; Rauh, Virginia

2013-01-01

Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. We evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7 years. We did not observe a remediating effect of a high quality home environment (either parental nurturance or environmental stimulation) on the adverse effects of prenatal CPF exposure on working memory. However, we detected a borderline significant interaction between prenatal exposure to CPF and child sex (B (95% CI) for interaction term = −1.714 (−3.753 to 0.326)) suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, we detected a borderline interaction between parental nurturance and child sex (B (95% CI) for interaction term = 1.490 (−0.518 to 3.499)) suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. To our knowledge, this is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure. PMID:22824009

Brain anomalies in children exposed prenatally to a common organophosphate pesticide

PubMed Central

Rauh, Virginia A.; Perera, Frederica P.; Horton, Megan K.; Whyatt, Robin M.; Bansal, Ravi; Hao, Xuejun; Liu, Jun; Barr, Dana Boyd; Slotkin, Theodore A.; Peterson, Bradley S.

2012-01-01

Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9–11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure × IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose–response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain. PMID:22547821

The In Vivo Quantitation of Diazinon, chlorpyrifos, and Their Major Metabolites in Rat Blood for the Refinement of a Physiologically-Based Pharmacokinetic/Pharmacodynamic Models

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

Busby, A.; Kousba, A.; Timchalk, C.

2004-01-01

Chlorpyrifos (CPF)(O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate, CAS 2921-88-2), and diazinon (DZN)(O,O-diethyl-O-2-isopropyl-4-methyl-6-pyrimidyl thiophosphate, CAS 333-41-5) are commonly encountered organophosphorus insecticides whose oxon metabolites (CPF-oxon and DZN-oxon) have the ability to strongly inhibit acetylcholinesterase, an enzyme responsible for the breakdown of acetylcholine at nerve synapses. Chlorpyrifos-oxon and DZN-oxon are highly unstable compounds that degrade via hepatic, peripheral blood, and intestinal metabolism to the more stable metabolites, TCP (3,5,6-trichloro-2-pyridinol, CAS not assigned) and IMHP (2-isopropyl-6-methyl-4-pyrimidinol, CAS 2814-20-2), respectively. Studies have been performed to understand and model the chronic and acute toxic effects of CPF and DZN individually but little is known about their combined effects. The purposemore » of this study was to improve physiologically based pharmacokinetic/ pharmacodynamic (PBPK/PD) computational models by quantifying concentrations of CPF and DZN and their metabolites TCP and IMHP in whole rat blood, following exposure to the chemicals individually or as a mixture. Male Sprague-Dawley rats were orally dosed with 60 mg/kg of CPF, DZN, or a mixture of these two pesticides. When administered individually DZN and CPF were seen to reach their maximum concentration at ~3 hours post-dosing. When given as a mixture, both DZN and CPF peak blood concentrations were not achieved until ~6 hours post-dosing and the calculated blood area under the curve (AUC) for both chemicals exceeded those calculated following the single dose. Blood concentrations of IMHP and TCP correlated with these findings. It is proposed that the higher AUC obtained for both CPF and DZN as a mixture resulted from competition for the same metabolic enzyme systems.« less

A Novel Speed Compensation Method for ISAR Imaging with Low SNR

PubMed Central

Liu, Yongxiang; Zhang, Shuanghui; Zhu, Dekang; Li, Xiang

2015-01-01

In this paper, two novel speed compensation algorithms for ISAR imaging under a low signal-to-noise ratio (SNR) condition have been proposed, which are based on the cubic phase function (CPF) and the integrated cubic phase function (ICPF), respectively. These two algorithms can estimate the speed of the target from the wideband radar echo directly, which breaks the limitation of speed measuring in a radar system. With the utilization of non-coherent accumulation, the ICPF-based speed compensation algorithm is robust to noise and can meet the requirement of speed compensation for ISAR imaging under a low SNR condition. Moreover, a fast searching implementation strategy, which consists of coarse search and precise search, has been introduced to decrease the computational burden of speed compensation based on CPF and ICPF. Experimental results based on radar data validate the effectiveness of the proposed algorithms. PMID:26225980

Lethal and sublethal responses in the fish, Odontesthes bonariensis, exposed to chlorpyrifos alone or under mixtures with endosulfán and lambda-cyhalothrin.

PubMed

López Aca, Viviana; Gonzalez, Patricia Verónica; Carriquiriborde, Pedro

2018-05-09

Need for ecotoxicological information on local species has been recently highlighted as a priority issue in Latin America. In addition, little information has been found on concentration distances between lethal and sublethal effects, and the effect of mixtures at these two levels of analysis. Chlorpyrifos (CPF) is an organophosphate insecticide broadly used in soybean crops which has dramatically expanded in Latin America and other regions of the world. The aim of the present study was to evaluate lethal and sublethal effects of CPF, singly or in mixtures, on the inland "Pejerrey" (Odontesthes bonariensis) under laboratory conditions. Bioassays were performed using 15-30 d post hatch Pejerrey larvae. Six toxicity tests were run for estimating the average inter-assay dose-response curve of CPF and other six for assessing the effects of mixtures of CPF with endosulfan (EN) or lambda-cyhalothrin (LC), at three toxic units (TU) proportions (25:75, 50:50, 75:25). In addition, four assays were performed to describe the average inter-assay dose-response inhibition curve of acetylcholinesterase (AchE) for CPF alone and two for assessing the mixtures. The estimated 96 h-LC 50 for CPF was 2.26 ± 1.11 µg/L and the incipiency value was 0.048 ± 0.012 µg/L, placing this Neotropical species among the 13% of worldwide fish more sensitive to CPF. In addition, the 96 h-LC 50 for EN and LC were 0.30 ± 0.012 µg/L and 0.043 ± 0.031 µg/L, respectively. Therefore, relative toxicity of the three soybean insecticides for O. bonariensis was LC > EN > CPF. Effects of mixtures with EN and LC were variable, but in general fitted to both, independent action (IA) and concentration addition (CA) models. Slight antagonism was found when CPF TU proportions were above 50%. Therefore, from the regulatory point of view, the use of both mixture models, CA or IA, would be precautionary. Differential sensitivity to CPF was found for AchE inhibition at the head (96 h-IC 50  = 0.065 ± 0.058 µg/L) and the body (96 h-IC 50  = 0.48 ± 0.17 µg/L). In addition, whereas no significant effects induced by mixtures was observed in body AchE activity, antagonism was induced in head AchE inhibition in presence of both, EN and LC in the mixture. The lethal to sublethal ratio was close to 25.2 and 3.4 when comparing the CPF-LC 50 and IC 50 s for head and body AchE activity, respectively. However, considerable overlapping was observed between concentration-response curves, indicating that the use of AchE as biomarker for environmental monitoring would be limited.

Potential protective effect of Pistacia lentiscus oil against chlorpyrifos-induced hormonal changes and oxidative damage in ovaries and thyroid of female rats.

PubMed

Chebab, Samira; Mekircha, Fatiha; Leghouchi, Essaid

2017-12-01

The purpose of this study was to evaluate the protective effect of Pistacia lentiscus oil (PLO), known for its antioxidant properties, on chlorpyrifos (CPF)-induced alterations in the thyroid, reproductive hormone levels, and oxidative damage in the ovaries and thyroid of adult Wistar rats. The animals were treated with orally administered PLO (2 mL/kg), CPF (6.75 mg/kg), and a combination of CPF and PLO for 30 days. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (Pg), estradiol (E 2 ), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were assessed using chemiluminescence assay. Malondialdehyde (MDA), protein carbonyl (PC), and reduced glutathione (GSH) levels were examined in the ovaries and thyroid glands. The oil principal volatile compounds detected by gas chromatography analysis were: myrcene, α-pinene and limonene (26.21, 22.66 and 10.33%, respectively). No significant differences were observed between serum concentrations of TSH and FSH in the examined experimental groups. However, serum concentrations of LH, E 2 , Pg, T3, and T4 decreased significantly in CPF-treated rats in comparison with the controls. The body weight and relative weight of ovaries and thyroids in this group were also significantly reduced. The MDA and PC content increased significantly, while the GSH content was markedly depressed in the thyroid and ovaries of rats treated with CPF. Co-administration of PLO and CPF effectively ameliorated the adverse effects; the oxidative damage was reduced and the levels of thyroid and reproductive hormones restored to a normal range. In conclusion, it appears that PLO substantially alleviates the CPF-induced oxidative damage and hormonal alterations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prenatal exposure to a common organophosphate insecticide delays motor development in a mouse model of idiopathic autism.

PubMed

De Felice, Alessia; Scattoni, Maria Luisa; Ricceri, Laura; Calamandrei, Gemma

2015-01-01

Autism spectrum disorders are characterized by impaired social and communicative skills and repetitive behaviors. Emerging evidence supported the hypothesis that these neurodevelopmental disorders may result from a combination of genetic susceptibility and exposure to environmental toxins in early developmental phases. This study assessed the effects of prenatal exposure to chlorpyrifos (CPF), a widely diffused organophosphate insecticide endowed with developmental neurotoxicity at sub-toxic doses, in the BTBR T+tf/J mouse strain, a validated model of idiopathic autism that displays several behavioral traits relevant to the autism spectrum. To this aim, pregnant BTBR mice were administered from gestational day 14 to 17 with either vehicle or CPF at a dose of 6 mg/kg/bw by oral gavages. Offspring of both sexes underwent assessment of early developmental milestones, including somatic growth, motor behavior and ultrasound vocalization. To evaluate the potential long-term effects of CPF, two different social behavior patterns typically altered in the BTBR strain (free social interaction with a same-sex companion in females, or interaction with a sexually receptive female in males) were also examined in the two sexes at adulthood. Our findings indicate significant effects of CPF on somatic growth and neonatal motor patterns. CPF treated pups showed reduced weight gain, delayed motor maturation (i.e., persistency of immature patterns such as pivoting at the expenses of coordinated locomotion) and a trend to enhanced ultrasound vocalization. At adulthood, CPF associated alterations were found in males only: the altered pattern of investigation of a sexual partner, previously described in BTBR mice, was enhanced in CPF males, and associated to increased ultrasonic vocalization rate. These findings strengthen the need of future studies to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders.

Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?

PubMed

Horton, Megan K; Kahn, Linda G; Perera, Frederica; Barr, Dana Boyd; Rauh, Virginia

2012-01-01

Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. We evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7years. We did not observe a remediating effect of a high quality home environment (either parental nurturance or environmental stimulation) on the adverse effects of prenatal CPF exposure on working memory. However, we detected a borderline significant interaction between prenatal exposure to CPF and child sex (B (95% CI) for interaction term=-1.714 (-3.753 to 0.326)) suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, we detected a borderline interaction between parental nurturance and child sex (B (95% CI) for interaction term=1.490 (-0.518 to 3.499)) suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. To our knowledge, this is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

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

Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles

Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the lastmore » nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.« less

The effects of Candida albicans cell wall protein fraction on dendritic cell maturation.

PubMed

Roudbary, Maryam; Roudbar Mohammadi, Shahla; Bozorgmehr, Mahmood; Moazzeni, Seyed Mohammad

2009-06-01

Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are carbohydrates such as mannans, beta glucans and chitins, and proteins that partially modulate the host immune responses. Dendritic cells (DC), as the most important antigen-presenting cells of the immune system, play a critical role in inducing immune responses against different pathogens. We investigated the effect of the cell wall protein fraction (CPF) of C. albicans on DC maturation. The CPF of C. albicans cells was extracted by a lysis buffer containing sodium dodecyl sulphate, 2-mercaptoethanol and phosphate-buffered saline. The extract was dialyzed and its protein pattern was evaluated by electrophoresis. Dendritic cells were purified from Balb/c mice spleens through a three-step method including mononuclear cell separation, as well as 2-h and overnight cultures. The purified CPF was added at different concentrations to DC. The purity and maturation status of DC were determined by flow cytometry using monoclonal antibodies against CD11c, MHC-II, CD40 and CD86. Treatment of DC with 10 microg/ml of CPF increased the expression of maturation markers including MHC-II, CD86 and CD40 on DC compared to the control group. In this study we used C. albicans CPF with the molecular weight of 40-45 kDa for pulsing and maturation of dendritic cells. Since according to our results CPF significantly increased the expression of maturation markers on DC, we suggest that CPF may act as an efficient immunomodulator, or may be used as a potential adjuvant to boost the host immune system against infections.

Effect of atrazine and chlorpyrifos exposure on cytochrome P450 contents and enzyme activities in common carp gills.

PubMed

Fu, Yao; Li, Ming; Liu, Ci; Qu, Jian-Ping; Zhu, Wen-Jun; Xing, Hou-Juan; Xu, Shi-Wen; Li, Shu

2013-08-01

Chlorpyrifos (CPF) and atrazine (ATR) are the most widely used organophosphate insecticides and triazine herbicides, respectively, worldwide. This study aimed at investigating the effects of ATR, CPF and mixture on common carp gills following 40-d exposure and 40-d recovery experiments. Cytochrome P450 content, activities of aminopyrine N-demethylase (APND) and erythromycin N-demethylase (ERND) and the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) were determined. In total, 220 common carps were divided into eleven groups, and each group was treated with a specific concentration of ATR (4.28, 42.8 and 428 μg/L), CPF (1.16, 11.6 and 116 μg/L) or ATR-CPF mixture (1.13, 11.3 and 113 μg/L). The results showed that P450 content and activities of APND and ERND in fish exposed to ATR and mixture were significantly higher than those in the control group. After the 40-d recovery treatment (i.e., depuration), the P450 content and the activities of APND and ERND in fish decreased to the background levels. A similar tendency was also found in the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) in common carp gills. The CPF-treated fish showed no significant difference from the control groups, except for a significant CYP1C induction. These results indicated that CYP enzyme levels are induced by ATR but were only slightly affected by CPF in common carp gills. In addition, the ATR and CPF exposure showed an antagonistic effect on P450 enzymes in common carp gills. Copyright © 2013 Elsevier Inc. All rights reserved.

Immunoprotective activity and antioxidant properties of cactus (Opuntia ficus indica) extract against chlorpyrifos toxicity in rats.

PubMed

Smida, Amani; Ncibi, Saida; Taleb, Jihen; Ben Saad, Anouar; Ncib, Sana; Zourgui, Lazhar

2017-04-01

Opuntia ficus indica (family Cactaceae) is a typical Mediterranean plant, mainly used in food and traditional folk medicine. The present study was designed to evaluate the protective effect of Opuntia ficus indica extract against chlorpyrifos (CPF)-induced immunotoxicity in rats. The experimental animals consisted of four groups of Wistar rats (5-6 weeks old) of eight each: a control group, a group treated with CPF (10mg/kg), a group treated with Opuntia ficus indica extract (100mg/kg), and a group treated with cactus extract then treated with CPF. These components were daily administered by gavage for 30days. After treatment, immunotoxicity was estimated by a count of thymocytes, splenocytes, stem cells in the bone marrow, relative weights of thymus and spleen, DNA aspects, and oxidative stress status in these organs. Results showed that CPF could induce thymus atrophy, splenomegaly, and a decrease in the cell number in the bone marrow. It also increased the oxidative stress markers resulting in elevated levels of the lipid peroxidation with a concomitant decrease in the levels of enzymatic antioxidants (SOD, CAT, GPx) in both spleen and thymus, and also degradation of thymocyte and splenocyte DNA. Consistent histological changes were found in the spleen and thymus under CPF treatment. However, administration of Opuntia ficus indica extract was found to alleviate this CPF-induced damage. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Electrochemistry coupled online to liquid chromatography-mass spectrometry for fast simulation of biotransformation reactions of the insecticide chlorpyrifos.

PubMed

Mekonnen, Tessema F; Panne, Ulrich; Koch, Matthias

2017-05-01

An automated method is presented for fast simulation of (bio)transformation products (TPs) of the organophosphate insecticide chlorpyrifos (CPF) based on electrochemistry coupled online to liquid chromatography-mass spectrometry (EC-LC-MS). Oxidative TPs were produced by a boron doped diamond (BDD) electrode, separated by reversed phase HPLC and online detected by electrospray ionization-mass spectrometry (ESI-MS). Furthermore, EC oxidative TPs were investigated by HPLC-tandem mass spectrometry (LC-MS/MS) and FT-ICR high resolution mass spectrometry (HRMS) and compared to in vitro assay metabolites (rat and human liver microsomes). Main phase I metabolites of CPF: chlorpyrifos oxon (CPF oxon), trichloropyridinol (TCP), diethylthiophosphate (DETP), diethylphosphate (DEP), desethyl chlorpyrifos (De-CPF), and desethyl chlorpyrifos oxon (De-CPF oxon), were successfully identified by the developed EC-LC-MS method. The EC-LC-MS method showed similar metabolites compared to the in vitro assay with possibilities of determining reactive species. Our results reveal that online EC-(LC)-MS brings an advantage on time of analysis by eliminating sample preparation steps and matrix complexity compared to conventional in vivo or in vitro methods.

Acute high dose of chlorpyrifos alters performance of rats in the elevated plus-maze and the elevated T-maze.

PubMed

López-Crespo, G A; Flores, P; Sánchez-Santed, F; Sánchez-Amate, M C

2009-11-01

Chlorpyrifos (CPF) is a broad spectrum organophosphate (OP) pesticide widely used in agriculture, industry and household. Several animal studies indicate emotional disturbances after CPF exposure, although the results are sometimes puzzling. Thus, both anxiolytic and anxiogenic effects of CPF have been reported in different animal models of anxiety [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92; Sánchez-Amate MC, Dávila E, Cañadas F, Flores P, Sánchez-Santed F. Chlorpyrifos shares stimulus properties with pentilenetetrazol as evaluated by and operant drug discrimination task. Neurotoxicology 2002;23:795-803; López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7]. On the other hand, other behavioural effects of CPF are time-dependent [López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7], raising the question that the effects of CPF could be task and post-administration time dependent. To test this hypothesis, three groups of rats were treated with a single high dose of CPF (250 mg/kg); one of the groups was tested on day 5 on the elevated plus-maze, to complete our previous study on day 2 [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92]. The remaining groups were tested on the elevated T-maze on days 2 and 5. CPF produced an increased open arm activity on the elevated plus-maze on day 5, an increased escape latency on the elevated T-maze on day 2 and an impaired inhibitory avoidance on day 5. Data are discussed taking together all studies carried out in our laboratory, confirming that CPF effects on emotional behaviour are dependent on both task contingencies and post-administration time.

Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.

PubMed

Carr, Russell L; Armstrong, Nathan H; Buchanan, Alenda T; Eells, Jeffrey B; Mohammed, Afzaal N; Ross, Matthew K; Nail, Carole A

2017-03-01

Exposure to chlorpyrifos (CPF) during the late preweanling period in rats inhibits the endocannabinoid metabolizing enzymes fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), resulting in accumulation of their respective substrates anandamide (AEA) and 2-arachidonylglycerol (2-AG). This occurs at 1.0mg/kg, but at a lower dosage (0.5mg/kg) only FAAH and AEA are affected with no measurable inhibition of either cholinesterase (ChE) or MAGL. The endocannabinoid system plays a vital role in nervous system development and may be an important developmental target for CPF. The endocannabinoid system plays an important role in the regulation of anxiety and, at higher dosages, developmental exposure to CPF alters anxiety-like behavior. However, it is not clear whether exposure to low dosages of CPF that do not inhibit ChE will cause any persistent effects on anxiety-like behavior. To determine if this occurs, 10-day old rat pups were exposed daily for 7 days to either corn oil or 0.5, 0.75, or 1.0mg/kg CPF by oral gavage. At 12h following the last CPF administration, 1.0mg/kg resulted in significant inhibition of FAAH, MAGL, and ChE, whereas 0.5 and 0.75mg/kg resulted in significant inhibition of only FAAH. AEA levels were significantly elevated in all three treatment groups as were palmitoylethanolamide and oleoylethanolamide, which are also substrates for FAAH. 2-AG levels were significantly elevated by 0.75 and 1.0mg/kg but not 0.5mg/kg. On day 25, the latency to emerge from a dark container into a highly illuminated novel open field was measured as an indicator of anxiety. All three CPF treatment groups spent significantly less time in the dark container prior to emerging as compared to the control group, suggesting a decreased level of anxiety. This demonstrates that repeated preweanling exposure to dosages of CPF that do not inhibit brain ChE can induce a decline in the level of anxiety that is detectable during the early postweanling period. Copyright © 2015 Elsevier B.V. All rights reserved.

Decreased Anxiety in Juvenile Rats Following Exposure to Low Levels of Chlorpyrifos During Development

PubMed Central

Carr, Russell L.; Armstrong, Nathan H.; Buchanan, Alenda T.; Eells, Jeffrey B.; Mohammed, Afzaal N.; Ross, Matthew K.; Nail, Carole A.

2016-01-01

Exposure to chlorpyrifos (CPF) during the late preweanling period in rats inhibits the endocannabinoid metabolizing enzymes fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), resulting in accumulation of their respective substrates anandamide (AEA) and 2-arachidonylglycerol (2-AG). This occurs at 1.0 mg/kg, but at a lower dosage (0.5 mg/kg) only FAAH and AEA are affected with no measurable inhibition of either cholinesterase (ChE) or MAGL. The endocannabinoid system plays a vital role in nervous system development and may be an important developmental target for CPF. The endocannabinoid system plays an important role in the regulation of anxiety and, at higher dosages, developmental exposure to CPF alters anxiety-like behavior. However, it is not clear whether exposure to low dosages of CPF that do not inhibit ChE will cause any persistent effects on anxiety-like behavior. To determine if this occurs, 10-day old rat pups were exposed daily for 7 days to either corn oil or 0.5, 0.75, or 1.0 mg/kg CPF by oral gavage. At 12 h following the last CPF administration, 1.0 mg/kg resulted in significant inhibition of FAAH, MAGL, and ChE, whereas 0.5 and 0.75 mg/kg resulted in significant inhibition of only FAAH. AEA levels were significantly elevated in all three treatment groups as were palmitoylethanolamide and oleoylethanolamide, which are also substrates for FAAH. 2-AG levels were significantly elevated by 0.75 and 1.0 mg/kg but not 0.5 mg/kg. On day 25, the latency to emerge from a dark container into a highly illuminated novel open field was measured as an indicator of anxiety. All three CPF treatment groups spent significantly less time in the dark container prior to emerging as compared to the control group, suggesting a decreased level of anxiety. This demonstrates that repeated preweanling exposure to dosages of CPF that do not inhibit brain ChE can induce a decline in the level of anxiety that is detectable during the early postweanling period. PMID:26642910

Formulation and characterization of bread using coconut-pulp flour and wheat flour composite with addition of xanthan-gum

NASA Astrophysics Data System (ADS)

Erminawati; Sidik, W.; Listanti, R.; Zulfakar, H.

2018-01-01

Coconut-pulp flour is coconut flour made from by-product of coconut-milk based food products. The flour contains no gluten and high fibre, which can be considered as functional potential food. Bread made from composite-flour of coconut-pulp flour and wheat flour was studied for its physic-chemical and sensory characteristics. Addition of hydrocolloid, like xanthan-gum, was aimed to provide viscoelasticity for the dough which is essential for baked product. Composite-flour proportion used in this study was; 10CPF/90WF, 15CPF/85WF and 20CPF/80WF; and xanthan gum to total flour of 0,1% and 0,4%. Variable observed were; crumb-texture, crumb-colour, taste of coconut, preference and flavour; moisture, ash, fiber and soluble-protein contents. The research showed that addition of coconut-pulp flour in the composite-flour decreased specific volume value and increased the bread texture produced. It also increased the bread moisture-content, ash-content, fibre-content and soluble protein-content. Moreover, the xanthan-gum addition resulted in decreased specific-volume value and increased texture and fiber-content of the bread produced. Overall, the sensory characteristic of crumb colour, flavour and panellist preference revealed better than control bread made from wheat flour, however its crumb texture harder compare to control bread made from wheat flour. This study showed that coconut-pulp flour potential to be developed for production of functional food.

Microbial degradation on glacier surface is the missing piece of environmental fate of pesticides in cold areas

NASA Astrophysics Data System (ADS)

Ambrosini, Roberto; Ferrario, Claudia; Pittino, Francesca; Tagliaferri, Ilario; Gandolfi, Isabella; Bestetti, Giuseppina; Azzoni, Roberto S.; Diolaiuti, Guglielmina A.; Smiraglia, Claudio; Franzetti, Andrea; Villa, Sara

2017-04-01

Organic contaminants deposited on glacier surfaces undergo different partition and degradation processes which determine their environmental fate and accumulation into the trophic chains. Among these processes, biodegradation by supraglacial bacteria has been neglected so far. To assess the relevance of biodegradative processes, in situ microcosm experiments were conducted simulating cryoconite hole systems on an Alpine glacier exposed to the organophosphorus insecticide chlorpyrifos (CPF) as model of xenobiotic molecule which accumulate on glaciers after medium range transports. Results showed that biodegradation is the most efficient process contributing to the removal of CPF on the glacier surface. The high concentrations of CPF in cryoconite and its half-life in the range of 35 - 69 days indicated that biodegradation process can significantly contrast the release of CPF transported on glaciers. Moreover, the metabolic versatility of cryoconite bacteria suggest that these habitats might contribute to the degradation of a wide class of pollutants with different physical-chemical properties. Metagenomics data indicated that photoheterotrophic bacteria might be involved in the biodegradation of CPF by using light to supplement their metabolic demands, thus contributing to the biological removal of CPF without the constrain of using this pesticide as sole energy source. In conclusion. cryoconite might act as a "biofilter" for organic pollutants on glaciers by accumulating them and promoting their biodegradation. Owing to its relevance, the contribution of cryoconite to the removal of organic pollutants should be included in the models predicting the environmental fate of these compounds in cold areas.

An Innovative Program to Support Internationally Educated Health Professionals and Their Instructors: Role of the Clinical Practice Facilitator.

PubMed

Daniel, Sylvia; Lee, Annemarie L; Switzer-McIntyre, Sharon; Evans, Cathy

2016-01-01

Internationally educated health professionals immigrating to other countries may experience difficulty in clinical practice, due to linguistic and cultural factors. An important element of bridging is the opportunity for internationally educated health professionals to practice in a clinical environment. To support these health professionals and their clinical instructors, a Clinical Practice Facilitator (CPF) role was created. This study aimed to examine the CPF from internationally educated health professionals and clinical instructors' perspective. A quantitative survey was conducted with two cohorts (2013 and 2015) of internationally educated physical therapists and clinical instructors who were asked about the nature of interaction with CPFs, mentor, and education roles and the benefits and challenges of the role. Thirty-five internationally educated physical therapists and 37 clinical instructors participated and were satisfied with the interaction with CPFs via face-to-face or e-mail communication. There was strong agreement (>80%) that the CPF educator role was to facilitate learner's reflection on clinical practice while the mentor role (>70%) was to answer questions, provide feedback, and investigate clinical concerns and conflicts. There was insufficient time for access to CPFs and resolution of learners' learning needs. There were differences (P = 0.04) in perspective on the benefit of the CPF in assisting with cultural differences. An innovative CPF role provided support encouragement, clinical, and professional advice. There were discordant views regarding the benefits of the CPF role in addressing cultural issues, which requires further examination.

New rhenium complexes with ciprofloxacin as useful models for understanding the properties of [99mTc]-ciprofloxacin radiopharmaceutical.

PubMed

Lecina, Joan; Cortés, Pilar; Llagostera, Montserrat; Piera, Carlos; Suades, Joan

2014-07-01

Rhenium complexes with the antibiotic ciprofloxacin have been prepared to be studied as models of technetium radiopharmaceuticals. With this aim, the new rhenium complexes 1 {[ReO(Cpf)2]Cl}, 2 {[ReO(CpfH)2]Cl3} and 3 {fac-[Re(CO)3(H2O)(Cpf)]} with ciprofloxacin (CpfH=ciprofloxacin; Cpf=conjugated base of ciprofloxacin) have been synthesised and characterised by elemental analyses, IR, NMR ((1)H, (19)F and (13)C CP-MAS) spectroscopy, as well as MS measurements. All spectroscopic data are consistent with the coordination of ciprofloxacin in all these complexes through the carbonyl and the carboxylate oxygen atoms with the formation of a six member chelate ring. The study of a Tc-ciprofloxacin solution by ESI-MS reveals the presence of [TcO(Cpf)2](+) cations, which agrees with the hypothesis that complexes 1 and 2 can be seen as model rhenium complexes of this radiopharmaceutical. Antimicrobial and DNA gyrase inhibition studies performed with complexes 2 and 3 have shown a very similar behaviour between complex 2 and the free antibiotic, whereas complex 3 exhibit a lower antimicrobial activity. Based on a joint analysis of the data reported in the literature and the chemical and biological results obtained in this study, a tentative proposal to explain some aspects of the behaviour of Tc-ciprofloxacin radiopharmaceutical has been made. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exposure to an organophosphate pesticide, individually or in combination with other Gulf War agents, impairs synaptic integrity and neuronal differentiation, and is accompanied by subtle microvascular injury in a mouse model of Gulf War agent exposure.

PubMed

Ojo, Joseph O; Abdullah, Laila; Evans, James; Reed, Jon Mike; Montague, Hannah; Mullan, Michael J; Crawford, Fiona C

2014-04-01

Gulf War illness (GWI) is a currently untreatable multi-symptom disorder experienced by 1990-1991 Persian Gulf War (GW) veterans. The characteristic hallmarks of GWI include cognitive dysfunction, tremors, migraine, and psychological disturbances such as depression and anxiety. Meta-analyses of epidemiological studies have consistently linked these symptomatic profiles to the combined exposure of GW agents such as organophosphate-based and pyrethroid-based pesticides (e.g. chlorpyrifos (CPF) and permethrin (PER) respectively) and the prophylactic use of pyridostigmine bromide (PB) as a treatment against neurotoxins. Due to the multi-symptomatic presentation of this illness and the lack of available autopsy tissue from GWI patients, very little is currently known about the distinct early pathological profile implicated in GWI (including its influence on synaptic function and aspects of neurogenesis). In this study, we used preclinical models of GW agent exposure to investigate whether 6-month-old mice exposed to CPF alone, or a combined dose of CPF, PB and PER daily for 10 days, demonstrate any notable pathological changes in hippocampal, cortical (motor, piriform) or amygdalar morphometry. We report that at an acute post-exposure time point (after 3 days), both exposures resulted in the impairment of synaptic integrity (reducing synaptophysin levels) in the CA3 hippocampal region and altered neuronal differentiation in the dentate gyrus (DG), demonstrated by a significant reduction in doublecortin positive cells. Both exposures also significantly increased astrocytic GFAP immunoreactivity in the piriform cortex, motor cortex and the basolateral amygdala and this was accompanied by an increase in (basal) brain acetylcholine (ACh) levels. There was no evidence of microglial activation or structural deterioration of principal neurons in these regions following exposure to CPF alone or in combination with PB and PER. Evidence of subtle microvascular injury was demonstrated by the reduction of platelet endothelial cell adhesion molecule (PECAM)-1 levels in CPF+PB+PER exposed group compared to control. These data support early (subtle) neurotoxic effects on the brain following exposure to GW agents. © 2013 Japanese Society of Neuropathology.

A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing.

PubMed

Sun, Huihui; Li, Fanfan; Liu, Jie; Yang, Fayu; Zeng, Zhenhai; Lv, Xiujuan; Tu, Mengjun; Liu, Yeqing; Ge, Xianglian; Liu, Changbao; Zhao, Junzhao; Zhang, Zongduan; Qu, Jia; Song, Zongming; Gu, Feng

2018-06-15

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Inducible, tunable and multiplex human gene regulation using CRISPR-Cpf1-based transcription factors | Office of Cancer Genomics

Cancer.gov

Targeted and inducible regulation of mammalian gene expression is a broadly important research capability that may also enable development of novel therapeutics for treating human diseases. Here we demonstrate that a catalytically inactive RNA-guided CRISPR-Cpf1 nuclease fused to transcriptional activation domains can up-regulate endogenous human gene expression. We engineered drug-inducible Cpf1-based activators and show how this system can be used to tune the regulation of endogenous gene transcription in human cells.

Chlorpyrifos-induced hormesis in insecticide-resistant and -susceptible Plutella xylostella under normal and high temperatures.

PubMed

Deng, Z Z; Zhang, F; Wu, Z L; Yu, Z Y; Wu, G

2016-06-01

Hormesis induced by insecticides at the dosage lower than what ostensibly directly causes death on insects was studied. This paper reports the effects of the in vivo application of varied concentrations of chlorpyrifos (CPF) on Plutella xylostella (DBM). The insecticide concentrations applied included 0.000025-2.5 mg l-1, which are far lower than LC1 (7.2 mg l-1), for the CPF-susceptable (Si) DBM, and 250 mg l-1 which is far below LC1 (1286 mg l-1), for the CPF-resistant (Rc) DBM, as well as LC10- and LC50-doses for both strains. Significant hormesis was found with the 'hermetic-CPFs', i.e., 0.0025 mg l-1 for Si DBM and 2.5 mg l-1 for Rc DBM, at the normal or high temperature either in a 24 h or under a long-term treatment. These doses of CPF significantly stimulated the development and increased the fecundity of Si and Rc DBM at 25°C with approximately 23.5-29.8% activity increase on acetylcholinesterase (AChE) and 30.5-91.3% increase on glutathione S-transferases (GSTs) at 25 or 38°C in 4-24 h. The enzymatic activities were significantly reduced by LC50-CPF at 25°C in vivo, but the inhibition was relieved significantly, if the insects were first subjected to a hormetic-CPF pretreatment. It was remarkable that the average rates of enzymatic activity increase were 67.5-76.6% for AChE and 366-546% for GSTs. Consequently, it was concluded that the hormesis on Si and Rc DBM could be induced by CPF doses far below LC1 at normal or high temperature in short- or long-term treatment. These findings might help to improve the current insect control practices in the field.

Development of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model to Determine Dosimetry and Cholinesterase Inhibition for a Binary Mixture of Chlorpyrifos and Diazinon in the Rat

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

Timchalk, Chuck; Poet, Torka S.

2008-05-01

Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models have been developed and validated for the organophosphorus (OP) insecticides chlorpyrifos (CPF) and diazinon (DZN). Based on similar pharmacokinetic and mode of action properties it is anticipated that these OPs could interact at a number of important metabolic steps including: CYP450 mediated activation/detoxification, and blood/tissue cholinesterase (ChE) binding/inhibition. We developed a binary PBPK/PD model for CPF, DZN and their metabolites based on previously published models for the individual insecticides. The metabolic interactions (CYP450) between CPF and DZN were evaluated in vitro and suggests that CPF is more substantially metabolized to its oxon metabolite than ismore » DZN. These data are consistent with their observed in vivo relative potency (CPF>DZN). Each insecticide inhibited the other’s in vitro metabolism in a concentration-dependent manner. The PBPK model code used to described the metabolism of CPF and DZN was modified to reflect the type of inhibition kinetics (i.e. competitive vs. non-competitive). The binary model was then evaluated against previously published rodent dosimetry and ChE inhibition data for the mixture. The PBPK/PD model simulations of the acute oral exposure to single- (15 mg/kg) vs. binary-mixtures (15+15 mg/kg) of CFP and DZN at this lower dose resulted in no differences in the predicted pharmacokinetics of either the parent OPs or their respective metabolites; whereas, a binary oral dose of CPF+DZN at 60+60 mg/kg did result in observable changes in the DZN pharmacokinetics. Cmax was more reasonably fit by modifying the absorption parameters. It is anticipated that at low environmentally relevant binary doses, most likely to be encountered in occupational or environmental related exposures, that the pharmacokinetics are expected to be linear, and ChE inhibition dose-additive.« less

Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications

PubMed Central

Mamczarz, Jacek; Pescrille, Joseph D.; Gavrushenko, Lisa; Burke, Richard D.; Fawcett, William P.; DeTolla, Louis J.; Chen, Hegang; Pereira, Edna F.R.; Albuquerque, Edson X.

2017-01-01

Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25 mg/kg, s.c.) or vehicle (peanut oil) for 10 days starting on presumed gestation day (GD) 53–55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. PMID:27296654

Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

PubMed

Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

2007-01-01

Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level.

Ameliorative effect of vitamin E to mouse dams and their pups following exposure of mothers to chlorpyrifos during gestation and lactation periods.

PubMed

Mansour, Sameeh Abdel-Kader; Gamet-Payrastre, Laurence

2016-07-01

Pesticides are omnipresent in environment, water, fruits, and vegetables and are considered as risk factors for human health. Consumers are mainly exposed to pesticides through diet, and the main question to be answered concerns the impact of such exposure on health. In this study, we developed a mouse model to mimic consumer exposure. During gestation and lactation periods, the experimental mouse dams (M) received one of the following treatments: (a) diet-free of pesticides; (b) diet enriched with chlorpyrifos (CPF; 44.0 μg kg(-1)); c) diet + oral vitamin E (vit. E; α-tocopherol; 200 mg/kg/mouse); and (d) diet enriched with CPF (44.0 μg/kg + oral vit. E (200 mg/kg/mouse). At weaning, pups (P) and dams were killed, and organs as well as blood samples were collected. Compared with control results, CPF induced alteration of measured parameters (e.g. organ weight, alkaline phosphatase, urea, malondialdehyde, superoxide dismutase, and cholinesterase) either in mouse dams or in their offspring. Also, CPF induced histological impairment in kidney, liver, and ovary. Administration of vit. E in conjunction with CPF clearly alleviated deviation of these parameters than those of control ones. In conclusion, a dietary exposure of mice during gestation and lactation to low dose of CPF led to significant changes in the mother but also in the weaned animals that have not been directly exposed to this pesticide. These biological and histological modifications could be reversed by an oral supplementation of vit. E. © The Author(s) 2014.

Clinical and echocardiographic characteristics of papillary fibroelastomas: a retrospective and prospective study in 162 patients

NASA Technical Reports Server (NTRS)

Sun, J. P.; Asher, C. R.; Yang, X. S.; Cheng, G. G.; Scalia, G. M.; Massed, A. G.; Griffin, B. P.; Ratliff, N. B.; Stewart, W. J.; Thomas, J. D.

2001-01-01

BACKGROUND: Cardiac papillary fibroelastoma (CPF) is a primary cardiac neoplasm that is increasingly detected by echocardiography. The clinical manifestations of this entity are not well described. METHODS AND RESULTS: In a 16-year period, we identified patients with CPF from our pathology and echocardiography databases. A total of 162 patients had pathologically confirmed CPF. Echocardiography was performed in 141 patients with 158 CPFs, and 48 patients had CPFs that were not visible by echocardiography (<0.2 cm), leaving an echocardiographic subgroup of 93 patients with 110 CPFs. An additional 45 patients with a presumed diagnosis of CPF were identified. The mean age of the patients was 60+/-16 years of age, and 46.1% were male. Echocardiographically, the mean size of the CPFs was 9+/-4.6 mm; 82.7% occurred on valves (aortic more than mitral), 43.6% were mobile, and 91.4% were single. During a follow-up period of 11+/-22 months, 23 of 26 patients with a prospective diagnosis of CPF that was confirmed by pathological examination had symptoms that could be attributable to embolization. In the group of 45 patients with a presumed diagnosis of CPF, 3 patients had symptoms that were likely due to embolization (incidence, 6.6%) during a follow-up period of 552+/-706 days. CONCLUSIONS: CPFs are generally small and single, occur most often on valvular surfaces, and may be mobile, resulting in embolization. Because of the potential for embolic events, symptomatic patients, patients undergoing cardiac surgery for other lesions, and those with highly mobile and large CPFs should be considered for surgical excision.

Airborne heavy metals in two cities of North Rhine Westphalia - Performing inhalation cancer risk assessment in terms of atmospheric circulation.

PubMed

Dimitriou, Konstantinos; Kassomenos, Pavlos

2017-11-01

The main objective of this study was to examine the levels of four heavy metals (As, Cd, Pb and Ni) in PM 10 samples collected in two urban background stations in Dortmund and Bielefeld, in relation to atmospheric circulation. Pollution roses, Conditional Probability Function (CPF) roses and backward air mass trajectory clusters were used to identify air currents associated with the importation of PM 10 and of the included metal constituents. In addition, PM 10 , NO 2 , SO 2 , O 3 , As, Cd, Ni and Pb concentrations were analyzed by a Principal Component Analysis (PCA) to reveal major local emission sources of PM 10 metal content. Traffic was the main emitter of PM 10 , As, Cd, and Pb in both cities, highlighting the existence of non-negligible lead quantities in unleaded gasoline, whilst nickel emissions were associated with heavy fuel oil combustion in industries and primarily for domestic heating. The created CPF roses and trajectory clusters were in good agreement, clearly revealing that eastern air currents enriched the locally produced PM 10 load with additional aerosols from Eastern Europe. The concentrations of arsenic and cadmium were also enhanced by the arrival of air parcels from the East, indicating the anthropogenic origin of the exogenous aerosols due to combustion. The induced cancer risk (CR inh ) for adults, due to inhalation of individual metal constituents, was also estimated in terms of atmospheric circulation, indicating higher risk in Dortmund than in Bielefeld. CR inh values for arsenic exceeded the limit of 1 × 10 -6 in both cities, primarily during the influence of eastern circulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

ANTIOXIDANT AND IMMUNOSTIMULANT EFFECT OF CARICA PAPAYA LINN. AQUEOUS EXTRACT IN ACRYLAMIDE INTOXICATED RATS

PubMed Central

Mohamed Sadek, Kadry

2012-01-01

Introduction: The present study was conducted to evaluate the antioxidant and immunostimulant effects of The Carica papaya fruit aqueous extract (CPF, Caricaceae) against acrylamide induced oxidative stress and improvement of Immune functions which affected by free radicals liberating acrylamide in rats. Material and methods: Sixty male wistar albino rats (195-230g) were assigned to four groups, (fifteen/group). The first group used as control group and received normal physiological saline orally daily. The second group was supplemented with acrylamide 0.05% in drinking water. The third group was gastro-gavaged with 250 mg/kg of papaya fruit extract orally on daily basis. The fourth group was supplemented with acrylamide 0.05% in drinking water and gastro-gavaged with 250 mg/kg of papaya fruit extract orally on daily basis. The chosen dose of papaya fruit extract was based on the active pharmacological dose range obtained from the orientation study earlier conducted. The experimental period was extended to forty day. At the expiration of the experimental period and night fasting, blood samples were collected from the orbital venous sinus. The sera were separated and used for determining of IgG and IgM and the stomach, liver and kidney homogenates for estimation of MDA, GSH level, SOD and CAT activity as a biomarker of lipid peroxidation and antioxidative stress. Results and discussion: The obtained results revealed that, acrylamide caused significant increases in MDA and decrease of GSH level, SOD and CAT activity due to the oxidative stress induced by acrylamide on membrane polyunsaturated fatty acids in rat’s stomach, liver and kidney while administration of CPF aqueous extract, was significantly ameliorated the increased levels of MDA and decline of GSH, SOD and CAT activity in the stomach, liver and kidney tissues caused by acrylamide toxicity. Meanwhile, CPF aqueous extract significantly increased immune functions (IgG and IgM) while acrylamide significantly decrease it specially IgG. Thus, this study suggests that acrylamide-induced oxidative stress in rats can be ameliorated by administration of CPF aqueous extract. PMID:23322975

Design and use of a quantitative scale for measuring presyncope.

PubMed

Sheldon, Robert S; Amuah, Joseph E; Connolly, Stuart J; Rose, Sarah; Morillo, Carlos A; Talajic, Mario; Kus, Teresa; Fouad-Tarazi, Fetnat; Klingenheben, Thomas; Krahn, Andrew D; Sheldon, Aaron; Koshman, Mary-Lou; Ritchie, Debbie

2009-08-01

Vasovagal syncope is common and distressing. One important symptom is presyncope, but there are no clinimetric measures of this. We developed the Calgary Presyncope Form (CPF) and used it to test whether metoprolol reduces presyncope in a randomized trial. The CPF captures the frequency, duration, and severity of presyncope. We administered it to participants in the Prevention of Syncope Trial (POST), a randomized clinical trial that tested the hypothesis that metoprolol reduces syncope and presyncope in adult patients with vasovagal syncope. The CPF was completed by 44 patients on metoprolol and 39 patients on placebo, of a total of 208 subjects. Completion of the CPF for each of the threedimensions was 84-87% in the 83 respondents. Results were centrally distributed in duration and severity dimensions, but not in frequency. Patients had a median of 1.2 presyncopal spells per day, with a median moderate severity, lasting a median 10 minutes. The 3 scales were statistically independent of each other. These results were independent of subject age, and results in all 3 dimensions were stable over the observation period. There was no significant difference between patients on metoprolol and placebo in any dimension. The 3-dimensional CPF is simple, easy to use, stable over time, measures 3 independent variables, and documents that metoprolol does not reduce presyncope.

Subsurface imaging in a sector of Cerro Prieto transform fault near to pull-apart basin, Mexicali Valley, Baja California, Mexico, based on crooked lines 2D seismic reflection.

NASA Astrophysics Data System (ADS)

Mares-Agüero, M. A.; González-Escobar, M.; Arregui, S.

2016-12-01

In the transition zone between San Andres continental transformation system and the coupled transform faults system and rifting of Gulf of California is located the Cerro Prieto pull-apart basin delimitated by Imperial fault (northeast) and Cerro Prieto fault (CPF) (southwest), this last, is the limit west of Cerro Prieto geothermic field (CPGF). Crooked lines 2D seismic reflection, covering a portion near the intersection of CPF and CPGF are processed and interpreted. The seismic data were obtained in the early 80's by Petróleos Mexicanos (PEMEX). By decades, technical and investigation works in Cerro Prieto geothermic field and its vicinity had mapped faults at several depths but do not stablish a clear limit where this faults and CPF interact due the complex hydrothermal effects imaging the subsurface. The profiles showing the presence of a zone of uplift effect due to CPF. Considering the proximity of the profiles to CPF, it is surprising almost total absence of faults. A strong reflector around 2 km of depth, it is present in all profiles. This seismic reflector is considered a layer of shale, result of the correlation with a well located in the same region.

An evaluation of controlled permeability formwork for long-term durability of structural concrete elements

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

Suryavanshi, A.K.; Swamy, R.N.

1997-07-01

The long-term performance of a concrete slab (CPF slab) exposed to chloride ingress and atmospheric carbonation from the surface generated by controlled permeability formwork (CPF) is investigated. The results are compared with a similar slab exposed to long-term chloride ingress and atmospheric carbonation from the cast face (Control slab). Techniques such as X-ray diffraction (XRD) and differential thermal analyses (DTA) were employed to determine the resistance against carbonation while, mercury porosimetry was used for investigating the pore size distribution at the surface of the slabs. Amount of acid soluble chlorides was determined by using Volhard`s method. The CPF employed atmore » the bottom of the mould was not fully effective in its intended purpose of generating a permanent and dense impermeable concrete layer adjacent to it when the design water-cement (w/c) ration of the concrete mix was 0.60. This resulted in an almost similar extent of carbonation at the surface for both CPF and control slabs as shown by XRD and DTA studies. Similarly, there were no significant differences in the amount of chlorides and their depths of penetration for both CPF and control slabs, although the former was marginally superior in chloride penetration resistance at the surface.« less

Chlorpyrifos exposure affects fgf8, sox9, and bmp4 expression required for cranial neural crest morphogenesis and chondrogenesis in Xenopus laevis embryos.

PubMed

Tussellino, Margherita; Ronca, Raffaele; Carotenuto, Rosa; Pallotta, Maria M; Furia, Maria; Capriglione, Teresa

2016-10-01

Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos. This study investigated the effects of exposure to different CPF concentrations (10, 15 and 20 mg/L) on Xenopus laevis embryos from stage 4/8 to stage 46. Some of the morphological changes we detected in CPF-exposed embryos included cranial neural crest cell (NCC)-derived structures. For this reason, we analyzed the expression of select genes involved in hindbrain patterning (egr2), cranial neural crest chondrogenesis, and craniofacial development (fgf8, bmp4, sox9, hoxa2 and hoxb2). We found that CPF exposure induced a reduction in transcription of all the genes involved in NCC-dependent chondrogenesis, with largest reductions in fgf8 and sox9; whereas, in hindbrain, we did not find any alterations in egr2 expression. Changes in the expression of fgf8, bmp4, and sox9, which are master regulators of several developmental pathways, have important implications. If these changes are confirmed to belong to a general pattern of alterations in vertebrates prenatally exposed to OP, they might be useful to assess damage during vertebrate embryo development. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice.

PubMed

Peris-Sampedro, Fiona; Cabré, Maria; Basaure, Pia; Reverte, Ingrid; Domingo, José L; Teresa Colomina, Maria

2015-10-01

Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Our recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Thus, we aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. We examined body weight status, food and water intake, lipid and glucose homeostasis, metabolic biomarkers concentrations, insulin levels and insulin resistance, and leptin and ghrelin profiles. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Different Levels of Pressure Relieving Air-Mattress Firmness on Cough Strength

PubMed Central

Kamikawa, Norimichi; Taito, Shunsuke; Takahashi, Makoto; Sekikawa, Kiyokazu; Hamada, Hironobu

2016-01-01

Cough is an important host-defense mechanism. The elderly and patients who are severely ill cannot cough effectively when lying in the supine position. Furthermore, pressure relieving air-mattresses are recommended for preventing the development of pressure ulcers. In this study, we clarified whether or not the cough peak flow (CPF), an index of cough strength, is affected by different firmness levels of a pressure relieving air-mattress in healthy volunteers in the supine position. Fifty-two healthy young men participated. All the measurements were carried out on each participant in the supine position on a pressure relieving air-mattress. The participants were assessed at two firmness levels, a “hard” and “soft” mode. The CPF, forced vital capacity (FVC), maximal expiratory pressure (PEmax), and maximal inspiratory pressure (PImax) were determined for each mode. The sinking distance of the body into the mattress was measured without any activity and the difference between the sinking distances of the two firmness levels was determined. The CPF, FVC, PEmax, and PImax were determined for each mode. The sinking distance of the body into the mattress was measured and the difference between the sinking distances of the two firmness levels was determined. The CPF, FVC, PEmax and PImax values of the participants coughing on the mattress were significantly lower when the mattress was in “soft” than in “hard” mode. The differences between the sinking distances of the mattress in “soft” and “hard” modes were larger for the anterior superior iliac spine. A harder mattress may lead to increased CPF in healthy young men lying in the supine position, and increased CPF may be important for host defense. PMID:26741497

Effect of Different Levels of Pressure Relieving Air-Mattress Firmness on Cough Strength.

PubMed

Kamikawa, Norimichi; Taito, Shunsuke; Takahashi, Makoto; Sekikawa, Kiyokazu; Hamada, Hironobu

2016-01-01

Cough is an important host-defense mechanism. The elderly and patients who are severely ill cannot cough effectively when lying in the supine position. Furthermore, pressure relieving air-mattresses are recommended for preventing the development of pressure ulcers. In this study, we clarified whether or not the cough peak flow (CPF), an index of cough strength, is affected by different firmness levels of a pressure relieving air-mattress in healthy volunteers in the supine position. Fifty-two healthy young men participated. All the measurements were carried out on each participant in the supine position on a pressure relieving air-mattress. The participants were assessed at two firmness levels, a "hard" and "soft" mode. The CPF, forced vital capacity (FVC), maximal expiratory pressure (PEmax), and maximal inspiratory pressure (PImax) were determined for each mode. The sinking distance of the body into the mattress was measured without any activity and the difference between the sinking distances of the two firmness levels was determined. The CPF, FVC, PEmax, and PImax were determined for each mode. The sinking distance of the body into the mattress was measured and the difference between the sinking distances of the two firmness levels was determined. The CPF, FVC, PEmax and PImax values of the participants coughing on the mattress were significantly lower when the mattress was in "soft" than in "hard" mode. The differences between the sinking distances of the mattress in "soft" and "hard" modes were larger for the anterior superior iliac spine. A harder mattress may lead to increased CPF in healthy young men lying in the supine position, and increased CPF may be important for host defense.

AGE-RELATED EFFECTS OF CHLORPYRIFOS ON ACETYLCHOLINE RELEASE IN RAT BRAIN. (R825811)

EPA Science Inventory

Chlorpyrifos (CPF) is an organophosphorus insecticide that elicits toxicity through inhibition of acetylcholinesterase (AChE). Young animals are markedly more sensitive than adults to the acute toxicity of CPF. We evaluated acetylcholine (ACh) release and its muscarinic recept...

Sublethal effects of pesticides on queen rearing success

USDA-ARS?s Scientific Manuscript database

The effects of sublethal pesticide exposure on queen emergence and virus titers were examined. Queen rearing colonies were fed pollen with chlorpyrifos (CPF) alone (pollen-1) and with CPF and the fungicide Pristine ® (pollen-2). Fewer queens emerged when larvae from open foraging ...

Ameliorative effect of nanoencapsulated flavonoid against chlorpyrifos-induced hepatic oxidative damage and immunotoxicity in Wistar rats.

PubMed

Suke, Sanvidhan G; Sherekar, Prasad; Kahale, Vivek; Patil, Shaktipal; Mundhada, Dharmendra; Nanoti, Vivek M

2018-04-18

The theme of the present work is to evaluate the protective effect of nanoencapsulated quercetin (NEQ) against chlorpyrifos (CPF)-induced hepatic damage and immune alterations in animals. Nanoparticles (NP) drug encapsulation was prepared. Forty male Wistar rats were divided into eight groups. Two groups served as control and CPF (13.5 mg/kg) treatment for 28 days. Other three groups were free quercetin (QC), NP and NEQ treated with 3 mg/kg respectively for 15 days; whereas remaining three groups received treatment of CPF and QC, NP, NEQ, respectively, for 15 days. The results show that significantly altered oxidative stress in the liver tissue and liver enzyme parameters in blood and immune responses in CPF-treated rats compared to controls. Administration of NEQ attenuated biochemical and immunological parameters. The liver histopathological analysis confirmed pathological improvement. Hence, use of NEQ appeared to be beneficial to a great extent in attenuating and restoring hepatic oxidative damage and immune alteration sustained by pesticide exposure. © 2018 Wiley Periodicals, Inc.

Implementation of control point form of algebraic grid-generation technique

NASA Technical Reports Server (NTRS)

Choo, Yung K.; Miller, David P.; Reno, Charles J.

1991-01-01

The control point form (CPF) provides explicit control of physical grid shape and grid spacing through the movement of the control points. The control point array, called a control net, is a space grid type arrangement of locations in physical space with an index for each direction. As an algebraic method CPF is efficient and works well with interactive computer graphics. A family of menu-driven, interactive grid-generation computer codes (TURBO) is being developed by using CPF. Key features of TurboI (a TURBO member) are discussed and typical results are presented. TurboI runs on any IRIS 4D series workstation.

Attenuating effects of caffeic acid phenethyl ester with intralipid on hepatotoxicity of chlorpyrifos in the case of rats.

PubMed

Dokuyucu, Recep; Bilgili, Ali; Hanedan, Basak; Dogan, Hatice; Dokuyucu, Ahmet; Celik, Muhammed Murat

2016-12-22

Chlorpyrifos (CPF), insecticide widely used in agriculture, may cause poisonings in the case of humans. As a result, there is a large amount of treatment research underway to focus on the possibility of chlorpyrifos induced poisonings. The aim of this study has been to evaluate the effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity induced by chlorpyrifos in the case of rats. The rats in this study were treated with CPF (10 mg/kg body weight (b.w.), orally), CAPE (10 μmol/kg b.w., intraperitoneally), IL (18.6 ml/kg b.w., orally), CPF+CAPE, CPF+IL, and CPF+CAPE+IL. The plasma total oxidant capacity (TOC), total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Liver histopathology and immunohistochemical staining were performed. Chlorpyrifos statistically significantly decreased the TAC levels in the rats' plasma and increased the apoptosis and the TOC and OSI levels. In the chlorpyrifos induced liver injury, CAPE and CAPE+IL significantly decreased the plasma OSI levels and the apoptosis, and significantly increased the plasma TAC levels. This study revealed that CAPE and CAPE+IL attenuate chlorpyrifos induced liver injuries by decreasing oxidative stress and apoptosis. Med Pr 2016;67(6):743-749. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Assembly of Francisella novicida Cpf1 endonuclease in complex with guide RNA and target DNA

PubMed Central

Montoya, Guillermo; Stella, Stefano

2017-01-01

Bacteria and archaea use the CRISPR–Cas system as an adaptive response against infection by foreign nucleic acids. Owing to its remarkable flexibility, this mechanism has been harnessed and adopted as a powerful tool for genome editing. The CRISPR–Cas system includes two classes that are subdivided into six types and 19 subtypes according to conservation of the cas gene and loci organization. Recently, a new protein with endonuclease activity belonging to class 2 type V has been identified. This endonuclease, termed Cpf1, in complex with a single CRISPR RNA (crRNA) is able to recognize and cleave a target DNA preceded by a 5′-TTN-3′ protospacer-adjacent motif (PAM) complementary to the RNA guide. To obtain structural insight into the inner workings of Cpf1, the crystallization of an active complex containing the full extent of the crRNA and a 31-nucleotide dsDNA target was attempted. The gene encoding Cpf1 from Francisella novicida was cloned, overexpressed and purified. The crRNA was transcribed and purified in vitro. Finally, the ternary FnCpf1–crRNA–DNA complex was assembled and purified by preparative electrophoresis before crystallization. Crystals belonging to space group C2221, with unit-cell parameters a = 85.2, b = 137.6, c = 320.5 Å, were obtained and subjected to preliminary diffraction experiments. PMID:28695850

Host-defense peptides from skin secretions of Fraser's clawed frog Xenopus fraseri (Pipidae): Further insight into the evolutionary history of the Xenopodinae.

PubMed

Conlon, J Michael; Mechkarska, Milena; Kolodziejek, Jolanta; Nowotny, Norbert; Coquet, Laurent; Leprince, Jérôme; Jouenne, Thierry; Vaudry, Hubert

2014-12-01

Peptidomic analysis of norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus fraseri Boulenger, 1905 (Pipidae) led to identification of 13 host-defense peptides. The primary structures of the peptides demonstrate that they belong to the magainin (3 peptides), peptide glycine-leucine-amide, PGLa (4 peptides), and xenopsin-precursor fragment, XPF (2 peptides) families, first identified in Xenopus laevis, together with caerulein precursor fragment-related peptides, CPF-RP (4 peptides), first identified in Silurana tropicalis. In addition, the secretions contain a molecular variant of xenopsin displaying the substitution Arg(4)→Lys compared with X. laevis xenopsin and peptide glycine-tyrosine-amide (PGYa) (GRIIPIYPEFERVFA KKVYPLY.NH2) whose function is unknown. The most potent antimicrobial peptide identified is CPF-RP-F1 (GFGSVLGKALKFGANLL.NH2) with MIC=12.5μM against Staphylococcus aureus and 50μM against Escherichia coli. On the basis of similarities in morphology and advertisement calls, X. fraseri has been placed in a species group that includes the octoploids Xenopus amieti and Xenopus andrei, and the tetraploid Xenopus pygmaeus. Cladistic analyses based upon the primary structures of magainin, PGLa, and CPF-RP peptides support a close evolutionary relationship between X. fraseri, X. amieti and X. andrei but suggest a more distant relationship with X. pygmaeus. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells

EPA Science Inventory

Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-trichloro-2-pyridinol), the primary metabolite of CPF, is often used as a generi...

BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF ACUTE CHLORPYRIFOS IN RATS: TOLERANCE TO PROLONGED INHIBITION OF CHOLINESTERASE

EPA Science Inventory

Chlorpyrifos (CPF), a commercially prevalent organophosphate (OP) pesticide, inhibits blood and brain cholinesterase for up to 10 weeks after acute s.c. injection in rats. his prolonged inhibition suggested that acute CPF may affect muscarinic receptors and behavior as does repea...

DOES THE DEVELOPMENTAL NEUROTOXICITY OF CHLORPYRIFOS INVOLVE GLIAL TARGETS? (U915722)

EPA Science Inventory

The widespread use of chlorpyrifos (CPF) has raised major concerns about its potential to cause fetal or neonatal neurobehavioral damage, even at doses that do not evoke acute toxicity. CPF has been shown to inhibit replication of brain cells, to elicit alterations in neurotro...

--RNA Polymerase II Transcription Attenuation at the Yeast DNA Repair Gene, DEF1, Involves Sen1-Dependent and Polyadenylation Site-Dependent Termination.

PubMed

Whalen, Courtney; Tuohy, Christine; Tallo, Thomas; Kaufman, James W; Moore, Claire; Kuehner, Jason N

2018-04-23

Termination of RNA Polymerase II (Pol II) activity serves a vital cellular function by separating ubiquitous transcription units and influencing RNA fate and function. In the yeast Saccharomyces cerevisiae , Pol II termination is carried out by cleavage and polyadenylation factor (CPF-CF) and Nrd1-Nab3-Sen1 (NNS) complexes, which operate primarily at mRNA and non-coding RNA genes, respectively. Premature Pol II termination (attenuation) contributes to gene regulation, but there is limited knowledge of its prevalence and biological significance. In particular, it is unclear how much crosstalk occurs between CPF-CF and NNS complexes and how Pol II attenuation is modulated during stress adaptation. In this study, we have identified an attenuator in the DEF1 DNA repair gene, which includes a portion of the 5'-untranslated region (UTR) and upstream open reading frame (ORF). Using a plasmid-based reporter gene system, we conducted a genetic screen of 14 termination mutants and their ability to confer Pol II read-through defects. The DEF1 attenuator behaved as a hybrid terminator, relying heavily on CPF-CF and Sen1 but without Nrd1 and Nab3 involvement. Our genetic selection identified 22 cis -acting point mutations that clustered into four regions, including a polyadenylation site efficiency element that genetically interacts with its cognate binding-protein Hrp1. Outside of the reporter gene context, a DEF1 attenuator mutant increased mRNA and protein expression, exacerbating the toxicity of a constitutively active Def1 protein. Overall, our data support a biologically significant role for transcription attenuation in regulating DEF1 expression, which can be modulated during the DNA damage response. Copyright © 2018, G3: Genes, Genomes, Genetics.

Long-lasting reductions of ethanol drinking, enhanced ethanol-induced sedation, and decreased c-fos expression in the Edinger-Westphal nucleus in Wistar rats exposed to the organophosphate chlorpyrifos.

PubMed

Carvajal, Francisca; López-Grancha, Matilde; Navarro, Montserrat; Sánchez-Amate, Maria del Carmen; Cubero, Inmaculada

2007-04-01

Intermittent or continuous exposure to a wide variety of chemically unrelated environmental pollutants might result in the development of multiple chemical intolerance and increased sensitivity to drugs of abuse. Interestingly, clinical evidence suggests that exposure to organophosphates might be linked to increased ethanol sensitivity and reduced voluntary consumption of ethanol-containing beverages in humans. The growing body of clinical and experimental evidence emerging in this new scientific field that bridges environmental health sciences, toxicology, and drug research calls for well-controlled studies aimed to analyze the nature of the neurobiological interactions of drugs and pollutants. Present study specifically evaluated neurobiological and behavioral responses to ethanol in Wistar rats that were previously exposed to the pesticide organophosphate chlorpyrifos (CPF). In agreement with clinical data, animals pretreated with a single injection of CPF showed long-lasting ethanol avoidance that was not secondary to altered gustatory processing or enhancement of the aversive properties of ethanol. Furthermore, CPF pretreatment increased ethanol-induced sedation without altering blood ethanol levels. An immunocytochemical assay revealed reduced c-fos expression in the Edinger-Westphal nucleus following CPF treatment, a critical brain area that has been implicated in ethanol intake and sedation. We hypothesize that CPF might modulate cellular mechanisms (decreased intracellular cAMP signaling, alpha-7-nicotinic receptors, and/or cerebral acetylcholinesterase inhibition) in neuronal pathways critically involved in neurobiological responses to ethanol.

Kinetics of biotransformation of chlorpyrifos in aqueous and soil slurry environments.

PubMed

Tiwari, Manoj K; Guha, Saumyen

2014-03-15

The attenuation of chlorpyrifos (CPF) by the enriched indigenous soil microorganism was studied in 15 d aerobic and 60 d anaerobic batch experiments in aqueous and soil slurry (1:3 w/w) media. At the end of the batch experiments, 2.78 ± 0.11 μM of CPF was degraded by 82% in aerobic and 66% in anaerobic aqueous environments, while 12.4 ± 0.5 μM of CPF was degraded by 48% in aerobic and 31% in anaerobic soil slurries. The reduced degradation in the soil slurries was due to the significantly (2-10 times) slower rate of degradation of soil phase CPF compared with its degradation rate in water. The pathways of degradation of CPF were identified, including a partial anaerobic degradation pathway that is constructed for the first time. The simulation of the various conversions in the degradation pathways using first order kinetics was used to analyze relative persistence of metabolites. The common metabolite 3,5,6-trichloro-2-pyridinol (TCP) accumulated (increased monotonically during the period of experiments) in aerobic soil slurry and in anaerobic aqueous as well as soil slurry systems but did not accumulate in aerobic aqueous system. The most toxic compound in the pathway, chlorpyrifos oxon (CPFO) was not detected in anaerobic environment. In aerobic environment, CPFO was short lived in aqueous medium, but accumulated slowly in the soils. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of the In Vitro Kinetic Interaction of Chlorpyrifos-Oxon with Rat Salivary Cholinesterase: A Potential Biomonitoring Matrix

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

Kousba, Ahmed A.; Poet, Torka S.; Timchalk, Charles

2003-02-12

Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). The primary mechanism of action for CPF involves the inhibition of acetylcholinesterase (AChE) by the active metabolite, CPF-oxon, with subsequent accumulation of acetylcholine (ACh) resulting in a wide range of neutotoxicity. CPF-oxon, can likewise inhibit other non-target cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker of exposure/response. Biological monitoring for OPs has focused on measuring parent chemical or metabolite in blood and urine or blood ChE inhibition. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure; however, theremore » are a limited number of studies exploring its use for OPs. To evaluate the use of salivary ChE as a biological monitor for OP exposure, the current study characterized salivary ChE activity in Sprague-Dawley rats through its comparison with brain and plasma ChE using BW284C51 and iso-OMPA as selective inhibitors of AChE and BuChE, respectively. The study also estimated the kinetic constants describing BuChE interaction with CPF-oxon. A modified Ellman assay in conjunction with pharmacodynamic (PD) modeling was used to characterize the in vitro titration of diluted rat salivary ChE enzyme with CPF-oxon. The results indicated that, more than 95% of rat salivary ChE activity was associated with BuChE activity, total BuChE active site concentration was 0.0012 0.00013 nmol/ml saliva, reactivation rate constant (Kr) was 0.068 0.008 h-1 and inhibitory (Ki) rate constant of 8.825 and 9.80 nM-1h-1 determined experimentally and using model optimization respectively. These study results would be helpful for further evaluating the potential utility of salivary ChE as a practical tool for biological monitor of OP exposures.« less

Comparative Pharmacokinetics of the Organophosphorus Insecticide Chlorpyrifos and its Major Metabolites Diethylphosphate, Diethylthiophosphate and 3,5,6-Trichloro-2-pyridinol in the Rat

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

Timchalk, Chuck; Busby, Andrea L; Campbell, James A

2007-07-31

Abstract Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of metabolism and of environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. However, because these same chemicals can result from metabolism or by biodegradation, monitoring total urinary metabolite levels may be reflective of not only an individual’s contact with the parent pesticide, but also exposure with the metabolites, which are present in the environment. The objective of the current study was to compare the pharmacokinetics of orally administered DEP, DETP and TCPy with theirmore » kinetics following oral dosing with the parent insecticide CPF in the rat. Groups of rats were orally administered CPF, DEP, TCPy or DETP at doses of 140 μmol/kg body weight, and the time-courses of the metabolites were evaluated in blood and urine. Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1-3 h post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72 h post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, ~50% of the orally administered dose was recovered in the urine. The CPF oral dose was likewise rapidly absorbed and metabolized to DEP, TCPy and DETP, with the distribution of metabolites in the urine followed the order: TCPy (22 ± 3 μmol) > DETP (14 ± 2 μmol) > DEP (1.4 ± 0.7 μmol). Based upon the total amount of TCPy detected in the urine a minimum of 63% of the oral CPF dose was absorbed. These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans.« less

Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism.

PubMed

De Felice, Alessia; Greco, Anita; Calamandrei, Gemma; Minghetti, Luisa

2016-06-14

Autism spectrum disorders (ASD) are emerging as polygenic and multifactorial disorders in which complex interactions between defective genes and early exposure to environmental stressors impact on the correct neurodevelopment and brain processes. Organophosphate insecticides, among which chlorpyrifos (CPF), are widely diffused environmental toxicants associated with neurobehavioral deficits and increased risk of ASD occurrence in children. Oxidative stress and dysregulated immune responses are implicated in both organophosphate neurodevelopmental effects and ASD etiopathogenesis. BTBR T+tf/J mice, a well-studied model of idiopathic autism, show several behavioral and immunological alterations found in ASD children, and we recently showed that CPF gestational exposure strengthened some of these autistic-like traits. In the present study, we aimed at investigating whether the behavioral effects of gestational CPF administration are associated with brain increased oxidative stress and altered lipid mediator profile. Brain levels of F2-isoprostanes (15-F2t-IsoP), as index of in vivo oxidative stress, and prostaglandin E2 (PGE2), a major arachidonic acid metabolite released by immune cells and by specific glutamatergic neuron populations mainly in cortex and hippocampus, were assessed by specific enzyme-immuno assays in brain homogenates from BTBR T+tf/J and C57Bl6/J mice, exposed during gestation to either vehicle or CPF. Measures were performed in mice of both sexes, at different postnatal stages (PNDs 1, 21, and 70). At birth, BTBR T+tf/J mice exhibited higher baseline 15-F2t-IsoP levels as compared to C57Bl6/J mice, suggestive of greater oxidative stress processes. Gestational treatment with CPF-enhanced 15-F2t-IsoP and PGE2 levels in strain- and age-dependent manner, with 15-F2t-IsoP increased in BTBR T+tf/J mice at PNDs 1 and 21, and PGE2 elevated in BTBR T+tf/J mice at PNDs 21 and 70. At PND 21, CPF effects were sex-dependent being the increase of the two metabolites mainly associated with male mice. CPF treatment also induced a reduction of somatic growth, which reached statistical significance at PND 21. These findings indicate that the autistic-like BTBR T+tf/J strain is highly vulnerable to environmental stressors during gestational period. The results further support the hypothesis that oxidative stress might be the link between environmental neurotoxicants such as CPF and ASD. The increased levels of oxidative stress during early postnatal life could result in delayed and long-lasting alterations in specific pathways relevant to ASD, of which PGE2 signaling represents an important one.

The effects of pesticides on queen rearing and virus titers in honey bees (Apis mellifera L.)

USDA-ARS?s Scientific Manuscript database

The effects of sublethal pesticide exposure on queen emergence and virus titers were examined. Queen rearing colonies were fed pollen with chlorpyrifos (CPF) alone (pollen-1) and with CPF and the fungicide Pristine® (pollen-2). Fewer queens emerged when larvae from open foraging (i.e., outside) colo...

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

Shinichi Aose; Takafumi Kitajima; Kouji Ogasawara

CPF (Chemical Processing Facility) was constructed at Nuclear Fuel Cycle Engineering Laboratories of JAEA (Japan Atomic Energy Agency) in 1980 as a basic research field where spent fuel pins from fast reactor (FR) and high level liquid waste can be dealt with. The renovation consists of remodeling of the CA-3 cell and the laboratory A, installation of globe boxes, hoods and analytical equipments to the laboratory C and the analytical laboratory. Also maintenance equipments in the CA-5 cell which had been out of order were repaired. The CA-3 cell is the main cell in which important equipments such as amore » dissolver, a clarifier and extractors are installed for carrying out the hot test using the irradiated FR fuel. Since the CPF had specialized originally in the research function for the Purex process, it was desired to execute the research and development of such new, various reprocessing processes. Formerly, equipments were arranged in wide space and connected with not only each other but also with utility supply system mainly by fixed stainless steel pipes. It caused shortage of operation space in flexibility for basic experimental study. Old equipments in the CA-3 cell including vessels and pipes were removed after successful decontamination, and new equipments were installed conformably to the new design. For the purpose of easy installation and rearranging the experimental equipments, equipments are basically connected by flexible pipes. Since dissolver is able to be easily replaced, various dissolution experiments is conducted. Insoluble residue generated by dissolution of spent fuel is clarified by centrifugal. This small apparatus is effective to space-saving. Mini mixer settlers or centrifugal contactors are put on to the prescribed limited space in front of the backside wall. Fresh reagents such as solvent, scrubbing and stripping solution are continuously fed from the laboratory A to the extractor by the reagent supply system with semi-automatic observation system. The in-cell crane in CA-5 was renovated to increase driving efficiency. At the renovation for the in-cell crane, full scale mockup test and 3D simulation test had been executed in advance. After the renovation, hot tests in the CPF had been resumed from JFY 2002. New equipments such as dissolver, extractor, electrolytic device, etc. were installed in CA-3 conformably to the new design laid out in order to ensure the function and space. Glove boxes in the analysis laboratory were renewed in order to let it have flexibility from the viewpoint of conducting basic experiments (ex. U crystallization). Glove boxes and hoods were newly installed in the laboratory A for basic research and analysis, especially on MA chemistries. One laboratory (the laboratory C) was established to research about dry reprocessing. The renovation of the CPF has been executed in order to contribute to the development on the advanced fast reactor fuel cycle system, which will give us many sort of technical subject and experimental theme to be solved in the 2. Generation of the CPF.« less

Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population.

PubMed Central

Perera, Frederica P; Rauh, Virginia; Tsai, Wei-Yann; Kinney, Patrick; Camann, David; Barr, Dana; Bernert, Tom; Garfinkel, Robin; Tu, Yi-Hsuan; Diaz, Diurka; Dietrich, Jessica; Whyatt, Robin M

2003-01-01

Inner-city, minority populations are high-risk groups for adverse birth outcomes and also are more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), and pesticides. In a sample of 263 nonsmoking African-American and Dominican women, we evaluated the effects on birth outcomes of prenatal exposure to airborne PAHs monitored during pregnancy by personal air sampling, along with ETS estimated by plasma cotinine, and an organophosphate pesticide (OP) estimated by plasma chlorpyrifos (CPF). Plasma CPF was used as a covariate because it was the most often detected in plasma and was highly correlated with other pesticides frequently detected in plasma. Among African Americans, high prenatal exposure to PAHs was associated with lower birth weight (p = 0.003) and smaller head circumference (p = 0.01) after adjusting for potential confounders. CPF was associated with decreased birth weight and birth length overall (p = 0.01 and p = 0.003, respectively) and with lower birth weight among African Americans (p = 0.04) and reduced birth length in Dominicans (p < 0.001), and was therefore included as a covariate in the model with PAH. After controlling for CPF, relationships between PAHs and birth outcomes were essentially unchanged. In this analysis, PAHs and CPF appear to be significant independent determinants of birth outcomes. Further analyses of pesticides will be carried out. Possible explanations of the failure to find a significant effect of PAHs in the Hispanic subsample are discussed. This study provides evidence that environmental pollutants at levels currently encountered in New York City adversely affect fetal development. PMID:12573906

Efficacy of fibre additions to flatbread flour mixes for reducing post-meal glucose and insulin responses in healthy Indian subjects.

PubMed

Boers, Hanny M; MacAulay, Katrina; Murray, Peter; Dobriyal, Rajendra; Mela, David J; Spreeuwenberg, Maria A M

2017-02-01

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, including in developing countries, particularly in South Asia. Intakes of foods generating a high postprandial glucose (PPG) response have been positively associated with T2DM. As part of efforts to identify effective and feasible strategies to reduce the glycaemic impact of carbohydrate-rich staples, we previously found that addition of guar gum (GG) and chickpea flour (CPF) to wheat flour could significantly reduce the PPG response to flatbread products. On the basis of the results of an exploratory study with Caucasian subjects, we have now tested the effect of additions of specific combinations of CPF with low doses of GG to a flatbread flour mix for their impacts on PPG and postprandial insulin (PPI) responses in a South-Asian population. In a randomised, placebo-controlled full-cross-over design, fifty-six healthy Indian adults consumed flatbreads made with a commercial flatbread mix (100 % wheat flour) with no further additions (control) or incorporating 15 % CPF in combination with 2, 3 or 4 % GG. The flatbreads with CPF and 3 or 4 % GG significantly reduced PPG (both ≥15 % reduction in positive incremental AUC, P<0·01) and PPI (both ≥28 % reduction in total AUC, P<0·0001) compared with flatbreads made from control flour. These results confirm the efficacy and feasibility of the addition of CPF with GG to flatbread flour mixes to achieve significant reductions in both PPG and PPI in Indian subjects.

Chlorpyrifos-induced biochemical changes in Cyprinus carpio: Ameliorative effect of curcumin.

PubMed

Yonar, M Enis

2018-04-30

The aim of this study was to determine protective effects of curcumin on some haematological values and oxidant/antioxidant status in Cyprinus carpio exposed to chlorpyrifos. The fish were exposed to two sublethal concentrations of chlorpyrifos (0.040 and 0.080mgL), and curcumin (100mg per kg of fish weight) was simultaneously administered for 14 days. Blood and tissue (liver, kidney, and gill) samples were collected at the end of the experiment and analysed to determine the haematological profile (red blood cell count, white blood cell count, haemoglobin concentration, and haematocrit level) and oxidant/antioxidant status (malondialdehyde level and superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities) of the fish. There was a significant decrease in the red blood cell count, the haemoglobin concentration, and the haematocrit level and a increase in the white blood cell count of CPF-treated fish. The results revealed a significant increase in the malondialdehyde levels of the groups that were exposed to CPF. Conversely, the MDA levels were significantly decreased by curcumin. Also, CPF exposure caused a significant increase in the superoxide dismutase and glutathione-S-transferase activities and a significant decrease in the catalase and glutathione peroxidase activities. However, curcumin reversed the superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities. In conclusion, this study demonstrated that CPF had a negative effect on the haematological values and the oxidant/antioxidant status of the fish. The simultaneous administration of curcumin was neutralised CPF-induced toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Qzone Weblog for Critical Peer Feedback to Improve Business English Writing: A Case of Chinese Undergraduates

ERIC Educational Resources Information Center

Xianwei, Gao; Samuel, Moses; Asmawi, Adelina

2016-01-01

This study explores Qzone weblog for critical peer feedback (CPF) in Business English writing (BEW) among the Chinese undergraduates. A qualitative case study is conducted by Nvivo 8 to analyze the three research data of semi-structured interviews, BEW writing assignments, and CPF artifacts on Qzone weblog. Three research questions are focused to…

An optical method for characterizing carbon content in ceramic pot filters.

PubMed

Goodwin, J Y; Elmore, A C; Salvinelli, C; Reidmeyer, Mary R

2017-08-01

Ceramic pot filter (CPF) technology is a relatively common means of household water treatment in developing areas, and performance characteristics of CPFs have been characterized using production CPFs, experimental CPFs fabricated in research laboratories, and ceramic disks intended to be CPF surrogates. There is evidence that CPF manufacturers do not always fire their products according to best practices and the result is incomplete combustion of the pore forming material and the creation of a carbon core in the final CPFs. Researchers seldom acknowledge the existence of potential existence of carbon cores, and at least one CPF producer has postulated that the carbon may be beneficial in terms of final water quality because of the presence of activated carbon in consumer filters marketed in the Western world. An initial step in characterizing the presence and impact of carbon cores is the characterization of those cores. An optical method which may be more viable to producers relative to off-site laboratory analysis of carbon content has been developed and verified. The use of the optical method is demonstrated via preliminary disinfection and flowrate studies, and the results of these studies indicate that the method may be of use in studying production kiln operation.

Response surface methodology modeling to improve degradation of Chlorpyrifos in agriculture runoff using TiO2 solar photocatalytic in a raceway pond reactor.

PubMed

Amiri, Hoda; Nabizadeh, Ramin; Silva Martinez, Susana; Jamaleddin Shahtaheri, Seyed; Yaghmaeian, Kamyar; Badiei, Alireza; Nazmara, Shahrokh; Naddafi, Kazem

2018-01-01

This paper deals with the use of a raceway pond reactor (RPR) as an alternative photoreactor for solar photocatalytic applications. Raceway pond reactors are common low-cost reactors which can treat large volumes of water. The experiments were carried out with TiO 2 in the agriculture effluent spiked with Chlorpyrifos (CPF) at circumneutral pH. The Response Surface Methodology (RSM) was used to find the optimum process parameters to maximize CPF oxidation from the mathematical model equations developed in this study using R software. By ANOVA, p-value of lack of fit > 0.05 indicated that, the equation was well-fitted. The theoretical efficiency of CPF removal, under the optimum oxidation conditions with UV solar energy of around 697 ± 5.33 lux, was 84.01%, which is in close agreement with the mean experimental value (80 ± 1.42%) confirming that the response model was suitable for the optimization. As far as the authors know, this is the first study of CPF removal using RPR in agriculture runoff at circumneutral pH. Copyright © 2017. Published by Elsevier Inc.

The Role of Protein Radicals in Chronic Neuroimmune Dysfunction and Neuropathology in Response to a Multiple-Hit Model of Gulf War Exposure

DTIC Science & Technology

2014-10-01

potential neurotoxicants and triggers of inflammation, such as persistent peripheral inflammation and the organophosphate pesticide chlorpyrifos (CPF...War Illness Mouse Model, Chlorpyrifos , LPS, NF-KB p50, microglia, chronic neuroinflammation, serum markers, neuropathology 16. SECURITY...neurotoxicants and triggers of inflammation, such as persistent infections, and the organophosphate pesticide chlorpyrifos (CPF) may interact to

Estrous Cyclicity of Mice During Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Moyer, Eric; Talyansky, Yuli; Scott, Ryan; Tash, Joseph; Christenson, Lane; Alwood, Joshua; Ronca, April

2017-01-01

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n22), normally loaded HU Cage Pair-Fed controls (CPF; n22), and Vivarium controls fed ad libitum (VIV; n10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, andor due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5 vs 3.0, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system.

In Vivo MR Imaging of Dual MRI Reporter Genes and Deltex-1 Gene-modified Human Mesenchymal Stem Cells in the Treatment of Closed Penile Fracture.

PubMed

Guo, Ruomi; Li, Qingling; Yang, Fei; Hu, Xiaojun; Jiao, Ju; Guo, Yu; Wang, Jin; Zhang, Yong

2018-06-01

The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF). Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology. The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology. The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice following postnatal exposure to chlorpyrifos: relation to expression of brain acetylcholinesterase mRNA

PubMed Central

Oriel, Sarit; Kofman, Ora

2015-01-01

Following reports of emotional psychopathology in children and adults exposed to organophosphates, the effects of postnatal chlorpyrifos (CPF) on fear-conditioning and depression-like behaviors were tested in adult mice. Concomitant changes in expression of mRNA for synaptic and soluble splice variants of acetylcholinesterase (AChE) were examined in mouse pups and adults of the Balb/C and C57Bl/6 (B6) strains, which differ in their behavioral and hormonal stress response. Mice were injected subcutaneously with 1 mg/kg CPF on postnatal days 4–10 and tested as adults for conditioned fear, sucrose preference, and forced swim. Acetylcholinesterase activity was assessed in the brains of pups on the first and last day of treatment. Expression of soluble and synaptic AChE mRNA was assessed in brains of treated pups and fear-conditioned adults using real-time PCR. Adult Balb/C mice exposed postnatally to CPF showed exacerbated fear-conditioning and impaired active avoidance. Adult B6 mice exposed postnatally to CPF showed a more specific fear response to tones and less freezing in the inter-tone intervals, in contrast to the vehicle-pretreated mice. Chlorpyrifos also attenuated sweet preference and enhanced climbing in the forced swim test. Chlorpyrifos-treated mice had increased expression of both synaptic and readthrough AChE transcripts in the hippocampus of Balb/C mice and decreased expression in the amygdala following fear-conditioning. In conclusion, postnatal CPF had long-term effects on fear and depression, as well as on expression of AChE mRNA. These changes may be related to alteration in the interaction between hippocampus and amygdala in regulating negative emotions. PMID:25972795

Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva

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

Timchalk, Chuck; Campbell, James A.; Liu, Guodong

2007-03-01

Abstract Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantify dosimetry utilizing readily obtainable body fluids, such as saliva. In the current study, rats were given single oral gavage doses (1, 10 or 50 mg/kg) of the insecticide chlorpyrifos (CPF), saliva and blood were collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and the samples were analyzed for the CPF metabolite trichlorpyridinol (TCP). Trichlorpyridinol was detected in both blood and saliva at all doses and the TCP concentration in blood exceeded saliva, although the kinetics in blood and saliva were comparable.more » A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF incorporated a compartment model to describe the time-course of TCP in blood and saliva. The model adequately simulated the experimental results over the dose ranges evaluated. A rapid and sensitive sequential injection (SI) electrochemical immunoassay was developed to monitor TCP, and the reported detection limit for TCP in water was 6 ng/L. Computer model simulation in the range of the Allowable Daily Intake (ADI) or Reference Dose (RfD) for CPF (0.01-0.003 mg/kg/day) suggest that the electrochemical immunoassay had adequate sensitivity to detect and quantify TCP in saliva at these low exposure levels. To validate this approach further studies are needed to more fully understand the pharmacokinetics of CPF and TCP excretion in saliva. The utilization of saliva as a biomonitoring matrix, coupled to real-time quantitation and PBPK/PD modeling represents a novel approach with broad application for evaluating both occupational and environmental exposures to insecticides.« less

Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

PubMed Central

Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

2012-01-01

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

Architecture of eukaryotic mRNA 3′-end processing machinery

PubMed Central

Hill, Chris H.; Easter, Ashley D.; Emsley, Paul; Degliesposti, Gianluca; Gordiyenko, Yuliya; Santhanam, Balaji; Wolf, Jana; Wiederhold, Katrin; Dornan, Gillian L.; Skehel, Mark; Robinson, Carol V.; Passmore, Lori A.

2018-01-01

Newly transcribed eukaryotic precursor messenger RNAs (pre-mRNAs) are processed at their 3′ ends by the ~1-megadalton multiprotein cleavage and polyadenylation factor (CPF). CPF cleaves pre-mRNAs, adds a polyadenylate tail, and triggers transcription termination, but it is unclear how its various enzymes are coordinated and assembled. Here, we show that the nuclease, polymerase, and phosphatase activities of yeast CPF are organized into three modules. Using electron cryomicroscopy, we determined a 3.5-angstrom-resolution structure of the ~200-kilodalton polymerase module. This revealed four β propellers, in an assembly markedly similar to those of other protein complexes that bind nucleic acid. Combined with in vitro reconstitution experiments, our data show that the polymerase module brings together factors required for specific and efficient polyadenylation, to help coordinate mRNA 3′-end processing. PMID:29074584

Effect of body weight loss on cardiopulmonary function assessed by 6-minute walk test and arterial blood gas analysis in obese dogs.

PubMed

Manens, J; Ricci, R; Damoiseaux, C; Gault, S; Contiero, B; Diez, M; Clercx, C

2014-01-01

Few studies show the detrimental effect of canine obesity on cardiopulmonary function (CPF). The 6-Minute Walk Test (6MWT) is a noninvasive exercise test easy to perform in clinical settings. The aim of this study was to investigate the effect of obesity and body weight loss (BWL) on CPF assessed by the 6MWT and arterial blood gas analysis. Six experimental Beagles and 9 privately owned obese dogs were enrolled in a diet-induced BWL program. Arterial blood gas analysis and 6MWT were repeated in obese subjects (BCS 8-9/9), in the middle of BWL (overweight, BCS 6-7/9), and in lean dogs (BCS 5/9). Heart rate (HRp) and oxygen saturation (SpO2 ) were measured by pulse oximetry before the 6MWT, at midtest, and during a 5-minute recovery period. Twelve dogs completed the BWL program (initial BW, 27.3 ± 2.9 kg; final BW, 20.85 ± 2.9, lsmeans ± SE, P ≤ .001). BWL caused a significant increase in 6MWT walked distance (WD; obese: 509 ± 35 m; overweight: 575 ± 36 m; lean: 589 ± 36 m; P ≤ .05). Resting arterial blood gas results were not influenced by BWL. Including all time points, obese dogs showed higher HRp and lower SpO2 compared to overweight and lean dogs. SpO2 at the end of the walk was significantly lower in obese dogs. Obesity negatively affects 6MWT performances in dogs. The 6MWT may be used to demonstrate the efficacy of BWL to improve CPF and quality of life in obese dogs. Although BWL induced significant improvement of cardiopulmonary parameters before ideal BW, WD improved until the end of the BWL program. Copyright © 2013 by the American College of Veterinary Internal Medicine.

CRISPR-Cpf1: A New Tool for Plant Genome Editing.

PubMed

Zaidi, Syed Shan-E-Ali; Mahfouz, Magdy M; Mansoor, Shahid

2017-07-01

Clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated proteins (CRISPR-Cas), a groundbreaking genome-engineering tool, has facilitated targeted trait improvement in plants. Recently, CRISPR-CRISPR from Prevotella and Francisella 1 (Cpf1) has emerged as a new tool for efficient genome editing, including DNA-free editing in plants, with higher efficiency, specificity, and potentially wider applications than CRISPR-Cas9. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Protein Radicals in Chronic Neuroimmune Dysfunction and Neuropathology in Response to a Multiple-Hit Model of Gulf War Exposures

DTIC Science & Technology

2015-10-01

neurotoxicants and triggers of inflammation, such as persistent peripheral inflammation and the organophosphate pesticide chlorpyrifos (CPF) may interact to...Model, Chlorpyrifos , LPS, NF-KB p50, microglia, chronic neuroinflammation, serum markers, neuropathology 16. SECURITY CLASSIFICATION OF: 17...potential neurotoxicants and triggers of inflammation, such as persistent infections, and the organophosphate pesticide chlorpyrifos (CPF) may

Localised hydrogen peroxide sensing for reproductive health

NASA Astrophysics Data System (ADS)

Purdey, Malcolm S.; Schartner, Erik P.; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; Thompson, Jeremy G.; Monro, Tanya M.; Abell, Andrew D.

2015-05-01

The production of reactive oxygen species (ROS) is known to affect the developmental competence of embryos. Hydrogen peroxide (H2O2) an important reactive oxygen species, is also known to causes DNA damage and defective sperm function. Current techniques require incubating a developing embryo with an organic fluorophore which is potentially hazardous for the embryo. What we need is a localised ROS sensor which does not require fluorophores in solution and hence will allow continuous monitoring of H2O2 production without adversely affect the development of the embryo. Here we report studies on such a fibre-based sensor for the detection of H2O2 that uses a surface-bound aryl boronate fluorophore carboxyperoxyfluor-1(CPF1). Optical fibres present a unique platform due to desirable characteristics as dip sensors in biological solutions. Attempts to functionalise the fibre tips using polyelectrolyte layers and (3-aminopropyl)triethoxysilane (APTES) coatings resulted in a limited signal and poor fluorescent response to H2O2 due to a low tip surface density of the fluorophore. To increase the surface density, CPF1 was integrated into a polymer matrix formed on the fibre tip by a UV-catalysed polymerisation process of acrylamide onto a methacrylate silane layer. The polyacrylamide containing CPF1 gave a much higher surface density than previous surface attachment methods and the sensor was found to effectively detect H2O2. Using this method, biologically relevant concentrations of H2O2 were detected, enabling remote sensing studies into ROS releases from embryos throughout early development.

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

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

Halwachs, Sandra

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim,more » chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [{sup 14}C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2 substrates. - Highlights: • Generation of MDCKII-rbABCG2 monolayers with epithelial barrier function • Detection of rbABCG2 in the apical plasma membrane of polarized MDCKII cells • Several pesticides interact with the ABCG2 transporter from rabbit placenta. • rbABCG2 mediates transport of the insecticide chlorpyrifos. • MDCKII-rbABCG2 cells are a suitable model to study transport in rabbit placenta.« less

Use of Homogeneously-Sized Carbon Steel Ball Bearings to Study Microbially-Influenced Corrosion in Oil Field Samples

PubMed Central

Voordouw, Gerrit; Menon, Priyesh; Pinnock, Tijan; Sharma, Mohita; Shen, Yin; Venturelli, Amanda; Voordouw, Johanna; Sexton, Aoife

2016-01-01

Microbially-influenced corrosion (MIC) contributes to the general corrosion rate (CR), which is typically measured with carbon steel coupons. Here we explore the use of carbon steel ball bearings, referred to as beads (55.0 ± 0.3 mg; Ø = 0.238 cm), for determining CRs. CRs for samples from an oil field in Oceania incubated with beads were determined by the weight loss method, using acid treatment to remove corrosion products. The release of ferrous and ferric iron was also measured and CRs based on weight loss and iron determination were in good agreement. Average CRs were 0.022 mm/yr for eight produced waters with high numbers (105/ml) of acid-producing bacteria (APB), but no sulfate-reducing bacteria (SRB). Average CRs were 0.009 mm/yr for five central processing facility (CPF) waters, which had no APB or SRB due to weekly biocide treatment and 0.036 mm/yr for 2 CPF tank bottom sludges, which had high numbers of APB (106/ml) and SRB (108/ml). Hence, corrosion monitoring with carbon steel beads indicated that biocide treatment of CPF waters decreased the CR, except where biocide did not penetrate. The CR for incubations with 20 ml of a produced water decreased from 0.061 to 0.007 mm/yr when increasing the number of beads from 1 to 40. CRs determined with beads were higher than those with coupons, possibly also due to a higher weight of iron per unit volume used in incubations with coupons. Use of 1 ml syringe columns, containing carbon steel beads, and injected with 10 ml/day of SRB-containing medium for 256 days gave a CR of 0.11 mm/yr under flow conditions. The standard deviation of the distribution of residual bead weights, a measure for the unevenness of the corrosion, increased with increasing CR. The most heavily corroded beads showed significant pitting. Hence the use of uniformly sized carbon steel beads offers new opportunities for screening and monitoring of corrosion including determination of the distribution of corrosion rates, which allows estimation of the probability of high rate events that may lead to failure. PMID:27047467

Repeated Exposure to Neurotoxic Levels of Chlorpyriphos Alters Hippocampal Expression of Neurotrophins and Neuropeptides

DTIC Science & Technology

2016-01-13

Institute for Science and Engineering, Oak Ridge, TN 37831, United States bUnited States Army Center for Environmental Health Research (USACEHR...online 13 January 2016 Keywords: Chlorpyrifos Cholinesterase inhibition Gene expression Microarray miRNA Organophosphorus pesticide A B S T R A C T...Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not

Short-term and persistent impacts on behaviors related to locomotion, anxiety, and startle responses of Japanese medaka (Oryzias latipes) induced by acute, sublethal exposure to chlorpyrifos.

PubMed

Qiu, Xuchun; Nomichi, Sayaka; Chen, Kun; Honda, Masato; Kang, Ik Joon; Shimasaki, Yohei; Oshima, Yuji

2017-11-01

Although most exposures to chlorpyrifos (CPF) in natural flowing waters are brief and episodic, there have been a few reports of the persistence of abnormal fish behaviors caused by such acute exposure. The present study focused on the behavioral and biochemical responses of Japanese medaka (Oryzias latipes) to acute, sublethal exposure to CPF, as well as the persistence of the effects during a 3-week recovery test in CPF-free water. The medaka became hyperactive and exhibited an elevated anxiety state after a 4-day exposure to 0.024mg/L of CPF, but they recovered from these abnormal behavioral responses within 7days of recovery treatment. In contrast, persistent impacts on some startle responses to a sudden stimulation (induced by a ball drop) were observed in medaka exposed to CPF. The reaction latency did not change immediately after the 4-day exposure, but was significantly prolonged by as much as 21days after the termination of exposure. The post-stimulus swimming distance within 5s significantly decreased on the day immediately after the 4-day exposure, but it significantly increased after 7days of recovery treatment. The activity of acetylcholinesterase (AChE) in the brains of medaka was significantly inhibited on the day immediately after the 4-day exposure, but it returned to 80% and 110% of that in control fish on days 7 and 21 of the recovery period, respectively. However, AChE activities in the eyes of exposed medaka were persistently inhibited and declined to 33%, 71%, and 72% of that in control fish on days 0 (immediately after the 4-day exposure), 7, and 21 of recovery, respectively. Correlation analysis suggested that the changes of AChE activities in the brains of medaka may underlie some of the observed acute behavioral changes, and the changes of AChE activities in the eyes may contribute to the persistence of the abnormalities in the reaction latency of the startle response. Our findings suggest that medaka need a long time to recover from acute, sublethal exposure to CPF, and the persistence of the behavioral abnormalities might affect their fitness in natural habitats. Copyright © 2017 Elsevier B.V. All rights reserved.

Cas9 versus Cas12a/Cpf1: Structure-function comparisons and implications for genome editing.

PubMed

Swarts, Daan C; Jinek, Martin

2018-05-22

Cas9 and Cas12a are multidomain CRISPR-associated nucleases that can be programmed with a guide RNA to bind and cleave complementary DNA targets. The guide RNA sequence can be varied, making these effector enzymes versatile tools for genome editing and gene regulation applications. While Cas9 is currently the best-characterized and most widely used nuclease for such purposes, Cas12a (previously named Cpf1) has recently emerged as an alternative for Cas9. Cas9 and Cas12a have distinct evolutionary origins and exhibit different structural architectures, resulting in distinct molecular mechanisms. Here we compare the structural and mechanistic features that distinguish Cas9 and Cas12a, and describe how these features modulate their activity. We discuss implications for genome editing, and how they may influence the choice of Cas9 or Cas12a for specific applications. Finally, we review recent studies in which Cas12a has been utilized as a genome editing tool. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes. © 2018 Wiley Periodicals, Inc.

Impedance dispersion analysis of drug-membrane interactions

NASA Astrophysics Data System (ADS)

Tacheva, Bilyana; Paarvanova, Boyana; Ivanov, Ivan T.; Karabaliev, Miroslav

2017-11-01

Thin lipid films modified glassy carbon electrodes (GCE) were used in this work as model system for studying the interactions between two antipsychotic phenothiazine drugs, chlorpromazine and thioridazine, and the lipid fraction of the biomembranes. The lipid films on the electrode surface were obtained through the thinning of film-forming lipid solution deposited between an electrolyte phase and the working GC electrode. The effects of the drugs on the lipid film structure were investigated by electrochemical impedance spectroscopy (EIS). To characterize the electric properties of the lipid film the impedance of the working GCE is modeled with an equivalent circuit consisting of parallel capacitance Cp and resistance Rp. These capacitance and resistance are not frequency independent but could be calculated as equivalent Cp and Rp for each measured frequency of the impedance spectrum and presented as functions of the frequency f, Cp = Cp(f) and Rp= Rp(f). For the lipid films used in this work, it is demonstrated that both Cp(f) and Rp(f) are well approximated with power-law functions. This behavior implies that the impedance Z of the films could be analysed in terms of the well-known constant-phase angle element (CPE), which is often used to describe the interfacial impedance of solid working electrodes.

Deletion of Melanin Concentrating Hormone Receptor-1 disrupts overeating in the presence of food cues.

PubMed

Sherwood, Andrew; Holland, Peter C; Adamantidis, Antoine; Johnson, Alexander W

2015-12-01

Exposure to environmental cues associated with food can evoke eating behavior in the absence of hunger. This capacity for reward cues to promote feeding behaviors under sated conditions can be examined in the laboratory using cue-potentiated feeding (CPF). The orexigenic neuropeptide Melanin Concentrating Hormone (MCH) is expressed throughout brain circuitry critical for CPF. We examined whether deletion of the MCH receptor, MCH-1R, would in KO mice disrupt overeating in the presence of a Pavlovian CS+ associated with sucrose delivery. While both wild-type controls and KO mice showed comparable food magazine approach responses during the CPF test, MCH-1R deletion significantly impaired the ability of the CS+ to evoke overeating of sucrose under satiety. Through the use of a refined analysis of meal intake, it was revealed that this disruption to overeating behavior in KO mice reflected a reduction in the capacity for the CS+ to initiate and maintain bursts of licking behavior. These findings suggest that overeating during CPF requires intact MCH-1R signaling and may be due to an influence of the CS+ on the palatability of food and on regulatory mechanisms of peripheral control. Thus, disruptions to MCH-1R signaling may be a useful pharmacological tool to inhibit this form of overeating behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Bacteria contribute to pesticide degradation in cryoconite holes in an Alpine glacier.

PubMed

Ferrario, Claudia; Pittino, Francesca; Tagliaferri, Ilario; Gandolfi, Isabella; Bestetti, Giuseppina; Azzoni, Roberto Sergio; Diolaiuti, Guglielmina; Franzetti, Andrea; Ambrosini, Roberto; Villa, Sara

2017-11-01

Organic contaminants deposited on glacier snow and ice are subject to partitioning and degradation processes that determine their environmental fate and, consequently, their accumulation in ice bodies. Among these processes, organic compound degradation by supraglacial bacteria has been investigated to a lesser extent than photo- and chemical degradation. We investigated biodegradation of the organophosphorus insecticide chlorpyrifos (CPF), a xenobiotic tracer that accumulates on glaciers after atmospheric medium- and long-range transport, by installing in situ microcosms on an Alpine glacier to simulate cryoconite hole systems. We found that biodegradation contributed to the removal of CPF from the glacier surface more than photo- and chemical degradation. The high concentration of CPF (2-3 μg g -1 w.w.) detected in cryoconite holes and the estimated half-life of this compound (35-69 days in glacier environment) indicated that biodegradation can significantly reduce CPF concentrations on glaciers and its runoff to downstream ecosystems. The metabolic versatility of cryoconite bacteria suggests that these habitats might contribute to the degradation of a wide class of pollutants. We therefore propose that cryoconite acts as a "biofilter" by accumulating both pollutants and biodegradative microbial communities. The contribution of cryoconite to the removal of organic pollutants should be included in models predicting the environmental fate of these compounds in cold areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (P-15) in the treatment isolated Class I gingival recession of defects: a pilot study.

PubMed

Nazareth, Carlos A; Cury, Patricia R

2011-05-01

This study clinically evaluates the treatment outcome of coronally positioned flap (CPF) associated with anorganic bone mineral/peptide-15 (ABM/P-15) in terms of root coverage and gain in clinical attachment level (CAL) and bone height (BH) in isolated Class I gingival recession (GR) defects. Fifteen healthy subjects with bilateral and comparable Miller Class I GR defects were selected. The defects were randomly assigned either to the test group (CPF with ABM/P-15) or to the control group (CPF only). Six months after surgery, a reduction in GR was observed in the test and control groups (2.20 ± 0.54 and 2.40 ± 0.80 mm, respectively; P <0.001) with no intergroup difference (P = 0.33). Complete root coverage was obtained in 10 and 11 defects in the test and control groups, respectively. In the test group 85.56% ± 21.69% and in the control group 90.00% ± 18.42% of the exposed root was covered. Although not clinically significant, a statistically greater increase in the gingival thickness was observed in the test group (0.03 mm; P = 0.01). CAL gain was significant in both groups (test group, 1.93 ± 0.44 mm; control group, 2.13 ± 1.15 mm; P <0.001) with no intergroup difference (P = 0.42). Intergroup and intragroup differences in width of keratinized tissue and BH were not significant (P ≥0.16). In the test group, a positive correlation was observed between BH at baseline and the reduction in GR (r = 0.56; P = 0.03). In isolated Class I GR defects, CPF associated with ABM/P-15 provided no significant difference in root coverage and CAL gain compared to CPF alone. In the ABM/P-15 group, a greater reduction in GR was associated with higher bone level at baseline.

Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions

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

Aldridge, Justin E.; Meyer, Armando; Centro de Estudos da Saude do Trabalhador e Ecologia Humana, Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro

2005-03-01

Developmental exposure to unrelated neurotoxicants can nevertheless produce similar neurobehavioral outcomes. We examined the effects of developmental exposure to terbutaline, a tocolytic {beta}{sub 2}-adrenoceptor agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and CPF (5 mg/kg) on PN11-14, with assessments conducted on PN45, comparing each agent alone as well as sequential administration of both. Although neither treatment affected growth or viability, each elicited similar alterations in factors that are critical tomore » the function of the 5HT synapse: 5HT{sub 1A} receptors, 5HT{sub 2} receptors, and the presynaptic 5HT transporter (5HTT). Either agent elicited global increases in 5HT receptors and the 5HTT in brain regions possessing 5HT cell bodies (midbrain, brainstem) as well as in the hippocampus, which contains 5HT projections. For both terbutaline and CPF, males were affected more than females, although there were some regional disparities in the sex selectivity between the two agents. Both altered 5HT receptor-mediated cell signaling, suppressing stimulatory effects on adenylyl cyclase and enhancing inhibitory effects. When animals were exposed sequentially to both agents, the outcomes were no more than additive and, for many effects, less than additive, suggesting convergence of the two agents on a common set of developmental mechanisms. Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens.« less

Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

DTIC Science & Technology

2013-10-01

chlorpyrifos (CPF), and a representative, nerve agent, diisopropylfluorophosphate (DFP) in rats. The first year of this proposal has been dedicated...to date (N=4-6): 1) baseline MRI scans; 2) daily injections of vehicle or chlorpyrifos (3.0-18.0 mg/kg) x 14 days; 2) a second MRI scan on the day...affected individuals. We are studying two OPs, a representative insecticide that was used in the first gulf war, chlorpyrifos (CPF), and a

Estrous Cyclicity in Mice During Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Moyer, E. L.; Talyansky, Y.; Scott, R. T.; Tash, J. S.; Christenson, L. K.; Alwood, J. S.; Ronca, A. E.

2017-01-01

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n=22), normally loaded HU Cage Pair-Fed controls (CPF; n=22), and Vivarium controls fed ad libitum (VIV; n=10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8+/- 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, and/or due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5% vs 3.0%, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system. Research supported by NNX15AB48G to JST.

Schemes generating entangled states and entanglement swapping between photons and three-level atoms inside optical cavities for quantum communication

NASA Astrophysics Data System (ADS)

Heo, Jino; Kang, Min-Sung; Hong, Chang-Ho; Yang, Hyeon; Choi, Seong-Gon

2017-01-01

We propose quantum information processing schemes based on cavity quantum electrodynamics (QED) for quantum communication. First, to generate entangled states (Bell and Greenberger-Horne-Zeilinger [GHZ] states) between flying photons and three-level atoms inside optical cavities, we utilize a controlled phase flip (CPF) gate that can be implemented via cavity QED). Subsequently, we present an entanglement swapping scheme that can be realized using single-qubit measurements and CPF gates via optical cavities. These schemes can be directly applied to construct an entanglement channel for a communication system between two users. Consequently, it is possible for the trust center, having quantum nodes, to accomplish the linked channel (entanglement channel) between the two separate long-distance users via the distribution of Bell states and entanglement swapping. Furthermore, in our schemes, the main physical component is the CPF gate between the photons and the three-level atoms in cavity QED, which is feasible in practice. Thus, our schemes can be experimentally realized with current technology.

Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilities.

PubMed

Garcia, Stephanie J; Seidler, Frederic J; Slotkin, Theodore A

2003-03-01

The developmental neurotoxicity of the organophosphate pesticide chlorpyrifos (CPF) is thought to involve both neurons and glia, thus producing a prolonged window of vulnerability. To characterize the cell types and brain regions involved in these effects, we administered CPF to developing rats and examined neuroprotein markers for oligodendrocytes (myelin basic protein, MBP), for neuronal cell bodies (neurofilament 68 kDa, NF68), and for developing axons (neurofilament 200 kDa, NF200). Prenatal CPF administration on gestational days (GDs) 17-20 elicited an immediate (GD21) enhancement of MBP and NF68; by postnatal day (PN) 30, however, there were deficits in all three biomarkers, with the effect restricted to females. Exposure in the early postnatal period, PN1-4, did not evoke significant short-term or long-term changes in the neuroproteins. However, with treatment on PN11-14, we found reductions in MBP in the immediate posttreatment period (PN15, PN20) throughout the brain, and deficiencies across all three proteins emerged by PN30. With this regimen, males were targeted preferentially. The sex-selective effects seen here for the GD17-20 and PN11-14 regimens match those reported earlier for subsequent behavioral performance. These results indicate a shift in the populations of neural cells targeted by CPF, dependent upon the period of exposure. Similarly, developmental differences in the sex selectivity of the biochemical mechanisms underlying neurotoxicant actions are likely to contribute to discrete behavioral outcomes.

Organophosphorus pesticides effect on early stages of the axolotl Ambystoma mexicanum (Amphibia: Caudata).

PubMed

Robles-Mendoza, C; García-Basilio, C; Cram-Heydrich, S; Hernández-Quiroz, M; Vanegas-Pérez, C

2009-02-01

Ambystoma mexicanum is an endemic salamander of Xochimilco, a wetland of the basin of Mexico valley. Nowadays, axolotl populations are decreasing due environmental stressors. Particularly, studies about organophosphorus pesticides (OPPs; i.e. chlorpyrifos and malathion) toxicity are of great importance due to their intensive use in agricultural activities in Xochimilco. Thus, the aim of this study was to evaluate under controlled conditions the toxicity of chlorpyrifos (CPF) and malathion (MLT) on embryos and larvae (stage 44 and 54) of A. mexicanum. Embryos and larvae were exposure 96h from 0.5 to 3mg CPFL(-1) and from 10 to 30mg MLTL(-1) in independent tests. Embryos at the end of this period were maintained 9d without pesticide in order to identify possible recuperation. Differences obtained in mortality, hatching success, development, morphological abnormalities, behaviour and activity, suggest that toxicity of CPF and MLT differs in embryos and larval stages. Embryos were less sensitive to OPPs acute exposure than axolotl larvae; additionally, toxicity of CPF in larval stages was greater than MLT. On the other hand, data obtained in axolotl embryos during the period of recuperation to CPF in particular as delay and inhibition of development, malformations and success of hatching, indicated that these responses turned out more sensitive than mortality. This study allowed to identify the toxicological potential of OPPs on early developmental stages of A. mexicanum and it is a valuable contribution for the future management of the axolotl wild population.

The effect of chlorpyrifos on thermogenic capacity of bank voles selected for increased aerobic exercise metabolism.

PubMed

Dheyongera, Geoffrey; Grzebyk, Katherine; Rudolf, Agata M; Sadowska, Edyta T; Koteja, Paweł

2016-04-01

Agro-chemicals potentially cause adverse effects in non-target organisms. The rate of animal energy metabolism can influence their susceptibility to pesticides by influencing food consumption, biotransformation and elimination rates of toxicants. We used experimental evolution to study the effects of inherent differences in energy metabolism rate and exposure to the organophosphate insecticide, chlorpyrifos (CPF) on thermogenic capacity in a wild rodent, the bank vole (Myodes = Clethrionomys glareolus). The voles were sampled from four replicate lines selected for high swim-induced aerobic metabolism (A) and four unselected control (C) lines. Thermogenic capacity, measured as the maximum cold-induced rate of oxygen consumption (VO2cold), was higher in the A - than C lines, and it decreased after continuous exposure to CPF via food or after a single dose administered via oral gavage, but only when measured shortly after exposure. VO2cold measured 24 h after repeated exposure was not affected. In addition, gavage with a single dose led to decreased food consumption and loss in body mass. Importantly, the adverse effects of CPF did not differ between the selected and control lines. Therefore, exposure to CPF has adverse effects on thermoregulatory performance and energy balance in this species. The effects are short-lived and their magnitude is not associated with the inherent level of energy metabolism. Even without severe symptoms of poisoning, fitness can be compromised under harsh environmental conditions, such as cold and wet weather. Copyright © 2016. Published by Elsevier Ltd.

Estimation of local and external contributions of biomass burning to PM2.5 in an industrial zone included in a large urban settlement.

PubMed

Benetello, Francesca; Squizzato, Stefania; Hofer, Angelika; Masiol, Mauro; Khan, Md Badiuzzaman; Piazzalunga, Andrea; Fermo, Paola; Formenton, Gian Maria; Rampazzo, Giancarlo; Pavoni, Bruno

2017-01-01

A total of 85 PM 2.5 samples were collected at a site located in a large industrial zone (Porto Marghera, Venice, Italy) during a 1-year-long sampling campaign. Samples were analyzed to determine water-soluble inorganic ions, elemental and organic carbon, and levoglucosan, and results were processed to investigate the seasonal patterns, the relationship between the analyzed species, and the most probable sources by using a set of tools, including (i) conditional probability function (CPF), (ii) conditional bivariate probability function (CBPF), (iii) concentration weighted trajectory (CWT), and (iv) potential source contribution function (PSCF) analyses. Furthermore, the importance of biomass combustions to PM 2.5 was also estimated. Average PM 2.5 concentrations ranged between 54 and 16 μg m -3 in the cold and warm period, respectively. The mean value of total ions was 11 μg m -3 (range 1-46 μg m -3 ): The most abundant ion was nitrate with a share of 44 % followed by sulfate (29 %), ammonium (14 %), potassium (4 %), and chloride (4 %). Levoglucosan accounted for 1.2 % of the PM 2.5 mass, and its concentration ranged from few ng m -3 in warm periods to 2.66 μg m -3 during winter. Average concentrations of levoglucosan during the cold period were higher than those found in other European urban sites. This result may indicate a great influence of biomass combustions on particulate matter pollution. Elemental and organic carbon (EC, OC) showed similar behavior, with the highest contributions during cold periods and lower during summer. The ratios between biomass burning indicators (K + , Cl - , NO 3 - , SO 4 2- , levoglucosan, EC, and OC) were used as proxy for the biomass burning estimation, and the contribution to the OC and PM 2.5 was also calculated by using the levoglucosan (LG)/OC and LG/PM 2.5 ratios and was estimated to be 29 and 18 %, respectively.

Chaos synchronization communication using extremely unsymmetrical bidirectional injections.

PubMed

Zhang, Wei Li; Pan, Wei; Luo, Bin; Zou, Xi Hua; Wang, Meng Yao; Zhou, Zhi

2008-02-01

Chaos synchronization and message transmission between two semiconductor lasers with extremely unsymmetrical bidirectional injections (EUBIs) are discussed. By using EUBIs, synchronization is realized through injection locking. Numerical results show that if the laser subjected to strong injection serves as the receiver, chaos pass filtering (CPF) of the system is similar to that of unidirectional coupled systems. Moreover, if the other laser serves as the receiver, a stronger CPF can be obtained. Finally, we demonstrate that messages can be extracted successfully from either of the two transmission directions of the system.

Overview of Shipboard Data Fusion and Resource Management R&D Results and Rationale for Its Real-Time Implementation in the ASCACT Testbed

DTIC Science & Technology

1996-04-01

and IRST sensor simulations. More specifically, the CPF radars currently supported by the CASE_ATTI sensor module are the SG-150 Sea Giraffe and the...specifications. The current A WW sensor suite of the CPF comprises the SPS-49 long range 2-D radar, the Sea Giraffe medium range 2-D radar, the CANEWS ESM...Sea Giraffe . This represents an original novelty of our simulation environment. P435278.PDF [Page: 66 of 128] UNCLASSIFIED 50 The baseline

Anaerobic Degradation of Marine Algae, Seagrass and Tropical Climbing Vines to Produce a Renewable Energy Source and the Analysis of Their Anaerobic Microbial Communities

DTIC Science & Technology

2013-01-01

developed by the degradation of a variety of food products creating a competition for the destination of the crops harvested . To eliminate this problem it...short bacillus (Figure 33.A), a vibrio (Figure 33.B) and a long bacillus (Figure 33.C). These three morphologies were also present in other colonies...CPF4 (Figure 34). The fourth colony (CPF4) contained three morphologies: a vibrio (Figure 35.A), a possible spirochete (Figure 35.B) and a long

Comparison of acidic and neutral PH root conditioners prior to a coronally positioned flap to treat gingival recession

PubMed Central

Ahmadi, Roya Shariatmadar; Awwadi, Mohammd Reza; Moatazed, Shilan; Rezaei, Fatemeh; Hajisadeghi, Samira

2014-01-01

Background: Localized gingival recession can be treated successfully via coronally positioned flap (CPF) and additional use of root surface demineralization agents. The purpose of this study was to evaluate the effects of additional use of ethylene diamine tetraacetic acid (EDTA) and citric acid as a root conditioner in association with CPF to cover localized buccal gingival recessions. Materials and Methods: Twenty-seven patients with 66 Miller class I buccal gingival recession ≥ 2 mm on single-rooted teeth were studied. Patients were randomly assigned: CPF with EDTA gel (test 1) and CPF with saturated citric acid (test 2) or CPF alone (control). Clinical parameters were measured at baseline and 1, 2, 3 and 6 months after surgery; assessment included recession depth (RD), clinical attachment level (CAL), probing depth (PD) and height of keratinized gingiva (HKG). SPSS version-20 was used to perform all statistical analyses. Data was reported as Mean ± SD. Age, RD, CAL, PD, and HKG before treatment and after 6 months among study groups were compared by one-way ANOVA followed by the Tukey test. The level of significance was considered to be less than 0.05. Results: At 6 months, all treatment modalities showed significant root coverage and gain in CAL. RD was reduced from 2.86 ± 0.76 mm to 0.55±0.53 mm in the EDTA group and from 2.37±0.57 mm to 1.03±0.43 mm in the acid group and from 2.37±0.54 mm to 0.85±0.49 mm in the control group. The average percentage of root coverage for the EDTA, acid, and control groups were 80.73%, 52.16%, and 64.50%, respectively. At 6 months, there was a significant difference (P < 0.05) in all parameters for the EDTA group (except HKG that did not vary among the groups). Conclusion: Root preparation with EDTA was an effective procedure to cover localized gingival recessions and significantly improved the amount of root coverage obtained. PMID:25097639

Low Level Chlorpyrifos Exposure Increases Anandamide Accumulation in Juvenile Rat Brain in the Absence of Brain Cholinesterase Inhibition

PubMed Central

Carr, Russell L.; Graves, Casey A.; Mangum, Lee C.; Nail, Carole A.; Ross, Matthew K.

2014-01-01

The prevailing dogma is that chlorpyrifos (CPF) mediates its toxicity through inhibition of cholinesterase (ChE). However, in recent years, the toxicological effects of developmental CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We hypothesize that the endocannabinoid system may be an important target because of its vital role in nervous system development. We have previously reported that repeated exposure to CPF results in greater inhibition of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide (AEA), than inhibition of either forebrain ChE or monoacylglycerol lipase (MAGL), the enzyme that metabolizes the endocannabinoid 2-arachidonylglycerol (2-AG). This exposure resulted in the accumulation of 2-AG and AEA in the forebrain of juvenile rats; however, even at the lowest dosage level used (1.0 mg/kg), forebrain ChE inhibition was still present. Thus, it is not clear if FAAH activity would be inhibited at dosage levels that do not inhibit ChE. To determine this, 10 day old rat pups were exposed daily for 7 days to either corn oil or 0.5 mg/kg CPF by oral gavage. At 4 and 12 h post-exposure on the last day of administration, the activities of serum ChE and carboxylesterase (CES) and forebrain ChE, MAGL, and FAAH were determined as well as the forebrain AEA and 2-AG levels. Significant inhibition of serum ChE and CES was present at both 4 and 12 h. There was no significant inhibition of the activities of forebrain ChE or MAGL and no significant change in the amount of 2-AG at either time point. On the other hand, while no statistically significant effects were observed at 4 h, FAAH activity was significantly inhibited at 12 h resulting in a significant accumulation of AEA. Although it is not clear if this level of accumulation impacts brain maturation, this study demonstrates that developmental CPF exposure at a level that does not inhibit brain ChE can alter components of endocannabinoid signaling. PMID:24373905

A sensitive LC-MS/MS method for measurement of organophosphorus pesticides and their oxygen analogs in air sampling matrices

PubMed Central

ARMSTRONG, JENNA L.; DILLS, RUSSELL L.; YU, JIANBO; YOST, MICHAEL G.; FENSKE, RICHARD A.

2018-01-01

A rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed for determination of levels of the organophosphorus (OP) pesticides chlorpyrifos (CPF), azinphos methyl (AZM), and their oxygen analogs chlorpyrifos-oxon (CPF-O) and azinphos methyl-oxon (AZM-O) on common active air sampling matrices. XAD-2 resin and polyurethane foam (PUF) matrices were extracted with acetonitrile containing stable-isotope labeled internal standards (ISTD). Analysis was accomplished in Multiple Reaction Monitoring (MRM) mode, and analytes in unknown samples were identified by retention time (±0.1 min) and qualifier ratio (±30% absolute) as compared to the mean of calibrants. For all compounds, calibration linearity correlation coefficients were ≥0.996. Limits of detection (LOD) ranged from 0.15–1.1 ng/sample for CPF, CPF-O, AZM, and AZM-O on active sampling matrices. Spiked fortification recoveries were 78–113% from XAD-2 active air sampling tubes and 71–108% from PUF active air sampling tubes. Storage stability tests also yielded recoveries ranging from 74–94% after time periods ranging from 2–10 months. The results demonstrate that LC-MS/MS is a sensitive method for determining these compounds from two different matrices at the low concentrations that can result from spray drift and long range transport in non-target areas following agricultural applications. In an inter-laboratory comparison, the limit of quantification (LOQ) for LC-MS/MS was 100 times lower than a typical gas chromatography-mass spectrometry (GC-MS) method. PMID:24328542

A sensitive LC-MS/MS method for measurement of organophosphorus pesticides and their oxygen analogs in air sampling matrices.

PubMed

Armstrong, Jenna L; Dills, Russell L; Yu, Jianbo; Yost, Michael G; Fenske, Richard A

2014-01-01

A rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed for determination of levels of the organophosphorus (OP) pesticides chlorpyrifos (CPF), azinphos methyl (AZM), and their oxygen analogs chlorpyrifos-oxon (CPF-O) and azinphos methyl-oxon (AZM-O) on common active air sampling matrices. XAD-2 resin and polyurethane foam (PUF) matrices were extracted with acetonitrile containing stable-isotope labeled internal standards (ISTD). Analysis was accomplished in Multiple Reaction Monitoring (MRM) mode, and analytes in unknown samples were identified by retention time (±0.1 min) and qualifier ratio (±30% absolute) as compared to the mean of calibrants. For all compounds, calibration linearity correlation coefficients were ≥0.996. Limits of detection (LOD) ranged from 0.15-1.1 ng/sample for CPF, CPF-O, AZM, and AZM-O on active sampling matrices. Spiked fortification recoveries were 78-113% from XAD-2 active air sampling tubes and 71-108% from PUF active air sampling tubes. Storage stability tests also yielded recoveries ranging from 74-94% after time periods ranging from 2-10 months. The results demonstrate that LC-MS/MS is a sensitive method for determining these compounds from two different matrices at the low concentrations that can result from spray drift and long range transport in non-target areas following agricultural applications. In an inter-laboratory comparison, the limit of quantification (LOQ) for LC-MS/MS was 100 times lower than a typical gas chromatography-mass spectrometry (GC-MS) method.

Modulatory potentials of aqueous leaf and unripe fruit extracts of Carica papaya Linn. (Caricaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats.

PubMed

Awodele, Olufunsho; Yemitan, Omoniyi; Ise, Peter Uduak; Ikumawoyi, Victor Olabowale

2016-01-01

Carica papaya Linn is used in a traditional medicine for hepatobiliary disorders. This study investigated the hepatomodulatory effects of aqueous extracts of C. papaya leaf (CPL) and unripe fruit (CPF) at doses of 100 and 300 mg/kg on carbon tetrachloride (CCl4) and acetaminophen (ACM)-induced liver toxicities in rats. Rats were administered CCl4 (3 ml/kg in olive oil, i.p.) followed by oral administration of CPL and CPF at 2, 6 and 10 h intervals. The ACM model proceeded with the same method but inclusive of animals treated with N-acetyl cysteine (3 ml/kg i.p). At the end of the study, serum levels of liver biomarkers and antioxidant enzymes were assessed and histology of the liver tissues determined. There was a significant (P < 0.05) reduction in CCl4 and ACM-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and direct bilirubin at 100 and 300 mg/kg, respectively. The levels of catalase (CAT), superoxide dismutase and reduced GSH were decreased in both models with corresponding significantly (P < 0.05) elevated level of malondialdehyde. However, these antioxidant enzymes were significantly (P < 0.05) increased in CPL and CPF-treated rats. Histopathological assessment of the liver confirmed the protective effects of CPL and CPF on CCl4 and ACM-induced hepatic damage evidenced by the normal presentation of liver tissue architecture. These results indicate that aqueous extracts of C. papaya may be useful in preventing CCl4 and ACM-induced liver toxicities.

Negative Ion Chemical Ionization Mass Spectrometry for the Analysis of 3,5,6-trichloro-2-pyridinol in Saliva of Rats Exposed to Chlorpyrifos

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

Campbell, James A.; Timchalk, Chuck; Kousba, Ahmed A.

2005-05-01

Organophosphorus (OP) insecticides (e.g. chlorpyrifos) are widely used in a variety of applications, and the potential exists for significant occupational and environmental exposures. They have been associated with more occupational poisoning cases than any other class of insecticides. One of the best approaches for accurately assessing human dosimetry and determining risk from both occupational and environmental exposure is biomonitoring. Biological matrices such as blood and urine have been routinely used for biomonitoring; however, other matrices such as saliva represent a simple and readily obtainable fluid. As a result, saliva has been suggested as an alternative biological matrix for the evaluationmore » of a broad range of biomarkers such as environmental contaminants, drugs of abuse, hormones, chemotherapeutics, heavy metals, and pesticides. Chlorpyrifos (CPF), and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCP), have been quantified in urine and blood as a biomarker for exposure to OP insecticides. The purpose of this study was to develop an analytical approach for detecting and quantitating the levels of TCP in saliva obtained from rats exposed to CPF and to evaluate the potential of saliva as a non-invasive biomonitoring matrix. Adult male rats were administered CPF, and blood and saliva were humanely collected for analysis of TCP and CPF. TCP was detected and quantitated in saliva using negative ion chemical ionization mass spectrometry with selected ion monitoring. Initial results indicate that saliva may be potentially utilized as a non-invasive biomonitoring matrix to determine exposure to organophosphate insecticides.« less

Foetal and adult human CYP3A isoforms in the bioactivation of organophosphorothionate insecticides.

PubMed

Buratti, Franca M; Leoni, Claudia; Testai, Emanuela

2006-12-15

In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has been assessed by using recombinant enzymes. A comparison with the adult isoforms CYP3A4 and CYP3A5 has been also carried out. CYP3A7 was able to produce significant levels of oxon or sulfoxide from the four OPTs in the range of tested concentrations (0.05-200 microM). When the efficiencies of CYP3A isoforms were compared, the ranking, expressed as CLi values, were: CPF=3A4>3A5>3A7; PAR=3A4>3A7>3A5; MAL=3A4>3A7>3A5; FEN (sulfoxide formation)=3A4>3A5>3A7. The CYP3A5 efficiency appeared to be more dependent on the single insecticide than its related isozyme CYP3A4. Our results indicate that the levels of toxic metabolite formed in situ by CYP3A7 from CPF, MAL and PAR but not from FEN have the chance to inhibit acetylcholinesterase, following prenatal exposure to OPTs. However, due to the smaller weight of foetal liver, the contribution to total OPT biotransformation is relatively low. On the other hand, our results clearly indicate that at low CPF concentrations, the formation of the non-toxic metabolites is highly favoured in the foetus.

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

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

Yang Dongren; Howard, Angela; Bruun, Donald

2008-04-01

A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrationsmore » that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE{sup -/-}) versus wild type (AChE{sup +/+}) mice indicated that while these OPs inhibited axonal growth in AChE{sup +/+} DRG neurons, they had no effect on axonal growth in AChE{sup -/-} DRG neurons. However, transfection of AChE{sup -/-} DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.« less

Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure.

PubMed

Rodríguez-Fuentes, Gabriela; Rubio-Escalante, Fernando J; Noreña-Barroso, Elsa; Escalante-Herrera, Karla S; Schlenk, Daniel

2015-01-01

Organophosphate pesticides cause irreversible inhibition of AChE which leads to neuronal overstimulation and death. Thus, dogma indicates that the target of OP pesticides is AChE, but many authors postulate that these compounds also disturb cellular redox processes, and change the activities of antioxidant enzymes. Interestingly, it has also been reported that oxidative stress plays also a role in the regulation and activity of AChE. The aims of this study were to determine the effects of the antioxidant, vitamin C (VC), the oxidant, t-butyl hydroperoxide (tBOOH) and the organophosphate Chlorpyrifos (CPF), on AChE gene transcription and activity in zebrafish embryos after 72h exposure. In addition, oxidative stress was evaluated by measuring antioxidant enzymes activities and transcription, and quantification of total glutathione. Apical effects on the development of zebrafish embryos were also measured. With the exception of AChE inhibition and enhanced gene expression, limited effects of CPF on oxidative stress and apical endpoints were found at this developmental stage. Addition of VC had little effect on oxidative stress or AChE, but increased pericardial area and heartbeat rate through an unknown mechanism. TBOOH diminished AChE gene expression and activity, and caused oxidative stress when administered alone. However, in combination with CPF, only reductions in AChE activity were observed with no significant changes in oxidative stress suggesting the adverse apical endpoints in the embryos may have been due to AChE inhibition by CPF rather than oxidative stress. These results give additional evidence to support the role of prooxidants in AChE activity and expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Host-defense peptides from skin secretions of the octoploid frogs Xenopus vestitus and Xenopus wittei (Pipidae): insights into evolutionary relationships.

PubMed

Mechkarska, Milena; Coquet, Laurent; Leprince, Jérôme; Jouenne, Thierry; Vaudry, Hubert; Michalak, Katarzyna; Michalak, Pawel; Conlon, J Michael

2014-09-01

The primary structures of host-defense peptides have proved useful in elucidating the evolution history of frogs. Peptidomic analysis was used to compare the diversity of host-defense peptides in norepinephrine-stimulated skin secretions from the octoploid frogs, Xenopus vestitus (Kivu clawed frog) and Xenopus wittei (De Witte's clawed frog) in the family Pipidae. Structural characterization demonstrated that the X. vestitus peptides belong to the magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 4 peptides), xenopsin-precursor fragment (XPF; 1 peptide), and caerulein-precursor fragment (CPF; 5 peptides) families. The X. wittei peptides comprise magainin (4 peptides), PGLa (1 peptide), XPF (2 peptides), and CPF (7 peptides). In addition, secretions from both species contain caerulein, identical to the peptide from Xenopus laevis, but X. wittei secretions contains the novel peptide [R4K]xenopsin. The variability in the numbers of paralogs in each peptide family indicates a selective silencing of the host-defense peptide genes following the polyploidization events. The primary structures of the peptides provide insight into phylogenetic relationships among the octoploid Xenopus frogs. The data support a sister-group relationship between X. vestitus and Xenopus lenduensis, suggestive of bifurcating speciation after allopolyploidization, whereas X. wittei is more closely related to the Xenopus amieti-Xenopus andrei group suggesting a common tetraploid ancestor. Consistent with previous data, the CPF peptides showed the highest growth inhibitory activity against bacteria with CPF-W6 (GIGSLLAKAAKLAAGLV.NH2) combining high antimicrobial potency against Staphylococcus aureus (MIC=4 μM) with relatively low hemolytic activity (LC50=190 μM). Copyright © 2014 Elsevier Inc. All rights reserved.

Two cholinesterase inhibitors trigger dissimilar effects on behavior and body weight in C57BL/6 mice: The case of chlorpyrifos and rivastigmine.

PubMed

Basaure, Pia; Peris-Sampedro, Fiona; Cabré, Maria; Reverte, Ingrid; Colomina, Maria Teresa

2017-02-01

Cholinesterases (ChE) are common targets of organophosphate (OP) pesticides and play a critical role in the pathology of some dementias. While chlorpyrifos (CPF) remains one of the most commonly used OPs in the world, numerous investigations have reported its neurotoxic potential and highlighted behavioral disturbances upon its administration. Rivastigmine currently serves to treat Alzheimer's disease, but it may induce cholinergic overstimulation in non-demented individuals. The present investigation aimed to compare the acute and delayed effects caused by both ChE inhibitors in adult C57BL/6 male mice. The animals were daily fed either a standard, a CPF- (5mg/kg body weight) or a rivastigmine-supplemented diet (1 or 2mg/kg body weight) for 8 weeks. After the treatment, we established an 8-week washout period to assess recovery. ChE enzyme activity, biomarkers, physical effects, and behavioral alterations were evaluated at different time points during the exposure and after the washout period. Both rivastigmine doses induced a time-dependent weight increase. CPF and rivastigmine inhibited brain acetylcholinesterase following an isoform-specific pattern. As for behavioral assessment, CPF negatively modulated learning strategies and impaired memory in a Barnes maze task at the end of the exposure. On the other hand, the low dose of rivastigmine improved memory recall at the end of the washout period in a Morris water maze. Indeed, our results endorse the positive effects of low doses of rivastigmine following a drug-free period in young mice. Therefore, doses and periodicity of treatment to improve cognition in elderly people upon rivastigmine administration should be revised. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulatory potentials of aqueous leaf and unripe fruit extracts of Carica papaya Linn. (Caricaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats

PubMed Central

Awodele, Olufunsho; Yemitan, Omoniyi; Ise, Peter Uduak; Ikumawoyi, Victor Olabowale

2016-01-01

Introduction: Carica papaya Linn is used in a traditional medicine for hepatobiliary disorders. This study investigated the hepatomodulatory effects of aqueous extracts of C. papaya leaf (CPL) and unripe fruit (CPF) at doses of 100 and 300 mg/kg on carbon tetrachloride (CCl4) and acetaminophen (ACM)-induced liver toxicities in rats. Materials and Methods: Rats were administered CCl4 (3 ml/kg in olive oil, i.p.) followed by oral administration of CPL and CPF at 2, 6 and 10 h intervals. The ACM model proceeded with the same method but inclusive of animals treated with N-acetyl cysteine (3 ml/kg i.p). At the end of the study, serum levels of liver biomarkers and antioxidant enzymes were assessed and histology of the liver tissues determined. Results: There was a significant (P < 0.05) reduction in CCl4 and ACM-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and direct bilirubin at 100 and 300 mg/kg, respectively. The levels of catalase (CAT), superoxide dismutase and reduced GSH were decreased in both models with corresponding significantly (P < 0.05) elevated level of malondialdehyde. However, these antioxidant enzymes were significantly (P < 0.05) increased in CPL and CPF-treated rats. Histopathological assessment of the liver confirmed the protective effects of CPL and CPF on CCl4 and ACM-induced hepatic damage evidenced by the normal presentation of liver tissue architecture. Conclusion: These results indicate that aqueous extracts of C. papaya may be useful in preventing CCl4 and ACM-induced liver toxicities. PMID:27069723

Efficacy of different fibres and flour mixes in South-Asian flatbreads for reducing post-prandial glucose responses in healthy adults.

PubMed

Boers, Hanny M; MacAulay, Katrina; Murray, Peter; Seijen Ten Hoorn, Jack; Hoogenraad, Anne-Roos; Peters, Harry P F; Vente-Spreeuwenberg, Maria A M; Mela, David J

2017-09-01

Type 2 diabetes (T2DM) is increasing, particularly in South-East Asia. Intake of high-glycaemic foods has been positively associated with T2DM, and feasible routes to reduce the glycaemic response to carbohydrate-rich staple foods are needed. The research question was whether different fibre and legume flour mixes in flatbreads lower postprandial glucose (PPG) responses. Using a balanced incomplete block design, we tested the inclusion of guar gum (GG), konjac mannan (KM) and chickpea flour (CPF) in 10 combinations (2/4/6 g GG; 2/4 g KM; 15 g CPF, and 10 or 15 g CPF plus 2 or 4 g GG) in 100 g total of a control commercial high-fibre flatbread flour mix ("atta") on PPG in 38 normal-weight adults. Self-reported appetite was an additional exploratory outcome. An in vitro digestion assay was adapted for flatbreads and assessed for prediction of in vivo PPG. Flatbreads with 6 g GG, 4 g KM, and 15 g CPF plus 2 or 4 g GG reduced PPG ≥30 % (p < 0.01), while no other combinations differed significantly from the control. A statistical model with four in vitro parameters (rate of digestion, %RDS, AUC, carbohydrate level) was highly predictive of PPG results (adjusted R 2  = 0.89). Test products were similar to the control for appetite-related measures. The results confirm the efficacy of specific additions to flatbread flour mixes for reducing PPG and the value of the in vitro model as a predictive tool with these ingredients and product format. This trial is registered at ClinicalTrials.gov with identifier NCT02671214.

Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification

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

Nomura, Daniel K.; Fujioka, Kazutoshi; Issa, Roger S.

2008-04-01

Serine hydrolase KIAA1363 is an acetyl monoalkylglycerol ether (AcMAGE) hydrolase involved in tumor cell invasiveness. It is also an organophosphate (OP) insecticide-detoxifying enzyme. The key to understanding these dual properties was the use of KIAA1363 +/+ (wildtype) and -/- (gene deficient) mice to define the role of this enzyme in brain and other tissues and its effectiveness in vivo in reducing OP toxicity. KIAA1363 was the primary AcMAGE hydrolase in brain, lung, heart and kidney and was highly sensitive to inactivation by chlorpyrifos oxon (CPO) (IC{sub 50} 2 nM) [the bioactivated metabolite of the major insecticide chlorpyrifos (CPF)]. Although theremore » was no difference in hydrolysis product monoalkylglycerol ether (MAGE) levels in +/+ and -/- mouse brains in vivo, isopropyl dodecylfluorophosphonate (30 mg/kg) and CPF (100 mg/kg) resulted in 23-51% decrease in brain MAGE levels consistent with inhibition of AcMAGE hydrolase activity. On incubating +/+ and -/- brain membranes with AcMAGE and cytidine-5'-diphosphocholine, the absence of KIAA1363 activity dramatically increased de novo formation of platelet-activating factor (PAF) and lyso-PAF, signifying that metabolically-stabilized AcMAGE can be converted to this bioactive lipid in brain. On considering detoxification, KIAA1363 -/- mice were significantly more sensitive than +/+ mice to ip-administered CPF (100 mg/kg) and parathion (10 mg/kg) with increased tremoring and mortality that correlated for CPF with greater brain acetylcholinesterase inhibition. Docking AcMAGE and CPO in a KIAA1363 active site model showed similar positioning of their acetyl and trichloropyridinyl moieties, respectively. This study establishes the relevance of KIAA1363 in ether lipid metabolism and OP detoxification.« less

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

Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles

Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Bloodmore » flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.« less

Moving Beyond Quantum Mechanics in Search for a Generalized Theory of Superconductivity

NASA Astrophysics Data System (ADS)

Akpojotor, Godfrey; Animalu, Alexander

2012-02-01

Though there are infinite number of theories currently in the literature in the search for a generalized theory of superconductivity (SC), there may be three domineering mechanisms for the Cooper pair formation (CPF) and their emergent theories of SC. Two of these mechanisms, electron-phonon interactions and electron-electron correlations which are based on the quantum theory axiom of action-at-a distance, may be only an approximation of the third mechanism which is contact interaction of the wavepackets of the two electrons forming the Cooper pair as envisaged in hadronic mechanics to be responsible for natural bonding of elements. The application of this hydronic --type interaction to the superconducting cuprates, iron based compounds and heavy fermions leads to interesting results. It is therefore suggested that the future of the search for the theory of SC may be considered from this natural possible bonding that at short distances, the CPF is by a nonlinear, nonlocal and nonhamiltonian strong hadronic-type interactions due to deep wave-overlapping of spinning particles leading to Hulthen potential that is attractive between two electrons in singlet couplings while at large distances the CPF is by superexchange interaction which is purely a quantum mechanical affairs.

The Effects of Pesticides on Queen Rearing and Virus Titers in Honey Bees (Apis mellifera L.)

PubMed Central

DeGrandi-Hoffman, Gloria; Chen, Yanping; Simonds, Roger

2013-01-01

The effects of sublethal pesticide exposure on queen emergence and virus titers were examined. Queen rearing colonies were fed pollen with chlorpyrifos (CPF) alone (pollen-1) and with CPF and the fungicide Pristine® (pollen-2). Fewer queens emerged when larvae from open foraging (i.e., outside) colonies were reared in colonies fed pollen-1 or 2 compared with when those larvae were reared in outside colonies. Larvae grafted from and reared in colonies fed pollen-2 had lower rates of queen emergence than pollen-1 or outside colonies. Deformed wing virus (DWV) and black queen cell virus were found in nurse bees from colonies fed pollen-1 or 2 and in outside colonies. The viruses also were detected in queen larvae. However, we did not detect virus in emerged queens grafted from and reared in outside colonies. In contrast, DWV was found in all emerged queens grafted from colonies fed pollen-1 or 2 either reared in outside hives or those fed pollen-1 or 2. The results suggest that sublethal exposure of CPF alone but especially when Pristine® is added reduces queen emergence possibly due to compromised immunity in developing queens. PMID:26466796

Ceramic pot filters lifetime study in coastal Guatemala.

PubMed

Salvinelli, C; Elmore, A C; García Hernandez, B R; Drake, K D

2017-02-01

Ceramic pot filters (CPFs) are an effective means of household water treatment, but the characterization of CPF lifetimes is ongoing. This paper describes a lifetime field study in Guatemala which was made possible by a collaboration between researchers, CPF-using households, and local non-governmental organizations (NGOs). Disinfection data were collected periodically for two years using field coliform enumeration kits as were flow rate data with the assistance of NGO staff. Consumer acceptance was characterized by surveying householders in the four subject villages at the beginning and end of the study. Flow rate data showed that average CPF flow rates decreased below the recommended minimum of 1 L h -1 after 10 months of use; however, the survey results indicated that the consumers were tolerant of the lower flow rates, and it is reasonable to assume that the daily volume of treated water can be readily increased by refilling the CPFs more frequently. Of greater concern was the finding that disinfection efficacy decreased below the recommended bacterial reduction after 14 months of use because it would not be obvious to users that effectiveness had declined. Finally, the follow-up visits by the researchers and the NGO staff appeared to increase consumer acceptance of the CPFs.

Sublethal toxicity of chlorpyrifos to salmonid olfaction after hypersaline acclimation.

PubMed

Maryoung, Lindley A; Blunt, Brian; Tierney, Keith B; Schlenk, Daniel

2015-04-01

Salmonid habitats can be impacted by several environmental factors, such as salinization, which can also affect salmonid tolerance to anthropogenic stressors, such as pesticides. Previous studies have shown that hypersaline acclimation enhances the acute toxicity of certain organophosphate and carbamate pesticides to euryhaline fish; however, sublethal impacts have been far less studied. The current study aims to determine how hypersaline acclimation and exposure to the organophosphate chlorpyrifos (CPF) impact salmonid olfaction. Combined acclimation and exposure to CPF was shown to impact rainbow trout olfaction at the molecular, physiological, and behavioral levels. Concurrent exposure to hypersalinity and 0.5μg/L CPF upregulated four genes (chloride intracellular channel 4, G protein zgc:101761, calcium calmodulin dependent protein kinase II delta, and adrenergic alpha 2C receptor) that inhibit olfactory signal transduction. At the physiological level, hypersalinity and chlorpyrifos caused a decrease in sensory response to the amino acid l-serine and the bile salt taurocholic acid. Combined acclimation and exposure also negatively impacted behavior and reduced the avoidance of a predator cue (l-serine). Thus, acclimation to hypersaline conditions and exposure to environmentally relevant concentrations of chlorpyrifos caused an inhibition of olfactory signal transduction leading to a decreased response to odorants and impairment of olfactory mediated behaviors. Copyright © 2015 Elsevier B.V. All rights reserved.

Novel antimicrobial peptide CPF-C1 analogs with superior stabilities and activities against multidrug-resistant bacteria.

PubMed

Xie, Junqiu; Zhao, Qian; Li, Sisi; Yan, Zhibin; Li, Jing; Li, Yao; Mou, Lingyun; Zhang, Bangzhi; Yang, Wenle; Miao, Xiaokang; Jiang, Xianxing; Wang, Rui

2017-11-01

As numerous clinical isolates are resistant to most conventional antibiotics, infections caused by multidrug-resistant bacteria are associated with a higher death rate. Antimicrobial peptides show great potential as new antibiotics. However, a major obstacle to the development of these peptides as useful drugs is their low stability. To overcome the problem of the natural antimicrobial peptide CPF-C1, we designed and synthesized a series of analogs. Our results indicated that by introducing lysine, which could increase the number of positive charges, and by introducing tryptophan, which could increase the hydrophobicity, we could improve the antimicrobial activity of the peptides against multidrug-resistant strains. The introduction of d-amino acids significantly improved stability. Certain analogs demonstrated antibiofilm activities. In mechanistic studies, the analogs eradicated bacteria not just by interrupting the bacterial membranes, but also by linking to DNA, which was not impacted by known mechanisms of resistance. In a mouse model, certain analogs were able to significantly reduce the bacterial load. Among the analogs, CPF-9 was notable due to its greater antimicrobial potency in vitro and in vivo and its superior stability, lower hemolytic activity, and higher antibiofilm activity. This analog is a potential antibiotic candidate for treating infections induced by multidrug-resistant bacteria. © 2017 John Wiley & Sons A/S.

Plaque autofluorescence as potential diagnostic targets for oral malodor

NASA Astrophysics Data System (ADS)

Lee, Eun-Song; Yim, Hyun-Kyung; Lee, Hyung-Suk; Choi, Jong-Hoon; Kwon, Ho-Keun; Kim, Baek-Il

2016-08-01

The aim of this study was to determine whether the degree of tongue and interdental plaque can be used to assess oral malodor by quantifying their fluorescence as detected using quantitative light-induced fluorescence (QLF) technology. Ninety-nine subjects who complained of oral malodor were included. The level of oral malodor was quantified using the organoleptic score (OLS) and the concentration of volatile sulfur compounds (VSCs). The fluorescence properties of tongue and interdental plaque were quantified as scores calculated by multiplying the intensity and area of fluorescence in QLF-digital images, and the combined plaque fluorescence (CPF) score was obtained by summing the scores for the two regions. The associations of the scores with malodor levels and the diagnostic accuracy of the CPF score were analyzed. The two plaque fluorescence scores and their combined score differed significantly with the level of oral malodor (p<0.001). The CPF score was moderately correlated with OLS (r=0.64) and VSC levels (r=0.54), and its area under the receiver operating characteristic curve was 0.77 for identifying subjects with definite oral malodor (OLS≥2). In conclusion, plaque fluorescence from tongue and interdental sites as detected using QLF technology can be used to assess the level of oral malodor.

Study of commonly used organophosphate pesticides that induced oxidative stress and apoptosis in peripheral blood lymphocytes of rats.

PubMed

Ojha, A; Gupta, Y K

2017-11-01

In a previous study, we have found that organophosphate (OP) pesticides such as chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) significantly induced genotoxicity in peripheral blood lymphocytes of rats. To explore the mechanism of OP-induced genotoxicity, we measured the formation of DNA interstrand cross-links (DICs) and apoptosis in peripheral blood lymphocytes of rats. Peripheral blood lymphocytes of rats were treated with CPF, MPT, and MLT individually and in combination at concentrations of 0.1 and 0.25 LC 50 for 2, 4, 8, and 12 h at 37°C. Lipid peroxidation (LPO) was measured as a biomarker of oxidative stress. Apoptosis induced by CPF, MPT, and MLT individually and in combination was determined by measuring the intracellular level of active caspase-3 and caspase-9 by spectrofluorimetry. We found significant dose- and time-dependent increases in LPO, DICs formation and increase of intracellular active caspase-3 and caspase-9 in exposed peripheral blood lymphocytes of rats. These findings suggest that the studied pesticides have potential to induce oxidative stress, cause DNA adduct formation, and cause failure of adduct repair, which leads to apoptosis that is partially mediated by activation of intracellular caspase-3 and caspase-9.

Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

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

Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es

2015-07-15

Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT inductionmore » (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the acquisition of a malignant phenotype.« less

Ozone Climate Penalty and Mortality in a Changing World

NASA Astrophysics Data System (ADS)

Hakami, A.; Zhao, S.; Pappin, A.; Mesbah, M.

2013-12-01

The expected increase in ozone concentrations with temperature is referred to as the climate penalty factor (CPF). Observed ozone trends have resulted in estimations of regional CPFs in the range of 1-3 ppb/K in the Eastern US, and larger values around the globe. We use the adjoint of a regional model (CMAQ) for attributing changes in ozone mortality and attainment metrics to increased temperature levels at each location in North America during the summer of 2007. Unlike previous forward sensitivity analysis studies, we estimate how changes in temperatures at various locations influence such policy-relevant metrics. Our analysis accounts for separate temperature impact pathways through gas-phase chemistry, moisture abundance, and biogenic emissions. We find that water vapor impact, while mostly negative, is positive and large for temperature changes in urban areas. We also find that increased biogenic emissions plays an important role in the overall temperature influence. Our simulations show a wide range of spatial variability in CPFs between -0.4 and 6.2 ppb/K with largest values in urban areas. We also estimate mortality-based CPFs of up to 4 deaths/K for each grid cell, again with large localization in urban areas. This amounts to an estimated 370 deaths/K for the 3-month period of the simulation. We find that this number is almost equivalent to 5% reduction in anthropogenic NOx emissions for each degree increase in temperature. We show how the CPF will change as the result progressive NOx emission controls from various anthropogenic sectors and sources at different locations. Our findings suggest that urban NOx control can be regarded as an adaptation strategy with regards to ozone air quality. Also, the strong temperature dependence in urban environments suggests that the health and attainment burden of urban heat island may be more substantial than previously thought. Spatial distribution of average adjoint-based CPFs Adjoint-based CPF and Mortality CPF (domainwide)

Copper-induced ammonia N-H functionalization.

PubMed

Álvarez, María; Álvarez, Eleuterio; Fructos, Manuel R; Urbano, Juan; Pérez, Pedro J

2016-10-07

The activation of ammonia has been achieved with the aid of the Tp(Ms)Cu core (Tp(Ms) = hydrotris(3-mesityl-pyrazolyl)borate). Complexes of the general composition Tp(Ms)Cu(amine) (1-4) including the ammonia adduct Tp(Ms)Cu(NH3) (1) have been synthesized and fully spectroscopical- and structurally characterized. Coordinated ammonia in 1 has been reacted with Ph3CPF6 yielding Tp(Ms)Cu(NH2CPh3) (5) as a result of N-H cleavage and N-C bond formation. In a parallel manner the catalytic functionalization of ammonia with ethyl diazoacetate leading to glycinate derivatives has been developed with Tp(Ms)Cu(THF) as the catalyst, in the first example of this transformation with ammonia and a copper-based system.

Nuclear factor erythroid-derived 2-related factor 2 activates glutathione S-transferase expression in the midgut of Spodoptera litura (Lepidoptera: Noctuidae) in response to phytochemicals and insecticides.

PubMed

Chen, S; Lu, M; Zhang, N; Zou, X; Mo, M; Zheng, S

2018-05-10

Detoxication enzymes play an important role in insect resistance to xenobiotics such as insecticides and phytochemicals. We studied the pathway for activating the expression of glutathione S-transferases (GSTs) in response to selected xenobiotics. An assay of the promoter activity of GST epsilon 1 (Slgste1) of Spodoptera litura led to the discovery of a cis-regulating element. An antioxidant response element was activated in response to indole-3-carbinol (I3C) and chlorpyrifos (CPF) and was able to bind with the xenobiotic sensor protein nuclear factor erythroid-derived 2-related factor 2 (SlNrf2). SlNrf2 and Slgste1 were responsive to reactive oxygen species induced by I3C and CPF in a S. litura cell line, as well as in S. litura midguts. SlNrf2 RNA interference (RNAi) reduced the message RNA levels of Slgste1 and the peroxidase activity of GSTs in response to I3C, xanthotoxin, CPF and deltamethrin. SlNrf2 RNAi and inhibitor treatment of GST activity decreased the viability of I3C-treated cells. These results indicate that SlNrf2 activates the expression of GSTs in response to oxidative stresses caused by exposure to xenobiotics. © 2018 The Royal Entomological Society.

Alterations in juvenile diploid and triploid African catfish skin gelatin yield and amino acid composition: Effects of chlorpyrifos and butachlor exposures.

PubMed

Karami, Ali; Karbalaei, Samaneh; Zad Bagher, Fariba; Ismail, Amin; Simpson, Stuart L; Courtenay, Simon C

2016-08-01

Skin is a major by-product of the fisheries and aquaculture industries and is a valuable source of gelatin. This study examined the effect of triploidization on gelatin yield and proximate composition of the skin of African catfish (Clarias gariepinus). We further investigated the effects of two commonly used pesticides, chlorpyrifos (CPF) and butachlor (BUC), on the skin gelatin yield and amino acid composition in juvenile full-sibling diploid and triploid African catfish. In two separate experiments, diploid and triploid C. gariepinus were exposed for 21 days to graded CPF [mean measured: 10, 16, or 31 μg/L] or BUC concentrations [Mean measured: 22, 44, or 60 μg/L]. No differences in skin gelatin yield, amino acid or proximate compositions were observed between diploid and triploid control groups. None of the pesticide treatments affected the measured parameters in diploid fish. In triploids, however, gelatin yield was affected by CPF treatments while amino acid composition remained unchanged. Butachlor treatments did not alter any of the measured variables in triploid fish. To our knowledge, this study is the first to investigate changes in the skin gelatin yield and amino acid composition in any animal as a response to polyploidization and/or contaminant exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

PM2.5 and Black carbon enhancement at Socheongcho Ocean Research Station in the Yellow Sea

NASA Astrophysics Data System (ADS)

Jeon, H.; Rhee, H.; Lee, M.; JinYong, J.; Min, I.; Shim, J.

2017-12-01

Socheongcho Ocean Research Station (SORS) has been established in northern Yellow Sea by the Korea Institute of Ocean Science and Technology (KIOST). At SORS, PM2.5 and Black carbon (BC) were measured every 10 minutes during October 2014 June 2017 using beta-ray absorption method (FH62C14, Thermo. Inc, USA) and Multi Angle Absorption Photometer (MAAP; Model 5012, Thermo. Inc, USA), respectively. In addition, CO, CO2 and CH4 were determined by Cavity Ring Down Spectroscopy (CRDS; Model G2401, Picarro. Inc, USA). Measurements were intermittently interrupted for SORS maintenance reasons. For BC and PM2.5, the mean, 90th %tile and maximum concentrations were 1.16, 2.29, and 20.07 ug/m3 and 25, 48, and 177 ug/m3, respectively. There was no clear diurnal variation observed for both species. PM2.5 and BC concentrations were higher in cold seasons than in warm seasons. The highest PM2.5 and BC concentrations (>99th %tile) were more frequently observed in winter. Particularly, the extremely high BC were sporadically observed and lasted for no longer than 1 hour. The possible sources of PM2.5 and BC were examined using Conditional Probability Function (CPF), Potential Source Contribution (PSCF), and Concentration Weighted Trajectory (CWT) analysis. The results suggest the dominant influence from China, particularly for high concentrations.

Modulations of eye movement patterns by spatial filtering during the learning and testing phases of an old/new face recognition task.

PubMed

Lemieux, Chantal L; Collin, Charles A; Nelson, Elizabeth A

2015-02-01

In two experiments, we examined the effects of varying the spatial frequency (SF) content of face images on eye movements during the learning and testing phases of an old/new recognition task. At both learning and testing, participants were presented with face stimuli band-pass filtered to 11 different SF bands, as well as an unfiltered baseline condition. We found that eye movements varied significantly as a function of SF. Specifically, the frequency of transitions between facial features showed a band-pass pattern, with more transitions for middle-band faces (≈5-20 cycles/face) than for low-band (≈<5 cpf) or high-band (≈>20 cpf) ones. These findings were similar for the learning and testing phases. The distributions of transitions across facial features were similar for the middle-band, high-band, and unfiltered faces, showing a concentration on the eyes and mouth; conversely, low-band faces elicited mostly transitions involving the nose and nasion. The eye movement patterns elicited by low, middle, and high bands are similar to those previous researchers have suggested reflect holistic, configural, and featural processing, respectively. More generally, our results are compatible with the hypotheses that eye movements are functional, and that the visual system makes flexible use of visuospatial information in face processing. Finally, our finding that only middle spatial frequencies yielded the same number and distribution of fixations as unfiltered faces adds more evidence to the idea that these frequencies are especially important for face recognition, and reveals a possible mediator for the superior performance that they elicit.

Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression.

PubMed

López-Granero, Caridad; Cardona, Diana; Giménez, Estela; Lozano, Rafael; Barril, José; Aschner, Michael; Sánchez-Santed, Fernando; Cañadas, Fernando

2014-01-01

Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent. A single subcutaneous dose of 250 mg/kg chlorpyrifos (CPF), 1.5mg/kg diisopropylphosphorofluoridate (DFP) or 15 mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was evaluated 72 h or 23 weeks after exposure, and impulsive choice was tested at 10 and 30 weeks following OPs administration (experiment 1 and 2, respectively). Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read-through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as alternative non-cholinergic target) were analyzed upon completion of the behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long-term CPF treatment caused statistically significant effects on spatial learning, while PTN treatment led only to statistically significant short-term effects. Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in the PTN treated group only AChE-S mRNA levels were decreased. However, after long-term OP exposure, soluble and membrane-bound AChE activity was indistinguishable from controls. Finally, no changes were noted in brain APH activity in response to OP treatment. Taken together, this study demonstrates long-term effects of OPs on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane-bound activity. Thus, changes in AChE mRNA expression imply non-catalytic properties of the AChE enzyme. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of peritoneal fluid from endometriosis patients on the release of vascular endothelial growth factor by neutrophils and monocytes.

PubMed

Na, Yong-Jin; Yang, Seung-Hong; Baek, Dae-Won; Lee, Dong-Hyung; Kim, Ki-Hyung; Choi, Young-Min; Oh, Sung-Tack; Hong, Young-Seoub; Kwak, Jong-Young; Lee, Kyu-Sup

2006-07-01

An increase in the level of the vascular endothelial growth factor (VEGF) production has been reported in the peritoneal fluid (PF) of endometriosis patients. This suggests that changes in the vascular permeability and angiogenesis play an important role in the pathophysiology of this disease. This study examined the effects of the PF obtained from endometriosis patients on the release of VEGF by neutrophils and monocytes. Neutrophils and monocytes were obtained from young healthy volunteers and cultured with the PF obtained from either endometriosis patients (EPF) (n=18) or a control group (CPF) (n=4). A human monocyte/macrophage cell line, THP-1, was cultured with either 10% EPF or 10% CPF. The PF and culture supernatants were assayed for VEGF using ELISA. Real-time PCR and Western blotting were used to measure the VEGF mRNA and protein expression level, respectively. The VEGF levels were higher in the EPF than in the CPF (591+/-75 versus 185+/-31 pg/ml, P<0.05). However, the level of VEGF released by THP-1 cells in CPF and EPF was similar. The EPF induced the release of VEGF by neutrophils, but no VEGF was released by monocytes. The VEGF mRNA expression levels in the neutrophils were higher in the EPF, which was abrogated by cycloheximide, suggesting that the EPF induces the production of VEGF in neutrophils. Neutralizing antibodies against IL-8 and TNF-alpha did not completely prevent the EPF-induced release of VEGF by the neutrophils, even though these growth factors stimulated the release of VEGF by neutrophils. There was a positive correlation between the VEGF and IL-10 concentrations in the EPF (correlation coefficient=0.549, P=0.012, n=18), but the neutralizing antibody of IL-10 did not affect the release of VEGF by the EPF-treated neutrophils. The EPF induced the production and release of VEGF by neutrophils, suggesting that neutrophils may be a source of peritoneal VEGF. In addition, neutrophil-derived VEGF might be a marker for diagnosing endometriosis.

Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility.

PubMed

Marí-Alexandre, Josep; Barceló-Molina, Moisés; Belmonte-López, Elisa; García-Oms, Javier; Estellés, Amparo; Braza-Boïls, Aitana; Gilabert-Estellés, Juan

2018-04-01

To define the microRNA (miRNA) profile and its relationship with cytokines content in peritoneal fluid (PF) from endometriosis patients. Case-control study. University hospital, research institute. One hundred twenty-six women with endometriosis (EPF) and 45 control women (CPF). MiRNA arrays were prepared from six EPF and six CPF. Quantitative reverse transcription-polymerase chain reaction validation of nine selected miRNAs (miR-29c-3p, -106b-3p, -130a-3p, -150-5p, -185-5p, -195-5p, -451a, -486-5p, and -1343-5p) was performed. Vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-3 (MMP3), tissue inhibitor of metalloproteinases type 1 (TIMP-1), interleukin (IL)-6, IL-8, IL-17A, macrophage inflammatory protein 1β (MIP1beta), platelet-derived growth factor α-polypeptide A, and regulated on activation, normal T cell expressed and secreted (RANTES) were quantified by ELISA and MILLIPLEX. MiRNA arrays showed 126 miRNAs differentially expressed (fold change ±1.2) (78 down-regulated, 48 up-regulated) in EPF. Validation showed higher levels of miR-106b-3p, -451a, -486-5p, IL-6, IL-8, uPA, and TIMP-1 in EPF. In menstrual phase, EPF presented up-regulation of miR-106b-3p, -130a-3p, -150-5p, -185-5p, -451a, -486-5p, VEGF-A, IL-8, MIF 1β, uPA, and PAI-1 compared with other phases; however, CPF did not. MiRNA-486-5p was up-regulated in sterile EPF compared with sterile controls, and VEGF-A, IL-8, and TIMP-1 were increased in sterile and fertile EPF compared with fertile CPF. MiRNAs seem to be involved in the peritoneal alterations in endometriosis, suggesting new mechanisms by which ectopic lesions could implant in endometriosis patients; and to serve as biomarkers for fertility outcome prediction. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.

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

Busby, Andrea L.; Kousba, Ahmed A.; Timchalk, Chuck

2004-12-01

Chlorpyrifos (CPF) and diazinon (DZN) are inhibitors of acetylcholinesterase due to the effects of their active oxon metabolites. The inhibition of acetylcholinesterase results in a buildup of acetylcholine within the nerve synapses leading to a variety of neurotoxic effects (Mileson et al., 1998). These effects are most clearly seen following acute high dose exposures but they can also be observed in lower dose chronic cases as well. Chlorpyrifos is the active ingredient in commonly used organophosphorous (OP) insecticides like DURSBAN and LORSBAN (Timchalk et. al, 2002). Chlorpyrifos and diazinon are used to eliminate pests in agricultural applications like cotton andmore » fruit crops. Every year globally there are approximately 3 million cases of organophosphate poisoning reported resulting in 200,000 deaths (Haywood et al., 2000). The public is exposed to these chemicals on a regular basis at chronic low levels from food and water contamination, dermal contact and inhalation. The United States National Health and Nutrition Examination Survey indicated that of approximately 3,600 persons from all 64 NHANES III locations, 70% tested positive for TCP in urine, suggesting exposure to chlorpyrifos (NHANES III, 1994). The chemical structures of chlorpyrifos, diazinon, and their major metabolites trichlorpyridinol (TCP), and isopropyl-methyl-hydroxypyrimidine (IMHP) are shown in Figure 1. The parent compounds, CPF and DZN, are metabolized to their potent inhibiting oxon forms via a desulfuration reaction initiated by cytochrome P450 (CYP)(Poet et al., 2003; Amitai et al., 1998). Competing with the formation of oxon is the detoxification metabolism of CPF to TCP and DZN to IMHP via a dearylation reaction utilizing the same enzymes. A-esterase (PON1) and other B-esterases also contribute to the production of TCP and IMHP through the metabolism of CPF-oxon and DZN-oxon, respectively (Poet et al., 2003; Ma et al., 1994). The ratio between the toxification/detoxification reactions determines the degree of enzyme inhibition and can be used to evaluate metabolism processes (Timchalk et al., 2002).« less

A possible structural model of members of the CPF family of cuticular proteins implicating binding to components other than chitin

PubMed Central

Papandreou, Nikos C.; Iconomidou, Vassiliki A.; Willis, Judith H.; Hamodrakas, Stavros J.

2010-01-01

The physical properties of cuticle are determined by the structure of its two major components, cuticular proteins (CPs) and chitin, and, also, by their interactions. A common consensus region (extended R&R Consensus) found in the majority of cuticular proteins, the CPRs, binds to chitin. Previous work established that β-pleated sheet predominates in the Consensus region and we proposed that it is responsible for the formation of helicoidal cuticle. Remote sequence similarity between CPRs and a lipocalin, bovine plasma retinol binding protein (RBP), led us to suggest an antiparallel β-sheet half-barrel structure as the basic folding motif of the R&R Consensus. There are several other families of cuticular proteins. One of the best defined is CPF. Its four members in Anopheles gambiae are expressed during the early stages of either pharate pupal or pharate adult development, suggesting that the proteins contribute to the outer regions of the cuticle, the epi- and/or exocuticle. These proteins did not bind to chitin in the same assay used successfully for CPRs. Although CPFs are distinct in sequence from CPRs, the same lipocalin could also be used to derive homology models for one Anopheles gambiae and one Drosophila melanogaster CPF. For the CPFs, the basic folding motif predicted is an eight-stranded, antiparallel β-sheet, full-barrel structure. Possible implications of this structure are discussed and docking experiments were carried out with one possible Drosophila ligand, 7(Z), 11(Z)-heptacosadiene. PMID:20417215

Use of a probabilistic PBPK/PD model to calculate Data Derived Extrapolation Factors for chlorpyrifos.

PubMed

Poet, Torka S; Timchalk, Charles; Bartels, Michael J; Smith, Jordan N; McDougal, Robin; Juberg, Daland R; Price, Paul S

2017-06-01

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells.

PubMed

Zhou, Miaojin; Hu, Zhiqing; Qiu, Liyan; Zhou, Tao; Feng, Mai; Hu, Qian; Zeng, Baitao; Li, Zhuo; Sun, Qianru; Wu, Yong; Liu, Xionghao; Wu, Lingqian; Liang, Desheng

2018-05-09

Spinal muscular atrophy (SMA) is a kind of neuromuscular disease characterized by progressive motor neuron loss in the spinal cord. It is caused by mutations in the survival motor neuron 1 (SMN1) gene. SMN1 has a paralogous gene, survival motor neuron 2 (SMN2), in humans that is present in almost all SMA patients. The generation and genetic correction of SMA patient-specific induced pluripotent stem cells (iPSCs) is a viable, autologous therapeutic strategy for the disease. Here, c-Myc-free and non-integrating iPSCs were generated from the urine cells of an SMA patient using an episomal iPSC reprogramming vector, and a unique crRNA was designed that does not have similar sequences (≤3 mismatches) anywhere in the human reference genome. In situ gene conversion of the SMN2 gene to an SMN1-like gene in SMA-iPSCs was achieved using CRISPR/Cpf1 and single-stranded oligodeoxynucleotide with a high efficiency of 4/36. Seamlessly gene-converted iPSC lines contained no exogenous sequences and retained a normal karyotype. Significantly, the SMN expression and gems localization were rescued in the gene-converted iPSCs and their derived motor neurons. This is the first report of an efficient gene conversion mediated by Cpf1 homology-directed repair in human cells and may provide a universal gene therapeutic approach for most SMA patients.

Aryl- and alkyl-phosphorus-containing flame retardants induced mitochondrial impairment and cell death in Chinese hamster ovary (CHO-k1) cells.

PubMed

Huang, Chao; Li, Na; Yuan, Shengwu; Ji, Xiaoya; Ma, Mei; Rao, Kaifeng; Wang, Zijian

2017-11-01

Phosphorus-containing flame retardants (PFRs) are increasingly in demand worldwide as replacements for brominated flame retardants (BFRs), but insufficient available toxicological information on PFRs makes assessing their health risks challenging. Mitochondria are important targets of various environmental pollutants, and mitochondrial dysfunction may lead to many common diseases. In the present study, mitochondria impairment-related endpoints were measured by a high content screening (HCS) assay for 11 selected non-halogen PFRs in Chinese hamster ovary (CHO-k1) cells. A cluster analysis was used to categorize these PFRs into three groups according to their structural characteristics and results from the HCS assay. Two groups, containing long-chain alkyl-PFRs and all aryl-PFRs, were found to cause mitochondrial impairment but showed different mechanisms of toxicity. Due to the high correlation between cell death and mitochondrial impairment, two PFRs with different structures, trihexyl phosphate (THP) and cresyl diphenyl phosphate (CDP), were selected and compared with chlorpyrifos (CPF) to elucidate their mechanism of inducing cell death. THP (an alkyl-PFR) was found to utilize a similar pathway as CPF to induce apoptosis. However, cell death induced by CDP (an aryl-PFR) was different from classical necrosis based on experiments to discriminate among the different modes of cell death. These results confirm that mitochondria might be important targets for some PFRs and that differently structured PFRs could function via distinct mechanisms of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accurate ab initio calculations which demonstrate a 3 Pi u ground state for Al2

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Partridge, Harry; Langhoff, Stephen R.; Taylor, Peter R.; Walch, Stephen P.

1986-01-01

The spectroscopic parameters and separations between the three low-lying X 3 Pi u, A 3 Sigma g -, and a 1 Sigma g + states of Al2 are studied as a function of both the one-particle and n-particle basis set. Approximate correlation treatments are calibrated against full Cl calculations correlating the six valence electrons in a double-zeta plus two d-function basis set. Since the CASSCF/MRCI 3 Pi u to 3 Sigma g - separation is in excellent agreement wtih the FCI value, the MRCI calculations were carried out in an extended (20s13p6d4f)/(6s5p3d2f) gaussian basis. Including a small correction for relativistic effects, the best estimate is that 3 Sigma g - state lies 174/cm above the 3 Pi u ground state. The 1 Sigma g + state lies at least 2000/cm higher in energy. At the CPF level, inclusion of 2s and 2p correlation has little effect on D sub e, reduces T sub e by only 26/cm, and shortens the bond lengths by about 0.02 a sub o. Further strong support for a 3 Pi u ground state comes from the experimental absorption spectra, since both observed transitions can be convincingly assigned as 3 Pi u yields 3 Pi g. The (2) 3 Pi g state is observed to be sensitive to the level of correlation treatment, and to have its minimum shifted to shorter rho values, such that the strongest experimental absorption peak probably corresponds to the 0 yields 2 transition.

Evaluation of background soil and air polychlorinated biphenyl (PCB) concentrations on a hill at the outskirts of a metropolitan city.

PubMed

Kuzu, S Levent; Saral, Arslan; Güneş, Gülten; Karadeniz, Aykut

2016-07-01

Air and soil sampling was conducted inside a forested area for 22 months. The sampling location is situated to the north of a metropolitan city. Average atmospheric gas and particle concentrations were found to be 180 and 28 pg m(-3) respectively, while that of soil phase was detected to be 3.2 ng g(-1) on dry matter, The congener pairs of PCB#4-10 had the highest contribution to each medium. TEQ concentration was 0.10 pg m(-3), 0.07 pg m(-3), 21.92 pg g(-1), for gas, particle and soil phases, respectively. PCB#126 and PCB#169 contributed to over 99% of the entire TEQ concentrations for each medium. Local sources were investigated by conditional probability function (CPF) and soil/air fugacity. Landfilling area and medical waste incinerator, located to the 8 km northeast, contributed to ambient concentrations, especially in terms of dioxin-like congeners. The industrial settlement (called Dilovasi being to the east southeast of 60 km distant) contributed from southeast direction. Further sources were identified by potential source contribution function (PSCF). Sources at close proximity had high contribution. Air mass transportation from Aliaga industrial region (being to the southwest of 300 km distant) moderately contributed to ambient concentrations. Low molecular weight congeners were released from soil body. 5-CBs and 6-CBs were close to equilibrium state between soil/air interfaces. PCB#171 was close to equilibrium and PCB#180 was likely to evaporate from soil, which constitute 7-CBs. PCB#199, representing 8-CBs deposited to soil. 9-CB (PCB#207) was in equilibrium between soil and air phases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Your Baby's First Year

MedlinePlus

... feeding, please see our CPF booklet and video series, Feeding Your Baby . An infant born with a cleft lip and/or palate should be ready to eat solid foods at the same time as any other baby. Foods should be offered ...

Magnetic Enzymatic Platform for Organophosphate Pesticide Detection Using Boron-doped Diamond Electrodes.

PubMed

Pino, Flavio; Ivandini, Tribidasari A; Nakata, Kazuya; Fujishima, Akira; Merkoçi, Arben; Einaga, Yasuaki

2015-01-01

A simple and reliable enzymatic system for organophosporus pesticide detection was successfully developed, by exploiting the synergy between the magnetic beads collection capacity and the outstanding electrochemistry property of boron-doped diamond electrodes. The determination of an organophosphate pesticide, chlorpyrifos (CPF), was performed based on the inhibition system of the enzyme acetylcholinesterase bonded to magnetic beads through a biotin-streptavidin complex system. A better sensitivity was found for a system with magnetic beads in the concentration range of 10(-9) to 10(-5) M. The estimated limits of detection based on IC10 (10% acetylcholinesterase (AChE) inhibition) have been detected and optimized to be 5.7 × 10(-10) M CPF. Spiked samples of water of Yokohama (Japan) have been measured to validate the efficiency of the enzymatic system. The results suggested that the use of magnetic beads to immobilize biomolecules or biosensing agents is suitable to maintain the superiority of BDD electrodes.

SERS-based pesticide detection by using nanofinger sensors

NASA Astrophysics Data System (ADS)

Kim, Ansoon; Barcelo, Steven J.; Li, Zhiyong

2015-01-01

Simple, sensitive, and rapid detection of trace levels of extensively used and highly toxic pesticides are in urgent demand for public health. Surface-enhanced Raman scattering (SERS)-based sensor was designed to achieve ultrasensitive and simple pesticide sensing. We developed a portable sensor system composed of high performance and reliable gold nanofinger sensor strips and a custom-built portable Raman spectrometer. Compared to the general procedure and previously reported studies that are limited to laboratory settings, our analytical method is simple, sensitive, rapid, and cost-effective. Based on the SERS results, the chemical interaction of two pesticides, chlorpyrifos (CPF) and thiabendazole (TBZ), with gold nanofingers was studied to determine a fingerprint for each pesticide. The portable SERS-sensor system was successfully demonstrated to detect CPF and TBZ pesticides within 15 min with a detection limit of 35 ppt in drinking water and 7 ppb on apple skin, respectively.

The laboratory demonstration and signal processing of the inverse synthetic aperture imaging ladar

NASA Astrophysics Data System (ADS)

Gao, Si; Zhang, ZengHui; Xu, XianWen; Yu, WenXian

2017-10-01

This paper presents a coherent inverse synthetic-aperture imaging ladar(ISAL)system to obtain high resolution images. A balanced coherent optics system in laboratory is built with binary phase coded modulation transmit waveform which is different from conventional chirp. A whole digital signal processing solution is proposed including both quality phase gradient autofocus(QPGA) algorithm and cubic phase function(CPF) algorithm. Some high-resolution well-focused ISAL images of retro-reflecting targets are shown to validate the concepts. It is shown that high resolution images can be achieved and the influences from vibrations of platform involving targets and radar can be automatically compensated by the distinctive laboratory system and digital signal process.

[Evaluation of drinking-water treatment by Lifestraw® and Ceramic-pot filters].

PubMed

Pérez-Vidal, Andrea; Díaz-Gómez, Jaime; Salamanca-Rojas, Karen L; Rojas-Torres, Leidy Y

2016-04-01

Objective To evaluate under laboratory conditions, the removal efficiency of turbidity and E. coli of two household water filters: LifeStraw® family (MF) and ceramic pot filter (CPF). Methods The two systems were operated over 6 months using two identical control units per system, treating 7.5 L/d of a synthetic substrate used as raw water. The turbidity of the substrate was adjusted with Kaolinite and the E. coli concentration, with a replica of the ATCC 95922 strain. The differences of effluent quality of the systems, in terms of turbidity and E. coli, were evaluated with Analysis of Variance (ANOVA). Operative and maintenance aspects, that could limit or enhance the use of the systems, were also considered in the evaluation. Results The water synthetic substrate quality had an average of 32.2 ± 2.8 NTU for turbidity and 3,9x105 UFC/100 mL for E. coli. Both systems reduce the turbidity to values below 2 NTU with an inactivation of 100 % of E. coli. Statistical differences were found between the systems in terms of turbidity removal, MF being more efficient than the CPF (99,2 ± 0.4 % and 97.6 % ± 1.14, respectively). Conclusions Both systems are suitable for household water supply treatment, acheiving the water quality standards established by Colombian regulations. The MF was more efficient for suspended solids removal and filtration rate, but when economic, operative, and maintenance aspects along with social acceptability and lifespan are considered, the CPF seems more suitable, especially in rural areas.

Sequencing and diversity analyses reveal extensive similarities between some epsilon-toxin-encoding plasmids and the pCPF5603 Clostridium perfringens enterotoxin plasmid.

PubMed

Miyamoto, Kazuaki; Li, Jihong; Sayeed, Sameera; Akimoto, Shigeru; McClane, Bruce A

2008-11-01

Clostridium perfringens type B and D isolates produce epsilon-toxin, the third most potent clostridial toxin. The epsilon-toxin gene (etx) is plasmid borne in type D isolates, but etx genetics have been poorly studied in type B isolates. This study reports the first sequencing of any etx plasmid, i.e., pCP8533etx, from type B strain NCTC8533. This etx plasmid is 64.7 kb, carries tcp conjugative transfer genes, and encodes additional potential virulence factors including beta2-toxin, sortase, and collagen adhesin but not beta-toxin. Interestingly, nearly 80% of pCP8533etx open reading frames (ORFs) are also present on pCPF5603, an enterotoxin-encoding plasmid from type A isolate F5603. Pulsed-field gel electrophoresis and overlapping PCR indicated that a pCP8533etx-like etx plasmid is also present in most, if not all, other type B isolates and some beta2-toxin-positive, cpe-negative type D isolates, while other type D isolates carry different etx plasmids. Sequences upstream of the etx gene vary between type B isolates and some type D isolates that do not carry a pCP8533etx-like etx plasmid. However, nearly all type B and D isolates have an etx locus with an upstream IS1151, and those etx loci typically reside near a dcm ORF. These results suggest that pCPF5603 and pCP8533etx evolved from insertion of mobile genetic elements carrying enterotoxin or etx genes, respectively, onto a common progenitor plasmid.

Residues at a Single Site Differentiate Animal Cryptochromes from Cyclobutane Pyrimidine Dimer Photolyases by Affecting the Proteins' Preferences for Reduced FAD.

PubMed

Xu, Lei; Wen, Bin; Wang, Yuan; Tian, Changqing; Wu, Mingcai; Zhu, Guoping

2017-06-19

Cryptochromes (CRYs) and photolyases belong to the cryptochrome/photolyase family (CPF). Reduced FAD is essential for photolyases to photorepair UV-induced cyclobutane pyrimidine dimers (CPDs) or 6-4 photoproducts in DNA. In Drosophila CRY (dCRY, a type I animal CRY), FAD is converted to the anionic radical but not to the reduced state upon illumination, which might induce a conformational change in the protein to relay the light signal downstream. To explore the foundation of these differences, multiple sequence alignment of 650 CPF protein sequences was performed. We identified a site facing FAD (Ala377 in Escherichia coli CPD photolyase and Val415 in dCRY), hereafter referred to as "site 377", that was distinctly conserved across these sequences: CPD photolyases often had Ala, Ser, or Asn at this site, whereas animal CRYs had Ile, Leu, or Val. The binding affinity for reduced FAD, but not the photorepair activity of E. coli photolyase, was dramatically impaired when replacing Ala377 with any of the three CRY residues. Conversely, in V415S and V415N mutants of dCRY, FAD was photoreduced to its fully reduced state after prolonged illumination, and light-dependent conformational changes of these mutants were severely inhibited. We speculate that the residues at site 377 play a key role in the different preferences of CPF proteins for reduced FAD, which differentiate animal CRYs from CPD photolyases. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of biochemical mechanisms of tolerance to chlorpyrifos in ancient and contemporary Daphnia pulicaria genotypes.

PubMed

Simpson, Adam M; Jeyasingh, Punidan D; Belden, Jason B

2017-12-01

The evolution of tolerance to environmental contaminants in non-target taxa has been largely studied by comparing extant populations experiencing contrasting exposure. Previous research has demonstrated that "resurrected" genotypes from a population of Daphnia pulicaria express temporal variation in sensitivity to the insecticide chlorpyrifos. Ancient genotypes (1301-1646AD.) were on average more sensitive to this chemical compared to the contemporary genotypes (1967-1977AD.). To determine the physiological mechanisms of tolerance, a series of biochemical assays was performed on three ancient and three contemporary genotypes; these six genotypes exhibited the most sensitive and most tolerant phenotypes within the population, respectively. Metabolic tolerance mechanisms were evaluated using acute toxicity testing, while target-site tolerance was assessed via in vitro acetylcholinesterase (AChE) assays. Acute toxicity tests were conducted using i) the toxic metabolite chlorpyrifos-oxon (CPF-oxon) and ii) CPF-oxon co-applied with piperonyl butoxide (PBO), a known Phase-I metabolic inhibitor. Both series of toxicity tests reduced the mean variation in sensitivity between tolerant and sensitive genotypes. Exposure to CPF-O reduced the disparity from a 4.7-fold to 1.6-fold difference in sensitivity. The addition of PBO further reduced the variation to a 1.2-fold difference in sensitivity. In vitro acetylcholinesterase assays yielded no significant differences in constitutive activity or target-site sensitivity. These findings suggest that pathways involving Phase-I detoxification and/or bioactivation of chlorpyrifos play a significant role in dictating the microevolutionary trajectories of tolerance in this population. Copyright © 2017 Elsevier B.V. All rights reserved.

A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae.

PubMed

Li, Ruiwen; Zhang, Ling; Shi, Qipeng; Guo, Yongyong; Zhang, Wei; Zhou, Bingsheng

2018-06-01

Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2-120 h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500 μg/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100 μg/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500 μg/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp, syn2a, and α1-tubulin) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0-500 μg/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1 nM) and inhibitor (chloroquine, CQ, 1 μM) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and а1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500 μg/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae. Copyright © 2018. Published by Elsevier B.V.

Developmental exposure to low concentrations of two brominated flame retardants, BDE-47 and BDE-99, causes life-long behavioral alterations in zebrafish.

PubMed

Glazer, Lilah; Wells, Corinne N; Drastal, Meghan; Odamah, Kathryn-Ann; Galat, Richard E; Behl, Mamta; Levin, Edward D

2018-05-01

Polybrominated diphenyl ethers (PBDEs) were widely used as flame retardants until the early 2000s, mainly in home furnishings and electronics. The persistence of PBDEs in the environment leads to continued ubiquitous exposure to low levels, with infants and children experiencing higher exposures than adults. Accumulating evidence suggest that low-level exposures during early life stages can affect brain development and lead to long-term behavioral impairments. We investigated the effects of zebrafish exposure to low doses of the two prominent PBDEs; 2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during embryo-development on short- and long-term behavioral endpoints. We included the organophosphate pesticide chlorpyrifos (CPF) due to its well documented neurotoxicity across species from zebrafish to humans. Zebrafish embryos were exposed to the following individual treatments; 0.1% DMSO (vehicle control); 0.3μM CPF; 0.01, 0.03, 0.1, 0.3μM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20μM BDE-99 from 5 until 120h post fertilization (hpf). Low exposure levels were determined as those not causing immediate overt toxicity, and behavior assays were conducted in the low-level range. At 144 hpf the larvae were tested for locomotor activity. At approximately 6 months of age adult zebrafish were tested in a behavioral battery including assays for anxiety-related behavior, sensorimotor response and habituation, social interaction, and predator avoidance. In the short-term, larval locomotor activity was reduced in larvae treated with 0.3μM CPF and 0.1μM BDE-47. BDE-99 treatment caused non-monotonic dose effects, with 0.3μM causing hyperactivity and 1μM or higher causing hypoactivity. In the long-term, adult anxiety-related behavior was reduced in all treatments as measured in both the novel tank dive test and tap test. We show that exposure of zebrafish embryos to low concentrations of the brominated flame retardants BDE-47 and BDE-99, and the organophosphate pesticide CPF, caused both short- and long-term behavioral impairments. Interestingly, we also found that at very low exposure concentrations, where there were no visible effects on larval activity, adult behavior was still strongly affected. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes of the serum antibiotic levels during open heart surgery (ceftazidim, ciprofloxacin, clindamycin).

PubMed

Lonský, V; Dominik, J; Mand'ák, J; Pozlerová, E; Hejzlar, M; Lonská, V; Marsíková, M; Kubícek, J; Snítilová, M

2000-01-01

Wound, mediastinal and intracardiac infections are still very serious complications of open-heart surgery. The incidence of it is still in the range of 0.4%-5%. The aims of our study were to assess the adequacy of regimen using ceftazidim (CTZ), ciprofloxacin (CPF) and clindamycin (CLIN) as prophylactic antibiotics and to verify whether cardiopulmonary bypass (CPB) can modify the time of antibiotic serum concentrations. That is why the serum levels of them were measured during open heart procedures. The prospective study comprised 75 consequent coronary patients randomized in to three groups receiving 1 g of CTZ or 400 mg of CPF or 900 mg of CLIN i.v. with anesthesia induction. Routine coronary surgery with left internal mammary artery harvesting, moderate body hypothermic (30 degrees C) CPB with crystaloid cardioplegia was performed. Serum antibiotic levels were determined before application, with skin incision, prior CPB induction, after cardioplegia infusion, every 20 minutes of CPB, prior end of CPB, in time of chest closure. Conventional cylinder-plate microbiological assay was used for antibiotic level measurement. All serum antibiotic concentrations showed a sharp decrease immediately after starting CPB and lasted until CPB ended. After initiating of CPB after cardioplegia administration serum concentrations of CTZ (105 min after initial dose) decreased by, on average 55%, CPF (97 min) by 42% and CLIN (116 min) by 78%. CPB can modify the time course of antibiotic serum concentrations. The serum levels of CTZ at the end of the longest procedures were found to be below the MICs for some of the suspected pathogens. We recommend to use higher antibiotic doses for prophylaxis and to administer the second dose with protamin sulphate to obtain maximum concentration in newly formed blood clots.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

PubMed

Na, Yong-Jin; Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Wang, Ji-Won; Jin, Jun-O; Kwak, Jong-Young; Lee, Kyu-Sup

2011-06-01

Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Voltage stability analysis in the new deregulated environment

NASA Astrophysics Data System (ADS)

Zhu, Tong

Nowadays, a significant portion of the power industry is under deregulation. Under this new circumstance, network security analysis is more critical and more difficult. One of the most important issues in network security analysis is voltage stability analysis. Due to the expected higher utilization of equipment induced by competition in a power market that covers bigger power systems, this issue is increasingly acute after deregulation. In this dissertation, some selected topics of voltage stability analysis are covered. In the first part, after a brief review of general concepts of continuation power flow (CPF), investigations on various matrix analysis techniques to improve the speed of CPF calculation for large systems are reported. Based on these improvements, a new CPF algorithm is proposed. This new method is then tested by an inter-area transaction in a large inter-connected power system. In the second part, the Arnoldi algorithm, the best method to find a few minimum singular values for a large sparse matrix, is introduced into the modal analysis for the first time. This new modal analysis is applied to the estimation of the point of voltage collapse and contingency evaluation in voltage security assessment. Simulations show that the new method is very efficient. In the third part, after transient voltage stability component models are investigated systematically, a novel system model for transient voltage stability analysis, which is a logical-algebraic-differential-difference equation (LADDE), is offered. As an example, TCSC (Thyristor controlled series capacitors) is addressed as a transient voltage stabilizing controller. After a TCSC transient voltage stability model is outlined, a new TCSC controller is proposed to enhance both fault related and load increasing related transient voltage stability. Its ability is proven by the simulation.

Effect of fibre additions to flatbread flour mixes on glucose kinetics: a randomised controlled trial.

PubMed

Boers, Hanny M; van Dijk, Theo H; Hiemstra, Harry; Hoogenraad, Anne-Roos; Mela, David J; Peters, Harry P F; Vonk, Roel J; Priebe, Marion G

2017-11-01

We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different 13C-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T 50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T 50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production.

Techniques for grid manipulation and adaptation. [computational fluid dynamics

NASA Technical Reports Server (NTRS)

Choo, Yung K.; Eisemann, Peter R.; Lee, Ki D.

1992-01-01

Two approaches have been taken to provide systematic grid manipulation for improved grid quality. One is the control point form (CPF) of algebraic grid generation. It provides explicit control of the physical grid shape and grid spacing through the movement of the control points. It works well in the interactive computer graphics environment and hence can be a good candidate for integration with other emerging technologies. The other approach is grid adaptation using a numerical mapping between the physical space and a parametric space. Grid adaptation is achieved by modifying the mapping functions through the effects of grid control sources. The adaptation process can be repeated in a cyclic manner if satisfactory results are not achieved after a single application.

BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.

PubMed

Yan, Winston X; Mirzazadeh, Reza; Garnerone, Silvano; Scott, David; Schneider, Martin W; Kallas, Tomasz; Custodio, Joaquin; Wernersson, Erik; Li, Yinqing; Gao, Linyi; Federova, Yana; Zetsche, Bernd; Zhang, Feng; Bienko, Magda; Crosetto, Nicola

2017-05-12

Precisely measuring the location and frequency of DNA double-strand breaks (DSBs) along the genome is instrumental to understanding genomic fragility, but current methods are limited in versatility, sensitivity or practicality. Here we present Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome-wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9 and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results establish BLISS as a versatile, sensitive and efficient method for genome-wide DSB mapping in many applications.

Stare and chase of space debris targets using real-time derived pointing data

NASA Astrophysics Data System (ADS)

Steindorfer, Michael A.; Kirchner, Georg; Koidl, Franz; Wang, Peiyuan; Antón, Alfredo; Fernández Sánchez, Jaime; Merz, Klaus

2017-09-01

We successfully demonstrate Stare & Chase: Space debris laser ranging to uncooperative targets has been achieved without a priori knowledge of any orbital information. An analog astronomy CCD with a standard objective, piggyback mounted on our 50 cm Graz SLR receive telescope, 'stares' into the sky in a fixed direction. The CCD records the stellar background within a field of view of approx. 7°. From the stellar X/Y positions on the sensor a plate solving algorithm determines the pointing data of the image center with an accuracy of approx. 15 arc seconds. If a sunlit target passes through this field of view, its equatorial coordinates are calculated, stored and a Consolidated Prediction Format (CPF) file is created in near real time. The derived CPF data is used to start laser ranging ('chase' the object) within the same pass to retrieve highly accurate distance information. A comparison of Stare & Chase CPFs with standard TLE predictions shows the possibilities and limits of this method.

Host-defense and trefoil factor family peptides in skin secretions of the Mawa clawed frog Xenopus boumbaensis (Pipidae).

PubMed

Conlon, J Michael; Mechkarska, Milena; Kolodziejek, Jolanta; Leprince, Jérôme; Coquet, Laurent; Jouenne, Thierry; Vaudry, Hubert; Nowotny, Norbert; King, Jay D

2015-10-01

Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation. Copyright © 2015 Elsevier Inc. All rights reserved.

Postural control in restless legs syndrome with medication intervention using pramipexole.

PubMed

Ahlgrén-Rimpiläinen, Aulikki; Lauerma, Hannu; Kähkönen, Seppo; Aalto, Heikki; Tuisku, Katinka; Holi, Matti; Pyykkö, Ilmari; Rimpiläinen, Ilpo

2014-02-01

Central dopamine regulation is involved in postural control and in the pathophysiology of restless legs syndrome (RLS) and Parkinson's disease (PD). Postural control abnormalities have been detected in PD, but there are no earlier studies with regard to RLS and postural control. Computerized force platform posturography was applied to measure the shift and the velocity (CPFV) of center point of forces (CPF) with eyes open (EO) and eyes closed (EC) in controls (n = 12) and prior and after a single day intervention with pramipexole in RLS subjects (n = 12). CPFV (EO) was significantly lower in the RLS group (p < 0.05) than in controls. After pramipexole intake, the difference disappeared and the subjective symptom severity diminished. Pramipexole did not significantly influence CPFV (EC) or CPF shift direction. Subjects with RLS used extensively visual mechanisms to control vestibule-spinal reflexes to improve or compensate the postural stability. Further research is needed to clarify altered feedback in the central nervous system and involvement of dopamine and vision in the postural control in RLS.

PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.

EPA Science Inventory

In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats.

PubMed

Alaa-Eldin, Eman Ahmad; El-Shafei, Dalia Abdallah; Abouhashem, Nehal S

2017-01-01

Commercial mixtures of chlorpyrifos and cypermethrin pesticides are widely used to enhance the toxic effects of cypermethrin on target insects. So, the purpose of the current study was to evaluate the individual and combined toxic effects of chlorpyrifos (CPF) and cypermethrin (CYP) on reproductive system of adult male albino rats. Forty adult male albino rats were randomized into main four groups: group I (control group) included 16 rats, subdivided into negative and positive control; group II (eight rats) received chlorpyrifos 6.75 mg/kg b.w./orally∕daily); group III (eight rats) (received cypermethrin 12.5 mg/kg b.w./orally∕daily); and group IV (eight rats) (received chlorpyrifos and cypermethrin at the same previously mentioned doses). All treatments were given by oral gavage for 12 weeks. We found that single CPF and CYP exposures significantly have adverse effects on reproductive function of adult male albino rats manifested by reduced testicular weight, decreased sperm count, motility and viability, significantly increased percent of morphologically abnormal spermatozoa, and significant increments in sperm DNA fragmentation index (DFI) with respect to control group. Furthermore, serum follicle stimulating hormone, luteinizing hormone, and testosterone levels were decreased significantly compared to control group. This was accompanied with histopathological changes in the testis of rats such as necrosis, degeneration, decreasing number of spermatogenic cells in some seminiferous tubules, edema, congested blood vessels, and exudate in interstitial tissue of the testis. Notably, all these changes were exaggerated in rats treated concomitantly with chlorpyrifos and cypermethrin rendering the mixture more toxic than the additive effects of each compound and causing greater damage on the reproductive system of male albino rats than the individual pesticides.

The Reliability of Using Urinary Biomarkers to Estimate Human Exposures to Chlorpyrifos and Diazinon

EPA Science Inventory

A few studies have reported concurrent levels of chlorpyrifos (CPF) and diazinon (DZN) and their environmentally occurring metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-6-methyl-4-pyrimidinol (IMP), in food and in environmental media. This information raises ques...

NEURODEVELOPMENTAL TOXICITY AND METABOLISM OF THE FLAME RETARDANT, TRIS (1,3-DICHLORO-2-PROPYL) PHOSPHATE

EPA Science Inventory

In the PC12 cell studies, it was found that exposure to an equimolar concentration of TDCPP resulted in deficits equivalent to or greater than that of CPF on measures of cellular replication and cell number, without affecting cell viability. TDCPP also altered the pattern o...

EXAMINATION OF THE EFFECTS OF CHLORPYRIFOS ON DEVELOPMENTAL PROCESSES: EVALUATION OF BIOCHEMICAL, MORPHOLOGICAL, AND BEHAVIORAL INDICES OF DEVELOPMENTAL NEUROTOXICITY.

EPA Science Inventory

Until recently, the organophosphate pesticide, chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] was one of the highest volume use pesticides in a non agricultural setting. The principal reason for restriction of use of this pesticide has been concern...

Authority Control for Creators in Italy: Theory and Practice

ERIC Educational Resources Information Center

Savoja, Maurizio; Vitali, Stefano

2007-01-01

The first part of the article illustrates the connections between the debate on "ISAAR(CPF)" and archival authority control and the discussions about the nature of archives and their relationships with their creators that have taken place within the Italian archival community during the twentieth century. The second part of the article…

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

CHARACTERIZATION OF THE IN VITRO KINETIC INTERACTION OF CHLORPYRIFOS-OXON WITH RAT SALIVARY CHOLINESTERASE: A POTENTIAL BIOMONITORING MATRIX. (R828608)

EPA Science Inventory

The primary mechanism of action for organophosphorus (OP) insecticides such as chlorpyrifos (CPF) involves the inhibition of acetylcholinesterase (AChE) by their active oxon metabolites resulting in a wide range of neurotoxic effects. These oxons also inhibit other cholinester...

Moving beyond the Name: Defining Corporate Entities to Support Provenance-Based Access

ERIC Educational Resources Information Center

Light, Michelle

2007-01-01

The second edition of the "International Standard Archival Authority Records for Corporate Bodies, Persons, and Families (ISAAR(CPF)2)" focuses on describing entities as they exist in reality, rather than on establishing authorized terms. This change allows authority records to include multiple authorized terms representing an entity as it changed…

Constructing a Cyber Preparedness Framework (CPF): The Lockheed Martin Case Study

ERIC Educational Resources Information Center

Beyer, Dawn M.

2014-01-01

The protection of sensitive data and technologies is critical in preserving United States (U.S.) national security and minimizing economic losses. However, during a cyber attack, the operational capability to constrain the exfiltrations of sensitive data and technologies may not be available. A cyber preparedness methodology (CPM) can improve…

NEUROBEHAVIORAL EVALUATION OF RATS EXPOSED TO CHLORPYRIFOS VIA CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos (CPF), and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350g body wei...

Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae

PubMed Central

Conlon, J. Michael; Mechkarska, Milena

2014-01-01

Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored. PMID:24434793

Safety Assessment of Bacillus thuringiensis Insecticidal Proteins Cry1C and Cry2A with a Zebrafish Embryotoxicity Test.

PubMed

Gao, Yan-Jie; Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Peng, Yu-Fa; Chen, Xiu-Ping

2018-05-02

As a result of the large-scale planting of transgenic Bacillus thuringiensis (Bt) crops, fish would be exposed to freely soluble Bt insecticidal protein(s) that are released from Bt crop tissues into adjacent bodies of water or by way of direct feeding on deposited plant material. To assess the safety of two Bt proteins Cry1C and Cry2A to fish, we used zebrafish as a representative species and exposed their embryos to 0.1, 1, and 10 mg/L of the two Cry proteins until 132 h post-fertilization and then several developmental, biochemical, and molecular parameters were evaluated. Chlorpyrifos (CPF), a known toxicant to aquatic organisms, was used as a positive control. Although CPF exposure resulted in significant developmental, biochemical, and molecular changes in the zebrafish embryos, there were almost no significant differences after Cry1C or Cry2A exposure. Thus, we conclude that zebrafish embryos are not sensitive to Cry1C and Cry2A insecticidal proteins at test concentrations.

Application of meteorology-based methods to determine local and external contributions to particulate matter pollution: A case study in Venice (Italy)

NASA Astrophysics Data System (ADS)

Squizzato, Stefania; Masiol, Mauro

2015-10-01

The air quality is influenced by the potential effects of meteorology at meso- and synoptic scales. While local weather and mixing layer dynamics mainly drive the dispersion of sources at small scales, long-range transports affect the movements of air masses over regional, transboundary and even continental scales. Long-range transport may advect polluted air masses from hot-spots by increasing the levels of pollution at nearby or remote locations or may further raise air pollution levels where external air masses originate from other hot-spots. Therefore, the knowledge of ground-wind circulation and potential long-range transports is fundamental not only to evaluate how local or external sources may affect the air quality at a receptor site but also to quantify it. This review is focussed on establishing the relationships among PM2.5 sources, meteorological condition and air mass origin in the Po Valley, which is one of the most polluted areas in Europe. We have chosen the results from a recent study carried out in Venice (Eastern Po Valley) and have analysed them using different statistical approaches to understand the influence of external and local contribution of PM2.5 sources. External contributions were evaluated by applying Trajectory Statistical Methods (TSMs) based on back-trajectory analysis including (i) back-trajectories cluster analysis, (ii) potential source contribution function (PSCF) and (iii) concentration weighted trajectory (CWT). Furthermore, the relationships between the source contributions and ground-wind circulation patterns were investigated by using (iv) cluster analysis on wind data and (v) conditional probability function (CPF). Finally, local source contribution have been estimated by applying the Lenschow' approach. In summary, the integrated approach of different techniques has successfully identified both local and external sources of particulate matter pollution in a European hot-spot affected by the worst air quality.

Exposure to β-lactams results in the alteration of penicillin-binding proteins in Clostridium perfringens.

PubMed

Park, Miseon; Rafii, Fatemeh

2017-06-01

Clostridium perfringens causes a variety of mild to severe infections in humans and other animals. A decrease in the affinity of penicillin-binding protein (PBP) transpeptidases for β-lactams is considered one of the mechanisms of β-lactam resistance in bacteria. Two strains of C. perfringens isolated from bovines and one isolated from a chicken, which had decreased susceptibility to β-lactams, had variations in the amino acid sequences of the central penicillin-binding regions of the PBPs. β-Lactam-resistant mutants of another C. perfringens strain, ATCC 13124, were selected in vitro to determine the effects of exposure to β-lactams on the PBP genes. Cultures of the wild type rapidly developed resistance to penicillin G, cephalothin and ceftriaxone. The susceptibilities of all of the selected mutants to some other β-lactams also decreased. The largest PBP found in C. perfringens, CPF_2395, appeared to be the primary target of all three drugs. Strain resistant to penicillin G had mutation resulting in the substitution of one amino acid within the central penicillin-binding/transpeptidase domain, but the ceftrioxane and cephalothin-resistant strains had mutations resulting in the substitution of two amino acids in this region. The cephalothin-resistant mutant also had additional mutations in the CPF_0340 and CPF_2218 genes in this critical region. No other mutations were observed in the three other PBPs of the in vitro resistant mutants. Resistance development also altered the growth rate and cell morphology of the mutants, so in addition to the PBPs, some other genes, including regulatory genes, may have been affected during the interaction with β-lactam antibiotics. This is the first study showing the effects of β-lactam drugs on the substitution of amino acids in PBPs of C. perfringens and points to the need for studies to detect other unknown alterations affecting the physiology of resistant strains. Published by Elsevier Ltd.

Effects of 17β-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.

PubMed

Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Kim, Hwi-Gon; Na, Young-Jin; Kwak, Jong-Young; Lee, Kyu-Sup

2012-03-01

Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17β-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways. Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins. E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes. The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Development of multi-functional streetscape green infrastructure using a performance index approach.

PubMed

Tiwary, A; Williams, I D; Heidrich, O; Namdeo, A; Bandaru, V; Calfapietra, C

2016-01-01

This paper presents a performance evaluation framework for streetscape vegetation. A performance index (PI) is conceived using the following seven traits, specific to the street environments - Pollution Flux Potential (PFP), Carbon Sequestration Potential (CSP), Thermal Comfort Potential (TCP), Noise Attenuation Potential (NAP), Biomass Energy Potential (BEP), Environmental Stress Tolerance (EST) and Crown Projection Factor (CPF). Its application is demonstrated through a case study using fifteen street vegetation species from the UK, utilising a combination of direct field measurements and inventoried literature data. Our results indicate greater preference to small-to-medium size trees and evergreen shrubs over larger trees for streetscaping. The proposed PI approach can be potentially applied two-fold: one, for evaluation of the performance of the existing street vegetation, facilitating the prospects for further improving them through management strategies and better species selection; two, for planning new streetscapes and multi-functional biomass as part of extending the green urban infrastructure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment outcomes of ligature-induced recession in the dog model using guided tissue regeneration or coronally positioned flap procedures.

PubMed

Papageorgiou, Athanasios; Vouros, Ioannis; Konstantinidis, Antonios

2009-04-01

The aims of the study were: (1) to determine the quality of the hard and soft tissues formed in segments treated with coronally positioned flaps alone (CPF group) or combined with a polylactic acid resorbable membrane (guided tissue regeneration--GTR group) in wide type defects (canine teeth), and (2) to evaluate the behaviour of the newly regenerated tissues to an experimentally induced inflammation initiated by microbial plaque at the submarginal level in recession type defects (premolar teeth). The randomized block design was used in the study, with each dog receiving both treatments (GTR and CPF). Gingival recession defects were surgically created in the 2nd and 4th mandibular premolars and, after 10 weeks, also in the maxillary canines of three dogs. The defects in the premolar area were created earlier than the defects in the canine teeth so that both areas would be ready for biopsy at the same time. Two months after the creation of the defects the exposed roots in the control group of teeth were surgically covered with coronally positioned flaps only (CPF group), and in the test group of teeth a coronally positioned flap was used in combination with a resorbable membrane (GTR group). In the premolar teeth only, after a healing period of five months, cotton ligatures were placed intrasulcularly and these areas were left without plaque control for 10 weeks. Following this, biopsies were taken from the canines and the premolars in order to examine (1) the quality of the hard and soft tissues formed after five months of healing in the canine teeth and (2) the response of the newly formed tissues to microbial accumulation induced by the subgingival ligature placement. In the wide defects of the canine teeth, the use of the membrane produced a mean new attachment formation of 44%, while the repositioned flap technique produced 22% new attachment. The regeneration of bone was limited to the apical area for both techniques and amounted to 15% and 10%, respectively. In the narrow defects of the premolars both techniques produced comparable mean root coverage percentages. The inflammatory conditions created in the study led to a comparable loss of mean clinical attachment and an increase in tissue recession and the extent of the inflammatory process for both groups. The use of resorbable membranes for the treatment of wide recession type defects in the canine teeth (GTR group) produced significantly better clinical results, with higher mean root coverage and increased regenerative capacity of the periodontal tissues, compared with the coronally positioned flap technique (CPF group). Additionally, the regenerated tissues created after the use of both techniques in narrow recession defects (premolar teeth) demonstrated comparable resistance to the microbial accumulation conditions created.

75 FR 34200 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System Pursuant to... of the signal, as detailed below. Docket Number: FRA-2010-0084. Applicant: Pan Am Railways, Mr... CPF-428, all associated appliances, and the installation of an automatic block signal at mile 428.27...

Airborne black carbon concentrations over an urban region in western India-temporal variability, effects of meteorology, and source regions.

PubMed

Bapna, Mukund; Sunder Raman, Ramya; Ramachandran, S; Rajesh, T A

2013-03-01

This study characterizes over 5 years of high time resolution (5 min), airborne black carbon (BC) concentrations (July 2003 to December 2008) measured over Ahmedabad, an urban region in western India. The data were used to obtain different time averages of BC concentrations, and these averages were then used to assess the diurnal, seasonal, and annual variability of BC over the study region. Assessment of diurnal variations revealed a strong association between BC concentrations and vehicular traffic. Peaks in BC concentration were co-incident with the morning (0730 to 0830, LST) and late evening (1930 to 2030, LST) rush hour traffic. Additionally, diurnal variability in BC concentrations during major festivals (Diwali and Dushera during the months of October/November) revealed an increase in BC concentrations due to fireworks displays. Maximum half hourly BC concentrations during the festival days were as high as 79.8 μg m(-3). However, the high concentrations rapidly decayed suggesting that local meteorology during the festive season was favorable for aerosol dispersion. A multiple linear regression (MLR) model with BC as the dependent variable and meteorological parameters as independent variables was fitted. The variability in temperature, humidity, wind speed, and wind direction accounted for about 49% of the variability in measured BC concentrations. Conditional probability function (CPF) analysis was used to identify the geographical location of local source regions contributing to the effective BC measured (at 880 nm) at the receptor site. The east north-east (ENE) direction to the receptor was identified as a major source region. National highway (NH8) and two coal-fired thermal power stations (at Gandhinagar and Sabarmati) were located in the identified direction, suggesting that local traffic and power plant emissions were likely contributors to the measured BC.

Sources and geographical origins of fine aerosols in Paris (France)

NASA Astrophysics Data System (ADS)

Bressi, M.; Sciare, J.; Ghersi, V.; Mihalopoulos, N.; Petit, J.-E.; Nicolas, J. B.; Moukhtar, S.; Rosso, A.; Féron, A.; Bonnaire, N.; Poulakis, E.; Theodosi, C.

2013-12-01

The present study aims at identifying and apportioning the major sources of fine aerosols in Paris (France) - the second largest megacity in Europe -, and determining their geographical origins. It is based on the daily chemical composition of PM2.5 characterised during one year at an urban background site of Paris (Bressi et al., 2013). Positive Matrix Factorization (EPA PMF3.0) was used to identify and apportion the sources of fine aerosols; bootstrapping was performed to determine the adequate number of PMF factors, and statistics (root mean square error, coefficient of determination, etc.) were examined to better model PM2.5 mass and chemical components. Potential Source Contribution Function (PSCF) and Conditional Probability Function (CPF) allowed the geographical origins of the sources to be assessed; special attention was paid to implement suitable weighting functions. Seven factors named ammonium sulfate (A.S.) rich factor, ammonium nitrate (A.N.) rich factor, heavy oil combustion, road traffic, biomass burning, marine aerosols and metals industry were identified; a detailed discussion of their chemical characteristics is reported. They respectively contribute 27, 24, 17, 14, 12, 6 and 1% of PM2.5 mass (14.7 μg m-3) on the annual average; their seasonal variability is discussed. The A.S. and A.N. rich factors have undergone north-eastward mid- or long-range transport from Continental Europe, heavy oil combustion mainly stems from northern France and the English Channel, whereas road traffic and biomass burning are primarily locally emitted. Therefore, on average more than half of PM2.5 mass measured in the city of Paris is due to mid- or long-range transport of secondary aerosols stemming from continental Europe, whereas local sources only contribute a quarter of the annual averaged mass. These results imply that fine aerosols abatement policies conducted at the local scale may not be sufficient to notably reduce PM2.5 levels at urban background sites in Paris, suggesting instead more coordinated strategies amongst neighbouring countries. Similar conclusions might be drawn in other continental urban background sites given the transboundary nature of PM2.5 pollution.

Sources and geographical origins of fine aerosols in Paris (France)

NASA Astrophysics Data System (ADS)

Bressi, M.; Sciare, J.; Ghersi, V.; Mihalopoulos, N.; Petit, J.-E.; Nicolas, J. B.; Moukhtar, S.; Rosso, A.; Féron, A.; Bonnaire, N.; Poulakis, E.; Theodosi, C.

2014-08-01

The present study aims at identifying and apportioning fine aerosols to their major sources in Paris (France) - the second most populated "larger urban zone" in Europe - and determining their geographical origins. It is based on the daily chemical composition of PM2.5 examined over 1 year at an urban background site of Paris (Bressi et al., 2013). Positive matrix factorization (EPA PMF3.0) was used to identify and apportion fine aerosols to their sources; bootstrapping was performed to determine the adequate number of PMF factors, and statistics (root mean square error, coefficient of determination, etc.) were examined to better model PM2.5 mass and chemical components. Potential source contribution function (PSCF) and conditional probability function (CPF) allowed the geographical origins of the sources to be assessed; special attention was paid to implement suitable weighting functions. Seven factors, namely ammonium sulfate (A.S.)-rich factor, ammonium nitrate (A.N.)-rich factor, heavy oil combustion, road traffic, biomass burning, marine aerosols and metal industry, were identified; a detailed discussion of their chemical characteristics is reported. They contribute 27, 24, 17, 14, 12, 6 and 1% of PM2.5 mass (14.7 μg m-3) respectively on the annual average; their seasonal variability is discussed. The A.S.- and A.N.-rich factors have undergone mid- or long-range transport from continental Europe; heavy oil combustion mainly stems from northern France and the English Channel, whereas road traffic and biomass burning are primarily locally emitted. Therefore, on average more than half of PM2.5 mass measured in the city of Paris is due to mid- or long-range transport of secondary aerosols stemming from continental Europe, whereas local sources only contribute a quarter of the annual averaged mass. These results imply that fine-aerosol abatement policies conducted at the local scale may not be sufficient to notably reduce PM2.5 levels at urban background sites in Paris, suggesting instead more coordinated strategies amongst neighbouring countries. Similar conclusions might be drawn in other continental urban background sites given the transboundary nature of PM2.5 pollution.

TESTING FOR DEPARTURES FROM ADDITIVITY FOR A 2:1 MIXTURE OF CHLORPYRIFOS AND CARBARYL ON CHOLINESTERASE ACTIVITY IN BRAIN, PLASMA, AND RED BLOOD CELLS OF LONG EVANS RATS.

EPA Science Inventory

Detecting and characterizing interactions among chemicals is an important environmental issue. This study was conducted to test for the existence of a significant departure from additivity for a mixture of two cholinesterase (ChE)-inhibiting pesticides: chlorpyrifos (CPF), an org...

Telomere Chromatin Condensation Assay (TCCA): a novel approach to study structural telomere integrity.

PubMed

Gonzalez-Vasconcellos, Iria; Alonso-Rodríguez, Silvia; López-Baltar, Isidoro; Fernández, José Luis

2015-01-01

Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes are essential for genome stability. Improper higher-order chromatin organization at the chromosome ends can give rise to telomeric recombination and genomic instability. We report the development of an assay to quantify differences in the condensation of telomeric chromatin, thereby offering new opportunities to study telomere biology and stability. We have combined a DNA nuclease digestion with a quantitative PCR (qPCR) assay of telomeric DNA, which we term the Telomere Chromatin Condensation Assay (TCCA). By quantifying the relative quantities of telomeric DNA that are progressively digested with the exonuclease Bal 31 the method can discriminate between different levels of telomeric chromatin condensation. The structural chromatin packaging at telomeres shielded against exonuclease digestion delivered an estimate, which we term Chromatin Protection Factor (CPF) that ranged from 1.7 to 2.3 fold greater than that present in unpacked DNA. The CPF was significantly decreased when cell cultures were incubated with the DNA hypomethylating agent 5-azacytidine, demonstrating the ability of the TCCA assay to discriminate between packaging levels of telomeric DNA. Copyright © 2014 Elsevier B.V. All rights reserved.

Atomic absorption spectroscopic, conductometric and colorimetric methods for determination of fluoroquinolone antibiotics using ammonium reineckate ion-pair complex formation

NASA Astrophysics Data System (ADS)

Ragab, Gamal H.; Amin, Alaa S.

2004-03-01

Three accurate, rapid and simple atomic absorption spectrometric, conductometric and colorimetric methods were developed for the determination of norfloxacin (NRF), ciprofloxacin (CIP), ofloxacin (OFL) and enrofloxacin (ENF). The proposed methods depend upon the reaction of ammonium reineckate with the studied drugs to form stable precipitate of ion-pair complexes, which was dissolved in acetone. The pink coloured complexes were determined either by AAS or colorimetrically at λmax 525 nm directly using the dissolved complex. Using conductometric titration, the studied drugs could be evaluated in 50% (v/v) acetone in the range 5.0-65, 4.0-48, 5.0-56 and 6.0-72 μg ml -1 of NRF, CPF, OFL and ENF, respectively. The optimizations of various experimental conditions were described. The results obtained showed good recoveries of 99.15±1.15, 99.30±1.40, 99.60±1.50, and 99.00±1.25% with relative standard deviations of 0.81, 1.06, 0.97, and 0.69% for NRF, CPF, OFL, and ENF, respectively. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented.

Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

DTIC Science & Technology

2014-10-01

between blood cholinesterase activity and neurobehavioral deficits (Rohlman et al., 2011). Finally, one additional argument against the premise that AChE...baseline scan (repeated exposure CPF group only). 2.4 Cholinesterase activity Cholinesterase activity was assessed in brain using the method of...Moser VC.2006. Behavioral toxicity of cholinesterase inhibitors. In: Gupta, RC., editor. Toxicology of Organophosphate and Carbamate Compounds

Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

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

Sindi, Ramya A., E-mail: ramya.sindi2010@my.ntu.ac

Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length ofmore » axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with hyperphosphorylation of neurofilament heavy chain (NFH). • Subsequent NFH dephosphorylation was associated with increased phosphatase activity. • Thus, the above changes reflect key events in chlorpyrifos induced neurodegeneration.« less

Isolation and antisense suppression of flavonoid 3', 5'-hydroxylase modifies flower pigments and colour in cyclamen.

PubMed

Boase, Murray R; Lewis, David H; Davies, Kevin M; Marshall, Gayle B; Patel, Deepa; Schwinn, Kathy E; Deroles, Simon C

2010-06-13

Cyclamen is a popular and economically significant pot plant crop in several countries. Molecular breeding technologies provide opportunities to metabolically engineer the well-characterized flavonoid biosynthetic pathway for altered anthocyanin profile and hence the colour of the flower. Previously we reported on a genetic transformation system for cyclamen. Our aim in this study was to change pigment profiles and flower colours in cyclamen through the suppression of flavonoid 3', 5'-hydroxylase, an enzyme in the flavonoid pathway that plays a determining role in the colour of anthocyanin pigments. A full-length cDNA putatively identified as a F3'5'H (CpF3'5'H) was isolated from cyclamen flower tissue. Amino acid and phylogeny analyses indicated the CpF3'5'H encodes a F3'5'H enzyme. Two cultivars of minicyclamen were transformed via Agrobacterium tumefaciens with an antisense CpF3'5'H construct. Flowers of the transgenic lines showed modified colour and this correlated positively with the loss of endogenous F3'5'H transcript. Changes in observed colour were confirmed by colorimeter measurements, with an overall loss in intensity of colour (C) in the transgenic lines and a shift in hue from purple to red/pink in one cultivar. HPLC analysis showed that delphinidin-derived pigment levels were reduced in transgenic lines relative to control lines while the percentage of cyanidin-derived pigments increased. Total anthocyanin concentration was reduced up to 80% in some transgenic lines and a smaller increase in flavonol concentration was recorded. Differences were also seen in the ratio of flavonol types that accumulated. To our knowledge this is the first report of genetic modification of the anthocyanin pathway in the commercially important species cyclamen. The effects of suppressing a key enzyme, F3'5'H, were wide ranging, extending from anthocyanins to other branches of the flavonoid pathway. The results illustrate the complexity involved in modifying a biosynthetic pathway with multiple branch points to different end products and provides important information for future flower colour modification experiments in cyclamen.

Isolation and antisense suppression of flavonoid 3', 5'-hydroxylase modifies flower pigments and colour in cyclamen

PubMed Central

2010-01-01

Background Cyclamen is a popular and economically significant pot plant crop in several countries. Molecular breeding technologies provide opportunities to metabolically engineer the well-characterized flavonoid biosynthetic pathway for altered anthocyanin profile and hence the colour of the flower. Previously we reported on a genetic transformation system for cyclamen. Our aim in this study was to change pigment profiles and flower colours in cyclamen through the suppression of flavonoid 3', 5'-hydroxylase, an enzyme in the flavonoid pathway that plays a determining role in the colour of anthocyanin pigments. Results A full-length cDNA putatively identified as a F3'5'H (CpF3'5'H) was isolated from cyclamen flower tissue. Amino acid and phylogeny analyses indicated the CpF3'5'H encodes a F3'5'H enzyme. Two cultivars of minicyclamen were transformed via Agrobacterium tumefaciens with an antisense CpF3'5'H construct. Flowers of the transgenic lines showed modified colour and this correlated positively with the loss of endogenous F3'5'H transcript. Changes in observed colour were confirmed by colorimeter measurements, with an overall loss in intensity of colour (C) in the transgenic lines and a shift in hue from purple to red/pink in one cultivar. HPLC analysis showed that delphinidin-derived pigment levels were reduced in transgenic lines relative to control lines while the percentage of cyanidin-derived pigments increased. Total anthocyanin concentration was reduced up to 80% in some transgenic lines and a smaller increase in flavonol concentration was recorded. Differences were also seen in the ratio of flavonol types that accumulated. Conclusion To our knowledge this is the first report of genetic modification of the anthocyanin pathway in the commercially important species cyclamen. The effects of suppressing a key enzyme, F3'5'H, were wide ranging, extending from anthocyanins to other branches of the flavonoid pathway. The results illustrate the complexity involved in modifying a biosynthetic pathway with multiple branch points to different end products and provides important information for future flower colour modification experiments in cyclamen. PMID:20540805

Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection.

PubMed

East-Seletsky, Alexandra; O'Connell, Mitchell R; Knight, Spencer C; Burstein, David; Cate, Jamie H D; Tjian, Robert; Doudna, Jennifer A

2016-10-13

Bacterial adaptive immune systems use CRISPRs (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage. Although most prokaryotic adaptive immune systems generally target DNA substrates, type III and VI CRISPR systems direct interference complexes against single-stranded RNA substrates. In type VI systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease (RNase). How this enzyme acquires mature CRISPR RNAs (crRNAs) that are essential for immune surveillance and how it carries out crRNA-mediated RNA cleavage remain unclear. Here we show that bacterial C2c2 possesses a unique RNase activity responsible for CRISPR RNA maturation that is distinct from its RNA-activated single-stranded RNA degradation activity. These dual RNase functions are chemically and mechanistically different from each other and from the crRNA-processing behaviour of the evolutionarily unrelated CRISPR enzyme Cpf1 (ref. 11). The two RNase activities of C2c2 enable multiplexed processing and loading of guide RNAs that in turn allow sensitive detection of cellular transcripts.

Peptidomic analysis of the extensive array of host-defense peptides in skin secretions of the dodecaploid frog Xenopus ruwenzoriensis (Pipidae).

PubMed

Coquet, Laurent; Kolodziejek, Jolanta; Jouenne, Thierry; Nowotny, Norbert; King, Jay D; Conlon, J Michael

2016-09-01

The Uganda clawed frog Xenopus ruwenzoriensis with a karyotype of 2n=108 is one of the very few vertebrates with dodecaploid status. Peptidomic analysis of norepinephrine-stimulated skin secretions from this species led to the isolation and structural characterization of 23 host-defense peptides belonging to the following families: magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 6 peptides), xenopsin precursor fragment (XPF; 3 peptides), caerulein precursor fragment (CPF; 8 peptides), and caerulein precursor fragment-related peptide (CPF-RP; 3 peptides). In addition, the secretions contained caerulein, identical to the peptide from Xenopus laevis, and two peptides that were identified as members of the trefoil factor family (TFF). The data indicate that silencing of the host-defense peptide genes following polyploidization has been appreciable and non-uniform. Consistent with data derived from comparison of nucleotide sequences of mitochrondrial and nuclear genes, cladistic analyses based upon the primary structures of the host-defense peptides provide support for an evolutionary scenario in which X. ruwenzoriensis arose from an allopolyploidization event involving an octoploid ancestor of the present-day frogs belonging to the Xenopus amieti species group and a tetraploid ancestor of Xenopus pygmaeus. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of reaction solvent on hydroxyapatite synthesis in sol-gel process

NASA Astrophysics Data System (ADS)

Nazeer, Muhammad Anwaar; Yilgor, Emel; Yagci, Mustafa Baris; Unal, Ugur; Yilgor, Iskender

2017-12-01

Synthesis of hydroxyapatite (HA) through sol-gel process in different solvent systems is reported. Calcium nitrate tetrahydrate (CNTH) and diammonium hydrogen phosphate (DAHP) were used as calcium and phosphorus precursors, respectively. Three different synthesis reactions were carried out by changing the solvent media, while keeping all other process parameters constant. A measure of 0.5 M aqueous DAHP solution was used in all reactions while CNTH was dissolved in distilled water, tetrahydrofuran (THF) and N,N-dimethylformamide (DMF) at a concentration of 0.5 M. Ammonia solution (28-30%) was used to maintain the pH of the reaction mixtures in the 10-12 range. All reactions were carried out at 40 ± 2°C for 4 h. Upon completion of the reactions, products were filtered, washed and calcined at 500°C for 2 h. It was clearly demonstrated through various techniques that the dielectric constant and polarity of the solvent mixture strongly influence the chemical structure and morphological properties of calcium phosphate synthesized. Water-based reaction medium, with highest dielectric constant, mainly produced β-calcium pyrophosphate (β-CPF) with a minor amount of HA. DMF/water system yielded HA as the major phase with a very minor amount of β-CPF. THF/water solvent system with the lowest dielectric constant resulted in the formation of pure HA.

The Impact of Fe-Ti Oxide Concentration on the Structural Rigidity of the Lower Oceanic Crust, Atlantis Bank, Southwest Indian Ridge

NASA Astrophysics Data System (ADS)

Deans, J. R.; Winkler, D. A.

2017-12-01

Fe-Ti oxides are important components of oceanic core complexes (OCC) formed at slow-spreading ridges, since Fe-Ti oxide phases form throughout the crustal column and are weaker than silicate phases. This study investigated the predicted relationship between the presence and concentration of Fe-Ti oxides and the presence/intensity of crystal-plastic deformation in samples from Atlantis Bank, Southwest Indian Ridge (SWIR). Atlantis Bank is an OCC that formed through the exhumation of lower oceanic crust along a detachment shear zone/fault. OCCs form along slow-spreading ridges and are characterized by the complex interactions between magmatism and crustal extension, thus, making them more susceptible to crystal-plastic deformation at higher temperatures and for weaker phases like Fe-Ti oxides to preferentially partition strain. Atlantis Bank has been the focus of many scientific expeditions to various sites including; Ocean Drilling Program (ODP) Holes 735B and 1105A, and the International Oceanic Discovery Program (IODP) Hole U1473A. A total of 589 thin sections from all three holes were analyzed using the software package Fiji to calculate the Fe-Ti oxide concentration within the thin sections. The Fe-Ti oxide percentage was correlated with the crystal-plastic fabric (CPF) intensity, from 0-5 (no foliation - ultramylonite), for each thin section using the statistical software R. All three holes show a positive correlation between the abundance of Fe-Ti oxides and the CPF intensity. Specifically, 76.3% of samples with a concentration of 5% or more Fe-Ti oxides have a corresponding CPF intensity value of 2 or more (porphyroclastic foliation - ultramylonitic). The positive correlation may be explained by the Fe-Ti oxides preferentially partitioning strain, especially at temperatures below where dry plagioclase can recrystallize. This allows for a mechanism of continued slip along the shear zone or form new shear zones at amphibolite grade conditions while the lower crust is being exhumed. Additionally, IODP U1473A and ODP 1105A had similar correlation values of 0.11 (on a scale of -1 to 1), whereas ODP Hole 735B had double the correlation value of 0.24. Since ODP Hole 735B has older rocks than the other two holes, it may have recorded more deformation comparatively speaking.

Exploiting endogenous CRISPR-Cas system for multiplex genome editing in Clostridium tyrobutyricum and engineer the strain for high-level butanol production.

PubMed

Zhang, Jie; Zong, Wenming; Hong, Wei; Zhang, Zhong-Tian; Wang, Yi

2018-03-09

Although CRISPR-Cas9/Cpf1 have been employed as powerful genome engineering tools, heterologous CRISPR-Cas9/Cpf1 are often difficult to introduce into bacteria and archaea due to their severe toxicity. Since most prokaryotes harbor native CRISPR-Cas systems, genome engineering can be achieved by harnessing these endogenous immune systems. Here, we report the exploitation of Type I-B CRISPR-Cas of Clostridium tyrobutyricum for genome engineering. In silico CRISPR array analysis and plasmid interference assay revealed that TCA or TCG at the 5'-end of the protospacer was the functional protospacer adjacent motif (PAM) for CRISPR targeting. With a lactose inducible promoter for CRISPR array expression, we significantly decreased the toxicity of CRISPR-Cas and enhanced the transformation efficiency, and successfully deleted spo0A with an editing efficiency of 100%. We further evaluated effects of the spacer length on genome editing efficiency. Interestingly, spacers ≤ 20 nt led to unsuccessful transformation consistently, likely due to severe off-target effects; while a spacer of 30-38 nt is most appropriate to ensure successful transformation and high genome editing efficiency. Moreover, multiplex genome editing for the deletion of spo0A and pyrF was achieved in a single transformation, with an editing efficiency of up to 100%. Finally, with the integration of the alcohol dehydrogenase gene (adhE1 or adhE2) to replace cat1 (the key gene responsible for butyrate production and previously could not be deleted), two mutants were created for n-butanol production, with the butanol titer reached historically record high of 26.2 g/L in a batch fermentation. Altogether, our results demonstrated the easy programmability and high efficiency of endogenous CRISPR-Cas. The developed protocol herein has a broader applicability to other prokaryotes containing endogenous CRISPR-Cas systems. C. tyrobutyricum could be employed as an excellent platform to be engineered for biofuel and biochemical production using the CRISPR-Cas based genome engineering toolkit. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

High-resolution sampling and analysis of ambient particulate matter in the Pearl River Delta region of southern China: source apportionment and health risk implications

NASA Astrophysics Data System (ADS)

Zhou, Shengzhen; Davy, Perry K.; Huang, Minjuan; Duan, Jingbo; Wang, Xuemei; Fan, Qi; Chang, Ming; Liu, Yiming; Chen, Weihua; Xie, Shanju; Ancelet, Travis; Trompetter, William J.

2018-02-01

Hazardous air pollutants, such as trace elements in particulate matter (PM), are known or highly suspected to cause detrimental effects on human health. To understand the sources and associated risks of PM to human health, hourly time-integrated major trace elements in size-segregated coarse (PM2.5-10) and fine (PM2.5) particulate matter were collected at the industrial city of Foshan in the Pearl River Delta region, China. Receptor modeling of the data set by positive matrix factorization (PMF) was used to identify six sources contributing to PM2.5 and PM10 concentrations at the site. Dominant sources included industrial coal combustion, secondary inorganic aerosol, motor vehicles and construction dust along with two intermittent sources (biomass combustion and marine aerosol). The biomass combustion source was found to be a significant contributor to peak PM2.5 episodes along with motor vehicles and industrial coal combustion. Conditional probability function (CPF) analysis was applied to estimate the source locations using the PMF-resolved source contribution coupled with the surface wind direction data. Health exposure risk of hazardous trace elements (Pb, As, Si, Cr, Mn and Ni) and source-specific values were estimated. The total hazard quotient (HQ) of PM2.5 was 2.09, higher than the acceptable limit (HQ = 1). The total carcinogenic risk (CR) was 3.37 × 10-3 for PM2.5, which was 3 times higher than the least stringent limit (1.0 × 10-4). Among the selected trace elements, As and Pb posed the highest non-carcinogenic and carcinogenic risks to human health, respectively. In addition, our results show that the industrial coal combustion source is the dominant non-carcinogenic and carcinogenic risk contributor, highlighting the need for stringent control of this source. This study provides new insight for policy makers to prioritize sources in air quality management and health risk reduction.

Wet deposition and sources of inorganic nitrogen in the Three Gorges Reservoir Region, China.

PubMed

Wang, Huanbo; Shi, Guangming; Tian, Mi; Chen, Yang; Qiao, Baoqing; Zhang, Liuyi; Yang, Fumo; Zhang, Leiming; Luo, Qiong

2018-02-01

Precipitation samples were collected at five rural and one urban sites in the Three Gorges Reservoir Region (TGR), China from March 2014 to February 2016. The inorganic reactive nitrogen (Nr) contents were analysed to investigate their wet deposition flux, budget, and sources in the area. Annual Nr wet deposition varied from 7.1 to 23.4 kg N ha -1 yr -1 over the six sites during the two-year study campaign. The six-site average Nr wet deposition flux was 17.1 and 11.7 kg N ha -1 yr -1 in 2014 and 2015, respectively, with 71% from NH 4 + and 29% from NO 3 - . Dry deposition flux was estimated using the inferential method, which combined the measured ambient concentrations and modelled dry deposition velocities. The total (dry + wet) Nr deposition fluxes were estimated to be 21.4 kg N ha -1 yr -1 in 2014 and 16.0 kg N ha -1 yr -1 in 2015 at rural sites, and 31.4 and 25.3 kg N ha -1 yr -1 at the urban site. Annual average volume weighted mean (VWM) concentrations in precipitation at all the six sites differed little for NO 3 - but up to a factor of 2.0 for NH 4 + with the highest value at the urban site. Industrial emissions, agricultural emissions, soil dust, and biomass burning were identified as potential sources of the major inorganic ions in precipitation using factor analysis and correlation analysis. Conditional probability function (CPF) analysis indicated that the urban site was predominantly affected by industrial emissions from a power plant, cement manufactory, and salt chemical facility located ∼13 km southeast of the sampling site. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Two Distinct RNase Activities of CRISPR-C2c2 Enable Guide RNA Processing and RNA Detection

PubMed Central

East-Seletsky, Alexandra; O’Connell, Mitchell R.; Knight, Spencer C.; Burstein, David; Cate, Jamie H. D.; Tjian, Robert; Doudna, Jennifer A.

2017-01-01

Bacterial adaptive immune systems employ CRISPRs (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage1,2. Although generally targeted to DNA substrates3–5, the Type III and Type VI CRISPR systems direct interference complexes against single-stranded RNA (ssRNA) substrates6–9. In Type VI systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease9,10. How this enzyme acquires mature CRISPR RNAs (crRNAs) essential for immune surveillance and its mechanism of crRNA-mediated RNA cleavage remain unclear. Here we show that C2c2 possesses a unique ribonuclease activity responsible for CRISPR RNA maturation that is distinct from its RNA-activated ssRNA-degradation activity. These dual ribonuclease functions are chemically and mechanistically different from each other and from the crRNA-processing behavior of the evolutionarily unrelated CRISPR enzyme Cpf111. We show that the two ribonuclease activities of C2c2 enable multiplexed processing and loading of guide RNAs that in turn allow for sensitive cellular transcript detection. PMID:27669025

CASE_ATTI: An Algorithm-Level Testbed for Multi-Sensor Data Fusion

DTIC Science & Technology

1995-05-01

Illumination Radar (STIR) control console, the SPS- 49 long-range radar, the Sea Giraffe medium-range radar and their associated CCS software modules. The...The current A WW sensor suite of the CPF comprises the SPS-49 long range 2-D radar, the Sea Giraffe medium range 2-D radar, the CANEWS ESM and the...and Sea Giraffe . . This represents an original novelty of our simulation environment. Conventional radar simulations such as CARPET are not fully

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting.

PubMed

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D

2017-04-07

Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR-Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR-Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting

PubMed Central

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D.

2017-01-01

Bacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification. PMID:28387220

Optical Tracking Data Validation and Orbit Estimation for Sparse Observations of Satellites by the OWL-Net.

PubMed

Choi, Jin; Jo, Jung Hyun; Yim, Hong-Suh; Choi, Eun-Jung; Cho, Sungki; Park, Jang-Hyun

2018-06-07

An Optical Wide-field patroL-Network (OWL-Net) has been developed for maintaining Korean low Earth orbit (LEO) satellites' orbital ephemeris. The OWL-Net consists of five optical tracking stations. Brightness signals of reflected sunlight of the targets were detected by a charged coupled device (CCD). A chopper system was adopted for fast astrometric data sampling, maximum 50 Hz, within a short observation time. The astrometric accuracy of the optical observation data was validated with precise orbital ephemeris such as Consolidated Prediction File (CPF) data and precise orbit determination result with onboard Global Positioning System (GPS) data from the target satellite. In the optical observation simulation of the OWL-Net for 2017, an average observation span for a single arc of 11 LEO observation targets was about 5 min, while an average optical observation separation time was 5 h. We estimated the position and velocity with an atmospheric drag coefficient of LEO observation targets using a sequential-batch orbit estimation technique after multi-arc batch orbit estimation. Post-fit residuals for the multi-arc batch orbit estimation and sequential-batch orbit estimation were analyzed for the optical measurements and reference orbit (CPF and GPS data). The post-fit residuals with reference show few tens-of-meters errors for in-track direction for multi-arc batch and sequential-batch orbit estimation results.

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

PubMed

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Procedure for Assessing the Structure of the CPF Considering the Loss of Strength Due to Corrosion

DTIC Science & Technology

1999-04-01

Model . . . . . . . A Typical Model Crossection Showing Strakes, Girders and Endpoints The Tranverse Bulkheads in the MAESTRO Model . . . . . . . 14...results show a tranverse redistribution of the the stress concentration found in the MAESTRO model, with the maximum of 261 MPa 5 occurring in the grid...of 350 MPa. The tranverse plate at the junction 7 with the superstructure reached a stress of -271 MPa in a material with a yield strength of 700

Bacteria and virus removal effectiveness of ceramic pot filters with different silver applications in a long term experiment.

PubMed

van der Laan, H; van Halem, D; Smeets, P W M H; Soppe, A I A; Kroesbergen, J; Wubbels, G; Nederstigt, J; Gensburger, I; Heijman, S G J

2014-03-15

In 2012 more than 4 million people used a ceramic pot filter (CPF) as household water treatment system for their daily drinking water needs. In the normal production protocol most low cost filters are impregnated with a silver solution to enhance the microbial removal efficiency. The aim of this study was to determine the role of silver during the filtration and subsequent storage. Twenty-two CPFs with three different silver applications (non, only outside and both sides) were compared in a long-term loading experiment with Escherichia coli (K12 and WR1) and MS2 bacteriophages in natural challenge water under highly controlled laboratory circumstances. No significant difference in Log Removal Values were found between the filters with different silver applications. The results show that the storage time in the receptacle is the dominant parameter to reach E. coli inactivation by silver, and not the contact time during the filtration phase. The hypothesis that the absence of silver would enhance the virus removal, due to biofilm formation on the ceramic filter element, could not be confirmed. The removal effectiveness for viruses is still of major concern for the CPF. This study suggests that the ceramic pot filter characteristics, such as burnt material content, do not determine E. coli removal efficacies, but rather the contact time with silver during storage is the dominant parameter to reach E. coli inactivation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measurement of atmospheric pollutants associated with oil and natural gas exploration and production activity in Pennsylvania's Allegheny National Forest.

PubMed

Pekney, Natalie J; Veloski, Garret; Reeder, Matthew; Tamilia, Joseph; Rupp, Erik; Wetzel, Alan

2014-09-01

Oil and natural gas exploration and production (E&P) activities generate emissions from diesel engines, compressor stations, condensate tanks, leaks and venting of natural gas, construction of well pads, and well access roads that can negatively impact air quality on both local and regional scales. A mobile, autonomous air quality monitoring laboratory was constructed to collect measurements of ambient concentrations of pollutants associated with oil and natural gas E&P activities. This air-monitoring laboratory was deployed to the Allegheny National Forest (ANF) in northwestern Pennsylvania for a campaign that resulted in the collection of approximately 7 months of data split between three monitoring locations between July 2010 and June 2011. The three monitoring locations were the Kane Experimental Forest (KEF) area in Elk County, which is downwind of the Sackett oilfield; the Bradford Ranger Station (BRS) in McKean County, which is downwind of a large area of historic oil and gas productivity; and the U.S. Forest Service Hearts Content campground (HC) in Warren County, which is in an area relatively unimpacted by oil and gas development and which therefore yielded background pollutant concentrations in the ANF. Concentrations of criteria pollutants ozone and NO2 did not vary significantly from site to site; averages were below National Ambient Air Quality Standards. Concentrations of volatile organic compounds (VOCs) associated with oil and natural gas (ethane, propane, butane, pentane) were highly correlated. Applying the conditional probability function (CPF) to the ethane data yielded most probable directions of the sources that were coincident with known location of existing wells and activity. Differences between the two impacted and one background site were difficult to discern, suggesting the that the monitoring laboratory was a great enough distance downwind of active areas to allow for sufficient dispersion with background air such that the localized plumes were not detected. Implications: Monitoring of pollutants associated with oil and natural gas exploration and production activity at three sites within the Allegheny National Forest (ANF) showed only slight site-to-site differences even with one site far removed from these activities. However, the impact was evident not in detection of localized plumes but in regional elevated ethane concentrations, as ethane can be considered a tracer species for oil and natural gas activity. The data presented serve as baseline conditions for evaluation of impacts from future development of Marcellus or Utica shale gas reserves.

Psychophysics of the probability weighting function

NASA Astrophysics Data System (ADS)

Takahashi, Taiki

2011-03-01

A probability weighting function w(p) for an objective probability p in decision under risk plays a pivotal role in Kahneman-Tversky prospect theory. Although recent studies in econophysics and neuroeconomics widely utilized probability weighting functions, psychophysical foundations of the probability weighting functions have been unknown. Notably, a behavioral economist Prelec (1998) [4] axiomatically derived the probability weighting function w(p)=exp(-() (0<α<1 and w(0)=1,w(1e)=1e,w(1)=1), which has extensively been studied in behavioral neuroeconomics. The present study utilizes psychophysical theory to derive Prelec's probability weighting function from psychophysical laws of perceived waiting time in probabilistic choices. Also, the relations between the parameters in the probability weighting function and the probability discounting function in behavioral psychology are derived. Future directions in the application of the psychophysical theory of the probability weighting function in econophysics and neuroeconomics are discussed.

Preparing and Training for the Full Spectrum of Military Challenges. Insights from the Experiences of China, France, the United Kingdom, India, and Israel

DTIC Science & Technology

2009-01-01

CPCO Centre de Planification et de Conduite des Opérations CPF Centre de Préparation des Forces CPX command post exercise CT collective training CTC...forces presides over the joint staff and commands French forces in the conduct of operations through the Centre de Planification et de Conduite des...i] t is difficult to identify a single concise statement of the government’s foreign policy.”17 The committee instead pointed to the mission state

Two Highly-Complementary Future Instruments for Climate Studies

NASA Astrophysics Data System (ADS)

Kopp, Greg; Pilewskie, Peter

2017-04-01

Measurements of the total solar irradiance (TSI) provide the most accurate knowledge of the net energy powering the Earth's climate system and thus give the incoming side of the Earth's radiative energy balance. The spectral distribution of this radiant energy, the spectral solar irradiance (SSI), determines how that incoming energy interacts with different components of the Earth's coupled ocean-atmosphere-surface climate system. Spatially- and spectrally-resolved Earth-reflected measurements of this shortwave radiation indicate the relative amount of the incident sunlight that is absorbed by different spatial regions and ecosystems around the globe. Particularly if very accurate and acquired over sufficiently long periods of time, those outgoing radiance measurements can lead to improved quantification of and physical understandings of the local and global processes causing climate change. Two upcoming and very complementary missions provide these measurements. The soon-to-be-launched Total and Spectral Solar Irradiance Sensor (TSIS) acquires the solar-irradiance measurements, with the Total Irradiance Monitor (TIM) providing highly-accurate values of the TSI and the Spectral Irradiance Monitor (SIM) measuring the SSI. The recently-selected CLARREO Pathfinder (CPF) is a technology-demonstration mission that measures the solar-reflected radiation via spatially- and spectrally-resolved observations of Earth scenes from its HyperSpectral Imager for Climate Science (HySICS), a spaceflight version of a high-altitude balloon-flight imaging spectrometer that achieves high radiometric accuracies via in-flight cross-calibrations directly tied to the SSI. We give an overview of the TSIS and the CPF, describing their instruments, the high complementarity of their measurements and intended uncertainties, and their planned timelines and current status.

Source apportionment of PAHs and n-alkanes in respirable particles in Tehran, Iran by wind sector and vertical profile.

PubMed

Moeinaddini, Mazaher; Esmaili Sari, Abbas; Riyahi bakhtiari, Alireza; Chan, Andrew Yiu-Chung; Taghavi, Seyed Mohammad; Hawker, Darryl; Connell, Des

2014-06-01

The vertical concentration profiles and source contributions of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes in respirable particle samples (PM4) collected at 10, 100, 200 and 300-m altitude from the Milad Tower of Tehran, Iran during fall and winter were investigated. The average concentrations of total PAHs and total n-alkanes were 16.7 and 591 ng/m(3), respectively. The positive matrix factorization (PMF) model was applied to the chemical composition and wind data to apportion the contributing sources. The five PAH source factors identified were: 'diesel' (56.3% of total PAHs on average), 'gasoline' (15.5%), 'wood combustion, and incineration' (13%), 'industry' (9.2%), and 'road soil particle' (6.0%). The four n-alkane source factors identified were: 'petrogenic' (65% of total n-alkanes on average), 'mixture of petrogenic and biomass burning' (15%), 'mixture of biogenic and fossil fuel' (11.5%), and 'biogenic' (8.5%). Source contributions by wind sector were also estimated based on the wind sector factor loadings from PMF analysis. Directional dependence of sources was investigated using the conditional probability function (CPF) and directional relative strength (DRS) methods. The calm wind period was found to contribute to 4.4% of total PAHs and 5.0% of total n-alkanes on average. Highest average concentrations of PAHs and n-alkanes were found in the 10 and 100 m samples, reflecting the importance of contributions from local sources. Higher average concentrations in the 300 m samples compared to those in the 200 m samples may indicate contributions from long-range transport. The vertical profiles of source factors indicate the gasoline and road soil particle-associated PAHs, and the mixture from biogenic and fossil fuel source-associated n-alkanes were mostly from local emissions. The smaller average contribution of diesel-associated PAHs in the lower altitude samples also indicates that the restriction of diesel-fueled vehicle use in the central area of Tehran has been effective in reducing the PAHs concentration.

High-resolution sampling and analysis of air particulate matter in the Pear River Delta region of Southern China: source apportionment and health risk assessment

NASA Astrophysics Data System (ADS)

Zhou, S.; Day, P. K.; Wang, X.

2017-12-01

Hazardous air pollutants, such as trace elements in particulate matters (PM), are known or highly suspected to cause detrimental effects on human health. To understand the sources and associated risks of PM to human health, hourly time-integrated major trace elements in size-segregated coarse (PM10-2.5) and fine (PM2.5) particulate matter were collected and examined in an industrial city of Foshan in the Pearl River Delta region, China. Receptor modeling of the dataset by positive matrix factorization (PMF) was used to identify six sources contributing to PM2.5 and PM10 concentrations at the site. Dominant sources included industrial coal combustion, secondary inorganic aerosol, motor vehicles and construction dust along with two intermittent sources, biomass combustion and marine aerosol. The biomass combustion source was found to be a significant contributor to peak PM2.5 episodes along with motor vehicles and industrial coal combustion. Conditional probability function (CPF) was applied to estimate the local source effects from wind direction using the PMF-resolved source contribution coupled with the surface wind direction data. Health exposure risk for hazardous trace elements (Pb, As, Cr, Ni, Zn, V, Cu, Mn, Fe) and source-specific values were estimated. The total hazard quotient (total HQ =HI) of PM2.5 was 2.09, which is two times higher than the acceptable limit (HQ = 1). The total carcinogenic risk was 3.37*10-3 for PM2.5, which was three orders higher than the acceptable limit (i.e. 1.0*10-6). Among the selected trace elements, As and Pb posed the highest non-carcinogenic and carcinogenic risks for human health, respectively. In additional, our results showed that industrial coal combustion source was the dominant non-carcinogenic and carcinogenic risks contributor, highlighting the need for stringent control of this source. This study can provide new insight for policy makers to prioritize sources in air quality management and health risk reduction.

Theoretical and Computational Studies of Stability, Transition and Flow Control in High-Speed Flows

DTIC Science & Technology

2011-02-22

A. H. Nayfeh. Nonparallel stability of boundary layers with pressure gradients and suction. Technical Report AGARD - CP -224, 1977. [Squ33] H. B. Squire...only. µ = µr ( T Tr )3/2 Tr + Ts T + Ts , (2.13) 8 K = µcp Pr , (2.14) where µr = 1.7894 × 10−5 Ns/m2, Tr = 288.0 K, Ts = 110.33 K, and cp is the...fraction of species s Cpf = frozen specific heat, cal/g-mole-K Cp ,s = specific heat at constant pressure of species s, cal/g-mole Dij = binary diffusion

Degradation of fluoroquinolone antibiotics and identification of metabolites/transformation products by liquid chromatography-tandem mass spectrometry.

PubMed

Maia, Alexandra S; Ribeiro, Ana R; Amorim, Catarina L; Barreiro, Juliana C; Cass, Quezia B; Castro, Paula M L; Tiritan, Maria Elizabeth

2014-03-14

Antibiotics are a therapeutic class widely found in environmental matrices and extensively studied due to its persistence and implications for multi-resistant bacteria development. This work presents an integrated approach of analytical multi-techniques on assessing biodegradation of fluorinated antibiotics at a laboratory-scale microcosmos to follow removal and formation of intermediate compounds. Degradation of four fluoroquinolone antibiotics, namely Ofloxacin (OFL), Norfloxacin (NOR), Ciprofloxacin (CPF) and Moxifloxacin (MOX), at 10 mg L(-1) using a mixed bacterial culture, was assessed for 60 days. The assays were followed by a developed and validated analytical method of LC with fluorescence detection (LC-FD) using a Luna Pentafluorophenyl (2) 3 μm column. The validated method demonstrated good selectivity, linearity (r(2)>0.999), intra-day and inter-day precisions (RSD<2.74%) and accuracy. The quantification limits were 5 μg L(-1) for OFL, NOR and CPF and 20 μg L(-1) for MOX. The optimized conditions allowed picturing metabolites/transformation products formation and accumulation during the process, stating an incomplete mineralization, also shown by fluoride release. OFL and MOX presented the highest (98.3%) and the lowest (80.5%) extent of degradation after 19 days of assay, respectively. A representative number of samples was selected and analyzed by LC-MS/MS with triple quadrupole and the molecular formulas were confirmed by a quadruple time of flight analyzer (QqTOF). Most of the intermediates were already described as biodegradation and/or photodegradation products in different conditions; however unknown metabolites were also identified. The microbial consortium, even when exposed to high levels of FQ, presented high percentages of degradation, never reported before for these compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells

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

Dishaw, Laura V.; Powers, Christina M.; Ryde, Ian T.

Organophosphate flame retardants (OPFRs) are used as replacements for the commercial PentaBDE mixture that was phased out in 2004. OPFRs are ubiquitous in the environment and detected at high concentrations in residential dust, suggesting widespread human exposure. OPFRs are structurally similar to neurotoxic organophosphate pesticides, raising concerns about exposure and toxicity to humans. This study evaluated the neurotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) compared to the organophosphate pesticide, chlorpyrifos (CPF), a known developmental neurotoxicant. We also tested the neurotoxicity of three structurally similar OPFRs, tris (2-chloroethyl) phosphate (TCEP), tris (1-chloropropyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP), and 2,2 Primemore » ,4,4 Prime -tetrabromodiphenyl ether (BDE-47), a major component of PentaBDE. Using undifferentiated and differentiating PC12 cells, changes in DNA synthesis, oxidative stress, differentiation into dopaminergic or cholinergic neurophenotypes, cell number, cell growth and neurite growth were assessed. TDCPP displayed concentration-dependent neurotoxicity, often with effects equivalent to or greater than equimolar concentrations of CPF. TDCPP inhibited DNA synthesis, and all OPFRs decreased cell number and altered neurodifferentiation. Although TDCPP elevated oxidative stress, there was no adverse effect on cell viability or growth. TDCPP and TDBPP promoted differentiation into both neuronal phenotypes, while TCEP and TCPP promoted only the cholinergic phenotype. BDE-47 had no effect on cell number, cell growth or neurite growth. Our results demonstrate that different OPFRs show divergent effects on neurodifferentiation, suggesting the participation of multiple mechanisms of toxicity. Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants.« less

Peritoneal fluid from endometriosis patients switches differentiation of monocytes from dendritic cells to macrophages.

PubMed

Na, Yong-Jin; Jin, Jun-O; Lee, Mi-Sook; Song, Min-Gyu; Lee, Kyu-Sup; Kwak, Jong-Young

2008-01-01

Immunological abnormalities of cell-mediated and humoral immunity might be associated with the pathogenesis of endometriosis. This study has examined the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the phenotypic characteristics of macrophages and dendritic cells (DCs) derived from monocytes. Monocytes were obtained from healthy young volunteers and cultured with ePF (n=12) or a control PF (cPF) (n=5) in the presence or absence of macrophage-colony stimulating factor (M-CSF) or IL-4 plus granulocyte macrophage-colony stimulating factor (GM-CSF). The ePF was demonstrated to increase expression levels of CD14 and CD64 on isolated monocytes in the presence or absence of M-CSF. Compared with cPF, addition of 10% ePF to GM-CSF plus IL-4-treated monocytes significantly down-regulated CD1a expression and up-regulated CD64 expression, but did not enhance expression levels of class II MHC. ePF had no effect, however, on tumor necrosis factor-alpha-induced maturation of DC. Levels of IL-6, IL-10 and M-CSF production were higher in ePF-treated than cPF-treated monocytes for both cell culture conditions with GM-CSF plus IL-4 and M-CSF. A neutralizing IL-6 antibody, but not an IL-10 antibody, abrogated the ePF-induced down-regulation of CD1a, up-regulation of CD64 and secretion of M-CSF. These results suggest that ePF favorably induces monocyte differentiation toward macrophages rather than DCs, and that this effect is mediated by IL-6. A reciprocal mode of cell differentiation between macrophages and DCs in response to ePF may be related to the pathogenesis of endometriosis.

Effects of chemical and thermal stress on acetylcholinesterase activity in the brain of the bank vole, Myodes glareolus.

PubMed

Świergosz-Kowalewska, Renata; Molenda, Patrycja; Halota, Anna

2014-08-01

One of the most important issues in ecotoxicology is better understanding the effects of interactions between chemical pollutants and physical environmental factors on animals. To fill this knowledge gap, changes in the activity of acetylcholinesterase (AChE) in the brain samples of bank voles Myodes (Clethrionomys) glareolus due to temperature effects, and two chemical stressors were studied in a full factorial laboratory experiment (27 treatments). The experiment was divided into three phases: acclimatisation (3 days), intoxication (42 days) and elimination (21 days). During the intoxication phase, animals were orally exposed to different concentrations of either nickel (0, 300 or 800 mg Ni/kg food), chlorpyrifos (CPF) (0, 50 or 350 mg CPF/kg food) or a mixture of both chemicals. During the acclimatisation and elimination phases, the bank voles were given uncontaminated food. The experiment was conducted at three different temperatures (10, 20 or 30 °C), and a 12 h:12 h light:dark regime. The animals were sacrificed at 0, 5, 10, 20, 42, 49 and 63 days after the beginning of the intoxication, and brain samples were obtained for chemical analysis. The nickel accumulation in the brain depended on the level of nickel exposure and on interactions between the temperature and other factors. Nickel exhibited no effect on AChE activity. In contrast, AChE was drastically inhibited by chlorpyrifos and low temperature, but interactions between all factors significantly influenced the enzyme activity during the elimination phase of the experiment. High mortality was observed in the groups exposed to high concentrations of nickel and chlorpyrifos. Copyright © 2014 Elsevier Inc. All rights reserved.

Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency

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

Giordano, Gennaro; Afsharinejad, Zhara; Guizzetti, Marina

2007-03-15

Over the past several years evidence has been accumulating from in vivo animal studies, observations in humans, and in vitro studies, that organophosphorus (OP) insecticides may induce oxidative stress. Such effects may contribute to some of the toxic manifestations of OPs, particularly upon chronic or developmental exposures. The aim of this study was to investigate the role of oxidative stress in the neurotoxicity of two commonly used OPs, chlorpyrifos (CPF) and diazinon (DZ), their oxygen analogs (CPO and DZO), and their 'inactive' metabolites (TCP and IMP), in neuronal cells from a genetic model of glutathione deficiency. Cerebellar granule neurons frommore » wild type mice (Gclm +/+) and mice lacking the modifier subunit of glutamate cysteine ligase (Gclm -/-), the first and limiting step in the synthesis of glutathione (GSH), were utilized. The latter display very low levels of GSH and are more susceptible to the toxicity of agents that increase oxidative stress. CPO and DZO were the most cytotoxic compounds, followed by CPF and DZ, while TCP and IMP displayed lower toxicity. Toxicity was significantly higher (10- to 25-fold) in neurons from Gclm (-/-) mice, and was antagonized by various antioxidants. Depletion of GSH from Gclm (+/+) neurons significantly increased their sensitivity to OP toxicity. OPs increased intracellular levels of reactive oxygen species and lipid peroxidation and in both cases the effects were greater in neurons from Gclm (-/-) mice. OPs did not alter intracellular levels of GSH, but significantly increased those of oxidized glutathione (GSSG). Cytotoxicity was not antagonized by cholinergic antagonists, but was decreased by the calcium chelator BAPTA-AM. These studies indicate that cytotoxicity of OPs involves generation of reactive oxygen species and is modulated by intracellular GSH, and suggest that it may involve disturbances in intracellular homeostasis of calcium.« less

20 Years of Air-Water Gas Exchange Observations for Pesticides in the Western Arctic Ocean.

PubMed

Jantunen, Liisa M; Wong, Fiona; Gawor, Anya; Kylin, Henrik; Helm, Paul A; Stern, Gary A; Strachan, William M J; Burniston, Deborah A; Bidleman, Terry F

2015-12-01

The Arctic has been contaminated by legacy organochlorine pesticides (OCPs) and currently used pesticides (CUPs) through atmospheric transport and oceanic currents. Here we report the time trends and air-water exchange of OCPs and CUPs from research expeditions conducted between 1993 and 2013. Compounds determined in both air and water were trans- and cis-chlordanes (TC, CC), trans- and cis-nonachlors (TN, CN), heptachlor exo-epoxide (HEPX), dieldrin (DIEL), chlorobornanes (ΣCHBs and toxaphene), dacthal (DAC), endosulfans and metabolite endosulfan sulfate (ENDO-I, ENDO-II, and ENDO SUL), chlorothalonil (CHT), chlorpyrifos (CPF), and trifluralin (TFN). Pentachloronitrobenzene (PCNB and quintozene) and its soil metabolite pentachlorothianisole (PCTA) were also found in air. Concentrations of most OCPs declined in surface water, whereas some CUPs increased (ENDO-I, CHT, and TFN) or showed no significant change (CPF and DAC), and most compounds declined in air. Chlordane compound fractions TC/(TC + CC) and TC/(TC + CC + TN) decreased in water and air, while CC/(TC + CC + TN) increased. TN/(TC + CC + TN) also increased in air and slightly, but not significantly, in water. These changes suggest selective removal of more labile TC and/or a shift in chlordane sources. Water-air fugacity ratios indicated net volatilization (FR > 1.0) or near equilibrium (FR not significantly different from 1.0) for most OCPs but net deposition (FR < 1.0) for ΣCHBs. Net deposition was shown for ENDO-I on all expeditions, while the net exchange direction of other CUPs varied. Understanding the processes and current state of air-surface exchange helps to interpret environmental exposure and evaluate the effectiveness of international protocols and provides insights for the environmental fate of new and emerging chemicals.

Fermions on the low-buckled honey-comb structured lattice plane and classical Casimir-Polder force

NASA Astrophysics Data System (ADS)

Goswami, Partha

2016-05-01

We start with the well-known expression for the vacuum polarization and suitably modify it for 2+1-dimensional spin-orbit coupled (SOC) fermions on the low-buckled honey-comb structured lattice plane described by the low-energy Liu-Yao-Feng-Ezawa (LYFE) model Hamiltonian involving the Dirac matrices in the chiral representation obeying the Clifford algebra. The silicene and germanene fit this description suitably. They have the Dirac cones similar to those of graphene and SOC is much stronger. The system could be normal or ferromagnetic in nature. The silicene turns into the latter type if there is exchange field arising due to the proximity coupling to a ferromagnet (FM) such as depositing Fe atoms to the silicene surface. For the silicene, we find that the many-body effects considerably change the bare Coulomb potential by way of the dependence of the Coulomb propagator on the real-spin, iso-spin and the potential due to an electric field applied perpendicular to the silicene plane. The computation aspect of the Casimir-Polder force (CPF) needs to be investigated in this paper. An important quantity in this process is the dielectric response function (DRF) of the material. The plasmon branch was obtained by finding the zeros of DRF in the long-wavelength limit. This leads to the plasmon frequencies. We find that the collective charge excitations at zero doping, i.e., intrinsic plasmons, in this system, are absent in the Dirac limit. The valley-spin-split intrinsic plasmons, however, come into being in the case of the massive Dirac particles with characteristic frequency close to 10 THz. Our scheme to calculate the Casimir-Polder interaction (CPI) of a micro-particle with a sheet involves replacing the dielectric constant of the sample in the CPI expression obtained on the basis of the Lifshitz theory by the static DRF obtained using the expressions for the polarization function we started with. Though the approach replaces a macroscopic constant by a microscopic quantity, it has the distinct advantage of the many-body effect inclusion seamlessly. We find the result that for the nontrivial susceptibility and polarizability values of the sheet and micro-particle, respectively, there is crossover between attractive and repulsive behavior. The transition depends only on these response functions apart from the ratio of the film thickness and the micro-particle separation (D/d) and temperature. Furthermore, there is a longitudinal electric field induced topological insulator (TI) to spin-valley-polarized metal (SVPM) transition in silicene, which is also referred to as the topological phase transition (TPT). The low-energy SVP carriers at TPT possess gapless (massless) and gapped (massive) energy spectra close to the two nodal points in the Brillouin zone with maximum spin-polarization. We find that the magnitude of the CPF at a given ratio of the film thickness and the separation between the micro-particle and the film are greater at TPT than at the TI and trivial insulator phases.

Identification and Characterization of Novel Chitin-Binding Proteins from the Larval Cuticle of Silkworm, Bombyx mori.

PubMed

Dong, Zhaoming; Zhang, Weiwei; Zhang, Yan; Zhang, Xiaolu; Zhao, Ping; Xia, Qingyou

2016-05-06

Cuticle is mainly made of chitin filaments embedded in a matrix of cuticular proteins (CPs). Cuticular chitins have minor differences, whereas CPs are widely variable with respect to their sequences and structures. To understand the molecular basis underlying the mechanical properties of cuticle, it is necessary to know which CPs interact with chitin and how they are assembled into the cuticle structure. In the present study, a chitin-binding assay was performed followed by liquid chromatography-tandem mass spectrometry to identify the extracted proteins from the larval cuticle of silkworm, Bombyx mori. There were 463 proteins identified from the silkworm larval cuticle, 200 of which were recovered in the chitin-binding fraction. A total of 103 proteins were annotated as CPs, which were classified into 11 CP families based on their conserved motifs, including CPR, CPAP, CPT, CPF and CPFL, CPCFC, chitin_bind 3, BmCPH2 homologues, BmCPH9 homologues, BmCPG1 homologues, BmCPG20 homologues, and BmCPG21 homologues. A total of five CP families were newly identified in the chitin-binding fraction, thereby providing new information and insight into the composition, structure, and function of the silkworm larval cuticle.

Progress and Prospects of CRISPR/Cas Systems in Insects and Other Arthropods.

PubMed

Sun, Dan; Guo, Zhaojiang; Liu, Yong; Zhang, Youjun

2017-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated gene Cas9 represent an invaluable system for the precise editing of genes in diverse species. The CRISPR/Cas9 system is an adaptive mechanism that enables bacteria and archaeal species to resist invading viruses and phages or plasmids. Compared with zinc finger nucleases and transcription activator-like effector nucleases, the CRISPR/Cas9 system has the advantage of requiring less time and effort. This efficient technology has been used in many species, including diverse arthropods that are relevant to agriculture, forestry, fisheries, and public health; however, there is no review that systematically summarizes its successful application in the editing of both insect and non-insect arthropod genomes. Thus, this paper seeks to provide a comprehensive and impartial overview of the progress of the CRISPR/Cas9 system in different arthropods, reviewing not only fundamental studies related to gene function exploration and experimental optimization but also applied studies in areas such as insect modification and pest control. In addition, we also describe the latest research advances regarding two novel CRISPR/Cas systems (CRISPR/Cpf1 and CRISPR/C2c2) and discuss their future prospects for becoming crucial technologies in arthropods.

Advancements in tailored hot stamping simulations: Cooling channel and distortion analyses

NASA Astrophysics Data System (ADS)

Billur, Eren; Wang, Chao; Bloor, Colin; Holecek, Martin; Porzner, Harald; Altan, Taylan

2013-12-01

Hot stamped components have been widely used in the automotive industry in the last decade where ultra high strength is required. These parts, however, may not provide sufficient toughness to absorb crash energy. Therefore, these components are "tailored" by controlling the microstructure at various locations. Simulation of tailored hot stamped components requires more detailed analysis of microstructural changes. Furthermore, since the part is not uniformly quenched, severe distortion can be observed. CPF, together with ESI have developed a number of techniques to predict the final properties of a tailored part. This paper discusses the recent improvements in modeling distortion and die design with cooling channels.

A Dual Sensor for pH and Hydrogen Peroxide Using Polymer-Coated Optical Fibre Tips.

PubMed

Purdey, Malcolm S; Thompson, Jeremy G; Monro, Tanya M; Abell, Andrew D; Schartner, Erik P

2015-12-17

This paper demonstrates the first single optical fibre tip probe for concurrent detection of both hydrogen peroxide (H₂O₂) concentration and pH of a solution. The sensor is constructed by embedding two fluorophores: carboxyperoxyfluor-1 (CPF1) and seminaphtharhodafluor-2 (SNARF2) within a polymer matrix located on the tip of the optical fibre. The functionalised fibre probe reproducibly measures pH, and is able to accurately detect H₂O₂ over a biologically relevant concentration range. This sensor offers potential for non-invasive detection of pH and H₂O₂ in biological environments using a single optical fibre.

Probability Weighting Functions Derived from Hyperbolic Time Discounting: Psychophysical Models and Their Individual Level Testing.

PubMed

Takemura, Kazuhisa; Murakami, Hajime

2016-01-01

A probability weighting function (w(p)) is considered to be a nonlinear function of probability (p) in behavioral decision theory. This study proposes a psychophysical model of probability weighting functions derived from a hyperbolic time discounting model and a geometric distribution. The aim of the study is to show probability weighting functions from the point of view of waiting time for a decision maker. Since the expected value of a geometrically distributed random variable X is 1/p, we formulized the probability weighting function of the expected value model for hyperbolic time discounting as w(p) = (1 - k log p)(-1). Moreover, the probability weighting function is derived from Loewenstein and Prelec's (1992) generalized hyperbolic time discounting model. The latter model is proved to be equivalent to the hyperbolic-logarithmic weighting function considered by Prelec (1998) and Luce (2001). In this study, we derive a model from the generalized hyperbolic time discounting model assuming Fechner's (1860) psychophysical law of time and a geometric distribution of trials. In addition, we develop median models of hyperbolic time discounting and generalized hyperbolic time discounting. To illustrate the fitness of each model, a psychological experiment was conducted to assess the probability weighting and value functions at the level of the individual participant. The participants were 50 university students. The results of individual analysis indicated that the expected value model of generalized hyperbolic discounting fitted better than previous probability weighting decision-making models. The theoretical implications of this finding are discussed.

Probability function of breaking-limited surface elevation. [wind generated waves of ocean

NASA Technical Reports Server (NTRS)

Tung, C. C.; Huang, N. E.; Yuan, Y.; Long, S. R.

1989-01-01

The effect of wave breaking on the probability function of surface elevation is examined. The surface elevation limited by wave breaking zeta sub b(t) is first related to the original wave elevation zeta(t) and its second derivative. An approximate, second-order, nonlinear, non-Gaussian model for zeta(t) of arbitrary but moderate bandwidth is presented, and an expression for the probability density function zeta sub b(t) is derived. The results show clearly that the effect of wave breaking on the probability density function of surface elevation is to introduce a secondary hump on the positive side of the probability density function, a phenomenon also observed in wind wave tank experiments.

Statistical tests for whether a given set of independent, identically distributed draws comes from a specified probability density.

PubMed

Tygert, Mark

2010-09-21

We discuss several tests for determining whether a given set of independent and identically distributed (i.i.d.) draws does not come from a specified probability density function. The most commonly used are Kolmogorov-Smirnov tests, particularly Kuiper's variant, which focus on discrepancies between the cumulative distribution function for the specified probability density and the empirical cumulative distribution function for the given set of i.i.d. draws. Unfortunately, variations in the probability density function often get smoothed over in the cumulative distribution function, making it difficult to detect discrepancies in regions where the probability density is small in comparison with its values in surrounding regions. We discuss tests without this deficiency, complementing the classical methods. The tests of the present paper are based on the plain fact that it is unlikely to draw a random number whose probability is small, provided that the draw is taken from the same distribution used in calculating the probability (thus, if we draw a random number whose probability is small, then we can be confident that we did not draw the number from the same distribution used in calculating the probability).

Computation of the Complex Probability Function

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

Trainer, Amelia Jo; Ledwith, Patrick John

The complex probability function is important in many areas of physics and many techniques have been developed in an attempt to compute it for some z quickly and e ciently. Most prominent are the methods that use Gauss-Hermite quadrature, which uses the roots of the n th degree Hermite polynomial and corresponding weights to approximate the complex probability function. This document serves as an overview and discussion of the use, shortcomings, and potential improvements on the Gauss-Hermite quadrature for the complex probability function.

Probability and Quantum Paradigms: the Interplay

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

Kracklauer, A. F.

Since the introduction of Born's interpretation of quantum wave functions as yielding the probability density of presence, Quantum Theory and Probability have lived in a troubled symbiosis. Problems arise with this interpretation because quantum probabilities exhibit features alien to usual probabilities, namely non Boolean structure and non positive-definite phase space probability densities. This has inspired research into both elaborate formulations of Probability Theory and alternate interpretations for wave functions. Herein the latter tactic is taken and a suggested variant interpretation of wave functions based on photo detection physics proposed, and some empirical consequences are considered. Although incomplete in a fewmore » details, this variant is appealing in its reliance on well tested concepts and technology.« less

Probability and Quantum Paradigms: the Interplay

NASA Astrophysics Data System (ADS)

Kracklauer, A. F.

2007-12-01

Since the introduction of Born's interpretation of quantum wave functions as yielding the probability density of presence, Quantum Theory and Probability have lived in a troubled symbiosis. Problems arise with this interpretation because quantum probabilities exhibit features alien to usual probabilities, namely non Boolean structure and non positive-definite phase space probability densities. This has inspired research into both elaborate formulations of Probability Theory and alternate interpretations for wave functions. Herein the latter tactic is taken and a suggested variant interpretation of wave functions based on photo detection physics proposed, and some empirical consequences are considered. Although incomplete in a few details, this variant is appealing in its reliance on well tested concepts and technology.

Progress and Prospects of CRISPR/Cas Systems in Insects and Other Arthropods

PubMed Central

Sun, Dan; Guo, Zhaojiang; Liu, Yong; Zhang, Youjun

2017-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated gene Cas9 represent an invaluable system for the precise editing of genes in diverse species. The CRISPR/Cas9 system is an adaptive mechanism that enables bacteria and archaeal species to resist invading viruses and phages or plasmids. Compared with zinc finger nucleases and transcription activator-like effector nucleases, the CRISPR/Cas9 system has the advantage of requiring less time and effort. This efficient technology has been used in many species, including diverse arthropods that are relevant to agriculture, forestry, fisheries, and public health; however, there is no review that systematically summarizes its successful application in the editing of both insect and non-insect arthropod genomes. Thus, this paper seeks to provide a comprehensive and impartial overview of the progress of the CRISPR/Cas9 system in different arthropods, reviewing not only fundamental studies related to gene function exploration and experimental optimization but also applied studies in areas such as insect modification and pest control. In addition, we also describe the latest research advances regarding two novel CRISPR/Cas systems (CRISPR/Cpf1 and CRISPR/C2c2) and discuss their future prospects for becoming crucial technologies in arthropods. PMID:28932198

Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos.

PubMed

Venerosi, A; Ricceri, L; Tait, S; Calamandrei, G

2012-12-01

The complexity of the neuroendocrine level of investigation requires the assessment of behavioral patterns that extend beyond the reproductive functions, which are age- and sex-specific in rodents, described by defined clusters of behavioral items regulated by genetic, hormonal, and epigenetic factors. The study of social behavior in laboratory rodents reveals sex-dimorphic effects of environmental chemicals that may be undetected either by a traditional neurotoxicological approach or referring to the classical definition of endocrine disrupting chemicals. Here we review data on the neurobehavioral effects of developmental exposure to the non-persistent organophosphorus insecticide chlorpyrifos, whose neurotoxic activity at low doses is currently a matter of concern for children's health. In mice exposed to chlorpyrifos in utero and/or in early development social/emotional responses are differently affected in the two sexes in parallel with sex-dependent interference on hypothalamic neuroendocrine pathways regulating social behaviors (vasopressin, oxytocin, and steroid regulated systems). Through the analysis of complex sex-dimorphic behavioral patterns we show that neurotoxic and endocrine disrupting activities of CPF overlap. This widely diffused organophosphorus pesticide might thus be considered as a neuroendocrine disruptor possibly representing a risk factor for sex-biased neurodevelopmental disorders in children. Copyright © 2012 Elsevier Inc. All rights reserved.

Uncertainty plus Prior Equals Rational Bias: An Intuitive Bayesian Probability Weighting Function

ERIC Educational Resources Information Center

Fennell, John; Baddeley, Roland

2012-01-01

Empirical research has shown that when making choices based on probabilistic options, people behave as if they overestimate small probabilities, underestimate large probabilities, and treat positive and negative outcomes differently. These distortions have been modeled using a nonlinear probability weighting function, which is found in several…

Water-soluble ions measured in fine particulate matter next to cement works

NASA Astrophysics Data System (ADS)

Galindo, N.; Yubero, E.; Nicolás, J. F.; Crespo, J.; Pastor, C.; Carratalá, A.; Santacatalina, M.

2011-04-01

PM2.5 samples were collected for one year in a suburban area close to an industrial complex formed by two cement factories and some quarries in southeastern Spain. Samples were analyzed by ion chromatography to determine the concentrations of major inorganic ions: Cl -, NO 3-, SO 42-, Na +, NH 4+, K +, Mg 2+ and Ca 2+. The average PM2.5 concentration (17.6 μg m -3) was within the interval reported for other Mediterranean suburban environments. Concentration peaks were registered during both winter and summer, concurrently with maxima levels of nitrate and sulfate, due to stagnation conditions and African dust episodes, respectively. Sulfate was found to be a main contributor to PM2.5 aerosol mass (4.2 μg m -3, 24%), followed by nitrate and ammonium (1.5 μg m -3, 9% each one). Correlation analyses demonstrated that fine sulfate was present as (NH 4) 2SO 4, CaSO 4 and Na 2SO 4 since ammonium concentrations were not high enough to neutralize both anions. The mean concentration of calcium (1.0 μg m -3), an element commonly found in the coarse fraction, was higher than those found in other locations of the Mediterranean basin. Additionally, the lowest levels were registered during summer, in contrast with previous findings. This was attributed to resuspension and transport of mineral dust from the neighboring quarries and cement plants during fall and winter, which was supported by the results of the CPF analysis. Atmospheric levels of potassium and chloride (0.28 and 0.51 μg m -3 annual average, respectively) also seemed to be affected by cement works, as suggested by correlation and CPF analyses. In the case of Cl -, a marked seasonality was observed, with mean winter concentrations considerably higher than summer ones, indicating a clear prevalence of anthropogenic sources over sea spray emissions.

Path probability of stochastic motion: A functional approach

NASA Astrophysics Data System (ADS)

Hattori, Masayuki; Abe, Sumiyoshi

2016-06-01

The path probability of a particle undergoing stochastic motion is studied by the use of functional technique, and the general formula is derived for the path probability distribution functional. The probability of finding paths inside a tube/band, the center of which is stipulated by a given path, is analytically evaluated in a way analogous to continuous measurements in quantum mechanics. Then, the formalism developed here is applied to the stochastic dynamics of stock price in finance.

Speech processing using conditional observable maximum likelihood continuity mapping

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

Hogden, John; Nix, David

A computer implemented method enables the recognition of speech and speech characteristics. Parameters are initialized of first probability density functions that map between the symbols in the vocabulary of one or more sequences of speech codes that represent speech sounds and a continuity map. Parameters are also initialized of second probability density functions that map between the elements in the vocabulary of one or more desired sequences of speech transcription symbols and the continuity map. The parameters of the probability density functions are then trained to maximize the probabilities of the desired sequences of speech-transcription symbols. A new sequence ofmore » speech codes is then input to the continuity map having the trained first and second probability function parameters. A smooth path is identified on the continuity map that has the maximum probability for the new sequence of speech codes. The probability of each speech transcription symbol for each input speech code can then be output.« less

Economic Choices Reveal Probability Distortion in Macaque Monkeys

PubMed Central

Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

2015-01-01

Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. PMID:25698750

Economic choices reveal probability distortion in macaque monkeys.

PubMed

Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

2015-02-18

Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

Diversity and evolution of class 2 CRISPR–Cas systems

PubMed Central

Shmakov, Sergey; Smargon, Aaron; Scott, David; Cox, David; Pyzocha, Neena; Yan, Winston; Abudayyeh, Omar O.; Gootenberg, Jonathan S.; Makarova, Kira S.; Wolf, Yuri I.; Severinov, Konstantin; Zhang, Feng; Koonin, Eugene V.

2018-01-01

Class 2 CRISPR–Cas systems are characterized by effector modules that consist of a single multidomain protein, such as Cas9 or Cpf1. We designed a computational pipeline for the discovery of novel class 2 variants and used it to identify six new CRISPR–Cas subtypes. The diverse properties of these new systems provide potential for the development of versatile tools for genome editing and regulation. In this Analysis article, we present a comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes, outline evolutionary scenarios for the independent origin of different class 2 CRISPR–Cas systems from mobile genetic elements, and propose an amended classification and nomenclature of CRISPR–Cas. PMID:28111461

Cyber-Physical Correlations for Infrastructure Resilience: A Game-Theoretic Approach

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

Rao, Nageswara S; He, Fei; Ma, Chris Y. T.

In several critical infrastructures, the cyber and physical parts are correlated so that disruptions to one affect the other and hence the whole system. These correlations may be exploited to strategically launch components attacks, and hence must be accounted for ensuring the infrastructure resilience, specified by its survival probability. We characterize the cyber-physical interactions at two levels: (i) the failure correlation function specifies the conditional survival probability of cyber sub-infrastructure given the physical sub-infrastructure as a function of their marginal probabilities, and (ii) the individual survival probabilities of both sub-infrastructures are characterized by first-order differential conditions. We formulate a resiliencemore » problem for infrastructures composed of discrete components as a game between the provider and attacker, wherein their utility functions consist of an infrastructure survival probability term and a cost term expressed in terms of the number of components attacked and reinforced. We derive Nash Equilibrium conditions and sensitivity functions that highlight the dependence of infrastructure resilience on the cost term, correlation function and sub-infrastructure survival probabilities. These results generalize earlier ones based on linear failure correlation functions and independent component failures. We apply the results to models of cloud computing infrastructures and energy grids.« less

Force Density Function Relationships in 2-D Granular Media

NASA Technical Reports Server (NTRS)

Youngquist, Robert C.; Metzger, Philip T.; Kilts, Kelly N.

2004-01-01

An integral transform relationship is developed to convert between two important probability density functions (distributions) used in the study of contact forces in granular physics. Developing this transform has now made it possible to compare and relate various theoretical approaches with one another and with the experimental data despite the fact that one may predict the Cartesian probability density and another the force magnitude probability density. Also, the transforms identify which functional forms are relevant to describe the probability density observed in nature, and so the modified Bessel function of the second kind has been identified as the relevant form for the Cartesian probability density corresponding to exponential forms in the force magnitude distribution. Furthermore, it is shown that this transform pair supplies a sufficient mathematical framework to describe the evolution of the force magnitude distribution under shearing. Apart from the choice of several coefficients, whose evolution of values must be explained in the physics, this framework successfully reproduces the features of the distribution that are taken to be an indicator of jamming and unjamming in a granular packing. Key words. Granular Physics, Probability Density Functions, Fourier Transforms

Modeling the effect of reward amount on probability discounting.

PubMed

Myerson, Joel; Green, Leonard; Morris, Joshua

2011-03-01

The present study with college students examined the effect of amount on the discounting of probabilistic monetary rewards. A hyperboloid function accurately described the discounting of hypothetical rewards ranging in amount from $20 to $10,000,000. The degree of discounting increased continuously with amount of probabilistic reward. This effect of amount was not due to changes in the rate parameter of the discounting function, but rather was due to increases in the exponent. These results stand in contrast to those observed with the discounting of delayed monetary rewards, in which the degree of discounting decreases with reward amount due to amount-dependent decreases in the rate parameter. Taken together, this pattern of results suggests that delay and probability discounting reflect different underlying mechanisms. That is, the fact that the exponent in the delay discounting function is independent of amount is consistent with a psychophysical scaling interpretation, whereas the finding that the exponent of the probability-discounting function is amount-dependent is inconsistent with such an interpretation. Instead, the present results are consistent with the idea that the probability-discounting function is itself the product of a value function and a weighting function. This idea was first suggested by Kahneman and Tversky (1979), although their prospect theory does not predict amount effects like those observed. The effect of amount on probability discounting was parsimoniously incorporated into our hyperboloid discounting function by assuming that the exponent was proportional to the amount raised to a power. The amount-dependent exponent of the probability-discounting function may be viewed as reflecting the effect of amount on the weighting of the probability with which the reward will be received.

Probability of the moiré effect in barrier and lenticular autostereoscopic 3D displays.

PubMed

Saveljev, Vladimir; Kim, Sung-Kyu

2015-10-05

The probability of the moiré effect in LCD displays is estimated as a function of angle based on the experimental data; a theoretical function (node spacing) is proposed basing on the distance between nodes. Both functions are close to each other. The connection between the probability of the moiré effect and the Thomae's function is also found. The function proposed in this paper can be used in the minimization of the moiré effect in visual displays, especially in autostereoscopic 3D displays.

Decision making generalized by a cumulative probability weighting function

NASA Astrophysics Data System (ADS)

dos Santos, Lindomar Soares; Destefano, Natália; Martinez, Alexandre Souto

2018-01-01

Typical examples of intertemporal decision making involve situations in which individuals must choose between a smaller reward, but more immediate, and a larger one, delivered later. Analogously, probabilistic decision making involves choices between options whose consequences differ in relation to their probability of receiving. In Economics, the expected utility theory (EUT) and the discounted utility theory (DUT) are traditionally accepted normative models for describing, respectively, probabilistic and intertemporal decision making. A large number of experiments confirmed that the linearity assumed by the EUT does not explain some observed behaviors, as nonlinear preference, risk-seeking and loss aversion. That observation led to the development of new theoretical models, called non-expected utility theories (NEUT), which include a nonlinear transformation of the probability scale. An essential feature of the so-called preference function of these theories is that the probabilities are transformed by decision weights by means of a (cumulative) probability weighting function, w(p) . We obtain in this article a generalized function for the probabilistic discount process. This function has as particular cases mathematical forms already consecrated in the literature, including discount models that consider effects of psychophysical perception. We also propose a new generalized function for the functional form of w. The limiting cases of this function encompass some parametric forms already proposed in the literature. Far beyond a mere generalization, our function allows the interpretation of probabilistic decision making theories based on the assumption that individuals behave similarly in the face of probabilities and delays and is supported by phenomenological models.

Failure detection system risk reduction assessment

NASA Technical Reports Server (NTRS)

Aguilar, Robert B. (Inventor); Huang, Zhaofeng (Inventor)

2012-01-01

A process includes determining a probability of a failure mode of a system being analyzed reaching a failure limit as a function of time to failure limit, determining a probability of a mitigation of the failure mode as a function of a time to failure limit, and quantifying a risk reduction based on the probability of the failure mode reaching the failure limit and the probability of the mitigation.

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Feng, Mary; Jackson, Andrew

Purpose: To develop a local and global function model in the liver based on regional and organ function measurements to support individualized adaptive radiation therapy (RT). Methods and Materials: A local and global model for liver function was developed to include both functional volume and the effect of functional variation of subunits. Adopting the assumption of parallel architecture in the liver, the global function was composed of a sum of local function probabilities of subunits, varying between 0 and 1. The model was fit to 59 datasets of liver regional and organ function measures from 23 patients obtained before, during, andmore » 1 month after RT. The local function probabilities of subunits were modeled by a sigmoid function in relating to MRI-derived portal venous perfusion values. The global function was fitted to a logarithm of an indocyanine green retention rate at 15 minutes (an overall liver function measure). Cross-validation was performed by leave-m-out tests. The model was further evaluated by fitting to the data divided according to whether the patients had hepatocellular carcinoma (HCC) or not. Results: The liver function model showed that (1) a perfusion value of 68.6 mL/(100 g · min) yielded a local function probability of 0.5; (2) the probability reached 0.9 at a perfusion value of 98 mL/(100 g · min); and (3) at a probability of 0.03 [corresponding perfusion of 38 mL/(100 g · min)] or lower, the contribution to global function was lost. Cross-validations showed that the model parameters were stable. The model fitted to the data from the patients with HCC indicated that the same amount of portal venous perfusion was translated into less local function probability than in the patients with non-HCC tumors. Conclusions: The developed liver function model could provide a means to better assess individual and regional dose-responses of hepatic functions, and provide guidance for individualized treatment planning of RT.« less

Organic Over-the-Horizon Targeting for the 2025 Surface Fleet

DTIC Science & Technology

2015-06-01

Detection Phit Probability of Hit Pk Probability of Kill PLAN People’s Liberation Army Navy PMEL Pacific Marine Environmental Laboratory...probability of hit ( Phit ). 2. Top-Level Functional Flow Block Diagram With the high-level functions of the project’s systems of systems properly

Uncertainty plus prior equals rational bias: an intuitive Bayesian probability weighting function.

PubMed

Fennell, John; Baddeley, Roland

2012-10-01

Empirical research has shown that when making choices based on probabilistic options, people behave as if they overestimate small probabilities, underestimate large probabilities, and treat positive and negative outcomes differently. These distortions have been modeled using a nonlinear probability weighting function, which is found in several nonexpected utility theories, including rank-dependent models and prospect theory; here, we propose a Bayesian approach to the probability weighting function and, with it, a psychological rationale. In the real world, uncertainty is ubiquitous and, accordingly, the optimal strategy is to combine probability statements with prior information using Bayes' rule. First, we show that any reasonable prior on probabilities leads to 2 of the observed effects; overweighting of low probabilities and underweighting of high probabilities. We then investigate 2 plausible kinds of priors: informative priors based on previous experience and uninformative priors of ignorance. Individually, these priors potentially lead to large problems of bias and inefficiency, respectively; however, when combined using Bayesian model comparison methods, both forms of prior can be applied adaptively, gaining the efficiency of empirical priors and the robustness of ignorance priors. We illustrate this for the simple case of generic good and bad options, using Internet blogs to estimate the relevant priors of inference. Given this combined ignorant/informative prior, the Bayesian probability weighting function is not only robust and efficient but also matches all of the major characteristics of the distortions found in empirical research. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Evaluation of the Three Parameter Weibull Distribution Function for Predicting Fracture Probability in Composite Materials

DTIC Science & Technology

1978-03-01

for the risk of rupture for a unidirectionally laminat - ed composite subjected to pure bending. (5D This equation can be simplified further by use of...C EVALUATION OF THE THREE PARAMETER WEIBULL DISTRIBUTION FUNCTION FOR PREDICTING FRACTURE PROBABILITY IN COMPOSITE MATERIALS. THESIS / AFIT/GAE...EVALUATION OF THE THREE PARAMETER WE1BULL DISTRIBUTION FUNCTION FOR PREDICTING FRACTURE PROBABILITY IN COMPOSITE MATERIALS THESIS Presented

Decomposition of conditional probability for high-order symbolic Markov chains.

PubMed

Melnik, S S; Usatenko, O V

2017-07-01

The main goal of this paper is to develop an estimate for the conditional probability function of random stationary ergodic symbolic sequences with elements belonging to a finite alphabet. We elaborate on a decomposition procedure for the conditional probability function of sequences considered to be high-order Markov chains. We represent the conditional probability function as the sum of multilinear memory function monomials of different orders (from zero up to the chain order). This allows us to introduce a family of Markov chain models and to construct artificial sequences via a method of successive iterations, taking into account at each step increasingly high correlations among random elements. At weak correlations, the memory functions are uniquely expressed in terms of the high-order symbolic correlation functions. The proposed method fills the gap between two approaches, namely the likelihood estimation and the additive Markov chains. The obtained results may have applications for sequential approximation of artificial neural network training.

Decomposition of conditional probability for high-order symbolic Markov chains

NASA Astrophysics Data System (ADS)

Melnik, S. S.; Usatenko, O. V.

2017-07-01

The main goal of this paper is to develop an estimate for the conditional probability function of random stationary ergodic symbolic sequences with elements belonging to a finite alphabet. We elaborate on a decomposition procedure for the conditional probability function of sequences considered to be high-order Markov chains. We represent the conditional probability function as the sum of multilinear memory function monomials of different orders (from zero up to the chain order). This allows us to introduce a family of Markov chain models and to construct artificial sequences via a method of successive iterations, taking into account at each step increasingly high correlations among random elements. At weak correlations, the memory functions are uniquely expressed in terms of the high-order symbolic correlation functions. The proposed method fills the gap between two approaches, namely the likelihood estimation and the additive Markov chains. The obtained results may have applications for sequential approximation of artificial neural network training.

High throughput nonparametric probability density estimation.

PubMed

Farmer, Jenny; Jacobs, Donald

2018-01-01

In high throughput applications, such as those found in bioinformatics and finance, it is important to determine accurate probability distribution functions despite only minimal information about data characteristics, and without using human subjectivity. Such an automated process for univariate data is implemented to achieve this goal by merging the maximum entropy method with single order statistics and maximum likelihood. The only required properties of the random variables are that they are continuous and that they are, or can be approximated as, independent and identically distributed. A quasi-log-likelihood function based on single order statistics for sampled uniform random data is used to empirically construct a sample size invariant universal scoring function. Then a probability density estimate is determined by iteratively improving trial cumulative distribution functions, where better estimates are quantified by the scoring function that identifies atypical fluctuations. This criterion resists under and over fitting data as an alternative to employing the Bayesian or Akaike information criterion. Multiple estimates for the probability density reflect uncertainties due to statistical fluctuations in random samples. Scaled quantile residual plots are also introduced as an effective diagnostic to visualize the quality of the estimated probability densities. Benchmark tests show that estimates for the probability density function (PDF) converge to the true PDF as sample size increases on particularly difficult test probability densities that include cases with discontinuities, multi-resolution scales, heavy tails, and singularities. These results indicate the method has general applicability for high throughput statistical inference.

High throughput nonparametric probability density estimation

PubMed Central

Farmer, Jenny

2018-01-01

In high throughput applications, such as those found in bioinformatics and finance, it is important to determine accurate probability distribution functions despite only minimal information about data characteristics, and without using human subjectivity. Such an automated process for univariate data is implemented to achieve this goal by merging the maximum entropy method with single order statistics and maximum likelihood. The only required properties of the random variables are that they are continuous and that they are, or can be approximated as, independent and identically distributed. A quasi-log-likelihood function based on single order statistics for sampled uniform random data is used to empirically construct a sample size invariant universal scoring function. Then a probability density estimate is determined by iteratively improving trial cumulative distribution functions, where better estimates are quantified by the scoring function that identifies atypical fluctuations. This criterion resists under and over fitting data as an alternative to employing the Bayesian or Akaike information criterion. Multiple estimates for the probability density reflect uncertainties due to statistical fluctuations in random samples. Scaled quantile residual plots are also introduced as an effective diagnostic to visualize the quality of the estimated probability densities. Benchmark tests show that estimates for the probability density function (PDF) converge to the true PDF as sample size increases on particularly difficult test probability densities that include cases with discontinuities, multi-resolution scales, heavy tails, and singularities. These results indicate the method has general applicability for high throughput statistical inference. PMID:29750803

Quantile Functions, Convergence in Quantile, and Extreme Value Distribution Theory.

DTIC Science & Technology

1980-11-01

Gnanadesikan (1968). Quantile functions are advocated by Parzen (1979) as providing an approach to probability-based data analysis. Quantile functions are... Gnanadesikan , R. (1968). Probability Plotting Methods for the Analysis of Data, Biomtrika, 55, 1-17.

Targeted Inactivation of DNA Photolyase Genes in Medaka Fish (Oryzias latipes).

PubMed

Ishikawa-Fujiwara, Tomoko; Shiraishi, Eri; Fujikawa, Yoshihiro; Mori, Toshio; Tsujimura, Tohru; Todo, Takeshi

2017-01-01

Proteins of the cryptochrome/photolyase family (CPF) exhibit sequence and structural conservation, but their functions are divergent. Photolyase is a DNA repair enzyme that catalyzes the light-dependent repair of ultraviolet (UV)-induced photoproducts, whereas cryptochrome acts as a photoreceptor or circadian clock protein. Two types of DNA photolyase exist: CPD photolyase, which repairs cyclobutane pyrimidine dimers (CPDs), and 6-4 photolyase, which repairs 6-4 pyrimidine-pyrimidone photoproducts (6-4PPs). Although the Cry-DASH protein is classified as a cryptochrome, it also has light-dependent DNA repair activity. To determine the significance of the three light-dependent repair enzymes in recovering from solar UV-induced DNA damage at the organismal level, we generated mutants in each gene in medaka using the CRISPR genome editing technique. The light-dependent repair activity of the mutants was examined in vitro in cultured cells and in vivo in skin tissue. Light-dependent repair of CPD was lost in the CPD photolyase-deficient mutant, whereas weak repair activity against 6-4PPs persisted in the 6-4 photolyase-deficient mutant. These results suggest the existence of a heretofore unknown 6-4PP repair pathway and thus improve our understanding of the mechanisms of defense against solar UV in vertebrates. © 2016 The Authors. Photochemistry and Photobiology published by Wiley Periodicals, Inc. on behalf of American Society for Photobiology.

Theoretical studies of the low-lying states of ScO, ScS, VO, and VS

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.

1986-01-01

Bonding in the low-lying states of ScO, ScS, VO, and VS is theoretically studied. Excellent agreement is obtained with experimental spectroscopic constants for the low-lying states of ScO and VO. The results for VS and ScS show that the bonding in the oxides and sulfides is similar, but that the smaller electronegativity in S leads to a smaller ionic component in the bonding. The computed D0 of the sulfides are about 86 percent of the corresponding oxides, and the low-lying excited states are lower in the sulfides than in the corresponding oxides. The CPF method is shown to be an accurate and cost-effective method for obtaining reliable spectroscopic constants for these systems.

Prospect evaluation as a function of numeracy and probability denominator.

PubMed

Millroth, Philip; Juslin, Peter

2015-05-01

This study examines how numeracy and probability denominator (a direct-ratio probability, a relative frequency with denominator 100, a relative frequency with denominator 10,000) affect the evaluation of prospects in an expected-value based pricing task. We expected that numeracy would affect the results due to differences in the linearity of number perception and the susceptibility to denominator neglect with different probability formats. An analysis with functional measurement verified that participants integrated value and probability into an expected value. However, a significant interaction between numeracy and probability format and subsequent analyses of the parameters of cumulative prospect theory showed that the manipulation of probability denominator changed participants' psychophysical response to probability and value. Standard methods in decision research may thus confound people's genuine risk attitude with their numerical capacities and the probability format used. Copyright © 2015 Elsevier B.V. All rights reserved.

Game-Theoretic strategies for systems of components using product-form utilities

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

Rao, Nageswara S; Ma, Cheng-Yu; Hausken, K.

Many critical infrastructures are composed of multiple systems of components which are correlated so that disruptions to one may propagate to others. We consider such infrastructures with correlations characterized in two ways: (i) an aggregate failure correlation function specifies the conditional failure probability of the infrastructure given the failure of an individual system, and (ii) a pairwise correlation function between two systems specifies the failure probability of one system given the failure of the other. We formulate a game for ensuring the resilience of the infrastructure, wherein the utility functions of the provider and attacker are products of an infrastructuremore » survival probability term and a cost term, both expressed in terms of the numbers of system components attacked and reinforced. The survival probabilities of individual systems satisfy first-order differential conditions that lead to simple Nash Equilibrium conditions. We then derive sensitivity functions that highlight the dependence of infrastructure resilience on the cost terms, correlation functions, and individual system survival probabilities. We apply these results to simplified models of distributed cloud computing and energy grid infrastructures.« less

Optimal estimation for discrete time jump processes

NASA Technical Reports Server (NTRS)

Vaca, M. V.; Tretter, S. A.

1977-01-01

Optimum estimates of nonobservable random variables or random processes which influence the rate functions of a discrete time jump process (DTJP) are obtained. The approach is based on the a posteriori probability of a nonobservable event expressed in terms of the a priori probability of that event and of the sample function probability of the DTJP. A general representation for optimum estimates and recursive equations for minimum mean squared error (MMSE) estimates are obtained. MMSE estimates are nonlinear functions of the observations. The problem of estimating the rate of a DTJP when the rate is a random variable with a probability density function of the form cx super K (l-x) super m and show that the MMSE estimates are linear in this case. This class of density functions explains why there are insignificant differences between optimum unconstrained and linear MMSE estimates in a variety of problems.

Optimal estimation for discrete time jump processes

NASA Technical Reports Server (NTRS)

Vaca, M. V.; Tretter, S. A.

1978-01-01

Optimum estimates of nonobservable random variables or random processes which influence the rate functions of a discrete time jump process (DTJP) are derived. The approach used is based on the a posteriori probability of a nonobservable event expressed in terms of the a priori probability of that event and of the sample function probability of the DTJP. Thus a general representation is obtained for optimum estimates, and recursive equations are derived for minimum mean-squared error (MMSE) estimates. In general, MMSE estimates are nonlinear functions of the observations. The problem is considered of estimating the rate of a DTJP when the rate is a random variable with a beta probability density function and the jump amplitudes are binomially distributed. It is shown that the MMSE estimates are linear. The class of beta density functions is rather rich and explains why there are insignificant differences between optimum unconstrained and linear MMSE estimates in a variety of problems.

Spatial correlations and probability density function of the phase difference in a developed speckle-field: numerical and natural experiments

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

Mysina, N Yu; Maksimova, L A; Ryabukho, V P

Investigated are statistical properties of the phase difference of oscillations in speckle-fields at two points in the far-field diffraction region, with different shapes of the scatterer aperture. Statistical and spatial nonuniformity of the probability density function of the field phase difference is established. Numerical experiments show that, for the speckle-fields with an oscillating alternating-sign transverse correlation function, a significant nonuniformity of the probability density function of the phase difference in the correlation region of the field complex amplitude, with the most probable values 0 and p, is observed. A natural statistical interference experiment using Young diagrams has confirmed the resultsmore » of numerical experiments. (laser applications and other topics in quantum electronics)« less

Performance of concatenated Reed-Solomon/Viterbi channel coding

NASA Technical Reports Server (NTRS)

Divsalar, D.; Yuen, J. H.

1982-01-01

The concatenated Reed-Solomon (RS)/Viterbi coding system is reviewed. The performance of the system is analyzed and results are derived with a new simple approach. A functional model for the input RS symbol error probability is presented. Based on this new functional model, we compute the performance of a concatenated system in terms of RS word error probability, output RS symbol error probability, bit error probability due to decoding failure, and bit error probability due to decoding error. Finally we analyze the effects of the noisy carrier reference and the slow fading on the system performance.

On defense strategies for system of systems using aggregated correlations

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

Rao, Nageswara S.; Imam, Neena; Ma, Chris Y. T.

2017-04-01

We consider a System of Systems (SoS) wherein each system Si, i = 1; 2; ... ;N, is composed of discrete cyber and physical components which can be attacked and reinforced. We characterize the disruptions using aggregate failure correlation functions given by the conditional failure probability of SoS given the failure of an individual system. We formulate the problem of ensuring the survival of SoS as a game between an attacker and a provider, each with a utility function composed of asurvival probability term and a cost term, both expressed in terms of the number of components attacked and reinforced.more » The survival probabilities of systems satisfy simple product-form, first-order differential conditions, which simplify the Nash Equilibrium (NE) conditions. We derive the sensitivity functions that highlight the dependence of SoS survival probability at NE on cost terms, correlation functions, and individual system survival probabilities.We apply these results to a simplified model of distributed cloud computing infrastructure.« less

Detecting background changes in environments with dynamic foreground by separating probability distribution function mixtures using Pearson's method of moments

NASA Astrophysics Data System (ADS)

Jenkins, Colleen; Jordan, Jay; Carlson, Jeff

2007-02-01

This paper presents parameter estimation techniques useful for detecting background changes in a video sequence with extreme foreground activity. A specific application of interest is automated detection of the covert placement of threats (e.g., a briefcase bomb) inside crowded public facilities. We propose that a histogram of pixel intensity acquired from a fixed mounted camera over time for a series of images will be a mixture of two Gaussian functions: the foreground probability distribution function and background probability distribution function. We will use Pearson's Method of Moments to separate the two probability distribution functions. The background function can then be "remembered" and changes in the background can be detected. Subsequent comparisons of background estimates are used to detect changes. Changes are flagged to alert security forces to the presence and location of potential threats. Results are presented that indicate the significant potential for robust parameter estimation techniques as applied to video surveillance.

A Tomographic Method for the Reconstruction of Local Probability Density Functions

NASA Technical Reports Server (NTRS)

Sivathanu, Y. R.; Gore, J. P.

1993-01-01

A method of obtaining the probability density function (PDF) of local properties from path integrated measurements is described. The approach uses a discrete probability function (DPF) method to infer the PDF of the local extinction coefficient from measurements of the PDFs of the path integrated transmittance. The local PDFs obtained using the method are compared with those obtained from direct intrusive measurements in propylene/air and ethylene/air diffusion flames. The results of this comparison are good.

Nonstationary envelope process and first excursion probability.

NASA Technical Reports Server (NTRS)

Yang, J.-N.

1972-01-01

The definition of stationary random envelope proposed by Cramer and Leadbetter, is extended to the envelope of nonstationary random process possessing evolutionary power spectral densities. The density function, the joint density function, the moment function, and the crossing rate of a level of the nonstationary envelope process are derived. Based on the envelope statistics, approximate solutions to the first excursion probability of nonstationary random processes are obtained. In particular, applications of the first excursion probability to the earthquake engineering problems are demonstrated in detail.

Properties of the probability density function of the non-central chi-squared distribution

NASA Astrophysics Data System (ADS)

András, Szilárd; Baricz, Árpád

2008-10-01

In this paper we consider the probability density function (pdf) of a non-central [chi]2 distribution with arbitrary number of degrees of freedom. For this function we prove that can be represented as a finite sum and we deduce a partial derivative formula. Moreover, we show that the pdf is log-concave when the degrees of freedom is greater or equal than 2. At the end of this paper we present some Turán-type inequalities for this function and an elegant application of the monotone form of l'Hospital's rule in probability theory is given.

Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures

PubMed Central

Sloma, Michael F.; Mathews, David H.

2016-01-01

RNA secondary structure prediction is widely used to analyze RNA sequences. In an RNA partition function calculation, free energy nearest neighbor parameters are used in a dynamic programming algorithm to estimate statistical properties of the secondary structure ensemble. Previously, partition functions have largely been used to estimate the probability that a given pair of nucleotides form a base pair, the conditional stacking probability, the accessibility to binding of a continuous stretch of nucleotides, or a representative sample of RNA structures. Here it is demonstrated that an RNA partition function can also be used to calculate the exact probability of formation of hairpin loops, internal loops, bulge loops, or multibranch loops at a given position. This calculation can also be used to estimate the probability of formation of specific helices. Benchmarking on a set of RNA sequences with known secondary structures indicated that loops that were calculated to be more probable were more likely to be present in the known structure than less probable loops. Furthermore, highly probable loops are more likely to be in the known structure than the set of loops predicted in the lowest free energy structures. PMID:27852924

Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

PubMed

Köhler, A; King, R; Bahls, M; Groß, S; Steveling, A; Gärtner, S; Schipf, S; Gläser, S; Völzke, H; Felix, S B; Markus, M R P; Dörr, M

2018-01-18

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A wave function for stock market returns

NASA Astrophysics Data System (ADS)

Ataullah, Ali; Davidson, Ian; Tippett, Mark

2009-02-01

The instantaneous return on the Financial Times-Stock Exchange (FTSE) All Share Index is viewed as a frictionless particle moving in a one-dimensional square well but where there is a non-trivial probability of the particle tunneling into the well’s retaining walls. Our analysis demonstrates how the complementarity principle from quantum mechanics applies to stock market prices and of how the wave function presented by it leads to a probability density which exhibits strong compatibility with returns earned on the FTSE All Share Index. In particular, our analysis shows that the probability density for stock market returns is highly leptokurtic with slight (though not significant) negative skewness. Moreover, the moments of the probability density determined under the complementarity principle employed here are all convergent - in contrast to many of the probability density functions on which the received theory of finance is based.

Delay, Probability, and Social Discounting in a Public Goods Game

ERIC Educational Resources Information Center

Jones, Bryan A.; Rachlin, Howard

2009-01-01

A human social discount function measures the value to a person of a reward to another person at a given social distance. Just as delay discounting is a hyperbolic function of delay, and probability discounting is a hyperbolic function of odds-against, social discounting is a hyperbolic function of social distance. Experiment 1 obtained individual…

Electron number probability distributions for correlated wave functions.

PubMed

Francisco, E; Martín Pendás, A; Blanco, M A

2007-03-07

Efficient formulas for computing the probability of finding exactly an integer number of electrons in an arbitrarily chosen volume are only known for single-determinant wave functions [E. Cances et al., Theor. Chem. Acc. 111, 373 (2004)]. In this article, an algebraic method is presented that extends these formulas to the case of multideterminant wave functions and any number of disjoint volumes. The derived expressions are applied to compute the probabilities within the atomic domains derived from the space partitioning based on the quantum theory of atoms in molecules. Results for a series of test molecules are presented, paying particular attention to the effects of electron correlation and of some numerical approximations on the computed probabilities.

A mechanism producing power law etc. distributions

NASA Astrophysics Data System (ADS)

Li, Heling; Shen, Hongjun; Yang, Bin

2017-07-01

Power law distribution is playing an increasingly important role in the complex system study. Based on the insolvability of complex systems, the idea of incomplete statistics is utilized and expanded, three different exponential factors are introduced in equations about the normalization condition, statistical average and Shannon entropy, with probability distribution function deduced about exponential function, power function and the product form between power function and exponential function derived from Shannon entropy and maximal entropy principle. So it is shown that maximum entropy principle can totally replace equal probability hypothesis. Owing to the fact that power and probability distribution in the product form between power function and exponential function, which cannot be derived via equal probability hypothesis, can be derived by the aid of maximal entropy principle, it also can be concluded that maximal entropy principle is a basic principle which embodies concepts more extensively and reveals basic principles on motion laws of objects more fundamentally. At the same time, this principle also reveals the intrinsic link between Nature and different objects in human society and principles complied by all.

Estimating the population size and colony boundary of subterranean termites by using the density functions of directionally averaged capture probability.

PubMed

Su, Nan-Yao; Lee, Sang-Hee

2008-04-01

Marked termites were released in a linear-connected foraging arena, and the spatial heterogeneity of their capture probabilities was averaged for both directions at distance r from release point to obtain a symmetrical distribution, from which the density function of directionally averaged capture probability P(x) was derived. We hypothesized that as marked termites move into the population and given sufficient time, the directionally averaged capture probability may reach an equilibrium P(e) over the distance r and thus satisfy the equal mixing assumption of the mark-recapture protocol. The equilibrium capture probability P(e) was used to estimate the population size N. The hypothesis was tested in a 50-m extended foraging arena to simulate the distance factor of field colonies of subterranean termites. Over the 42-d test period, the density functions of directionally averaged capture probability P(x) exhibited four phases: exponential decline phase, linear decline phase, equilibrium phase, and postequilibrium phase. The equilibrium capture probability P(e), derived as the intercept of the linear regression during the equilibrium phase, correctly projected N estimates that were not significantly different from the known number of workers in the arena. Because the area beneath the probability density function is a constant (50% in this study), preequilibrium regression parameters and P(e) were used to estimate the population boundary distance 1, which is the distance between the release point and the boundary beyond which the population is absent.

Know the risk, take the win: how executive functions and probability processing influence advantageous decision making under risk conditions.

PubMed

Brand, Matthias; Schiebener, Johannes; Pertl, Marie-Theres; Delazer, Margarete

2014-01-01

Recent models on decision making under risk conditions have suggested that numerical abilities are important ingredients of advantageous decision-making performance, but empirical evidence is still limited. The results of our first study show that logical reasoning and basic mental calculation capacities predict ratio processing and that ratio processing predicts decision making under risk. In the second study, logical reasoning together with executive functions predicted probability processing (numeracy and probability knowledge), and probability processing predicted decision making under risk. These findings suggest that increasing an individual's understanding of ratios and probabilities should lead to more advantageous decisions under risk conditions.

Israeli adolescents with ongoing exposure to terrorism: suicidal ideation, posttraumatic stress disorder, and functional impairment.

PubMed

Chemtob, Claude M; Pat-Horenczyk, Ruth; Madan, Anita; Pitman, Seth R; Wang, Yanping; Doppelt, Osnat; Burns, Kelly Dugan; Abramovitz, Robert; Brom, Daniel

2011-12-01

In this study, we examined the relationships among terrorism exposure, functional impairment, suicidal ideation, and probable partial or full posttraumatic stress disorder (PTSD) from exposure to terrorism in adolescents continuously exposed to this threat in Israel. A convenience sample of 2,094 students, aged 12 to 18, was drawn from 10 Israeli secondary schools. In terms of demographic factors, older age was associated with increased risk for suicidal ideation, OR = 1.33, 95% CI [1.09, 1.62], p < .01, but was protective against probable partial or full PTSD, OR = 0.72, 95% CI [0.54, 0.95], p < .05; female gender was associated with greater likelihood of probable partial or full PTSD, OR = 1.57, 95% CI [1.02, 2.40], p < .05. Exposure to trauma due to terrorism was associated with increased risk for each of the measured outcomes including probable partial or full PTSD, functional impairment, and suicidal ideation. When age, gender, level of exposure to terrorism, probable partial or full PTSD, and functional impairment were examined together, only terrorism exposure and functional impairment were associated with suicidal ideation. This study underscores the importance and feasibility of examining exposure to terrorism and functional impairment as risk factors for suicidal ideation. Copyright © 2011 International Society for Traumatic Stress Studies.

Tracking the Sensory Environment: An ERP Study of Probability and Context Updating in ASD

PubMed Central

Westerfield, Marissa A.; Zinni, Marla; Vo, Khang; Townsend, Jeanne

2014-01-01

We recorded visual event-related brain potentials (ERPs) from 32 adult male participants (16 high-functioning participants diagnosed with Autism Spectrum Disorder (ASD) and 16 control participants, ranging in age from 18–53 yrs) during a three-stimulus oddball paradigm. Target and non-target stimulus probability was varied across three probability conditions, whereas the probability of a third non-target stimulus was held constant in all conditions. P3 amplitude to target stimuli was more sensitive to probability in ASD than in TD participants, whereas P3 amplitude to non-target stimuli was less responsive to probability in ASD participants. This suggests that neural responses to changes in event probability are attention-dependant in high-functioning ASD. The implications of these findings for higher-level behaviors such as prediction and planning are discussed. PMID:24488156

Nematode Damage Functions: The Problems of Experimental and Sampling Error

PubMed Central

Ferris, H.

1984-01-01

The development and use of pest damage functions involves measurement and experimental errors associated with cultural, environmental, and distributional factors. Damage predictions are more valuable if considered with associated probability. Collapsing population densities into a geometric series of population classes allows a pseudo-replication removal of experimental and sampling error in damage function development. Recognition of the nature of sampling error for aggregated populations allows assessment of probability associated with the population estimate. The product of the probabilities incorporated in the damage function and in the population estimate provides a basis for risk analysis of the yield loss prediction and the ensuing management decision. PMID:19295865

MO-FG-CAMPUS-TeP2-04: Optimizing for a Specified Target Coverage Probability

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

Fredriksson, A

2016-06-15

Purpose: The purpose of this work is to develop a method for inverse planning of radiation therapy margins. When using this method the user specifies a desired target coverage probability and the system optimizes to meet the demand without any explicit specification of margins to handle setup uncertainty. Methods: The method determines which voxels to include in an optimization function promoting target coverage in order to achieve a specified target coverage probability. Voxels are selected in a way that retains the correlation between them: The target is displaced according to the setup errors and the voxels to include are selectedmore » as the union of the displaced target regions under the x% best scenarios according to some quality measure. The quality measure could depend on the dose to the considered structure alone or could depend on the dose to multiple structures in order to take into account correlation between structures. Results: A target coverage function was applied to the CTV of a prostate case with prescription 78 Gy and compared to conventional planning using a DVH function on the PTV. Planning was performed to achieve 90% probability of CTV coverage. The plan optimized using the coverage probability function had P(D98 > 77.95 Gy) = 0.97 for the CTV. The PTV plan using a constraint on minimum DVH 78 Gy at 90% had P(D98 > 77.95) = 0.44 for the CTV. To match the coverage probability optimization, the DVH volume parameter had to be increased to 97% which resulted in 0.5 Gy higher average dose to the rectum. Conclusion: Optimizing a target coverage probability is an easily used method to find a margin that achieves the desired coverage probability. It can lead to reduced OAR doses at the same coverage probability compared to planning with margins and DVH functions.« less

Surveillance system and method having an adaptive sequential probability fault detection test

NASA Technical Reports Server (NTRS)

Herzog, James P. (Inventor); Bickford, Randall L. (Inventor)

2005-01-01

System and method providing surveillance of an asset such as a process and/or apparatus by providing training and surveillance procedures that numerically fit a probability density function to an observed residual error signal distribution that is correlative to normal asset operation and then utilizes the fitted probability density function in a dynamic statistical hypothesis test for providing improved asset surveillance.

Surveillance system and method having an adaptive sequential probability fault detection test

NASA Technical Reports Server (NTRS)

Bickford, Randall L. (Inventor); Herzog, James P. (Inventor)

2006-01-01

System and method providing surveillance of an asset such as a process and/or apparatus by providing training and surveillance procedures that numerically fit a probability density function to an observed residual error signal distribution that is correlative to normal asset operation and then utilizes the fitted probability density function in a dynamic statistical hypothesis test for providing improved asset surveillance.

Surveillance System and Method having an Adaptive Sequential Probability Fault Detection Test

NASA Technical Reports Server (NTRS)

Bickford, Randall L. (Inventor); Herzog, James P. (Inventor)

2008-01-01

System and method providing surveillance of an asset such as a process and/or apparatus by providing training and surveillance procedures that numerically fit a probability density function to an observed residual error signal distribution that is correlative to normal asset operation and then utilizes the fitted probability density function in a dynamic statistical hypothesis test for providing improved asset surveillance.

Simple gain probability functions for large reflector antennas of JPL/NASA

NASA Technical Reports Server (NTRS)

Jamnejad, V.

2003-01-01

Simple models for the patterns as well as their cumulative gain probability and probability density functions of the Deep Space Network antennas are developed. These are needed for the study and evaluation of interference from unwanted sources such as the emerging terrestrial system, High Density Fixed Service, with the Ka-band receiving antenna systems in Goldstone Station of the Deep Space Network.

Buckley ANGB, Colorado. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1988-01-01

Weather Service (MAC) 3SAFETAr’ REVISED UNIFORM SUMMARY OF SURFACE WEATHER OBSERVATIONS BUCKLEY ANGB CO MSC # 724695 N 39 43 W 104 45 ELEV 5663 FT KBKF...chg- R uc kI y A N T;B , A u ro ra , C o lo rad o A NG J an 71 No v 8 0 N o cliq e N o ( iq (o 1i , 4 I )r 7() [1 Ii1 " 7 No change AN(; Nec NO sep R3...6,U3 Lr: 7,-49 1 STATICN NAME: fTUC LE Y AN6F CO |I’(-j11 (IF I[ COPD : 62.07 4 IOUR AMOUNTS IN N6-S -8-0- N-I -i-s - ALL 9711 z JAN FEC9 "AR CpF, JL N

Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures.

PubMed

Sloma, Michael F; Mathews, David H

2016-12-01

RNA secondary structure prediction is widely used to analyze RNA sequences. In an RNA partition function calculation, free energy nearest neighbor parameters are used in a dynamic programming algorithm to estimate statistical properties of the secondary structure ensemble. Previously, partition functions have largely been used to estimate the probability that a given pair of nucleotides form a base pair, the conditional stacking probability, the accessibility to binding of a continuous stretch of nucleotides, or a representative sample of RNA structures. Here it is demonstrated that an RNA partition function can also be used to calculate the exact probability of formation of hairpin loops, internal loops, bulge loops, or multibranch loops at a given position. This calculation can also be used to estimate the probability of formation of specific helices. Benchmarking on a set of RNA sequences with known secondary structures indicated that loops that were calculated to be more probable were more likely to be present in the known structure than less probable loops. Furthermore, highly probable loops are more likely to be in the known structure than the set of loops predicted in the lowest free energy structures. © 2016 Sloma and Mathews; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Video Shot Boundary Detection Using QR-Decomposition and Gaussian Transition Detection

NASA Astrophysics Data System (ADS)

Amiri, Ali; Fathy, Mahmood

2010-12-01

This article explores the problem of video shot boundary detection and examines a novel shot boundary detection algorithm by using QR-decomposition and modeling of gradual transitions by Gaussian functions. Specifically, the authors attend to the challenges of detecting gradual shots and extracting appropriate spatiotemporal features that affect the ability of algorithms to efficiently detect shot boundaries. The algorithm utilizes the properties of QR-decomposition and extracts a block-wise probability function that illustrates the probability of video frames to be in shot transitions. The probability function has abrupt changes in hard cut transitions, and semi-Gaussian behavior in gradual transitions. The algorithm detects these transitions by analyzing the probability function. Finally, we will report the results of the experiments using large-scale test sets provided by the TRECVID 2006, which has assessments for hard cut and gradual shot boundary detection. These results confirm the high performance of the proposed algorithm.

Discriminating Among Probability Weighting Functions Using Adaptive Design Optimization

PubMed Central

Cavagnaro, Daniel R.; Pitt, Mark A.; Gonzalez, Richard; Myung, Jay I.

2014-01-01

Probability weighting functions relate objective probabilities and their subjective weights, and play a central role in modeling choices under risk within cumulative prospect theory. While several different parametric forms have been proposed, their qualitative similarities make it challenging to discriminate among them empirically. In this paper, we use both simulation and choice experiments to investigate the extent to which different parametric forms of the probability weighting function can be discriminated using adaptive design optimization, a computer-based methodology that identifies and exploits model differences for the purpose of model discrimination. The simulation experiments show that the correct (data-generating) form can be conclusively discriminated from its competitors. The results of an empirical experiment reveal heterogeneity between participants in terms of the functional form, with two models (Prelec-2, Linear in Log Odds) emerging as the most common best-fitting models. The findings shed light on assumptions underlying these models. PMID:24453406

Descriptive and Experimental Analyses of Potential Precursors to Problem Behavior

PubMed Central

Borrero, Carrie S.W; Borrero, John C

2008-01-01

We conducted descriptive observations of severe problem behavior for 2 individuals with autism to identify precursors to problem behavior. Several comparative probability analyses were conducted in addition to lag-sequential analyses using the descriptive data. Results of the descriptive analyses showed that the probability of the potential precursor was greater given problem behavior compared to the unconditional probability of the potential precursor. Results of the lag-sequential analyses showed a marked increase in the probability of a potential precursor in the 1-s intervals immediately preceding an instance of problem behavior, and that the probability of problem behavior was highest in the 1-s intervals immediately following an instance of the precursor. We then conducted separate functional analyses of problem behavior and the precursor to identify respective operant functions. Results of the functional analyses showed that both problem behavior and the precursor served the same operant functions. These results replicate prior experimental analyses on the relation between problem behavior and precursors and extend prior research by illustrating a quantitative method to identify precursors to more severe problem behavior. PMID:18468281

Cross-Sectional Relationships of Physical Activity and Sedentary Behavior With Cognitive Function in Older Adults With Probable Mild Cognitive Impairment.

PubMed

Falck, Ryan S; Landry, Glenn J; Best, John R; Davis, Jennifer C; Chiu, Bryan K; Liu-Ambrose, Teresa

2017-10-01

Mild cognitive impairment (MCI) represents a transition between normal cognitive aging and dementia and may represent a critical time frame for promoting cognitive health through behavioral strategies. Current evidence suggests that physical activity (PA) and sedentary behavior are important for cognition. However, it is unclear whether there are differences in PA and sedentary behavior between people with probable MCI and people without MCI or whether the relationships of PA and sedentary behavior with cognitive function differ by MCI status. The aims of this study were to examine differences in PA and sedentary behavior between people with probable MCI and people without MCI and whether associations of PA and sedentary behavior with cognitive function differed by MCI status. This was a cross-sectional study. Physical activity and sedentary behavior in adults dwelling in the community (N = 151; at least 55 years old) were measured using a wrist-worn actigraphy unit. The Montreal Cognitive Assessment was used to categorize participants with probable MCI (scores of <26/30) and participants without MCI (scores of ≥26/30). Cognitive function was indexed using the Alzheimer Disease Assessment Scale-Cognitive-Plus (ADAS-Cog Plus). Physical activity and sedentary behavior were compared based on probable MCI status, and relationships of ADAS-Cog Plus with PA and sedentary behavior were examined by probable MCI status. Participants with probable MCI (n = 82) had lower PA and higher sedentary behavior than participants without MCI (n = 69). Higher PA and lower sedentary behavior were associated with better ADAS-Cog Plus performance in participants without MCI (β = -.022 and β = .012, respectively) but not in participants with probable MCI (β < .001 for both). This study was cross-sectional and therefore could not establish whether conversion to MCI attenuated the relationships of PA and sedentary behavior with cognitive function. The diagnosis of MCI was not confirmed with a physician; therefore, this study could not conclude how many of the participants categorized as having probable MCI would actually have been diagnosed with MCI by a physician. Participants with probable MCI were less active and more sedentary. The relationships of these behaviors with cognitive function differed by MCI status; associations were found only in participants without MCI. © 2017 American Physical Therapy Association

Negative values of quasidistributions and quantum wave and number statistics

NASA Astrophysics Data System (ADS)

Peřina, J.; Křepelka, J.

2018-04-01

We consider nonclassical wave and number quantum statistics, and perform a decomposition of quasidistributions for nonlinear optical down-conversion processes using Bessel functions. We show that negative values of the quasidistribution do not directly represent probabilities; however, they directly influence measurable number statistics. Negative terms in the decomposition related to the nonclassical behavior with negative amplitudes of probability can be interpreted as positive amplitudes of probability in the negative orthogonal Bessel basis, whereas positive amplitudes of probability in the positive basis describe classical cases. However, probabilities are positive in all cases, including negative values of quasidistributions. Negative and positive contributions of decompositions to quasidistributions are estimated. The approach can be adapted to quantum coherence functions.

[Ecological executive function characteristics and effects of executive function on social adaptive function in school-aged children with epilepsy].

PubMed

Xu, X J; Wang, L L; Zhou, N

2016-02-23

To explore the characteristics of ecological executive function in school-aged children with idiopathic or probably symptomatic epilepsy and examine the effects of executive function on social adaptive function. A total of 51 school-aged children with idiopathic or probably symptomatic epilepsy aged 5-12 years at our hospital and 37 normal ones of the same gender, age and educational level were included. The differences in ecological executive function and social adaptive function were compared between the two groups with the Behavior Rating Inventory of Executive Function (BRIEF) and Child Adaptive Behavior Scale, the Pearson's correlation test and multiple stepwise linear regression were used to explore the impact of executive function on social adaptive function. The scores of school-aged children with idiopathic or probably symptomatic epilepsy in global executive composite (GEC), behavioral regulation index (BRI) and metacognition index (MI) of BRIEF ((62±12), (58±13) and (63±12), respectively) were significantly higher than those of the control group ((47±7), (44±6) and (48±8), respectively))(P<0.01). The scores of school-aged children with idiopathic or probably symptomatic epilepsy in adaptive behavior quotient (ADQ), independence, cognition, self-control ((86±22), (32±17), (49±14), (41±16), respectively) were significantly lower than those of the control group ((120±12), (59±14), (59±7) and (68±10), respectively))(P<0.01). Pearson's correlation test showed that the scores of BRIEF, such as GEC, BRI, MI, inhibition, emotional control, monitoring, initiation and working memory had significantly negative correlations with the score of ADQ, independence, self-control ((r=-0.313--0.741, P<0.05)). Also, GEC, inhibition, MI, initiation, working memory, plan, organization and monitoring had significantly negative correlations with the score of cognition ((r=-0.335--0.437, P<0.05)); Multiple stepwise linear regression analysis showed that BRI, inhibition and working memory were closely related with the social adaptive function of school-aged children with idiopathic or probably symptomatic epilepsy. School-aged children with idiopathic or probably symptomatic epilepsy may have significantly ecological executive function impairment and social adaptive function reduction. The aspects of BRI, inhibition and working memory in ecological executive function are significantly related with social adaptive function in school-aged children with epilepsy.

Interpretation of the results of statistical measurements. [search for basic probability model

NASA Technical Reports Server (NTRS)

Olshevskiy, V. V.

1973-01-01

For random processes, the calculated probability characteristic, and the measured statistical estimate are used in a quality functional, which defines the difference between the two functions. Based on the assumption that the statistical measurement procedure is organized so that the parameters for a selected model are optimized, it is shown that the interpretation of experimental research is a search for a basic probability model.

Delay, probability, and social discounting in a public goods game.

PubMed

Jones, Bryan A; Rachlin, Howard

2009-01-01

A human social discount function measures the value to a person of a reward to another person at a given social distance. Just as delay discounting is a hyperbolic function of delay, and probability discounting is a hyperbolic function of odds-against, social discounting is a hyperbolic function of social distance. Experiment 1 obtained individual social, delay, and probability discount functions for a hypothetical $75 reward; participants also indicated how much of an initial $100 endowment they would contribute to a common investment in a public good. Steepness of discounting correlated, across participants, among all three discount dimensions. However, only social and probability discounting were correlated with the public-good contribution; high public-good contributors were more altruistic and also less risk averse than low contributors. Experiment 2 obtained social discount functions with hypothetical $75 rewards and delay discount functions with hypothetical $1,000 rewards, as well as public-good contributions. The results replicated those of Experiment 1; steepness of the two forms of discounting correlated with each other across participants but only social discounting correlated with the public-good contribution. Most participants in Experiment 2 predicted that the average contribution would be lower than their own contribution.

Computer routines for probability distributions, random numbers, and related functions

USGS Publications Warehouse

Kirby, W.

1983-01-01

Use of previously coded and tested subroutines simplifies and speeds up program development and testing. This report presents routines that can be used to calculate various probability distributions and other functions of importance in statistical hydrology. The routines are designed as general-purpose Fortran subroutines and functions to be called from user-written main progress. The probability distributions provided include the beta, chi-square, gamma, Gaussian (normal), Pearson Type III (tables and approximation), and Weibull. Also provided are the distributions of the Grubbs-Beck outlier test, Kolmogorov 's and Smirnov 's D, Student 's t, noncentral t (approximate), and Snedecor F. Other mathematical functions include the Bessel function, I sub o, gamma and log-gamma functions, error functions, and exponential integral. Auxiliary services include sorting and printer-plotting. Random number generators for uniform and normal numbers are provided and may be used with some of the above routines to generate numbers from other distributions. (USGS)

Computer routines for probability distributions, random numbers, and related functions

USGS Publications Warehouse

Kirby, W.H.

1980-01-01

Use of previously codes and tested subroutines simplifies and speeds up program development and testing. This report presents routines that can be used to calculate various probability distributions and other functions of importance in statistical hydrology. The routines are designed as general-purpose Fortran subroutines and functions to be called from user-written main programs. The probability distributions provided include the beta, chisquare, gamma, Gaussian (normal), Pearson Type III (tables and approximation), and Weibull. Also provided are the distributions of the Grubbs-Beck outlier test, Kolmogorov 's and Smirnov 's D, Student 's t, noncentral t (approximate), and Snedecor F tests. Other mathematical functions include the Bessel function I (subzero), gamma and log-gamma functions, error functions and exponential integral. Auxiliary services include sorting and printer plotting. Random number generators for uniform and normal numbers are provided and may be used with some of the above routines to generate numbers from other distributions. (USGS)

Singular solution of the Feller diffusion equation via a spectral decomposition.

PubMed

Gan, Xinjun; Waxman, David

2015-01-01

Feller studied a branching process and found that the distribution for this process approximately obeys a diffusion equation [W. Feller, in Proceedings of the Second Berkeley Symposium on Mathematical Statistics and Probability (University of California Press, Berkeley and Los Angeles, 1951), pp. 227-246]. This diffusion equation and its generalizations play an important role in many scientific problems, including, physics, biology, finance, and probability theory. We work under the assumption that the fundamental solution represents a probability density and should account for all of the probability in the problem. Thus, under the circumstances where the random process can be irreversibly absorbed at the boundary, this should lead to the presence of a Dirac delta function in the fundamental solution at the boundary. However, such a feature is not present in the standard approach (Laplace transformation). Here we require that the total integrated probability is conserved. This yields a fundamental solution which, when appropriate, contains a term proportional to a Dirac delta function at the boundary. We determine the fundamental solution directly from the diffusion equation via spectral decomposition. We obtain exact expressions for the eigenfunctions, and when the fundamental solution contains a Dirac delta function at the boundary, every eigenfunction of the forward diffusion operator contains a delta function. We show how these combine to produce a weight of the delta function at the boundary which ensures the total integrated probability is conserved. The solution we present covers cases where parameters are time dependent, thereby greatly extending its applicability.

Singular solution of the Feller diffusion equation via a spectral decomposition

NASA Astrophysics Data System (ADS)

Gan, Xinjun; Waxman, David

2015-01-01

Feller studied a branching process and found that the distribution for this process approximately obeys a diffusion equation [W. Feller, in Proceedings of the Second Berkeley Symposium on Mathematical Statistics and Probability (University of California Press, Berkeley and Los Angeles, 1951), pp. 227-246]. This diffusion equation and its generalizations play an important role in many scientific problems, including, physics, biology, finance, and probability theory. We work under the assumption that the fundamental solution represents a probability density and should account for all of the probability in the problem. Thus, under the circumstances where the random process can be irreversibly absorbed at the boundary, this should lead to the presence of a Dirac delta function in the fundamental solution at the boundary. However, such a feature is not present in the standard approach (Laplace transformation). Here we require that the total integrated probability is conserved. This yields a fundamental solution which, when appropriate, contains a term proportional to a Dirac delta function at the boundary. We determine the fundamental solution directly from the diffusion equation via spectral decomposition. We obtain exact expressions for the eigenfunctions, and when the fundamental solution contains a Dirac delta function at the boundary, every eigenfunction of the forward diffusion operator contains a delta function. We show how these combine to produce a weight of the delta function at the boundary which ensures the total integrated probability is conserved. The solution we present covers cases where parameters are time dependent, thereby greatly extending its applicability.

Digital simulation of two-dimensional random fields with arbitrary power spectra and non-Gaussian probability distribution functions.

PubMed

Yura, Harold T; Hanson, Steen G

2012-04-01

Methods for simulation of two-dimensional signals with arbitrary power spectral densities and signal amplitude probability density functions are disclosed. The method relies on initially transforming a white noise sample set of random Gaussian distributed numbers into a corresponding set with the desired spectral distribution, after which this colored Gaussian probability distribution is transformed via an inverse transform into the desired probability distribution. In most cases the method provides satisfactory results and can thus be considered an engineering approach. Several illustrative examples with relevance for optics are given.

[Determinants of pride and shame: outcome, expected success and attribution].

PubMed

Schützwohl, A

1991-01-01

In two experiments we investigated the relationship between subjective probability of success and pride and shame. According to Atkinson (1957), pride (the incentive of success) is an inverse linear function of the probability of success, shame (the incentive of failure) being a negative linear function. Attribution theory predicts an inverse U-shaped relationship between subjective probability of success and pride and shame. The results presented here are at variance with both theories: Pride and shame do not vary with subjective probability of success. However, pride and shame are systematically correlated with internal attributions of action outcome.

Stochastic transfer of polarized radiation in finite cloudy atmospheric media with reflective boundaries

NASA Astrophysics Data System (ADS)

Sallah, M.

2014-03-01

The problem of monoenergetic radiative transfer in a finite planar stochastic atmospheric medium with polarized (vector) Rayleigh scattering is proposed. The solution is presented for an arbitrary absorption and scattering cross sections. The extinction function of the medium is assumed to be a continuous random function of position, with fluctuations about the mean taken as Gaussian distributed. The joint probability distribution function of these Gaussian random variables is used to calculate the ensemble-averaged quantities, such as reflectivity and transmissivity, for an arbitrary correlation function. A modified Gaussian probability distribution function is also used to average the solution in order to exclude the probable negative values of the optical variable. Pomraning-Eddington approximation is used, at first, to obtain the deterministic analytical solution for both the total intensity and the difference function used to describe the polarized radiation. The problem is treated with specular reflecting boundaries and angular-dependent externally incident flux upon the medium from one side and with no flux from the other side. For the sake of comparison, two different forms of the weight function, which introduced to force the boundary conditions to be fulfilled, are used. Numerical results of the average reflectivity and average transmissivity are obtained for both Gaussian and modified Gaussian probability density functions at the different degrees of polarization.

Probability distribution for the Gaussian curvature of the zero level surface of a random function

NASA Astrophysics Data System (ADS)

Hannay, J. H.

2018-04-01

A rather natural construction for a smooth random surface in space is the level surface of value zero, or ‘nodal’ surface f(x,y,z)  =  0, of a (real) random function f; the interface between positive and negative regions of the function. A physically significant local attribute at a point of a curved surface is its Gaussian curvature (the product of its principal curvatures) because, when integrated over the surface it gives the Euler characteristic. Here the probability distribution for the Gaussian curvature at a random point on the nodal surface f  =  0 is calculated for a statistically homogeneous (‘stationary’) and isotropic zero mean Gaussian random function f. Capitalizing on the isotropy, a ‘fixer’ device for axes supplies the probability distribution directly as a multiple integral. Its evaluation yields an explicit algebraic function with a simple average. Indeed, this average Gaussian curvature has long been known. For a non-zero level surface instead of the nodal one, the probability distribution is not fully tractable, but is supplied as an integral expression.

Models of multidimensional discrete distribution of probabilities of random variables in information systems

NASA Astrophysics Data System (ADS)

Gromov, Yu Yu; Minin, Yu V.; Ivanova, O. G.; Morozova, O. N.

2018-03-01

Multidimensional discrete distributions of probabilities of independent random values were received. Their one-dimensional distribution is widely used in probability theory. Producing functions of those multidimensional distributions were also received.

WE-AB-202-01: Evaluating the Toxicity Reduction with CT-Ventilation Functional Avoidance Radiation Therapy

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

Vinogradskiy, Y; Miyasaka, Y; Kadoya, N

Purpose: CT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Studies have proposed to use 4DCT-ventilation imaging for functional avoidance radiotherapy which implies designing treatment plans to spare functional portions of the lung. Although retrospective studies have been performed to evaluate the dosimetric gains to functional lung; no work has been done to translate the dosimetric gains to an improvement in pulmonary toxicity. The purpose of our work was to evaluate the potential reduction in toxicity for 4DCT-ventilation based functional avoidance. Methods: 70 lung cancer patients with 4DCT imaging were used for the study. CT-ventilationmore » maps were calculated using the patient’s 4DCT, deformable image registrations, and a density-change-based algorithm. Radiation pneumonitis was graded using imaging and clinical information. Log-likelihood methods were used to fit a normal-tissue-complication-probability (NTCP) model predicting grade 2+ radiation pneumonitis as a function of doses (mean and V20) to functional lung (>15% ventilation). For 20 patients a functional plan was generated that reduced dose to functional lung while meeting RTOG 0617-based constraints. The NTCP model was applied to the functional plan to determine the reduction in toxicity with functional planning Results: The mean dose to functional lung was 16.8 and 17.7 Gy with the functional and clinical plans respectively. The corresponding grade 2+ pneumonitis probability was 26.9% with the clinically-used plan and 24.6% with the functional plan (8.5% reduction). The V20-based grade 2+ pneumonitis probability was 23.7% with the clinically-used plan and reduced to 19.6% with the functional plan (20.9% reduction). Conclusion: Our results revealed a reduction of 9–20% in complication probability with functional planning. To our knowledge this is the first study to apply complication probability to convert dosimetric results to toxicity improvement. The results presented in the current work provide seminal data for prospective clinical trials in functional avoidance. YV discloses funding from State of Colorado. TY discloses National Lung Cancer Partnership; Young Investigator Research grant.« less

Functional-diversity indices can be driven by methodological choices and species richness.

PubMed

Poos, Mark S; Walker, Steven C; Jackson, Donald A

2009-02-01

Functional diversity is an important concept in community ecology because it captures information on functional traits absent in measures of species diversity. One popular method of measuring functional diversity is the dendrogram-based method, FD. To calculate FD, a variety of methodological choices are required, and it has been debated about whether biological conclusions are sensitive to such choices. We studied the probability that conclusions regarding FD were sensitive, and that patterns in sensitivity were related to alpha and beta components of species richness. We developed a randomization procedure that iteratively calculated FD by assigning species into two assemblages and calculating the probability that the community with higher FD varied across methods. We found evidence of sensitivity in all five communities we examined, ranging from a probability of sensitivity of 0 (no sensitivity) to 0.976 (almost completely sensitive). Variations in these probabilities were driven by differences in alpha diversity between assemblages and not by beta diversity. Importantly, FD was most sensitive when it was most useful (i.e., when differences in alpha diversity were low). We demonstrate that trends in functional-diversity analyses can be largely driven by methodological choices or species richness, rather than functional trait information alone.

Vacuum quantum stress tensor fluctuations: A diagonalization approach

NASA Astrophysics Data System (ADS)

Schiappacasse, Enrico D.; Fewster, Christopher J.; Ford, L. H.

2018-01-01

Large vacuum fluctuations of a quantum stress tensor can be described by the asymptotic behavior of its probability distribution. Here we focus on stress tensor operators which have been averaged with a sampling function in time. The Minkowski vacuum state is not an eigenstate of the time-averaged operator, but can be expanded in terms of its eigenstates. We calculate the probability distribution and the cumulative probability distribution for obtaining a given value in a measurement of the time-averaged operator taken in the vacuum state. In these calculations, we study a specific operator that contributes to the stress-energy tensor of a massless scalar field in Minkowski spacetime, namely, the normal ordered square of the time derivative of the field. We analyze the rate of decrease of the tail of the probability distribution for different temporal sampling functions, such as compactly supported functions and the Lorentzian function. We find that the tails decrease relatively slowly, as exponentials of fractional powers, in agreement with previous work using the moments of the distribution. Our results lend additional support to the conclusion that large vacuum stress tensor fluctuations are more probable than large thermal fluctuations, and may have observable effects.

Optimized Vertex Method and Hybrid Reliability

NASA Technical Reports Server (NTRS)

Smith, Steven A.; Krishnamurthy, T.; Mason, B. H.

2002-01-01

A method of calculating the fuzzy response of a system is presented. This method, called the Optimized Vertex Method (OVM), is based upon the vertex method but requires considerably fewer function evaluations. The method is demonstrated by calculating the response membership function of strain-energy release rate for a bonded joint with a crack. The possibility of failure of the bonded joint was determined over a range of loads. After completing the possibilistic analysis, the possibilistic (fuzzy) membership functions were transformed to probability density functions and the probability of failure of the bonded joint was calculated. This approach is called a possibility-based hybrid reliability assessment. The possibility and probability of failure are presented and compared to a Monte Carlo Simulation (MCS) of the bonded joint.

Quantum Jeffreys prior for displaced squeezed thermal states

NASA Astrophysics Data System (ADS)

Kwek, L. C.; Oh, C. H.; Wang, Xiang-Bin

1999-09-01

It is known that, by extending the equivalence of the Fisher information matrix to its quantum version, the Bures metric, the quantum Jeffreys prior can be determined from the volume element of the Bures metric. We compute the Bures metric for the displaced squeezed thermal state and analyse the quantum Jeffreys prior and its marginal probability distributions. To normalize the marginal probability density function, it is necessary to provide a range of values of the squeezing parameter or the inverse temperature. We find that if the range of the squeezing parameter is kept narrow, there are significant differences in the marginal probability density functions in terms of the squeezing parameters for the displaced and undisplaced situations. However, these differences disappear as the range increases. Furthermore, marginal probability density functions against temperature are very different in the two cases.

Time-dependent landslide probability mapping

USGS Publications Warehouse

Campbell, Russell H.; Bernknopf, Richard L.; ,

1993-01-01

Case studies where time of failure is known for rainfall-triggered debris flows can be used to estimate the parameters of a hazard model in which the probability of failure is a function of time. As an example, a time-dependent function for the conditional probability of a soil slip is estimated from independent variables representing hillside morphology, approximations of material properties, and the duration and rate of rainfall. If probabilities are calculated in a GIS (geomorphic information system ) environment, the spatial distribution of the result for any given hour can be displayed on a map. Although the probability levels in this example are uncalibrated, the method offers a potential for evaluating different physical models and different earth-science variables by comparing the map distribution of predicted probabilities with inventory maps for different areas and different storms. If linked with spatial and temporal socio-economic variables, this method could be used for short-term risk assessment.

Generalized Wishart Mixtures for Unsupervised Classification of PolSAR Data

NASA Astrophysics Data System (ADS)

Li, Lan; Chen, Erxue; Li, Zengyuan

2013-01-01

This paper presents an unsupervised clustering algorithm based upon the expectation maximization (EM) algorithm for finite mixture modelling, using the complex wishart probability density function (PDF) for the probabilities. The mixture model enables to consider heterogeneous thematic classes which could not be better fitted by the unimodal wishart distribution. In order to make it fast and robust to calculate, we use the recently proposed generalized gamma distribution (GΓD) for the single polarization intensity data to make the initial partition. Then we use the wishart probability density function for the corresponding sample covariance matrix to calculate the posterior class probabilities for each pixel. The posterior class probabilities are used for the prior probability estimates of each class and weights for all class parameter updates. The proposed method is evaluated and compared with the wishart H-Alpha-A classification. Preliminary results show that the proposed method has better performance.

What is the correct cost functional for variational data assimilation?

NASA Astrophysics Data System (ADS)

Bröcker, Jochen

2018-03-01

Variational approaches to data assimilation, and weakly constrained four dimensional variation (WC-4DVar) in particular, are important in the geosciences but also in other communities (often under different names). The cost functions and the resulting optimal trajectories may have a probabilistic interpretation, for instance by linking data assimilation with maximum aposteriori (MAP) estimation. This is possible in particular if the unknown trajectory is modelled as the solution of a stochastic differential equation (SDE), as is increasingly the case in weather forecasting and climate modelling. In this situation, the MAP estimator (or "most probable path" of the SDE) is obtained by minimising the Onsager-Machlup functional. Although this fact is well known, there seems to be some confusion in the literature, with the energy (or "least squares") functional sometimes been claimed to yield the most probable path. The first aim of this paper is to address this confusion and show that the energy functional does not, in general, provide the most probable path. The second aim is to discuss the implications in practice. Although the mentioned results pertain to stochastic models in continuous time, they do have consequences in practice where SDE's are approximated by discrete time schemes. It turns out that using an approximation to the SDE and calculating its most probable path does not necessarily yield a good approximation to the most probable path of the SDE proper. This suggest that even in discrete time, a version of the Onsager-Machlup functional should be used, rather than the energy functional, at least if the solution is to be interpreted as a MAP estimator.

Bivariate normal, conditional and rectangular probabilities: A computer program with applications

NASA Technical Reports Server (NTRS)

Swaroop, R.; Brownlow, J. D.; Ashwworth, G. R.; Winter, W. R.

1980-01-01

Some results for the bivariate normal distribution analysis are presented. Computer programs for conditional normal probabilities, marginal probabilities, as well as joint probabilities for rectangular regions are given: routines for computing fractile points and distribution functions are also presented. Some examples from a closed circuit television experiment are included.

Off-diagonal long-range order, cycle probabilities, and condensate fraction in the ideal Bose gas.

PubMed

Chevallier, Maguelonne; Krauth, Werner

2007-11-01

We discuss the relationship between the cycle probabilities in the path-integral representation of the ideal Bose gas, off-diagonal long-range order, and Bose-Einstein condensation. Starting from the Landsberg recursion relation for the canonic partition function, we use elementary considerations to show that in a box of size L3 the sum of the cycle probabilities of length k>L2 equals the off-diagonal long-range order parameter in the thermodynamic limit. For arbitrary systems of ideal bosons, the integer derivative of the cycle probabilities is related to the probability of condensing k bosons. We use this relation to derive the precise form of the pik in the thermodynamic limit. We also determine the function pik for arbitrary systems. Furthermore, we use the cycle probabilities to compute the probability distribution of the maximum-length cycles both at T=0, where the ideal Bose gas reduces to the study of random permutations, and at finite temperature. We close with comments on the cycle probabilities in interacting Bose gases.

Analysis of the Bivariate Parameter Wind Differences Between Jimsphere and Windsonde

NASA Technical Reports Server (NTRS)

Susko, Michael

1987-01-01

An analysis is presented for the bivariate parameter differences between the FPS-16 Radar/Jimsphere and the Meteorological Sounding System (MSS) Windsonde. The Jimsphere is used as the standard to measure the ascent wind during the Space Shuttle launches at Kennedy Space Center, Florida, and the Windsonde is the backup system. In addition, a discussion of the terrestrial environment (below 20 km) and a description of the Jimsphere and Windsonde wind sensors are given. Computation of the wind statistics from 64 paired Jimsphere and Windsonde balloon releases in support of 14 Space Shuttle launches shows a good agreement between the two wind sensors. From the analysis of buildup and back-off data for various scales of distance and the comparison of the cumulative percent frequency (CPF) versus wind speed change, it is shown that the wind speed change for various scales of distances for the Jimsphere and Windsonde compare favorably.

The International Microgravity Laboratory, a Spacelab for materials and life sciences

NASA Technical Reports Server (NTRS)

Snyder, Robert S.

1992-01-01

The material science experiments performed on the International Microgravity Laboratory (IML-1), which is used to perform investigations which require the low gravity environment of space, are discussed. These experiments, the principal investigator, and associated organization are listed. Whether the experiment was a new development or was carried on an earlier space mission, such as the third Spacelab (SL-3) or the Shuttle Middeck, is also noted. The two major disciplines of materials science represented on IML-1 were the growth of crystals from the melt, solution, or vapor and the study of fluids (liquids and gases) in a reduced gravity environment. The various facilities on board IML-1 and their related experiments are described. The facilities include the Fluids Experiment System (FES) Vapor Crystal Growth System (VCGS) Organic Crystal Growth Facility (OCGF), Cryostat (CRY), and the Critical Point Facility (CPF).

Around Marshall

NASA Image and Video Library

1982-01-27

The primary payload for Space Shuttle Mission STS-42, launched January 22, 1992, was the International Microgravity Laboratory-1 (IML-1), a pressurized manned Spacelab module. The goal of IML-1 was to explore in depth the complex effects of weightlessness of living organisms and materials processing. Around-the-clock research was performed on the human nervous system's adaptation to low gravity and effects of microgravity on other life forms such as shrimp eggs, lentil seedlings, fruit fly eggs, and bacteria. Materials processing experiments were also conducted, including crystal growth from a variety of substances such as enzymes, mercury iodide, and a virus. The Huntsville Operations Support Center (HOSC) Spacelab Payload Operations Control Center (SL POCC) at the Marshall Space Flight Center (MSFC) was the air/ground communication channel used between the astronauts and ground control teams during the Spacelab missions. Featured is the Critical Point Facility (CPF) team in the SL POCC during the IML-1 mission.

Short-Arc Orbit Determination Results and Space Debris Test Observation of the OWL-Net

NASA Astrophysics Data System (ADS)

Choi, J.; Jo, J.; Yim, H.

Korea Astronomy and Space Science Institute had developed the Optical Wide-field patroL-Network (OWL-Net) for maintaining the domestic Low Earth Orbit satellites’ ephemeris and monitoring Geostationary Earth Orbit region. It also can be used to observe space debris. The orbit determination process was planned with batch least square orbit estimator for every week. The optical tracking window is very narrow, several times per week. Sequentialbatch type estimation strategy was attempted for more reliable orbit prediction. We compared the test operation results with Two Line Elements and CPF files to validate the system. This results can be used to estimate the performance of the OWL-Net operations. And also we had observation of the Astro-H debris. We got the dozens of photometric data of the Astro-H debris main part for a few seconds with the chopper system.

Instant power generation from an air-breathing paper and pencil based bacterial bio-fuel cell.

PubMed

Veerubhotla, Ramya; Bandopadhyay, Aditya; Das, Debabrata; Chakraborty, Suman

2015-06-21

We present a low-cost, disposable microbial fuel cell fabricated on a paper based platform, having a start-up time of 10 s. The platform deploys ordinary pencil strokes for graphite electrode deposition. The device uses a membrane-less design in a one-time injection (OTI) mode or a continuous capillary driven flow mode (CPF), where oxygen from the atmosphere is used up at the cathode for water formation, leading to the generation of bioelectricity. The performance of the fuel cell is evaluated using two bacterial strains, namely, Pseudomonas aeruginosa IIT BT SS1 and Shewanella putrefaciens. This flexible device is shown to retain bacteria for a period of at least one hour, resulting in the generation of almost 0.4 V using P. aeruginosa and a maximum current of 18 μA using S. putrefaciens without the use of any additional catalysts.

User’s guide for MapMark4—An R package for the probability calculations in three-part mineral resource assessments

USGS Publications Warehouse

Ellefsen, Karl J.

2017-06-27

MapMark4 is a software package that implements the probability calculations in three-part mineral resource assessments. Functions within the software package are written in the R statistical programming language. These functions, their documentation, and a copy of this user’s guide are bundled together in R’s unit of shareable code, which is called a “package.” This user’s guide includes step-by-step instructions showing how the functions are used to carry out the probability calculations. The calculations are demonstrated using test data, which are included in the package.

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

Friar, James Lewis; Goldman, Terrance J.; Pérez-Mercader, J.

In this paper, we apply the Law of Total Probability to the construction of scale-invariant probability distribution functions (pdf's), and require that probability measures be dimensionless and unitless under a continuous change of scales. If the scale-change distribution function is scale invariant then the constructed distribution will also be scale invariant. Repeated application of this construction on an arbitrary set of (normalizable) pdf's results again in scale-invariant distributions. The invariant function of this procedure is given uniquely by the reciprocal distribution, suggesting a kind of universality. Finally, we separately demonstrate that the reciprocal distribution results uniquely from requiring maximum entropymore » for size-class distributions with uniform bin sizes.« less

Clinical diagnosis of pneumonia, typical of experts.

PubMed

Miettinen, Olli S; Flegel, Kenneth M; Steurer, Johann

2008-04-01

Clinical diagnosis of pneumonia is a concern when a patient presents with recent cough--new or worsened--together with fever as the chief complaint. Given this presentation, the doctor would benefit from having access to software that specifies, first, what diagnostic indicators experts typically use in that diagnosis; then, upon entry of those facts, what experts' typical probability of pneumonia is in such a case; and finally, how much this probability might change upon adding the facts from chest radiography. We specified a set of 36 hypothetical presentations of this type by patients 20-70 years of age, involving a comprehensive set of clinical-diagnostic indicators. Members of three separate expert panels independently set the probability of pneumonia in each of these cases, and also the range of possible post-radiography probabilities. A logistic function of the diagnostic indicators was fitted to the medians of the probabilities. The median probability of pneumonia was a joint function of the patient's age and current rate of cigarette smoking; history as to the cough's duration, the fever's maximum, dyspnea (including whether on effort only) and rigors; and physical examination as to temperature, signs of upper respiratory infection, prolongation of expiration, dullness on percussion and some auscultation findings. Non-contributory were history of wheezing, pain on inspiration, type of sputum and signs of cold or influenza. This probability function, and the post-radiography functions based on the same indicators, are accessible at http://www.evimed.ch/pneumonia. The expert inputs to clinical diagnosis that were derived and made readily accessible provide for expertly clinical diagnosis of pneumonia, relevant for decisions about radiography and treatment without it.

Univariate Probability Distributions

ERIC Educational Resources Information Center

Leemis, Lawrence M.; Luckett, Daniel J.; Powell, Austin G.; Vermeer, Peter E.

2012-01-01

We describe a web-based interactive graphic that can be used as a resource in introductory classes in mathematical statistics. This interactive graphic presents 76 common univariate distributions and gives details on (a) various features of the distribution such as the functional form of the probability density function and cumulative distribution…

Investigation of estimators of probability density functions

NASA Technical Reports Server (NTRS)

Speed, F. M.

1972-01-01

Four research projects are summarized which include: (1) the generation of random numbers on the IBM 360/44, (2) statistical tests used to check out random number generators, (3) Specht density estimators, and (4) use of estimators of probability density functions in analyzing large amounts of data.

Dynamic Graphics in Excel for Teaching Statistics: Understanding the Probability Density Function

ERIC Educational Resources Information Center

Coll-Serrano, Vicente; Blasco-Blasco, Olga; Alvarez-Jareno, Jose A.

2011-01-01

In this article, we show a dynamic graphic in Excel that is used to introduce an important concept in our subject, Statistics I: the probability density function. This interactive graphic seeks to facilitate conceptual understanding of the main aspects analysed by the learners.

Bounding the Failure Probability Range of Polynomial Systems Subject to P-box Uncertainties

NASA Technical Reports Server (NTRS)

Crespo, Luis G.; Kenny, Sean P.; Giesy, Daniel P.

2012-01-01

This paper proposes a reliability analysis framework for systems subject to multiple design requirements that depend polynomially on the uncertainty. Uncertainty is prescribed by probability boxes, also known as p-boxes, whose distribution functions have free or fixed functional forms. An approach based on the Bernstein expansion of polynomials and optimization is proposed. In particular, we search for the elements of a multi-dimensional p-box that minimize (i.e., the best-case) and maximize (i.e., the worst-case) the probability of inner and outer bounding sets of the failure domain. This technique yields intervals that bound the range of failure probabilities. The offset between this bounding interval and the actual failure probability range can be made arbitrarily tight with additional computational effort.

Computing rates of Markov models of voltage-gated ion channels by inverting partial differential equations governing the probability density functions of the conducting and non-conducting states.

PubMed

Tveito, Aslak; Lines, Glenn T; Edwards, Andrew G; McCulloch, Andrew

2016-07-01

Markov models are ubiquitously used to represent the function of single ion channels. However, solving the inverse problem to construct a Markov model of single channel dynamics from bilayer or patch-clamp recordings remains challenging, particularly for channels involving complex gating processes. Methods for solving the inverse problem are generally based on data from voltage clamp measurements. Here, we describe an alternative approach to this problem based on measurements of voltage traces. The voltage traces define probability density functions of the functional states of an ion channel. These probability density functions can also be computed by solving a deterministic system of partial differential equations. The inversion is based on tuning the rates of the Markov models used in the deterministic system of partial differential equations such that the solution mimics the properties of the probability density function gathered from (pseudo) experimental data as well as possible. The optimization is done by defining a cost function to measure the difference between the deterministic solution and the solution based on experimental data. By evoking the properties of this function, it is possible to infer whether the rates of the Markov model are identifiable by our method. We present applications to Markov model well-known from the literature. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A rational decision rule with extreme events.

PubMed

Basili, Marcello

2006-12-01

Risks induced by extreme events are characterized by small or ambiguous probabilities, catastrophic losses, or windfall gains. Through a new functional, that mimics the restricted Bayes-Hurwicz criterion within the Choquet expected utility approach, it is possible to represent the decisionmaker behavior facing both risky (large and reliable probability) and extreme (small or ambiguous probability) events. A new formalization of the precautionary principle (PP) is shown and a new functional, which encompasses both extreme outcomes and expectation of all the possible results for every act, is claimed.

Robust location and spread measures for nonparametric probability density function estimation.

PubMed

López-Rubio, Ezequiel

2009-10-01

Robustness against outliers is a desirable property of any unsupervised learning scheme. In particular, probability density estimators benefit from incorporating this feature. A possible strategy to achieve this goal is to substitute the sample mean and the sample covariance matrix by more robust location and spread estimators. Here we use the L1-median to develop a nonparametric probability density function (PDF) estimator. We prove its most relevant properties, and we show its performance in density estimation and classification applications.

Data Analysis Techniques for Physical Scientists

NASA Astrophysics Data System (ADS)

Pruneau, Claude A.

2017-10-01

Preface; How to read this book; 1. The scientific method; Part I. Foundation in Probability and Statistics: 2. Probability; 3. Probability models; 4. Classical inference I: estimators; 5. Classical inference II: optimization; 6. Classical inference III: confidence intervals and statistical tests; 7. Bayesian inference; Part II. Measurement Techniques: 8. Basic measurements; 9. Event reconstruction; 10. Correlation functions; 11. The multiple facets of correlation functions; 12. Data correction methods; Part III. Simulation Techniques: 13. Monte Carlo methods; 14. Collision and detector modeling; List of references; Index.

Identification of Stochastically Perturbed Autonomous Systems from Temporal Sequences of Probability Density Functions

NASA Astrophysics Data System (ADS)

Nie, Xiaokai; Luo, Jingjing; Coca, Daniel; Birkin, Mark; Chen, Jing

2018-03-01

The paper introduces a method for reconstructing one-dimensional iterated maps that are driven by an external control input and subjected to an additive stochastic perturbation, from sequences of probability density functions that are generated by the stochastic dynamical systems and observed experimentally.

Probability of survival during accidental immersion in cold water.

PubMed

Wissler, Eugene H

2003-01-01

Estimating the probability of survival during accidental immersion in cold water presents formidable challenges for both theoreticians and empirics. A number of theoretical models have been developed assuming that death occurs when the central body temperature, computed using a mathematical model, falls to a certain level. This paper describes a different theoretical approach to estimating the probability of survival. The human thermal model developed by Wissler is used to compute the central temperature during immersion in cold water. Simultaneously, a survival probability function is computed by solving a differential equation that defines how the probability of survival decreases with increasing time. The survival equation assumes that the probability of occurrence of a fatal event increases as the victim's central temperature decreases. Generally accepted views of the medical consequences of hypothermia and published reports of various accidents provide information useful for defining a "fatality function" that increases exponentially with decreasing central temperature. The particular function suggested in this paper yields a relationship between immersion time for 10% probability of survival and water temperature that agrees very well with Molnar's empirical observations based on World War II data. The method presented in this paper circumvents a serious difficulty with most previous models--that one's ability to survive immersion in cold water is determined almost exclusively by the ability to maintain a high level of shivering metabolism.

The H-Function and Probability Density Functions of Certain Algebraic Combinations of Independent Random Variables with H-Function Probability Distribution

DTIC Science & Technology

1981-05-01

functions and the H- function," Boletin do la Academia de Ciencias Fisicas Matematicas v Naturales (Caracas), 31, 95- 102 (1971). 120. Jain, U. C...Society, 37, 329- 334 (1973). 32. Oliver, M. L., and S. L. Kalla, "On the derivative of Fox’s H- function," (Spanish) Acta 14,dlcana de Ciencia -v...34 Universidade de Lisboa Revista de Faculdade de Ciencias FMatematicas, II, Series A, 13, 109-114 (1969-70). 92. Bajpai, S. D., "On some results involving Fox’s H

The force distribution probability function for simple fluids by density functional theory.

PubMed

Rickayzen, G; Heyes, D M

2013-02-28

Classical density functional theory (DFT) is used to derive a formula for the probability density distribution function, P(F), and probability distribution function, W(F), for simple fluids, where F is the net force on a particle. The final formula for P(F) ∝ exp(-AF(2)), where A depends on the fluid density, the temperature, and the Fourier transform of the pair potential. The form of the DFT theory used is only applicable to bounded potential fluids. When combined with the hypernetted chain closure of the Ornstein-Zernike equation, the DFT theory for W(F) agrees with molecular dynamics computer simulations for the Gaussian and bounded soft sphere at high density. The Gaussian form for P(F) is still accurate at lower densities (but not too low density) for the two potentials, but with a smaller value for the constant, A, than that predicted by the DFT theory.

A Semi-Analytical Method for the PDFs of A Ship Rolling in Random Oblique Waves

NASA Astrophysics Data System (ADS)

Liu, Li-qin; Liu, Ya-liu; Xu, Wan-hai; Li, Yan; Tang, You-gang

2018-03-01

The PDFs (probability density functions) and probability of a ship rolling under the random parametric and forced excitations were studied by a semi-analytical method. The rolling motion equation of the ship in random oblique waves was established. The righting arm obtained by the numerical simulation was approximately fitted by an analytical function. The irregular waves were decomposed into two Gauss stationary random processes, and the CARMA (2, 1) model was used to fit the spectral density function of parametric and forced excitations. The stochastic energy envelope averaging method was used to solve the PDFs and the probability. The validity of the semi-analytical method was verified by the Monte Carlo method. The C11 ship was taken as an example, and the influences of the system parameters on the PDFs and probability were analyzed. The results show that the probability of ship rolling is affected by the characteristic wave height, wave length, and the heading angle. In order to provide proper advice for the ship's manoeuvring, the parametric excitations should be considered appropriately when the ship navigates in the oblique seas.

Topics in inference and decision-making with partial knowledge

NASA Technical Reports Server (NTRS)

Safavian, S. Rasoul; Landgrebe, David

1990-01-01

Two essential elements needed in the process of inference and decision-making are prior probabilities and likelihood functions. When both of these components are known accurately and precisely, the Bayesian approach provides a consistent and coherent solution to the problems of inference and decision-making. In many situations, however, either one or both of the above components may not be known, or at least may not be known precisely. This problem of partial knowledge about prior probabilities and likelihood functions is addressed. There are at least two ways to cope with this lack of precise knowledge: robust methods, and interval-valued methods. First, ways of modeling imprecision and indeterminacies in prior probabilities and likelihood functions are examined; then how imprecision in the above components carries over to the posterior probabilities is examined. Finally, the problem of decision making with imprecise posterior probabilities and the consequences of such actions are addressed. Application areas where the above problems may occur are in statistical pattern recognition problems, for example, the problem of classification of high-dimensional multispectral remote sensing image data.

Probabilities and statistics for backscatter estimates obtained by a scatterometer with applications to new scatterometer design data

NASA Technical Reports Server (NTRS)

Pierson, Willard J., Jr.

1989-01-01

The values of the Normalized Radar Backscattering Cross Section (NRCS), sigma (o), obtained by a scatterometer are random variables whose variance is a known function of the expected value. The probability density function can be obtained from the normal distribution. Models for the expected value obtain it as a function of the properties of the waves on the ocean and the winds that generated the waves. Point estimates of the expected value were found from various statistics given the parameters that define the probability density function for each value. Random intervals were derived with a preassigned probability of containing that value. A statistical test to determine whether or not successive values of sigma (o) are truly independent was derived. The maximum likelihood estimates for wind speed and direction were found, given a model for backscatter as a function of the properties of the waves on the ocean. These estimates are biased as a result of the terms in the equation that involve natural logarithms, and calculations of the point estimates of the maximum likelihood values are used to show that the contributions of the logarithmic terms are negligible and that the terms can be omitted.

Prediction of water intake and excretion flows in Holstein dairy cows under thermoneutral conditions.

PubMed

Khelil-Arfa, H; Boudon, A; Maxin, G; Faverdin, P

2012-10-01

The increase in the worldwide demand for dairy products, associated with global warming, will emphasize the issue of water use efficiency in dairy systems. The evaluation of environmental issues related to the management of animal dejections will also require precise biotechnical models that can predict effluent management in farms. In this study, equations were developed and evaluated for predicting the main water flows at the dairy cow level, based on parameters related to cow productive performance and diet under thermoneutral conditions. Two datasets were gathered. The first one comprised 342 individual measurements of water balance in dairy cows obtained during 18 trials at the experimental farm of Méjussaume (INRA, France). Predictive equations of water intake, urine and fecal water excretion were developed by multiple regression using a stepwise selection of regressors from a list of seven candidate parameters, which were milk yield, dry matter intake (DMI), body weight, diet dry matter content (DM), proportion of concentrate (CONC) and content of crude protein (CP) ingested with forage and concentrate (CPf and CPc, g/kg DM). The second dataset was used for external validation of the developed equations and comprised 196 water flow measurements on experimental lots obtained from 43 published papers related to water balance or digestibility measurements in dairy cows. Although DMI was the first predictor of the total water intake (TWI), with a partial r(2) of 0.51, DM was the first predictive parameter of free water intake (FWI), with a partial r(2) of 0.57, likely due to the large variability of DM in the first dataset (from 11.5 to 91.4 g/100 g). This confirmed the compensation between water drunk and ingested with diet when DM changes. The variability of urine volume was explained mainly by the CPf associated with DMI (r.s.d. 5.4 kg/day for an average flow of 24.0 kg/day) and that of fecal water was explained by the proportion of CONC in the diet and DMI. External validation showed that predictive equations excluding DMI as predictive parameters could be used for FWI, urine and fecal water predictions if cows were fed a well-known total mixed ration. It also appeared that TWI and FWI were underestimated when ambient temperature increased above 25°C and possible means of including climatic parameters in future predictive equations were proposed.

A discrimination method for the detection of pneumonia using chest radiograph.

PubMed

Noor, Norliza Mohd; Rijal, Omar Mohd; Yunus, Ashari; Abu-Bakar, S A R

2010-03-01

This paper presents a statistical method for the detection of lobar pneumonia when using digitized chest X-ray films. Each region of interest was represented by a vector of wavelet texture measures which is then multiplied by the orthogonal matrix Q(2). The first two elements of the transformed vectors were shown to have a bivariate normal distribution. Misclassification probabilities were estimated using probability ellipsoids and discriminant functions. The result of this study recommends the detection of pneumonia by constructing probability ellipsoids or discriminant function using maximum energy and maximum column sum energy texture measures where misclassification probabilities were less than 0.15. 2009 Elsevier Ltd. All rights reserved.

Ubiquity of Benford's law and emergence of the reciprocal distribution

DOE PAGES

Friar, James Lewis; Goldman, Terrance J.; Pérez-Mercader, J.

2016-04-07

In this paper, we apply the Law of Total Probability to the construction of scale-invariant probability distribution functions (pdf's), and require that probability measures be dimensionless and unitless under a continuous change of scales. If the scale-change distribution function is scale invariant then the constructed distribution will also be scale invariant. Repeated application of this construction on an arbitrary set of (normalizable) pdf's results again in scale-invariant distributions. The invariant function of this procedure is given uniquely by the reciprocal distribution, suggesting a kind of universality. Finally, we separately demonstrate that the reciprocal distribution results uniquely from requiring maximum entropymore » for size-class distributions with uniform bin sizes.« less

Probability density and exceedance rate functions of locally Gaussian turbulence

NASA Technical Reports Server (NTRS)

Mark, W. D.

1989-01-01

A locally Gaussian model of turbulence velocities is postulated which consists of the superposition of a slowly varying strictly Gaussian component representing slow temporal changes in the mean wind speed and a more rapidly varying locally Gaussian turbulence component possessing a temporally fluctuating local variance. Series expansions of the probability density and exceedance rate functions of the turbulence velocity model, based on Taylor's series, are derived. Comparisons of the resulting two-term approximations with measured probability density and exceedance rate functions of atmospheric turbulence velocity records show encouraging agreement, thereby confirming the consistency of the measured records with the locally Gaussian model. Explicit formulas are derived for computing all required expansion coefficients from measured turbulence records.

"Mysteries" of the First and Second Laws of Thermodynamics

ERIC Educational Resources Information Center

Battino, Rubin

2007-01-01

The thermodynamic concepts of First and Second Laws with respect to the entropy function are described using atoms and molecules and probability as manifested in statistical mechanics. The First Law is conceptually understood as [Delta]U = Q + W and the Second Law of Thermodynamics and the entropy function have provided the probability and…

Neural response to reward anticipation under risk is nonlinear in probabilities.

PubMed

Hsu, Ming; Krajbich, Ian; Zhao, Chen; Camerer, Colin F

2009-02-18

A widely observed phenomenon in decision making under risk is the apparent overweighting of unlikely events and the underweighting of nearly certain events. This violates standard assumptions in expected utility theory, which requires that expected utility be linear (objective) in probabilities. Models such as prospect theory have relaxed this assumption and introduced the notion of a "probability weighting function," which captures the key properties found in experimental data. This study reports functional magnetic resonance imaging (fMRI) data that neural response to expected reward is nonlinear in probabilities. Specifically, we found that activity in the striatum during valuation of monetary gambles are nonlinear in probabilities in the pattern predicted by prospect theory, suggesting that probability distortion is reflected at the level of the reward encoding process. The degree of nonlinearity reflected in individual subjects' decisions is also correlated with striatal activity across subjects. Our results shed light on the neural mechanisms of reward processing, and have implications for future neuroscientific studies of decision making involving extreme tails of the distribution, where probability weighting provides an explanation for commonly observed behavioral anomalies.

21 CFR 1316.10 - Administrative probable cause.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Administrative probable cause. 1316.10 Section 1316.10 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Inspections § 1316.10 Administrative probable cause. If the judge...

Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

PubMed Central

2012-01-01

Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

The Effects of the Previous Outcome on Probabilistic Choice in Rats

PubMed Central

Marshall, Andrew T.; Kirkpatrick, Kimberly

2014-01-01

This study examined the effects of previous outcomes on subsequent choices in a probabilistic-choice task. Twenty-four rats were trained to choose between a certain outcome (1 or 3 pellets) versus an uncertain outcome (3 or 9 pellets), delivered with a probability of .1, .33, .67, and .9 in different phases. Uncertain outcome choices increased with the probability of uncertain food. Additionally, uncertain choices increased with the probability of uncertain food following both certain-choice outcomes and unrewarded uncertain choices. However, following uncertain-choice food outcomes, there was a tendency to choose the uncertain outcome in all cases, indicating that the rats continued to “gamble” after successful uncertain choices, regardless of the overall probability or magnitude of food. A subsequent manipulation, in which the probability of uncertain food varied within each session as a function of the previous uncertain outcome, examined how the previous outcome and probability of uncertain food affected choice in a dynamic environment. Uncertain-choice behavior increased with the probability of uncertain food. The rats exhibited increased sensitivity to probability changes and a greater degree of win–stay/lose–shift behavior than in the static phase. Simulations of two sequential choice models were performed to explore the possible mechanisms of reward value computations. The simulation results supported an exponentially decaying value function that updated as a function of trial (rather than time). These results emphasize the importance of analyzing global and local factors in choice behavior and suggest avenues for the future development of sequential-choice models. PMID:23205915

The Finite-Size Scaling Relation for the Order-Parameter Probability Distribution of the Six-Dimensional Ising Model

NASA Astrophysics Data System (ADS)

Merdan, Ziya; Karakuş, Özlem

2016-11-01

The six dimensional Ising model with nearest-neighbor pair interactions has been simulated and verified numerically on the Creutz Cellular Automaton by using five bit demons near the infinite-lattice critical temperature with the linear dimensions L=4,6,8,10. The order parameter probability distribution for six dimensional Ising model has been calculated at the critical temperature. The constants of the analytical function have been estimated by fitting to probability function obtained numerically at the finite size critical point.

LFSPMC: Linear feature selection program using the probability of misclassification

NASA Technical Reports Server (NTRS)

Guseman, L. F., Jr.; Marion, B. P.

1975-01-01

The computational procedure and associated computer program for a linear feature selection technique are presented. The technique assumes that: a finite number, m, of classes exists; each class is described by an n-dimensional multivariate normal density function of its measurement vectors; the mean vector and covariance matrix for each density function are known (or can be estimated); and the a priori probability for each class is known. The technique produces a single linear combination of the original measurements which minimizes the one-dimensional probability of misclassification defined by the transformed densities.

Exact evaluations of some Meijer G-functions and probability of all eigenvalues real for the product of two Gaussian matrices

NASA Astrophysics Data System (ADS)

Kumar, Santosh

2015-11-01

We provide a proof to a recent conjecture by Forrester (2014 J. Phys. A: Math. Theor. 47 065202) regarding the algebraic and arithmetic structure of Meijer G-functions which appear in the expression for probability of all eigenvalues real for the product of two real Gaussian matrices. In the process we come across several interesting identities involving Meijer G-functions.

Statistics of intensity in adaptive-optics images and their usefulness for detection and photometry of exoplanets.

PubMed

Gladysz, Szymon; Yaitskova, Natalia; Christou, Julian C

2010-11-01

This paper is an introduction to the problem of modeling the probability density function of adaptive-optics speckle. We show that with the modified Rician distribution one cannot describe the statistics of light on axis. A dual solution is proposed: the modified Rician distribution for off-axis speckle and gamma-based distribution for the core of the point spread function. From these two distributions we derive optimal statistical discriminators between real sources and quasi-static speckles. In the second part of the paper the morphological difference between the two probability density functions is used to constrain a one-dimensional, "blind," iterative deconvolution at the position of an exoplanet. Separation of the probability density functions of signal and speckle yields accurate differential photometry in our simulations of the SPHERE planet finder instrument.

Minimal entropy probability paths between genome families.

PubMed

Ahlbrandt, Calvin; Benson, Gary; Casey, William

2004-05-01

We develop a metric for probability distributions with applications to biological sequence analysis. Our distance metric is obtained by minimizing a functional defined on the class of paths over probability measures on N categories. The underlying mathematical theory is connected to a constrained problem in the calculus of variations. The solution presented is a numerical solution, which approximates the true solution in a set of cases called rich paths where none of the components of the path is zero. The functional to be minimized is motivated by entropy considerations, reflecting the idea that nature might efficiently carry out mutations of genome sequences in such a way that the increase in entropy involved in transformation is as small as possible. We characterize sequences by frequency profiles or probability vectors, in the case of DNA where N is 4 and the components of the probability vector are the frequency of occurrence of each of the bases A, C, G and T. Given two probability vectors a and b, we define a distance function based as the infimum of path integrals of the entropy function H( p) over all admissible paths p(t), 0 < or = t< or =1, with p(t) a probability vector such that p(0)=a and p(1)=b. If the probability paths p(t) are parameterized as y(s) in terms of arc length s and the optimal path is smooth with arc length L, then smooth and "rich" optimal probability paths may be numerically estimated by a hybrid method of iterating Newton's method on solutions of a two point boundary value problem, with unknown distance L between the abscissas, for the Euler-Lagrange equations resulting from a multiplier rule for the constrained optimization problem together with linear regression to improve the arc length estimate L. Matlab code for these numerical methods is provided which works only for "rich" optimal probability vectors. These methods motivate a definition of an elementary distance function which is easier and faster to calculate, works on non-rich vectors, does not involve variational theory and does not involve differential equations, but is a better approximation of the minimal entropy path distance than the distance //b-a//(2). We compute minimal entropy distance matrices for examples of DNA myostatin genes and amino-acid sequences across several species. Output tree dendograms for our minimal entropy metric are compared with dendograms based on BLAST and BLAST identity scores.

On Replacing "Quantum Thinking" with Counterfactual Reasoning

NASA Astrophysics Data System (ADS)

Narens, Louis

The probability theory used in quantum mechanics is currently being employed by psychologists to model the impact of context on decision. Its event space consists of closed subspaces of a Hilbert space, and its probability function sometimes violate the law of the finite additivity of probabilities. Results from the quantum mechanics literature indicate that such a "Hilbert space probability theory" cannot be extended in a useful way to standard, finitely additive, probability theory by the addition of new events with specific probabilities. This chapter presents a new kind of probability theory that shares many fundamental algebraic characteristics with Hilbert space probability theory but does extend to standard probability theory by adjoining new events with specific probabilities. The new probability theory arises from considerations about how psychological experiments are related through counterfactual reasoning.

Estimation of the lower and upper bounds on the probability of failure using subset simulation and random set theory

NASA Astrophysics Data System (ADS)

Alvarez, Diego A.; Uribe, Felipe; Hurtado, Jorge E.

2018-02-01

Random set theory is a general framework which comprises uncertainty in the form of probability boxes, possibility distributions, cumulative distribution functions, Dempster-Shafer structures or intervals; in addition, the dependence between the input variables can be expressed using copulas. In this paper, the lower and upper bounds on the probability of failure are calculated by means of random set theory. In order to accelerate the calculation, a well-known and efficient probability-based reliability method known as subset simulation is employed. This method is especially useful for finding small failure probabilities in both low- and high-dimensional spaces, disjoint failure domains and nonlinear limit state functions. The proposed methodology represents a drastic reduction of the computational labor implied by plain Monte Carlo simulation for problems defined with a mixture of representations for the input variables, while delivering similar results. Numerical examples illustrate the efficiency of the proposed approach.

Probabilities for gravitational lensing by point masses in a locally inhomogeneous universe

NASA Technical Reports Server (NTRS)

Isaacson, Jeffrey A.; Canizares, Claude R.

1989-01-01

Probability functions for gravitational lensing by point masses that incorporate Poisson statistics and flux conservation are formulated in the Dyer-Roeder construction. Optical depths to lensing for distant sources are calculated using both the method of Press and Gunn (1973) which counts lenses in an otherwise empty cone, and the method of Ehlers and Schneider (1986) which projects lensing cross sections onto the source sphere. These are then used as parameters of the probability density for lensing in the case of a critical (q0 = 1/2) Friedmann universe. A comparison of the probability functions indicates that the effects of angle-averaging can be well approximated by adjusting the average magnification along a random line of sight so as to conserve flux.

ProbOnto: ontology and knowledge base of probability distributions.

PubMed

Swat, Maciej J; Grenon, Pierre; Wimalaratne, Sarala

2016-09-01

Probability distributions play a central role in mathematical and statistical modelling. The encoding, annotation and exchange of such models could be greatly simplified by a resource providing a common reference for the definition of probability distributions. Although some resources exist, no suitably detailed and complex ontology exists nor any database allowing programmatic access. ProbOnto, is an ontology-based knowledge base of probability distributions, featuring more than 80 uni- and multivariate distributions with their defining functions, characteristics, relationships and re-parameterization formulas. It can be used for model annotation and facilitates the encoding of distribution-based models, related functions and quantities. http://probonto.org mjswat@ebi.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Probability distribution functions in turbulent convection

NASA Technical Reports Server (NTRS)

Balachandar, S.; Sirovich, L.

1991-01-01

Results of an extensive investigation of probability distribution functions (pdfs) for Rayleigh-Benard convection, in hard turbulence regime, are presented. It is shown that the pdfs exhibit a high degree of internal universality. In certain cases this universality is established within two Kolmogorov scales of a boundary. A discussion of the factors leading to the universality is presented.

Simulation Of Wave Function And Probability Density Of Modified Poschl Teller Potential Derived Using Supersymmetric Quantum Mechanics

NASA Astrophysics Data System (ADS)

Angraini, Lily Maysari; Suparmi, Variani, Viska Inda

2010-12-01

SUSY quantum mechanics can be applied to solve Schrodinger equation for high dimensional system that can be reduced into one dimensional system and represented in lowering and raising operators. Lowering and raising operators can be obtained using relationship between original Hamiltonian equation and the (super) potential equation. In this paper SUSY quantum mechanics is used as a method to obtain the wave function and the energy level of the Modified Poschl Teller potential. The graph of wave function equation and probability density is simulated by using Delphi 7.0 programming language. Finally, the expectation value of quantum mechanics operator could be calculated analytically using integral form or probability density graph resulted by the programming.

Bivariate extreme value distributions

NASA Technical Reports Server (NTRS)

Elshamy, M.

1992-01-01

In certain engineering applications, such as those occurring in the analyses of ascent structural loads for the Space Transportation System (STS), some of the load variables have a lower bound of zero. Thus, the need for practical models of bivariate extreme value probability distribution functions with lower limits was identified. We discuss the Gumbel models and present practical forms of bivariate extreme probability distributions of Weibull and Frechet types with two parameters. Bivariate extreme value probability distribution functions can be expressed in terms of the marginal extremel distributions and a 'dependence' function subject to certain analytical conditions. Properties of such bivariate extreme distributions, sums and differences of paired extremals, as well as the corresponding forms of conditional distributions, are discussed. Practical estimation techniques are also given.

A brief introduction to probability.

PubMed

Di Paola, Gioacchino; Bertani, Alessandro; De Monte, Lavinia; Tuzzolino, Fabio

2018-02-01

The theory of probability has been debated for centuries: back in 1600, French mathematics used the rules of probability to place and win bets. Subsequently, the knowledge of probability has significantly evolved and is now an essential tool for statistics. In this paper, the basic theoretical principles of probability will be reviewed, with the aim of facilitating the comprehension of statistical inference. After a brief general introduction on probability, we will review the concept of the "probability distribution" that is a function providing the probabilities of occurrence of different possible outcomes of a categorical or continuous variable. Specific attention will be focused on normal distribution that is the most relevant distribution applied to statistical analysis.

RADC Multi-Dimensional Signal-Processing Research Program.

DTIC Science & Technology

1980-09-30

Formulation 7 3.2.2 Methods of Accelerating Convergence 8 3.2.3 Application to Image Deblurring 8 3.2.4 Extensions 11 3.3 Convergence of Iterative Signal... noise -driven linear filters, permit development of the joint probability density function oz " kelihood function for the image. With an expression...spatial linear filter driven by white noise (see Fig. i). If the probability density function for the white noise is known, Fig. t. Model for image

Maximum entropy approach to statistical inference for an ocean acoustic waveguide.

PubMed

Knobles, D P; Sagers, J D; Koch, R A

2012-02-01

A conditional probability distribution suitable for estimating the statistical properties of ocean seabed parameter values inferred from acoustic measurements is derived from a maximum entropy principle. The specification of the expectation value for an error function constrains the maximization of an entropy functional. This constraint determines the sensitivity factor (β) to the error function of the resulting probability distribution, which is a canonical form that provides a conservative estimate of the uncertainty of the parameter values. From the conditional distribution, marginal distributions for individual parameters can be determined from integration over the other parameters. The approach is an alternative to obtaining the posterior probability distribution without an intermediary determination of the likelihood function followed by an application of Bayes' rule. In this paper the expectation value that specifies the constraint is determined from the values of the error function for the model solutions obtained from a sparse number of data samples. The method is applied to ocean acoustic measurements taken on the New Jersey continental shelf. The marginal probability distribution for the values of the sound speed ratio at the surface of the seabed and the source levels of a towed source are examined for different geoacoustic model representations. © 2012 Acoustical Society of America

Random function representation of stationary stochastic vector processes for probability density evolution analysis of wind-induced structures

NASA Astrophysics Data System (ADS)

Liu, Zhangjun; Liu, Zenghui

2018-06-01

This paper develops a hybrid approach of spectral representation and random function for simulating stationary stochastic vector processes. In the proposed approach, the high-dimensional random variables, included in the original spectral representation (OSR) formula, could be effectively reduced to only two elementary random variables by introducing the random functions that serve as random constraints. Based on this, a satisfactory simulation accuracy can be guaranteed by selecting a small representative point set of the elementary random variables. The probability information of the stochastic excitations can be fully emerged through just several hundred of sample functions generated by the proposed approach. Therefore, combined with the probability density evolution method (PDEM), it could be able to implement dynamic response analysis and reliability assessment of engineering structures. For illustrative purposes, a stochastic turbulence wind velocity field acting on a frame-shear-wall structure is simulated by constructing three types of random functions to demonstrate the accuracy and efficiency of the proposed approach. Careful and in-depth studies concerning the probability density evolution analysis of the wind-induced structure have been conducted so as to better illustrate the application prospects of the proposed approach. Numerical examples also show that the proposed approach possesses a good robustness.

Stochastic optimal operation of reservoirs based on copula functions

NASA Astrophysics Data System (ADS)

Lei, Xiao-hui; Tan, Qiao-feng; Wang, Xu; Wang, Hao; Wen, Xin; Wang, Chao; Zhang, Jing-wen

2018-02-01

Stochastic dynamic programming (SDP) has been widely used to derive operating policies for reservoirs considering streamflow uncertainties. In SDP, there is a need to calculate the transition probability matrix more accurately and efficiently in order to improve the economic benefit of reservoir operation. In this study, we proposed a stochastic optimization model for hydropower generation reservoirs, in which 1) the transition probability matrix was calculated based on copula functions; and 2) the value function of the last period was calculated by stepwise iteration. Firstly, the marginal distribution of stochastic inflow in each period was built and the joint distributions of adjacent periods were obtained using the three members of the Archimedean copulas, based on which the conditional probability formula was derived. Then, the value in the last period was calculated by a simple recursive equation with the proposed stepwise iteration method and the value function was fitted with a linear regression model. These improvements were incorporated into the classic SDP and applied to the case study in Ertan reservoir, China. The results show that the transition probability matrix can be more easily and accurately obtained by the proposed copula function based method than conventional methods based on the observed or synthetic streamflow series, and the reservoir operation benefit can also be increased.

Defense strategies for asymmetric networked systems under composite utilities

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

Rao, Nageswara S.; Ma, Chris Y. T.; Hausken, Kjell

We consider an infrastructure of networked systems with discrete components that can be reinforced at certain costs to guard against attacks. The communications network plays a critical, asymmetric role of providing the vital connectivity between the systems. We characterize the correlations within this infrastructure at two levels using (a) aggregate failure correlation function that specifies the infrastructure failure probability giventhe failure of an individual system or network, and (b) first order differential conditions on system survival probabilities that characterize component-level correlations. We formulate an infrastructure survival game between an attacker and a provider, who attacks and reinforces individual components, respectively.more » They use the composite utility functions composed of a survival probability term and a cost term, and the previously studiedsum-form and product-form utility functions are their special cases. At Nash Equilibrium, we derive expressions for individual system survival probabilities and the expected total number of operational components. We apply and discuss these estimates for a simplified model of distributed cloud computing infrastructure« less

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Differential Gene Expression in Normal Human Mammary Epithelial Cells Treated with Malathion Monitored by DNA Microarrays

PubMed Central

Gwinn, Maureen R.; Whipkey, Diana L.; Tennant, Lora B.; Weston, Ainsley

2005-01-01

Organophosphate pesticides are a major source of occupational exposure in the United States. Moreover, malathion has been sprayed over major urban populations in an effort to control mosquitoes carrying West Nile virus. Previous research, reviewed by the U.S. Environmental Protection Agency, on the genotoxicity and carcinogenicity of malathion has been inconclusive, although malathion is a known endocrine disruptor. Here, interindividual variations and commonality of gene expression signatures have been studied in normal human mammary epithelial cells from four women undergoing reduction mammoplasty. The cell strains were obtained from the discarded tissues through the Cooperative Human Tissue Network (sponsors: National Cancer Institute and National Disease Research Interchange). Interindividual variation of gene expression patterns in response to malathion was observed in various clustering patterns for the four cell strains. Further clustering identified three genes with increased expression after treatment in all four cell strains. These genes were two aldo–keto reductases (AKR1C1 and AKR1C2) and an estrogen-responsive gene (EBBP). Decreased expression of six RNA species was seen at various time points in all cell strains analyzed: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1), and a gene of unknown function (GenBank accession no. AI859865). Expression changes in all these genes, detected by DNA microarrays, have been verified by real-time polymerase chain reaction. Differential changes in expression of these genes may yield biomarkers that provide insight into interindividual variation in malathion toxicity. PMID:16079077

A very efficient approach to compute the first-passage probability density function in a time-changed Brownian model: Applications in finance

NASA Astrophysics Data System (ADS)

Ballestra, Luca Vincenzo; Pacelli, Graziella; Radi, Davide

2016-12-01

We propose a numerical method to compute the first-passage probability density function in a time-changed Brownian model. In particular, we derive an integral representation of such a density function in which the integrand functions must be obtained solving a system of Volterra equations of the first kind. In addition, we develop an ad-hoc numerical procedure to regularize and solve this system of integral equations. The proposed method is tested on three application problems of interest in mathematical finance, namely the calculation of the survival probability of an indebted firm, the pricing of a single-knock-out put option and the pricing of a double-knock-out put option. The results obtained reveal that the novel approach is extremely accurate and fast, and performs significantly better than the finite difference method.

A Pearson VII distribution function for fast calculation of dechanneling and angular dispersion of beams

NASA Astrophysics Data System (ADS)

Shao, Lin; Peng, Luohan

2009-12-01

Although multiple scattering theories have been well developed, numerical calculation is complicated and only tabulated values have been available, which has caused inconvenience in practical use. We have found that a Pearson VII distribution function can be used to fit Lugujjo and Mayer's probability curves in describing the dechanneling phenomenon in backscattering analysis, over a wide range of disorder levels. Differentiation of the obtained function gives another function to calculate angular dispersion of the beam in the frameworks by Sigmund and Winterbon. The present work provides an easy calculation of both dechanneling probability and angular dispersion for any arbitrary combination of beam and target having a reduced thickness ⩾0.6, which can be implemented in modeling of channeling spectra. Furthermore, we used a Monte Carlo simulation program to calculate the deflection probability and compared them with previously tabulated data. A good agreement was reached.

Habitat suitability criteria via parametric distributions: estimation, model selection and uncertainty

USGS Publications Warehouse

Som, Nicholas A.; Goodman, Damon H.; Perry, Russell W.; Hardy, Thomas B.

2016-01-01

Previous methods for constructing univariate habitat suitability criteria (HSC) curves have ranged from professional judgement to kernel-smoothed density functions or combinations thereof. We present a new method of generating HSC curves that applies probability density functions as the mathematical representation of the curves. Compared with previous approaches, benefits of our method include (1) estimation of probability density function parameters directly from raw data, (2) quantitative methods for selecting among several candidate probability density functions, and (3) concise methods for expressing estimation uncertainty in the HSC curves. We demonstrate our method with a thorough example using data collected on the depth of water used by juvenile Chinook salmon (Oncorhynchus tschawytscha) in the Klamath River of northern California and southern Oregon. All R code needed to implement our example is provided in the appendix. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Characterization of nonGaussian atmospheric turbulence for prediction of aircraft response statistics

NASA Technical Reports Server (NTRS)

Mark, W. D.

1977-01-01

Mathematical expressions were derived for the exceedance rates and probability density functions of aircraft response variables using a turbulence model that consists of a low frequency component plus a variance modulated Gaussian turbulence component. The functional form of experimentally observed concave exceedance curves was predicted theoretically, the strength of the concave contribution being governed by the coefficient of variation of the time fluctuating variance of the turbulence. Differences in the functional forms of response exceedance curves and probability densities also were shown to depend primarily on this same coefficient of variation. Criteria were established for the validity of the local stationary assumption that is required in the derivations of the exceedance curves and probability density functions. These criteria are shown to depend on the relative time scale of the fluctuations in the variance, the fluctuations in the turbulence itself, and on the nominal duration of the relevant aircraft impulse response function. Metrics that can be generated from turbulence recordings for testing the validity of the local stationary assumption were developed.

Radar detection with the Neyman-Pearson criterion using supervised-learning-machines trained with the cross-entropy error

NASA Astrophysics Data System (ADS)

Jarabo-Amores, María-Pilar; la Mata-Moya, David de; Gil-Pita, Roberto; Rosa-Zurera, Manuel

2013-12-01

The application of supervised learning machines trained to minimize the Cross-Entropy error to radar detection is explored in this article. The detector is implemented with a learning machine that implements a discriminant function, which output is compared to a threshold selected to fix a desired probability of false alarm. The study is based on the calculation of the function the learning machine approximates to during training, and the application of a sufficient condition for a discriminant function to be used to approximate the optimum Neyman-Pearson (NP) detector. In this article, the function a supervised learning machine approximates to after being trained to minimize the Cross-Entropy error is obtained. This discriminant function can be used to implement the NP detector, which maximizes the probability of detection, maintaining the probability of false alarm below or equal to a predefined value. Some experiments about signal detection using neural networks are also presented to test the validity of the study.

Comorbid Trends in World Trade Center Cough Syndrome and Probable Posttraumatic Stress Disorder in Firefighters

PubMed Central

Niles, Justin K.; Gustave, Jackson; Cohen, Hillel W.; Zeig-Owens, Rachel; Kelly, Kerry J.; Glass, Lara; Prezant, David J.

2011-01-01

Background: We describe the relationship between World Trade Center (WTC) cough syndrome symptoms, pulmonary function, and symptoms consistent with probable posttraumatic stress disorder (PTSD) in WTC-exposed firefighters in the first year post-September 11, 2001 (baseline), and 3 to 4 years later (follow-up). Methods: Five thousand three hundred sixty-three firefighters completed pulmonary function tests (PFTs) and questionnaires at both times. Relationships among WTC cough syndrome, probable PTSD, and PFTs were analyzed using simple and multivariable models. We also examined the effects of cofactors, including WTC exposure. Results: WTC cough syndrome was found in 1,561 firefighters (29.1%) at baseline and 1,186 (22.1%) at follow-up, including 559 with delayed onset (present only at follow-up). Probable PTSD was found in 458 firefighters (8.5%) at baseline and 548 (10.2%) at follow-up, including 343 with delayed onset. Baseline PTSD symptom counts and probable PTSD were associated with WTC cough syndrome at baseline, at follow-up, and in those with delayed-onset WTC cough syndrome. Similarly, WTC cough syndrome symptom counts and WTC cough syndrome at baseline were associated with probable PTSD at baseline, at follow-up, and in those with delayed-onset probable PTSD. WTC arrival time and work duration were cofactors of both outcomes. A small but consistent association existed between pulmonary function and WTC cough syndrome, but none with PTSD. Conclusions: The study showed a moderate association between WTC cough syndrome and probable PTSD. The presence of one contributed to the likelihood of the other, even after adjustment for shared cofactors such as WTC exposure. PMID:21546435

Methods, apparatus and system for notification of predictable memory failure

DOEpatents

Cher, Chen-Yong; Andrade Costa, Carlos H.; Park, Yoonho; Rosenburg, Bryan S.; Ryu, Kyung D.

2017-01-03

A method for providing notification of a predictable memory failure includes the steps of: obtaining information regarding at least one condition associated with a memory; calculating a memory failure probability as a function of the obtained information; calculating a failure probability threshold; and generating a signal when the memory failure probability exceeds the failure probability threshold, the signal being indicative of a predicted future memory failure.

High probability neurotransmitter release sites represent an energy efficient design

PubMed Central

Lu, Zhongmin; Chouhan, Amit K.; Borycz, Jolanta A.; Lu, Zhiyuan; Rossano, Adam J; Brain, Keith L.; Zhou, You; Meinertzhagen, Ian A.; Macleod, Gregory T.

2016-01-01

Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High probability release sites are not uncommon but their advantages are not well understood. Here we test the hypothesis that high probability release sites represent an energy efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements we calculated release site probabilities to differ considerably between terminals (0.33 vs. 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high probability release site terminals were found to be more efficient (0.13 vs. 0.06). Our analytical model indicates that energy efficiency is optimal (~0.15) at high release site probabilities (~0.76). As limitations in energy supply constrain neural function, high probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high efficiency terminals depress significantly during episodic bursts of activity. PMID:27593375

Metocean design parameter estimation for fixed platform based on copula functions

NASA Astrophysics Data System (ADS)

Zhai, Jinjin; Yin, Qilin; Dong, Sheng

2017-08-01

Considering the dependent relationship among wave height, wind speed, and current velocity, we construct novel trivariate joint probability distributions via Archimedean copula functions. Total 30-year data of wave height, wind speed, and current velocity in the Bohai Sea are hindcast and sampled for case study. Four kinds of distributions, namely, Gumbel distribution, lognormal distribution, Weibull distribution, and Pearson Type III distribution, are candidate models for marginal distributions of wave height, wind speed, and current velocity. The Pearson Type III distribution is selected as the optimal model. Bivariate and trivariate probability distributions of these environmental conditions are established based on four bivariate and trivariate Archimedean copulas, namely, Clayton, Frank, Gumbel-Hougaard, and Ali-Mikhail-Haq copulas. These joint probability models can maximize marginal information and the dependence among the three variables. The design return values of these three variables can be obtained by three methods: univariate probability, conditional probability, and joint probability. The joint return periods of different load combinations are estimated by the proposed models. Platform responses (including base shear, overturning moment, and deck displacement) are further calculated. For the same return period, the design values of wave height, wind speed, and current velocity obtained by the conditional and joint probability models are much smaller than those by univariate probability. Considering the dependence among variables, the multivariate probability distributions provide close design parameters to actual sea state for ocean platform design.

Development and application of an empirical probability distribution for the prediction error of re-entry body maximum dynamic pressure

NASA Technical Reports Server (NTRS)

Lanzi, R. James; Vincent, Brett T.

1993-01-01

The relationship between actual and predicted re-entry maximum dynamic pressure is characterized using a probability density function and a cumulative distribution function derived from sounding rocket flight data. This paper explores the properties of this distribution and demonstrates applications of this data with observed sounding rocket re-entry body damage characteristics to assess probabilities of sustaining various levels of heating damage. The results from this paper effectively bridge the gap existing in sounding rocket reentry analysis between the known damage level/flight environment relationships and the predicted flight environment.

A Method for Evaluating Tuning Functions of Single Neurons based on Mutual Information Maximization

NASA Astrophysics Data System (ADS)

Brostek, Lukas; Eggert, Thomas; Ono, Seiji; Mustari, Michael J.; Büttner, Ulrich; Glasauer, Stefan

2011-03-01

We introduce a novel approach for evaluation of neuronal tuning functions, which can be expressed by the conditional probability of observing a spike given any combination of independent variables. This probability can be estimated out of experimentally available data. By maximizing the mutual information between the probability distribution of the spike occurrence and that of the variables, the dependence of the spike on the input variables is maximized as well. We used this method to analyze the dependence of neuronal activity in cortical area MSTd on signals related to movement of the eye and retinal image movement.

Using transportation accident databases to investigate ignition and explosion probabilities of flammable spills.

PubMed

Ronza, A; Vílchez, J A; Casal, J

2007-07-19

Risk assessment of hazardous material spill scenarios, and quantitative risk assessment in particular, make use of event trees to account for the possible outcomes of hazardous releases. Using event trees entails the definition of probabilities of occurrence for events such as spill ignition and blast formation. This study comprises an extensive analysis of ignition and explosion probability data proposed in previous work. Subsequently, the results of the survey of two vast US federal spill databases (HMIRS, by the Department of Transportation, and MINMOD, by the US Coast Guard) are reported and commented on. Some tens of thousands of records of hydrocarbon spills were analysed. The general pattern of statistical ignition and explosion probabilities as a function of the amount and the substance spilled is discussed. Equations are proposed based on statistical data that predict the ignition probability of hydrocarbon spills as a function of the amount and the substance spilled. Explosion probabilities are put forth as well. Two sets of probability data are proposed: it is suggested that figures deduced from HMIRS be used in land transportation risk assessment, and MINMOD results with maritime scenarios assessment. Results are discussed and compared with previous technical literature.

Structural Reliability Analysis and Optimization: Use of Approximations

NASA Technical Reports Server (NTRS)

Grandhi, Ramana V.; Wang, Liping

1999-01-01

This report is intended for the demonstration of function approximation concepts and their applicability in reliability analysis and design. Particularly, approximations in the calculation of the safety index, failure probability and structural optimization (modification of design variables) are developed. With this scope in mind, extensive details on probability theory are avoided. Definitions relevant to the stated objectives have been taken from standard text books. The idea of function approximations is to minimize the repetitive use of computationally intensive calculations by replacing them with simpler closed-form equations, which could be nonlinear. Typically, the approximations provide good accuracy around the points where they are constructed, and they need to be periodically updated to extend their utility. There are approximations in calculating the failure probability of a limit state function. The first one, which is most commonly discussed, is how the limit state is approximated at the design point. Most of the time this could be a first-order Taylor series expansion, also known as the First Order Reliability Method (FORM), or a second-order Taylor series expansion (paraboloid), also known as the Second Order Reliability Method (SORM). From the computational procedure point of view, this step comes after the design point identification; however, the order of approximation for the probability of failure calculation is discussed first, and it is denoted by either FORM or SORM. The other approximation of interest is how the design point, or the most probable failure point (MPP), is identified. For iteratively finding this point, again the limit state is approximated. The accuracy and efficiency of the approximations make the search process quite practical for analysis intensive approaches such as the finite element methods; therefore, the crux of this research is to develop excellent approximations for MPP identification and also different approximations including the higher-order reliability methods (HORM) for representing the failure surface. This report is divided into several parts to emphasize different segments of the structural reliability analysis and design. Broadly, it consists of mathematical foundations, methods and applications. Chapter I discusses the fundamental definitions of the probability theory, which are mostly available in standard text books. Probability density function descriptions relevant to this work are addressed. In Chapter 2, the concept and utility of function approximation are discussed for a general application in engineering analysis. Various forms of function representations and the latest developments in nonlinear adaptive approximations are presented with comparison studies. Research work accomplished in reliability analysis is presented in Chapter 3. First, the definition of safety index and most probable point of failure are introduced. Efficient ways of computing the safety index with a fewer number of iterations is emphasized. In chapter 4, the probability of failure prediction is presented using first-order, second-order and higher-order methods. System reliability methods are discussed in chapter 5. Chapter 6 presents optimization techniques for the modification and redistribution of structural sizes for improving the structural reliability. The report also contains several appendices on probability parameters.

On the conservative nature of intragenic recombination

PubMed Central

Drummond, D. Allan; Silberg, Jonathan J.; Meyer, Michelle M.; Wilke, Claus O.; Arnold, Frances H.

2005-01-01

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function. Here, we compare recombination of the distantly related β-lactamases PSE-4 and TEM-1 to mutation of PSE-4. We show that, among β-lactamase variants containing the same number of amino acid substitutions, variants created by recombination retain function with a significantly higher probability than those generated by random mutagenesis. We present a simple model that accurately captures the differing effects of mutation and recombination in real and simulated proteins with only four parameters: (i) the amino acid sequence distance between parents, (ii) the number of substitutions, (iii) the average probability that random substitutions will preserve function, and (iv) the average probability that substitutions generated by recombination will preserve function. Our results expose a fundamental functional enrichment in regions of protein sequence space accessible by recombination and provide a framework for evaluating whether the relative rates of mutation and recombination observed in nature reflect the underlying imbalance in their effects on protein function. PMID:15809422

On the conservative nature of intragenic recombination.

PubMed

Drummond, D Allan; Silberg, Jonathan J; Meyer, Michelle M; Wilke, Claus O; Arnold, Frances H

2005-04-12

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function. Here, we compare recombination of the distantly related beta-lactamases PSE-4 and TEM-1 to mutation of PSE-4. We show that, among beta-lactamase variants containing the same number of amino acid substitutions, variants created by recombination retain function with a significantly higher probability than those generated by random mutagenesis. We present a simple model that accurately captures the differing effects of mutation and recombination in real and simulated proteins with only four parameters: (i) the amino acid sequence distance between parents, (ii) the number of substitutions, (iii) the average probability that random substitutions will preserve function, and (iv) the average probability that substitutions generated by recombination will preserve function. Our results expose a fundamental functional enrichment in regions of protein sequence space accessible by recombination and provide a framework for evaluating whether the relative rates of mutation and recombination observed in nature reflect the underlying imbalance in their effects on protein function.

The Havriliak-Negami relaxation and its relatives: the response, relaxation and probability density functions

NASA Astrophysics Data System (ADS)

Górska, K.; Horzela, A.; Bratek, Ł.; Dattoli, G.; Penson, K. A.

2018-04-01

We study functions related to the experimentally observed Havriliak-Negami dielectric relaxation pattern proportional in the frequency domain to [1+(iωτ0){\\hspace{0pt}}α]-β with τ0 > 0 being some characteristic time. For α = l/k< 1 (l and k being positive and relatively prime integers) and β > 0 we furnish exact and explicit expressions for response and relaxation functions in the time domain and suitable probability densities in their domain dual in the sense of the inverse Laplace transform. All these functions are expressed as finite sums of generalized hypergeometric functions, convenient to handle analytically and numerically. Introducing a reparameterization β = (2-q)/(q-1) and τ0 = (q-1){\\hspace{0pt}}1/α (1 < q < 2) we show that for 0 < α < 1 the response functions fα, β(t/τ0) go to the one-sided Lévy stable distributions when q tends to one. Moreover, applying the self-similarity property of the probability densities gα, β(u) , we introduce two-variable densities and show that they satisfy the integral form of the evolution equation.

Aging ballistic Lévy walks

NASA Astrophysics Data System (ADS)

Magdziarz, Marcin; Zorawik, Tomasz

2017-02-01

Aging can be observed for numerous physical systems. In such systems statistical properties [like probability distribution, mean square displacement (MSD), first-passage time] depend on a time span ta between the initialization and the beginning of observations. In this paper we study aging properties of ballistic Lévy walks and two closely related jump models: wait-first and jump-first. We calculate explicitly their probability distributions and MSDs. It turns out that despite similarities these models react very differently to the delay ta. Aging weakly affects the shape of probability density function and MSD of standard Lévy walks. For the jump models the shape of the probability density function is changed drastically. Moreover for the wait-first jump model we observe a different behavior of MSD when ta≪t and ta≫t .

Probability density function of non-reactive solute concentration in heterogeneous porous formations

Treesearch

Alberto Bellin; Daniele Tonina

2007-01-01

Available models of solute transport in heterogeneous formations lack in providing complete characterization of the predicted concentration. This is a serious drawback especially in risk analysis where confidence intervals and probability of exceeding threshold values are required. Our contribution to fill this gap of knowledge is a probability distribution model for...

Parameterization of N2O5 Reaction Probabilities on the Surface of Particles Containing Ammonium, Sulfate, and Nitrate

EPA Science Inventory

A comprehensive parameterization was developed for the heterogeneous reaction probability (γ) of N₂O₅ as a function of temperature, relative humidity, particle composition, and phase state, for use in advanced air quality models. The reaction probabilities o...

An application of probability to combinatorics: a proof of Vandermonde identity

NASA Astrophysics Data System (ADS)

Paolillo, Bonaventura; Rizzo, Piermichele; Vincenzi, Giovanni

2017-08-01

In this paper, we give possible suggestions for a classroom lesson about an application of probability using basic mathematical notions. We will approach to some combinatoric results without using 'induction', 'polynomial identities' nor 'generating functions', and will give a proof of the 'Vandermonde Identity' using elementary notions of probability.

Concise calculation of the scaling function, exponents, and probability functional of the Edwards-Wilkinson equation with correlated noise

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

Yu, Y.; Pang, N.; Halpin-Healy, T.

1994-12-01

The linear Langevin equation proposed by Edwards and Wilkinson [Proc. R. Soc. London A 381, 17 (1982)] is solved in closed form for noise of arbitrary space and time correlation. Furthermore, the temporal development of the full probability functional describing the height fluctuations is derived exactly, exhibiting an interesting evolution between two distinct Gaussian forms. We determine explicitly the dynamic scaling function for the interfacial width for any given initial condition, isolate the early-time behavior, and discover an invariance that was unsuspected in this problem of arbitrary spatiotemporal noise.

The Lateral Trigger Probability function for the Ultra-High Energy Cosmic Ray showers detected by the Pierre Auger Observatory

NASA Astrophysics Data System (ADS)

Pierre Auger Collaboration; Abreu, P.; Aglietta, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antičić, T.; Anzalone, A.; Aramo, C.; Arganda, E.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Bäcker, T.; Balzer, M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Barroso, S. L. C.; Baughman, B.; Bäuml, J.; Beatty, J. J.; Becker, B. R.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; Benzvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Burton, R. E.; Caballero-Mora, K. S.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chudoba, J.; Clay, R. W.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Domenico, M.; de Donato, C.; de Jong, S. J.; de La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; de Mitri, I.; de Souza, V.; de Vries, K. D.; Decerprit, G.; Del Peral, L.; Deligny, O.; Dembinski, H.; Dhital, N.; di Giulio, C.; Diaz, J. C.; Díaz Castro, M. L.; Diep, P. N.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; Dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Etchegoyen, A.; Facal San Luis, P.; Fajardo Tapia, I.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Ferrero, A.; Fick, B.; Filevich, A.; Filipčič, A.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; García Gámez, D.; Garcia-Pinto, D.; Gascon, A.; Gemmeke, H.; Gesterling, K.; Ghia, P. L.; Giaccari, U.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gonçalves, P.; Gonzalez, D.; Gonzalez, J. G.; Gookin, B.; Góra, D.; Gorgi, A.; Gouffon, P.; Gozzini, S. R.; Grashorn, E.; Grebe, S.; Griffith, N.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Guzman, A.; Hague, J. D.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horneffer, A.; Hrabovský, M.; Huege, T.; Insolia, A.; Ionita, F.; Italiano, A.; Jarne, C.; Jiraskova, S.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuehn, F.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; Lachaud, C.; Lautridou, P.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Lemiere, A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Meurer, C.; Mićanović, S.; Micheletti, M. I.; Miller, W.; Miramonti, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, E.; Moreno, J. C.; Morris, C.; Mostafá, M.; Moura, C. A.; Mueller, S.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Nhung, P. T.; Niemietz, L.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Nyklicek, M.; Oehlschläger, J.; Olinto, A.; Oliva, P.; Olmos-Gilbaja, V. M.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parra, A.; Parsons, R. D.; Pastor, S.; Paul, T.; Pech, M.; Pȩkala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrinca, P.; Petrolini, A.; Petrov, Y.; Petrovic, J.; Pfendner, C.; Phan, N.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Ponce, V. H.; Pontz, M.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Robledo, C.; Rodrigues de Carvalho, W.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-D'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Salamida, F.; Salazar, H.; Salina, G.; Sánchez, F.; Santander, M.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulte, S.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Stapleton, J.; Stasielak, J.; Stephan, M.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tamashiro, A.; Tapia, A.; Tartare, M.; Taşcău, O.; Tavera Ruiz, C. G.; Tcaciuc, R.; Tegolo, D.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tiwari, D. K.; Tkaczyk, W.; Todero Peixoto, C. J.; Tomé, B.; Tonachini, A.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; Varela, E.; Vargas Cárdenas, B.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Warner, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Westerhoff, S.; Whelan, B. J.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Winders, L.; Winnick, M. G.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Ziolkowski, M.

2011-12-01

In this paper we introduce the concept of Lateral Trigger Probability (LTP) function, i.e., the probability for an Extensive Air Shower (EAS) to trigger an individual detector of a ground based array as a function of distance to the shower axis, taking into account energy, mass and direction of the primary cosmic ray. We apply this concept to the surface array of the Pierre Auger Observatory consisting of a 1.5 km spaced grid of about 1600 water Cherenkov stations. Using Monte Carlo simulations of ultra-high energy showers the LTP functions are derived for energies in the range between 1017 and 1019 eV and zenith angles up to 65°. A parametrization combining a step function with an exponential is found to reproduce them very well in the considered range of energies and zenith angles. The LTP functions can also be obtained from data using events simultaneously observed by the fluorescence and the surface detector of the Pierre Auger Observatory (hybrid events). We validate the Monte Carlo results showing how LTP functions from data are in good agreement with simulations.

Probability of satellite collision

NASA Technical Reports Server (NTRS)

Mccarter, J. W.

1972-01-01

A method is presented for computing the probability of a collision between a particular artificial earth satellite and any one of the total population of earth satellites. The collision hazard incurred by the proposed modular Space Station is assessed using the technique presented. The results of a parametric study to determine what type of satellite orbits produce the greatest contribution to the total collision probability are presented. Collision probability for the Space Station is given as a function of Space Station altitude and inclination. Collision probability was also parameterized over miss distance and mission duration.

Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment.

PubMed

Barch, Deanna M; Treadway, Michael T; Schoen, Nathan

2014-05-01

One of the most debilitating aspects of schizophrenia is an apparent interest in or ability to exert effort for rewards. Such "negative symptoms" may prevent individuals from obtaining potentially beneficial outcomes in educational, occupational, or social domains. In animal models, dopamine abnormalities decrease willingness to work for rewards, implicating dopamine (DA) function as a candidate substrate for negative symptoms given that schizophrenia involves dysregulation of the dopamine system. We used the effort-expenditure for rewards task (EEfRT) to assess the degree to which individuals with schizophrenia were wiling to exert increased effort for either larger magnitude rewards or for rewards that were more probable. Fifty-nine individuals with schizophrenia and 39 demographically similar controls performed the EEfRT task, which involves making choices between "easy" and "hard" tasks to earn potential rewards. Individuals with schizophrenia showed less of an increase in effort allocation as either reward magnitude or probability increased. In controls, the frequency of choosing the hard task in high reward magnitude and probability conditions was negatively correlated with depression severity and anhedonia. In schizophrenia, fewer hard task choices were associated with more severe negative symptoms and worse community and work function as assessed by a caretaker. Consistent with patterns of disrupted dopamine functioning observed in animal models of schizophrenia, these results suggest that 1 mechanism contributing to impaired function and motivational drive in schizophrenia may be a reduced allocation of greater effort for higher magnitude or higher probability rewards.

Suboptimal Decision Criteria Are Predicted by Subjectively Weighted Probabilities and Rewards

PubMed Central

Ackermann, John F.; Landy, Michael S.

2014-01-01

Subjects performed a visual detection task in which the probability of target occurrence at each of the two possible locations, and the rewards for correct responses for each, were varied across conditions. To maximize monetary gain, observers should bias their responses, choosing one location more often than the other in line with the varied probabilities and rewards. Typically, and in our task, observers do not bias their responses to the extent they should, and instead distribute their responses more evenly across locations, a phenomenon referred to as ‘conservatism.’ We investigated several hypotheses regarding the source of the conservatism. We measured utility and probability weighting functions under Prospect Theory for each subject in an independent economic choice task and used the weighting-function parameters to calculate each subject’s subjective utility (SU(c)) as a function of the criterion c, and the corresponding weighted optimal criteria (wcopt). Subjects’ criteria were not close to optimal relative to wcopt. The slope of SU (c) and of expected gain EG(c) at the neutral criterion corresponding to β = 1 were both predictive of subjects’ criteria. The slope of SU(c) was a better predictor of observers’ decision criteria overall. Thus, rather than behaving optimally, subjects move their criterion away from the neutral criterion by estimating how much they stand to gain by such a change based on the slope of subjective gain as a function of criterion, using inherently distorted probabilities and values. PMID:25366822

Suboptimal decision criteria are predicted by subjectively weighted probabilities and rewards.

PubMed

Ackermann, John F; Landy, Michael S

2015-02-01

Subjects performed a visual detection task in which the probability of target occurrence at each of the two possible locations, and the rewards for correct responses for each, were varied across conditions. To maximize monetary gain, observers should bias their responses, choosing one location more often than the other in line with the varied probabilities and rewards. Typically, and in our task, observers do not bias their responses to the extent they should, and instead distribute their responses more evenly across locations, a phenomenon referred to as 'conservatism.' We investigated several hypotheses regarding the source of the conservatism. We measured utility and probability weighting functions under Prospect Theory for each subject in an independent economic choice task and used the weighting-function parameters to calculate each subject's subjective utility (SU(c)) as a function of the criterion c, and the corresponding weighted optimal criteria (wc opt ). Subjects' criteria were not close to optimal relative to wc opt . The slope of SU(c) and of expected gain EG(c) at the neutral criterion corresponding to β = 1 were both predictive of the subjects' criteria. The slope of SU(c) was a better predictor of observers' decision criteria overall. Thus, rather than behaving optimally, subjects move their criterion away from the neutral criterion by estimating how much they stand to gain by such a change based on the slope of subjective gain as a function of criterion, using inherently distorted probabilities and values.

Delayed Matching to Sample: Probability of Responding in Accord with Equivalence as a Function of Different Delays

ERIC Educational Resources Information Center

Arntzen, Erik

2006-01-01

The present series of 4 experiments investigated the probability of responding in accord with equivalence in adult human participants as a function of increasing or decreasing delays in a many-to-one (MTO) or comparison-as-node and one-to-many (OTM) or sample-as-node conditional discrimination procedure. In Experiment 1, 12 participants started…

Stability Criteria Analysis for Landing Craft Utility

DTIC Science & Technology

2017-12-01

Square meter m/s Meters per Second m/s2 Meters per Second Squared n Vertical Displacement of Sea Water Free Surface n3 Ship’s Heave... Displacement n5 Ship’s Pitch Angle p(ξ) Rayleigh Distribution Probability Function POSSE Program of Ship Salvage Engineering pk...Spectrum Constant γ JONSWAP Wave Spectrum Peak Factor Γ(λ) Gamma Probability Function Δ Ship’s Displacement Δω Small Frequency

Efficient Transition Probability Computation for Continuous-Time Branching Processes via Compressed Sensing.

PubMed

Xu, Jason; Minin, Vladimir N

2015-07-01

Branching processes are a class of continuous-time Markov chains (CTMCs) with ubiquitous applications. A general difficulty in statistical inference under partially observed CTMC models arises in computing transition probabilities when the discrete state space is large or uncountable. Classical methods such as matrix exponentiation are infeasible for large or countably infinite state spaces, and sampling-based alternatives are computationally intensive, requiring integration over all possible hidden events. Recent work has successfully applied generating function techniques to computing transition probabilities for linear multi-type branching processes. While these techniques often require significantly fewer computations than matrix exponentiation, they also become prohibitive in applications with large populations. We propose a compressed sensing framework that significantly accelerates the generating function method, decreasing computational cost up to a logarithmic factor by only assuming the probability mass of transitions is sparse. We demonstrate accurate and efficient transition probability computations in branching process models for blood cell formation and evolution of self-replicating transposable elements in bacterial genomes.

Efficient Transition Probability Computation for Continuous-Time Branching Processes via Compressed Sensing

PubMed Central

Xu, Jason; Minin, Vladimir N.

2016-01-01

Branching processes are a class of continuous-time Markov chains (CTMCs) with ubiquitous applications. A general difficulty in statistical inference under partially observed CTMC models arises in computing transition probabilities when the discrete state space is large or uncountable. Classical methods such as matrix exponentiation are infeasible for large or countably infinite state spaces, and sampling-based alternatives are computationally intensive, requiring integration over all possible hidden events. Recent work has successfully applied generating function techniques to computing transition probabilities for linear multi-type branching processes. While these techniques often require significantly fewer computations than matrix exponentiation, they also become prohibitive in applications with large populations. We propose a compressed sensing framework that significantly accelerates the generating function method, decreasing computational cost up to a logarithmic factor by only assuming the probability mass of transitions is sparse. We demonstrate accurate and efficient transition probability computations in branching process models for blood cell formation and evolution of self-replicating transposable elements in bacterial genomes. PMID:26949377

Maximum predictive power and the superposition principle

NASA Technical Reports Server (NTRS)

Summhammer, Johann

1994-01-01

In quantum physics the direct observables are probabilities of events. We ask how observed probabilities must be combined to achieve what we call maximum predictive power. According to this concept the accuracy of a prediction must only depend on the number of runs whose data serve as input for the prediction. We transform each probability to an associated variable whose uncertainty interval depends only on the amount of data and strictly decreases with it. We find that for a probability which is a function of two other probabilities maximum predictive power is achieved when linearly summing their associated variables and transforming back to a probability. This recovers the quantum mechanical superposition principle.

Dense CO2 as a Solute, Co-Solute or Co-Solvent in Particle Formation Processes: A Review

PubMed Central

Nunes, Ana V. M.; Duarte, Catarina M. M.

2011-01-01

The application of dense gases in particle formation processes has attracted great attention due to documented advantages over conventional technologies. In particular, the use of dense CO2 in the process has been subject of many works and explored in a variety of different techniques. This article presents a review of the current available techniques in use in particle formation processes, focusing exclusively on those employing dense CO2 as a solute, co-solute or co-solvent during the process, such as PGSS (Particles from gas-saturated solutions®), CPF (Concentrated Powder Form®), CPCSP (Continuous Powder Coating Spraying Process), CAN-BD (Carbon dioxide Assisted Nebulization with a Bubble Dryer®), SEA (Supercritical Enhanced Atomization), SAA (Supercritical Fluid-Assisted Atomization), PGSS-Drying and DELOS (Depressurization of an Expanded Liquid Organic Solution). Special emphasis is given to modifications introduced in the different techniques, as well as the limitations that have been overcome. PMID:28824121

Propaganda, Public Information, and Prospecting: Explaining the Irrational Exuberance of Central Place Foragers During a Late Nineteenth Century Colorado Silver Rush.

PubMed

Glover, Susan M

2009-10-01

Traditionally, models of resource extraction assume individuals act as if they form strategies based on complete information. In reality, gathering information about environmental parameters may be costly. An efficient information gathering strategy is to observe the foraging behavior of others, termed public information. However, media can exploit this strategy by appearing to supply accurate information while actually shaping information to manipulate people to behave in ways that benefit the media or their clients. Here, I use Central Place Foraging (CPF) models to investigate how newspaper propaganda shaped ore foraging strategies of late nineteenth-century Colorado silver prospectors. Data show that optimistic values of silver ore published in local newspapers led prospectors to place mines at a much greater distance than was profitable. Models assuming perfect information neglect the possibility of misinformation among investors, and may underestimate the extent and degree of human impacts on areas of resource extraction.

Probability mapping of scarred myocardium using texture and intensity features in CMR images

PubMed Central

2013-01-01

Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

Exact probability distribution functions for Parrondo's games

NASA Astrophysics Data System (ADS)

Zadourian, Rubina; Saakian, David B.; Klümper, Andreas

2016-12-01

We study the discrete time dynamics of Brownian ratchet models and Parrondo's games. Using the Fourier transform, we calculate the exact probability distribution functions for both the capital dependent and history dependent Parrondo's games. In certain cases we find strong oscillations near the maximum of the probability distribution with two limiting distributions for odd and even number of rounds of the game. Indications of such oscillations first appeared in the analysis of real financial data, but now we have found this phenomenon in model systems and a theoretical understanding of the phenomenon. The method of our work can be applied to Brownian ratchets, molecular motors, and portfolio optimization.

Estimation of the four-wave mixing noise probability-density function by the multicanonical Monte Carlo method.

PubMed

Neokosmidis, Ioannis; Kamalakis, Thomas; Chipouras, Aristides; Sphicopoulos, Thomas

2005-01-01

The performance of high-powered wavelength-division multiplexed (WDM) optical networks can be severely degraded by four-wave-mixing- (FWM-) induced distortion. The multicanonical Monte Carlo method (MCMC) is used to calculate the probability-density function (PDF) of the decision variable of a receiver, limited by FWM noise. Compared with the conventional Monte Carlo method previously used to estimate this PDF, the MCMC method is much faster and can accurately estimate smaller error probabilities. The method takes into account the correlation between the components of the FWM noise, unlike the Gaussian model, which is shown not to provide accurate results.

Kullback-Leibler information function and the sequential selection of experiments to discriminate among several linear models

NASA Technical Reports Server (NTRS)

Sidik, S. M.

1972-01-01

The error variance of the process prior multivariate normal distributions of the parameters of the models are assumed to be specified, prior probabilities of the models being correct. A rule for termination of sampling is proposed. Upon termination, the model with the largest posterior probability is chosen as correct. If sampling is not terminated, posterior probabilities of the models and posterior distributions of the parameters are computed. An experiment was chosen to maximize the expected Kullback-Leibler information function. Monte Carlo simulation experiments were performed to investigate large and small sample behavior of the sequential adaptive procedure.

Effect of Non-speckle Echo Signals on Tissue Characteristics for Liver Fibrosis using Probability Density Function of Ultrasonic B-mode image

NASA Astrophysics Data System (ADS)

Mori, Shohei; Hirata, Shinnosuke; Yamaguchi, Tadashi; Hachiya, Hiroyuki

To develop a quantitative diagnostic method for liver fibrosis using an ultrasound B-mode image, a probability imaging method of tissue characteristics based on a multi-Rayleigh model, which expresses a probability density function of echo signals from liver fibrosis, has been proposed. In this paper, an effect of non-speckle echo signals on tissue characteristics estimated from the multi-Rayleigh model was evaluated. Non-speckle signals were determined and removed using the modeling error of the multi-Rayleigh model. The correct tissue characteristics of fibrotic tissue could be estimated with the removal of non-speckle signals.

Exact probability distribution functions for Parrondo's games.

PubMed

Zadourian, Rubina; Saakian, David B; Klümper, Andreas

2016-12-01

We study the discrete time dynamics of Brownian ratchet models and Parrondo's games. Using the Fourier transform, we calculate the exact probability distribution functions for both the capital dependent and history dependent Parrondo's games. In certain cases we find strong oscillations near the maximum of the probability distribution with two limiting distributions for odd and even number of rounds of the game. Indications of such oscillations first appeared in the analysis of real financial data, but now we have found this phenomenon in model systems and a theoretical understanding of the phenomenon. The method of our work can be applied to Brownian ratchets, molecular motors, and portfolio optimization.

Computing exact bundle compliance control charts via probability generating functions.

PubMed

Chen, Binchao; Matis, Timothy; Benneyan, James

2016-06-01

Compliance to evidenced-base practices, individually and in 'bundles', remains an important focus of healthcare quality improvement for many clinical conditions. The exact probability distribution of composite bundle compliance measures used to develop corresponding control charts and other statistical tests is based on a fairly large convolution whose direct calculation can be computationally prohibitive. Various series expansions and other approximation approaches have been proposed, each with computational and accuracy tradeoffs, especially in the tails. This same probability distribution also arises in other important healthcare applications, such as for risk-adjusted outcomes and bed demand prediction, with the same computational difficulties. As an alternative, we use probability generating functions to rapidly obtain exact results and illustrate the improved accuracy and detection over other methods. Numerical testing across a wide range of applications demonstrates the computational efficiency and accuracy of this approach.

Probabilistic #D data fusion for multiresolution surface generation

NASA Technical Reports Server (NTRS)

Manduchi, R.; Johnson, A. E.

2002-01-01

In this paper we present an algorithm for adaptive resolution integration of 3D data collected from multiple distributed sensors. The input to the algorithm is a set of 3D surface points and associated sensor models. Using a probabilistic rule, a surface probability function is generated that represents the probability that a particular volume of space contains the surface. The surface probability function is represented using an octree data structure; regions of space with samples of large conariance are stored at a coarser level than regions of space containing samples with smaller covariance. The algorithm outputs an adaptive resolution surface generated by connecting points that lie on the ridge of surface probability with triangles scaled to match the local discretization of space given by the algorithm, we present results from 3D data generated by scanning lidar and structure from motion.

Gravitational lensing, time delay, and gamma-ray bursts

NASA Technical Reports Server (NTRS)

Mao, Shude

1992-01-01

The probability distributions of time delay in gravitational lensing by point masses and isolated galaxies (modeled as singular isothermal spheres) are studied. For point lenses (all with the same mass) the probability distribution is broad, and with a peak at delta(t) of about 50 S; for singular isothermal spheres, the probability distribution is a rapidly decreasing function with increasing time delay, with a median delta(t) equals about 1/h month, and its behavior depends sensitively on the luminosity function of galaxies. The present simplified calculation is particularly relevant to the gamma-ray bursts if they are of cosmological origin. The frequency of 'recurrent' bursts due to gravitational lensing by galaxies is probably between 0.05 and 0.4 percent. Gravitational lensing can be used as a test of the cosmological origin of gamma-ray bursts.

Economic decision-making compared with an equivalent motor task.

PubMed

Wu, Shih-Wei; Delgado, Mauricio R; Maloney, Laurence T

2009-04-14

There is considerable evidence that human economic decision-making deviates from the predictions of expected utility theory (EUT) and that human performance conforms to EUT in many perceptual and motor decision tasks. It is possible that these results reflect a real difference in decision-making in the 2 domains but it is also possible that the observed discrepancy simply reflects typical differences in experimental design. We developed a motor task that is mathematically equivalent to choosing between lotteries and used it to compare how the same subject chose between classical economic lotteries and the same lotteries presented in equivalent motor form. In experiment 1, we found that subjects are more risk seeking in deciding between motor lotteries. In experiment 2, we used cumulative prospect theory to model choice and separately estimated the probability weighting functions and the value functions for each subject carrying out each task. We found no patterned differences in how subjects represented outcome value in the motor and the classical tasks. However, the probability weighting functions for motor and classical tasks were markedly and significantly different. Those for the classical task showed a typical tendency to overweight small probabilities and underweight large probabilities, and those for the motor task showed the opposite pattern of probability distortion. This outcome also accounts for the increased risk-seeking observed in the motor tasks of experiment 1. We conclude that the same subject distorts probability, but not value, differently in making identical decisions in motor and classical form.

Introducing a Method for Calculating the Allocation of Attention in a Cognitive “Two-Armed Bandit” Procedure: Probability Matching Gives Way to Maximizing

PubMed Central

Heyman, Gene M.; Grisanzio, Katherine A.; Liang, Victor

2016-01-01

We tested whether principles that describe the allocation of overt behavior, as in choice experiments, also describe the allocation of cognition, as in attention experiments. Our procedure is a cognitive version of the “two-armed bandit choice procedure.” The two-armed bandit procedure has been of interest to psychologistsand economists because it tends to support patterns of responding that are suboptimal. Each of two alternatives provides rewards according to fixed probabilities. The optimal solution is to choose the alternative with the higher probability of reward on each trial. However, subjects often allocate responses so that the probability of a response approximates its probability of reward. Although it is this result which has attracted most interest, probability matching is not always observed. As a function of monetary incentives, practice, and individual differences, subjects tend to deviate from probability matching toward exclusive preference, as predicted by maximizing. In our version of the two-armed bandit procedure, the monitor briefly displayed two, small adjacent stimuli that predicted correct responses according to fixed probabilities, as in a two-armed bandit procedure. We show that in this setting, a simple linear equation describes the relationship between attention and correct responses, and that the equation’s solution is the allocation of attention between the two stimuli. The calculations showed that attention allocation varied as a function of the degree to which the stimuli predicted correct responses. Linear regression revealed a strong correlation (r = 0.99) between the predictiveness of a stimulus and the probability of attending to it. Nevertheless there were deviations from probability matching, and although small, they were systematic and statistically significant. As in choice studies, attention allocation deviated toward maximizing as a function of practice, feedback, and incentives. Our approach also predicts the frequency of correct guesses and the relationship between attention allocation and response latencies. The results were consistent with these two predictions, the assumptions of the equations used to calculate attention allocation, and recent studies which show that predictiveness and reward are important determinants of attention. PMID:27014109

A method to deconvolve stellar rotational velocities II. The probability distribution function via Tikhonov regularization

NASA Astrophysics Data System (ADS)

Christen, Alejandra; Escarate, Pedro; Curé, Michel; Rial, Diego F.; Cassetti, Julia

2016-10-01

Aims: Knowing the distribution of stellar rotational velocities is essential for understanding stellar evolution. Because we measure the projected rotational speed v sin I, we need to solve an ill-posed problem given by a Fredholm integral of the first kind to recover the "true" rotational velocity distribution. Methods: After discretization of the Fredholm integral we apply the Tikhonov regularization method to obtain directly the probability distribution function for stellar rotational velocities. We propose a simple and straightforward procedure to determine the Tikhonov parameter. We applied Monte Carlo simulations to prove that the Tikhonov method is a consistent estimator and asymptotically unbiased. Results: This method is applied to a sample of cluster stars. We obtain confidence intervals using a bootstrap method. Our results are in close agreement with those obtained using the Lucy method for recovering the probability density distribution of rotational velocities. Furthermore, Lucy estimation lies inside our confidence interval. Conclusions: Tikhonov regularization is a highly robust method that deconvolves the rotational velocity probability density function from a sample of v sin I data directly without the need for any convergence criteria.

On Orbital Elements of Extrasolar Planetary Candidates and Spectroscopic Binaries

NASA Technical Reports Server (NTRS)

Stepinski, T. F.; Black, D. C.

2001-01-01

We estimate probability densities of orbital elements, periods, and eccentricities, for the population of extrasolar planetary candidates (EPC) and, separately, for the population of spectroscopic binaries (SB) with solar-type primaries. We construct empirical cumulative distribution functions (CDFs) in order to infer probability distribution functions (PDFs) for orbital periods and eccentricities. We also derive a joint probability density for period-eccentricity pairs in each population. Comparison of respective distributions reveals that in all cases EPC and SB populations are, in the context of orbital elements, indistinguishable from each other to a high degree of statistical significance. Probability densities of orbital periods in both populations have P(exp -1) functional form, whereas the PDFs of eccentricities can he best characterized as a Gaussian with a mean of about 0.35 and standard deviation of about 0.2 turning into a flat distribution at small values of eccentricity. These remarkable similarities between EPC and SB must be taken into account by theories aimed at explaining the origin of extrasolar planetary candidates, and constitute an important clue us to their ultimate nature.

Early diagnosis in glaucoma.

PubMed

Garway-Heath, David F

2008-01-01

This chapter reviews the evidence for the clinical application of vision function tests and imaging devices to identify early glaucoma, and sets out a scheme for the appropriate use and interpretation of test results in screening/case-finding and clinic settings. In early glaucoma, signs may be equivocal and the diagnosis is often uncertain. Either structural damage or vision function loss may be the first sign of glaucoma; neither one is consistently apparent before the other. Quantitative tests of visual function and measurements of optic-nerve head and retinal nerve fiber layer anatomy are useful to either raise or lower the probability that glaucoma is present. The posttest probability for glaucoma may be calculated from the pretest probability and the likelihood ratio of the diagnostic criterion, and the output of several diagnostic devices may be combined to achieve a final probability. However, clinicians need to understand how these diagnostic devices make their measurements, so that the validity of each test result can be adequately assessed. Only then should the result be used, together with the patient history and clinical examination, to derive a diagnosis.

Money, kisses, and electric shocks: on the affective psychology of risk.

PubMed

Rottenstreich, Y; Hsee, C K

2001-05-01

Prospect theory's S-shaped weighting function is often said to reflect the psychophysics of chance. We propose an affective rather than psychophysical deconstruction of the weighting function resting on two assumptions. First, preferences depend on the affective reactions associated with potential outcomes of a risky choice. Second, even with monetary values controlled, some outcomes are relatively affect-rich and others relatively affect-poor. Although the psychophysical and affective approaches are complementary, the affective approach has one novel implication: Weighting functions will be more S-shaped for lotteries involving affect-rich than affect-poor outcomes. That is, people will be more sensitive to departures from impossibility and certainty but less sensitive to intermediate probability variations for affect-rich outcomes. We corroborated this prediction by observing probability-outcome interactions: An affect-poor prize was preferred over an affect-rich prize under certainty, but the direction of preference reversed under low probability. We suggest that the assumption of probability-outcome independence, adopted by both expected-utility and prospect theory, may hold across outcomes of different monetary values, but not different affective values.

Reinforcement Probability Modulates Temporal Memory Selection and Integration Processes

PubMed Central

Matell, Matthew S.; Kurti, Allison N.

2013-01-01

We have previously shown that rats trained in a mixed-interval peak procedure (tone = 4s, light = 12s) respond in a scalar manner at a time in between the trained peak times when presented with the stimulus compound (Swanton & Matell, 2011). In our previous work, the two component cues were reinforced with different probabilities (short = 20%, long = 80%) to equate response rates, and we found that the compound peak time was biased toward the cue with the higher reinforcement probability. Here, we examined the influence that different reinforcement probabilities have on the temporal location and shape of the compound response function. We found that the time of peak responding shifted as a function of the relative reinforcement probability of the component cues, becoming earlier as the relative likelihood of reinforcement associated with the short cue increased. However, as the relative probabilities of the component cues grew dissimilar, the compound peak became non-scalar, suggesting that the temporal control of behavior shifted from a process of integration to one of selection. As our previous work has utilized durations and reinforcement probabilities more discrepant than those used here, these data suggest that the processes underlying the integration/selection decision for time are based on cue value. PMID:23896560